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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18356797 | Is it all about sex? Acupuncture for the treatment of pain from a biological and gender pe | 2008 Mar | Pain is a unique personal experience showing variability where gender and sex related effects might contribute. The mechanisms underlying the differences between women and men are currently unknown but are likely to be complex and involving interactions between biological, sociocultural and psychological aspects. In women, painful experimental stimuli are generally reported to produce a greater intensity of pain than in men. Clinical pain is often reported with higher severity and frequency, longer duration, and present in a greater number of body regions in women than in men. Women are also more likely to experience a number of painful conditions such as fibromyalgia, temporomandibular dysfunction, migraine, rheumatoid arthritis and irritable bowel syndrome. With regard to biological factors, quantitative as well as qualitative differences in the endogenous pain inhibitory systems have been implicated, as well as an influence of gonadal hormones. Psychosocial factors like sex role beliefs, pain coping strategies, and pain related expectancies may also contribute to the differences. Being exposed to repeated painful visceral events (eg menses, labour) during life may contribute to an increased sensitivity to, and greater prevalence of, pain among women. When assessing the outcome of pharmacological and non-pharmacological therapies in pain treatment, the factors of gender and sex should be taken into account as the response to an intervention may differ. Preferably, treatment recommendations should be based on studies using both women and men as the norm. Due to variability in results, findings from animal studies and experiments in healthy subjects should be interpreted with care. | |
18281229 | [Mesenchymal stem cells and the immune system--immunosuppression without drugs?]. | 2008 Feb 24 | Mesenchymal stem cells (MSC) - isolated from various tissues in humans and other species - are one of the most promising adult stem cell types due to their availability and the relatively simple requirements for in vitro expansion. They have the capacity to differentiate into several tissues, including bone, cartilage, tendon, muscle and adipose, and produce growth factors and cytokines that promote hematopoietic cell expansion and differentiation. In vivo, MSCs are able to repair damaged tissue from kidney, heart, liver, pancreas and gastrointestinal tract. Furthermore, they also have anti-proliferative, immunomodulatory and anti-inflammatory effects, but evoke only little immune reactivity. Although the mechanism underlying the immunosuppressive effects of MSCs has not been clearly defined, their immunosuppressive properties have already been exploited in the clinical setting. Therefore, in the future, MSCs might have implications for treatment of allograft rejection, graft-versus-host disease, rheumatoid arthritis, autoimmune inflammatory bowel disease and other disorders in which immunomodulation and tissue repair are required. The aim of this review is to critically analyze the field of MSC biology, particularly with respect to their immunomodulatory properties and potential clinical use in the future. | |
17985235 | Interactions between TNF and GnRH. | 2008 Apr | Tumour necrosis factor (TNF) ligand members and their associated TNF receptor (TNFR) superfamilies have many diverse physiological roles. TNF is thought to play a critical role in the pathophysiology of a range of diseases including refractory asthma, sepsis, ankylosing spondylitis, lupus, type II diabetes, multiple sclerosis and psoriasis. The recent continued expansion of the novel anti-TNF therapeutic agents (etanercept and infliximab) has seen major improvements in the treatment of some inflammatory-based human diseases including notably rheumatoid arthritis and Crohn's disease, with other conditions currently being trialled using anti-TNF agents. The cellular signalling machinery used by TNFRs to achieve their many cellular responses are discussed, as is the gonadotrophin-releasing hormone (GnRH) receptor signalling mechanisms. TNF is known to have many actions throughout the body including effects on the hypothalamic-pituitary-adrenal/gonadal axes, with many anti-gonadotrophic effects including a role in the development of endometriosis. These interactions between TNF, GnRH and gonadotrophs are discussed. | |
