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ID PMID Title PublicationDate abstract
19328049 Removal of autoantibodies by 4-mercaptoethylpyridine-based adsorbent. 2009 Apr 15 Extracorporeal immunoadsorption (ECI) therapy using Staphylococcal Protein A columns has proven effective for removing autoantibodies and circulating immune complexes from patients selectively, providing a promising treatment for autoimmune diseases. However, due to the drawbacks of Protein A in terms of cost and stability, the widespread use of Protein A based ECI is limited. In this study, we investigated the feasibility of 4-mercaptoethylpyridine (MEP, MW 139 Da), a simple and inexpensive synthetic compound, as an alternative to Protein A for autoantibody removal therapy. MEP-based adsorbents were prepared by coupling MEP to Sepharose CL-6B. We found that ligand density was an adjustable parameter for the synthesis of adsorbents aiming at different pathogenic factors, depending on the class of antibody. MEP-Sepharose with a ligand density of 98.8 micromol/ml could remove 80% of the anti-double-stranded DNA antibodies from human serum, whereas a ligand density of 64.5 micromol/ml was enough to remove 96% of the rheumatoid factor (RF) in the serum. Moreover, MEP-based adsorbents showed a lower degree of individual differences compared to Protein A-Sepharose. RF removal of 90% was achieved for all 12 serum samples from different individuals. Among the 14 serum samples derived from systemic lupus erythematosus patients, 11 samples had markedly reduced antinuclear antibody titers. In addition, non-specific adsorption of plasma components to MEP-Sepharose was limited, and the binding capacity of the absorbent for IgG was still about 20 mg/ml of gel after 10 cycles. The results indicated that MEP-based adsorbent could offer a new type of adsorber for the treatment of autoimmune diseases.
20004647 Pharmacological targeting reveals distinct roles for CXCR2/CXCR1 and CCR2 in a mouse model 2010 Jan 1 Neutrophils and monocytes are abundantly represented in the synovial fluid and tissue in rheumatoid arthritis patients. We therefore explored the effects of small molecule chemokine receptor antagonists to block migration of these cells in anti-collagen antibody-induced arthritis. Targeting neutrophil migration with the CXCR2/CXCR1 antagonist SCH563705 led to a dose-dependent decrease in clinical disease scores and paw thickness measurements and clearly reduced inflammation and bone and cartilage degradation based on histopathology and paw cytokine analyses. In contrast, targeting monocyte migration with the CCR2 antagonist MK0812 had no effect on arthritis disease severity. The pharmacodynamic activities of both SCH563705 and MK0812 were verified by assessing their effects on the peripheral blood monocyte and neutrophil populations. SCH563705 selectively reduced the peripheral blood neutrophil frequency, and caused an elevation in the CXCR2 ligand CXCL1. MK0812 selectively reduced the peripheral blood monocyte frequency, and caused an elevation in the CCR2 ligand CCL2. The much greater impact of CXCR2/CXCR1 antagonism relative to CCR2 antagonism in this model of arthritis highlights the therapeutic potential for targeting CXCR2/CXCR1 in human arthritides.