17965780 | Progress in immunotherapy rituximab. | 2007 Nov | Rituximab is an anti-CD20 chimeric monoclonal antibody that has shown substantial activity. Since its discovery, rituximab has been used with great success in a variety of hematological malignancies. Its success in the management of aggressive lymphomas led to expansion of its use in other conditions such as stem cell transplantation, post-transplant lymphoproliferative disorder, and other non-malignant conditions where B cell activation is thought to be important, such as idiopathic thrombocytopenic purpura and rheumatoid arthritis. The side effects have been remarkably few, particularly, infection is not more common than with chemotherapy alone. This article reviews the structure, mechanism of action, and uses of rituximab as monotherapy or in combination with chemotherapy. | |
17899236 | Range of motion measurement of an artificial hip joint using CT images. | 2007 Dec | Total hip arthroplasty (THA) is one of the most effective treatments for osteoarthritis and rheumatoid arthritis. Dislocation of the femoral head from the acetabular socket is a major problem of THA. To prevent dislocation, it is important to know the range of motion (ROM) after THA. Although various studies on the ROM were carried out, there exist only a few reports on ROM evaluation in individual patients. This is because in clinical cases, bone-to-bone and bone-to-component contacts must be considered besides the impingement of components. In this study, a new method for evaluating ROM of internal/external rotation, which takes into account all combinations of contacts between the bones and components, was proposed. A computer simulation demonstrated that the RMS error of the proposed method was approximately 3 degrees . The method was applied to 33 THAs under various conditions of flexion and adduction angles. The method was able to detect any type of impingement. The evaluated ROM was in good agreement with that measured during the THA operation (correlation coefficient = 0.91). | |
17895946 | [Human milk, immune responses and health effects]. | 2007 Sep 20 | BACKGROUND: Besides providing optimal nutrition to infants, human milk contains a multitude of immunological components. These components are important for protection against infections and also support the development and maturation of the infant's own immune system. This review focuses on the function of some classical immunocomponents of human milk. Relevant studies are presented that describe health benefits of human milk for the child and of lactation for the mother. MATERIAL AND METHODS: Relevant articles were found mainly by searching PubMed. RESULTS AND INTERPRETATION: Humoral and cellular components of human milk confer protection against infections in the respiratory--, gastrointestinal--and urinary tract. Human milk also protects premature children from neonatal sepsis and necrotizing enterocolitis. There is evidence that human milk may confer long-term benefits such as lower risk of certain autoimmune diseases, inflammatory bowel disease and probably some malignancies. Human milk possibly affects components of the metabolic syndrome. Recent studies demonstrate long-term health benefits of lactation also for the mother. A reduced incidence of breast cancer is best documented. An increasing number of studies indicate protection against ovarian cancer, rheumatoid arthritis and type II diabetes. | |
17718227 | [Retinal pigment epithelium--the point about safety of antimalarial agents]. | 2007 | The antimalarial agents Chloroquine and Hydroxychloroquine are used for the treatment of inflammatory disorders such as rheumatoid arthritis and lupus erythematosus. The first published reports of retinal toxicity appeared in 1959. Despite a low incidence for low doses and a short period of time, a regular ophthalmological screening is recommended to detect this maculopathy early. High risk criteria are: > 3 mg/kg/d of Chloroquine or > 6.5 mg/kg/d of Hydroxychloroquine, duration of treatment > 5 years, obesity, renal or hepatic disease, old age or pre-existing macular disease. Annual screening, and in some cases every 6 months, is recommended for high risk patients. Low risk patients will have an ophthalmologic examination every 18 months. The baseline examination includes visual acuity, Amsler grid, biomicroscopy, automated perimetry (central 10 degrees), color vision testing and fundus. Fluoroangiography and (multifocal) electroretinography should be considered if baseline screening is doubtfull or if toxicity is suspected. If relative paracentral bilateral scotomas or subtle alterations of retinal pigmentary epithelium are documented, the drug should be stopped. The collaboration with the internist and good information to the patient are necessary. | |
17505610 | The role of tumor necrosis factor-alpha (TNF-alpha) in bone resorption present in middle e | 2007 Jan | Cholesteatoma may cause bone erosion, with high morbidity and mortality rates. Tumor necrosis factor-alpha (TNF-a) is one of the main cytokines involved in this process. Our goal was to evaluate the role of TNF-a in Bone Resorption and its effect on cholesteatoma. MATERIAL AND METHODS: analysis and critical literature review. RESULTS: Different studies have demonstrated that TNF-a is capable of causing bone erosion. It may stimulate the differentiation and maturation of osteoclasts or it may act on the bone matrix, exposing it to the action of the osteoclasts. It is possible to inhibit TNF-a, reducing its effects and prevent bone loss in illnesses such as rheumatoid arthritis,and there has been no specific investigation regarding cholesteatomas. All studies agree on the importance of TNF-a in the bone resorption process present in cholesteatomas, and on the degree of destruction observed; however, there is no consensus as to its location. These differences are probably due to receptor site. CONCLUSION: TNF-a, present in cholesteatomas, promotes bone resorption, along with other cytokines (RANKL and IL-1) related to complications. | |
17400533 | Reactivation of tuberculosis by tumor necrosis factor neutralization. | 2007 Mar | Tumor necrosis factor (TNF) is required in the control of infection with Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis. TNF is essential and non-redundant for forming microbiocidal granulomas, and cannot be replaced by other members of the TNF family. We established a model of latent Mtb infection in mice, allowing investigation of the reactivation of latent Mtb as observed in patients receiving TNF-neutralizing therapy used in rheumatoid arthritis and Crohn's disease. Antibody neutralization of TNF is able to reactivate clinically silent Mtb infection. Using mutant mice expressing solely membrane, but not soluble TNF, we demonstrated that membrane TNF is sufficient to control acute Mtb infection. Therefore, we hypothesize that TNF-neutralizing therapy, sparing membrane TNF, may have an advantage as compared to complete neutralization. In conclusion, endogenous TNF is critical for the control of tuberculosis infection. Genetic absence or pharmacological neutralization of TNF results in uncontrolled infection, while selective neutralization might retain the desired anti-inflammatory effect but reduce the infectious risk. | |
16964846 | Imaging of joints with laser-based photoacoustic tomography: an animal study. | 2006 Aug | Photoacoustic tomography (PAT), a nonionizing, noninvasive, laser-based technology was adapted to joint imaging for the first time. Pulsed laser light in the near-infrared region was directed toward a joint with resultant ultrasonic signals recorded and used to reconstruct images that present the optical properties in subsurface joint tissues. The feasibility of this joint imaging system was validated on a Sprague Dawley rat tail model and verified through comparison with histology. With sufficient penetration depth, PAT realized tomographic imaging of a joint as a whole organ noninvasively. Based on the optical contrast, various intra- and extra-articular tissues, including skin, fat, muscle, blood vessels, synovium and bone, were presented successfully in images with satisfactory spatial resolution that was primarily limited by the bandwidth of detected photoacoustic signals rather than optical diffusion as occurs in traditional optical imaging. PAT, with its intrinsic advantages, may provide a unique opportunity to enable the early diagnosis of inflammatory joint disorders, e.g., rheumatoid arthritis, and to monitor therapeutic outcomes with high sensitivity and accuracy. | |