20845087 Anti-tumor necrosis factor-α therapy and changes of flow-mediated vasodilatation in psori 2010 Dec For a long time, the endothelial covering of the vessels has been considered an inert surface. On the contrary, the endothelial cells are active and dynamic elements in the interaction between blood and tissues. The control of the vessel basal tone is obtained by the complex balance between the relaxing and contracting endothelial factors. Previous clinical studies show that patients suffering from rheumatoid arthritis and other autoimmune rheumatologic pathologies are at high risk of death being prematurely affected by atherosclerosis and cardiovascular diseases. Blocking tumor necrosis factor (TNF)-α by biological drugs improves the endothelial function. The aim of our study was to evaluate the effects of two anti-TNF-α drugs (infliximab and etanercept) on the endothelial function by evaluating the flow-mediated dilatation (FMD), which was measured in the brachial artery before and after treatment and after 8-12 weeks. We enrolled 36 patients (average age 52 ± 9.8 years, 12 men and 24 women), 25 of them were affected by rheumatoid arthritis (RA) and 11 were affected by psoriatic arthritis (PsA) and they were divided into three groups: 10 patients were treated with etanercept, 13 patients were treated with infliximab, 13 patients were treated with DMARDs. We measured the common carotid intimal-medial thickness (ccIMT) and the endothelial function was evaluated by FMD measurement in the brachial artery, before treatment, 1 h after the beginning of treatment and after 8-12 weeks. No statistically significant difference between the three groups was found for the ultrasonographic evaluation of the carotid IMT. On the contrary, the differences between FMD values before and after the treatment in the patients treated with etanercept (13.1 ± 0.01 vs. 18.8 ± 0.01%, p < 0.01) and in the patients treated with infliximab (11.8 ± 0.09 vs. 16.7 ± 0.09%, p < 0.01) were statistically significant. Long-term evaluation for infliximab and etanercept was performed by comparing the FMD values, respectively, 8 and 12 weeks after the first treatment. After 8 weeks, FMD value was similar to the value recorded at enrollment in the infliximab group (11.9 ± 0.03 vs. 13.54 ± 0.04%, p = 0.236) and the FMD values in the etanercept group after 12 weeks showed a not statistically significant reduction of vasodilatating effect (13.01 ± 0.03 vs. 15.67 ± 0.02%, p = 0.197). In conclusion, the use of biological drugs in patients affected by autoimmune arthritis can modify the endothelial function, as indicated by the induced FMD changes, but the long-term effect tends to be considerably reduced.
20099229 Fundus autofluorescence and spectral domain optical coherence tomography in early detectio 2010 Jul PURPOSE: To report fundus autofluorescence (FAF) and spectral-domain optical coherence tomography (SD-OCT) findings in a patient with early hydroxychloroquine maculopathy. METHODS: A 50-year-old man presented with complaints of ring-like shadows in front of his eyes. He had been on hydroxychloroquine (Plaquenil) 400 mg orally twice daily for 10 years (5.14 mg/kg/day). Fundus examination revealed granular hypopigmentation in an arcuate pattern in the inferior parafoveal area bilaterally. The patient underwent further evaluation with SD-OCT and FAF imaging. Functional changes were assessed by microperimetry. RESULTS: Hypopigmented lesions on the fundus were autofluorescent and SD-OCT corresponding to this area revealed loss of inner segment-outer segment, suggesting loss of photoreceptor layer in the affected area with underling dysfunctional retinal pigment epithelium. CONCLUSIONS: Findings on SD-OCT and FAF imaging support the histopathologic findings described in cases of hydroxychloroquine maculopathy.
19248117 Association of the autoimmunity locus 4q27 with juvenile idiopathic arthritis. 2009 Mar OBJECTIVE: Juvenile idiopathic arthritis (JIA) is characterized by chronic arthritis and an autoimmune etiology. In several autoimmune diseases, including rheumatoid arthritis (RA), an association with the 4q27 locus has been reported. We undertook this study to investigate the possible role of the 4q27 locus in JIA. METHODS: A case-control association study was conducted, with a total of 655 Caucasian JIA patients and 791 healthy controls divided into 2 independent sample sets. The rs6822844 marker in the 4q27 locus was genotyped. RESULTS: In the first and larger sample set, a 5% decrease in T allele frequency was observed in patients compared with controls (allelic odds ratio [OR] 0.72 [95% confidence interval 0.55-0.95], P = 0.019), and in the second set, a 3% decrease was observed (allelic OR 0.81 [95% confidence interval 0.61-1.09], P = 0.169). The combined data set generated an OR of 0.76 (95% confidence interval 0.62-0.93, P = 7.08 x 10(-3)). When the different JIA subtypes were analyzed individually, significant decreases were seen in the subtypes with a polyarticular course of disease (extended oligoarthritis [P = 0.019] and rheumatoid factor-negative polyarthritis [P = 0.038]). CONCLUSION: Our findings suggest that the 4q27 locus, previously reported to be associated with RA, type 1 diabetes mellitus, celiac disease, and psoriatic arthritis, is also associated with susceptibility to JIA.