16912549 | Assessment of inflammatory markers and endothelial function. | 2006 Sep | PURPOSE OF REVIEW: To describe the background and assessment of inflammatory markers and endothelial function in atherosclerosis. RECENT FINDINGS: Recent observations have related several inflammation markers, including cytokines and chemokines, soluble adhesion molecules, and acute-phase reactants, to the pathophysiology of atherosclerosis. Chronic inflammatory states such as rheumatoid arthritis and systemic lupus erythematosus have been identified as independent risk factors for early atherosclerosis. The role of endothelial function in atherosclerosis has been elucidated by clinical studies that have demonstrated that the status of vascular endothelium may modify the effects of risk factors on the development of atherosclerosis. These observations support the response-to-injury theory of atherosclerosis that emphasizes the role of endothelium in atherosclerosis. SUMMARY: Inflammation and endothelial function play significant roles in the pathogenesis of atherosclerosis. Elevations in certain inflammatory mediators as well as evidence of endothelial dysfunction are related to increased risk of future cardiovascular morbidity. The value of measuring inflammatory markers and endothelial function in clinical practice remains to be defined. | |
16904077 | Allele-specific MMP-3 transcription under in vivo conditions. | 2006 Sep 29 | A common matrix metalloproteinases-3 (MMP-3) -1612 5A/6A promoter polymorphism is associated with risk for cardiovascular disease, rheumatoid arthritis, and other diseases. Here we used the haplotype chromatin immunoprecipitation method to study allele-specific MMP-3 expression under in vivo conditions in heterozygous THP-1 cells. Pyrosequencing was used to analyse the ratio of 5A-allele to 6A-allele after chromatin immunoprecipitation using an antibody against phosphorylated active RNA polymerase II. There was no allele-specific difference in transcriptional activity during basal conditions, i.e., in unstimulated monocytic THP-1 cells. However, after stimulation of MMP-3 expression by monocyte differentiation or incubation with IL-1beta, the haplotype containing the 5A-allele was associated with higher transcriptional activity compared with the 6A-containing haplotype. Electromobility shift assay demonstrated increased binding of nuclear proteins to the 5A-allele after monocyte differentiation. In conclusion, the common MMP-3 5A/6A promoter polymorphism appears to be functional only during specific environmental conditions involving inflammation. | |
16901312 | Toll-like receptor 2 Arg753Gln gene polymorphism in Turkish patients with Behçet's diseas | 2006 Sep | Having considered the impact of the function of TLR2 in the recognition of several microorganisms that are thought to have an association with Behçet's disease (BD), we aimed to determine a possible association between the TLR2 Arg753Gln polymorphism and susceptibility to BD. We genotyped 83 patients with BD, 95 ethnically matched healthy controls, 12 patients with recurrent aphthous stomatitis (RAS) and 21 patients with rheumatoid arthritis (RA) by restriction fragment length polymorphism after PCR amplification of the genomic region encompassing the polymorphic site. Comparison of the TLR2 Arg753Gln A allele and A/G genotype frequencies did not show a significant difference between patients with BD and healthy controls (1.2% vs. 0.6%, and 2.1% vs. 1.1%, respectively). None of the patients from the RAS and RA groups had the A allele or A/G genotype. Our results indicate that the TLR2 Arg753Gln polymorphism does not play a role in the aetiopathogenesis of BD. | |
16771479 | Discovery of a TNF-alpha antagonist using chondroitin sulfate microarrays. | 2006 Jun 21 | We report the first example of synthetic chondroitin sulfate (CS) microarrays to rapidly identify glycosaminoglycan-protein interactions and probe the specificity of proteins for distinct sulfation sequences. Using the microarrays, we identify a novel interaction between CS and TNF-alpha, a proinflammatory cytokine involved in rheumatoid arthritis, Crohn's disease, and psoriasis. Moreover, we demonstrate that CS-E tetrasaccharides and polysaccharides enriched in the CS-E sulfation motif can inhibit the activity of this therapeutically important cytokine. We anticipate that carbohydrate microarrays will accelerate our understanding of glycosaminoglycan-protein interactions and the role of sulfation in modulating physiological and disease states. | |
16540375 | Prostaglandin E2 synthesis and secretion: the role of PGE2 synthases. | 2006 Jun | Prostaglandin E2 (PGE2) is a principal mediator of inflammation in diseases such as rheumatoid arthritis and osteoarthritis. Nonsteroidal anti-inflammatory medications (NSAIDs) and selective cyclooxygenase-2 (COX-2) inhibitors reduce PGE2 production to diminish the inflammation seen in these diseases, but have toxicities that may include both gastrointestinal bleeding and prothrombotic tendencies. In cells, arachidonic acid is transformed into PGE2 via cyclooxygenase (COX) enzymes and terminal prostaglandin E synthases (PGES). Accumulating data suggest that the interaction of various enzymes in the PGE2 synthetic pathway is complex and tightly regulated. In this review, we summarize the synthesis and secretion of PGE2. In particular, we focus on the three isoforms of the terminal PGES, and discuss the potential of targeting PGES as a more precise strategy for inhibiting PGE2 production. | |
16529141 | B cells in health and disease. | 2006 Mar | B cells play a key role in regulating the immune system by producing antibodies, acting as antigen-presenting cells, providing support to other mononuclear cells, and contributing directly to Inflammatory pathways. Accumulating evidence points to disruption of these tightly regulated processes in the pathogenesis of autoimmune disorders. Although the exact mechanisms involved remain to be elucidated, a fundamental feature of many autoimmune disorders is a loss of B-cell tolerance and the inappropriate production of autoantibodies. Dysfunctional immune responses resulting from genetic mutations that cause intrinsic B-cell abnormalities and induction of autoimmunity in the T-cell compartment by B cells that have broken tolerance may also contribute to these disorders. These findings provide the rationale for B-cell depletion as a potential therapeutic strategy in autoimmune disorders and other disease states characterized by inappropriate immune responses. Preliminary results with the CD20-targeted monoclonal antibody rituximab indicate that rituximab can improve symptoms in a number of autoimmune and neurologic disorders (including rheumatoid arthritis, systemic lupus erythematosus, and paraneoplastic neurologic syndromes). Additional studies are warranted to further characterize the role of B cells in autoimmune diseases and the therapeutic utility of B-cell depletion. | |
18041205 | [Work performance as a risk factor for carpal tunnel syndrome]. | 2007 | Certification of carpal tunnel syndrome (CTS) as an occupational disease should be based on evidence that the job performance is a dominant factor responsible for its development. Features of the way the job is performed, which can increase the constriction in carpal tunnel and their quantitative analysis are presented. They include a specific position of the hand during the job performance (dorsal bending, alternate bending and extension), e.g., overcoming resistance with fingers, pincher grip, object catching and holding, exerting pressure on the hand, repeated movements or work with vibratory tools. These features characterize work of persons employed in meat processing, fitting of sub-assemblies, packing of products, or employed as supermarket cashiers. CTS occurrence in persons working with computers and thus using a keyboard or a mouse is now greatly limited owing to the improvement in ergonomic parameters of computer-equipped workposts. The paper indicates CTS risk factors (carpal tunnel size, post-traumatic lesions, rheumatoid arthritis, female gender, hormonal changes during menopause and pregnancy, and other hormonal disorders like hypothyreosis, diabetes, obesity, hypercholesterolemia, cigarette smoking, high alcohol consumption), which have been very well evidenced. In the summary, the attention was also paid to improper estimation of burden to upper limbs by listing jobs performed and stressing the need to quantitatively define hand burdening factors and estimate duration of such burdens. | |
18315972 | Medial malleolar osteotomy for the correction of varus deformity during total ankle arthro | 2008 Feb | BACKGROUND: Preoperative deformity in the frontal plane in the arthritic ankle is a risk factor for failure after total ankle arthroplasty. Medial malleolar lengthening osteotomy was developed to correct varus malalignment. MATERIALS AND METHODS: From 1998 to 2005 total ankle arthroplasty combined with medial malleolar lengthening osteotomy was done in 15 ankles (13 patients) with a mean preoperative varus deformity of 14.9 (SD, 7.8) degrees. Diagnosis was arthritis with instability in 11 ankles (9 patients) and inflammatory joint disease in 4 ankles. Two mobile-bearing designs were used. Osteosynthesis of the osteotomy was done in 2 ankles; for the remaining 13 osteotomies, no fixation was used. RESULTS: Followup was 5 (range 2 to 8) years. Neutral alignment was obtained in all ankles. In 3 patients residual hindfoot varus remained, for which a second-stage hindfoot correction was done. Two rheumatoid ankles developed a symptom-free nonunion of the medial malleolus, all other malleolar osteotomies united. One tibial component, implanted with too much anterior slope, developed early aseptic loosening and was revised. Debridement for talar-malleolar arthritis was done in two ankles. Of the 14 ankles in followup, 12 were rated as excellent or good, one as fair. One ankle with subsidence of the talar component was rated as unsatisfactory. AOFAS score increased from 30.8 preoperative to 81.0 at followup (p < 0.01). CONCLUSION: Medial malleolar lengthening osteotomy is an easy technique for the realignment of the varus ankle at the time of total ankle arthroplasty, and served as an alternative to medial ligament release or lateral ligament reconstruction. | |
16339288 | Evidence for differential acquired drug resistance to anti-tumour necrosis factor agents i | 2006 Jun | BACKGROUND: Acquired drug resistance or gradual drug failure has been described with most disease modifying antirheumatic drugs (DMARDs) and is also starting to be recognised with anti-tumour necrosis factor (anti-TNF) agents. OBJECTIVE: To study acquired drug resistance to anti-TNF agents in rheumatoid arthritis (RA). METHODS: Swiss health authorities requested continuous monitoring of patients receiving biological agents. Intensification of co-therapy with traditional DMARDs, gradual dose escalation, and drug discontinuation rates in all patients receiving infliximab, etanercept, or adalimumab, adjusting for potential confounders, were analysed. Intensification of DMARD co-therapy and time to discontinuation of the three anti-TNF agents were analysed using a proportional hazards models. Dose escalation and evolution of RA disease activity (DAS28) were analysed using a longitudinal regression model. RESULTS: 1198 patients contributing 1450 patient-years of anti-TNF treatment met the inclusion criteria. The rate of intensification of traditional DMARD co-therapy over time was significantly higher with infliximab (hazards ratio = 1.73 (99% confidence interval (CI) 1.19 to 2.51)) than with the two other agents. Infliximab also showed significant dose escalation over time, with an average dose increase of +12% (99% CI 8% to 16%) after 1 year, and +18% (99% CI 11% to 25%) after 2 years. No significant differences in discontinuation rates were seen between the three anti-TNF agents (ANOVA, p = 0.67). Evolution of disease activity over time indicated a lower therapeutic response to infliximab (DAS28, p<0.001) compared with etanercept, after 6 months' treatment. CONCLUSIONS: In this population, infliximab was associated with a higher risk of requiring intensification of DMARD co-therapy than the other anti-TNF agents and a significant dose escalation over time. Analysis of RA disease activity indicated a reduced therapeutic response to infliximab after the first 6 months of treatment, suggestive of acquired drug resistance. | |
19016697 | Outcomes of methotrexate therapy for psoriasis and relationship to genetic polymorphisms. | 2009 Feb | BACKGROUND: The use of methotrexate is limited by interindividual variability in response. Previous studies in patients with either rheumatoid arthritis or psoriasis suggest that genetic variation across the methotrexate metabolic pathway might enable prediction of both efficacy and toxicity of the drug. OBJECTIVES: To assess if single nucleotide polymorphisms (SNPs) across four genes that are relevant to methotrexate metabolism [folypolyglutamate synthase (FPGS), gamma-glutamyl hydrolase (GGH), methylenetetrahydrofolate reductase (MTHFR) and 5-aminoimidazole-4-carboxamide ribonucleotide transformylase (ATIC)] are related to treatment outcomes in patients with psoriasis. METHODS: DNA was collected from 374 patients with psoriasis who had been treated with methotrexate. Data were available on individual outcomes to therapy, namely efficacy and toxicity. Haplotype-tagging SNPs (r(2) > 0.8) for the four genes with a minor allele frequency of > 5% were selected from the HAPMAP phase II data. Genotyping was undertaken using the MassARRAY spectrometric method (Sequenom). RESULTS: There were no significant associations detected between clinical outcomes in patients with psoriasis treated with methotrexate and SNPs in the four genes investigated. CONCLUSIONS: Genetic variation in four key genes relevant to the intracellular metabolism of methotrexate does not appear to predict response to methotrexate therapy in patients with psoriasis. |