20060725 The role of the cemented all-polyethylene tibial component in total knee replacement: a 30 2010 Dec Use of an all-polyethylene tibial component in primary total knee arthroplasty remains an attractive option considering the reported durability of the construct, the lowered cost compared to modular metal-backed tibia, and the elimination of backside wear. The two major intra-operative disadvantages include the inability to alter the tibial component thickness after permanent implant placement and the inability to use varus-valgus constrained designs. The long-term disadvantage is the inability to perform a modular insert exchange should this be required. We report the 30-year outcome of a single patient using the duopatellar total knee replacement system. Based on a critical review of the literature we would recommend use in patients 80 years of age or older, consideration in patients 75 to 79 years, and possibly in younger yet less active patients. These three groups would be the least likely to require a modular tibial liner exchange in their lifetime.
19946833 Real-time sonoelastography: findings in patients with symptomatic achilles tendons and com 2010 Aug PURPOSE: Real-time sonoelastography (SE), a newly introduced ultrasound technique, has already shown conclusive results in breast, prostate, and thyroid tumor diagnostics. This study investigated the performance of SE for the differentiation of Achilles tendon alterations of tendinopathy compared to clinical examination and conventional ultrasound (US). MATERIALS AND METHODS: Achilles tendons in 25 consecutive patients with chronic Achilles tendinopathy and 25 healthy volunteers were examined clinically by US and by SE. RESULTS: In the healthy volunteers, SE showed the tendon to be hard (93 %), while distinct softening was found in 57 % of the patients. SE showed more frequent involvement of the distal (64 %) and middle third (80 %) than the proximal third (28 %) of the Achilles tendon. Using SE a mean sensitivity of 94 %, specificity of 99 %, and accuracy of 97 % were found when clinical examination was used as the reference standard. The correlation to US was 0.89. Mild softening was found in 7 % of the healthy volunteers and in 11 % of the patients. CONCLUSION: Our results emphasize that only distinct softening of Achilles tendons is comparable to clinical examination and US findings. However, mild softening might be explained by very early changes in tissue elasticity in the case of Achilles tendinopathy, which should be assessed in follow-up studies.
18836787 Telescope allograft method to reconstitute the diaphysis in limb salvage surgery. 2009 Jul We propose a surgical technique for structural allograft reconstitution of the diaphysis of long bones, maximizing surface contact between host and allograft bone. This method, analogous to a telescope, overlaps the graft and host bone, theoretically increasing bone surface contact substantially. We report the outcome of 22 telescoped allograft junction sites in 19 patients who lacked sufficient host bone to accommodate a regular-length stemmed implant. This joint-sparing reconstruction preserved 15 of 16 adjacent joints at risk for replacement. Five patients needed additional surgery, but none for nonunion. The diaphyseal length could be reconstructed enough so that a short prosthesis (less than the critical 40% of total bone length) could be used. This biologic method to reconstruct major segments of the diaphysis is best suited for patients with quantitatively or qualitatively deficient residual bone stock after tumor resection or prosthetic revision. We believe it is an excellent technique for revision knee megaprostheses when there is a short remnant of proximal femur. LEVEL OF EVIDENCE: Level IV, therapeutic study.
20043578 [Coeliac disease and other autoimmunological disorders coexistance]. 2009 Coeliac disease (gluten enteropathy) is a chronic inflammatory disease of the gastrointestinal (GI) tract of autoimmune etiology in genetically predisposed individuals. It is the most frequent enteropathy with frequency of 1/100 and 1/300 in the adult population in America and Europe respectively. Typical form of celiac disease including abdominal pain, weight loss, nausea is quite rare in adults. In some coeliac patients, symptoms persist in spite of strict gluten free diet. One of the reasons of this is interference of the autoimmune diseases. Results of our studies revealed in the group of 110 patients with diagnosed gluten enteropathy, coexistence of autoimmune disease, such as diabetes mellitus type 1 in 7.2% cases, hyperthyreosis on 1.8% of cases, vitiligo in 0.9% of cases, primary biliary cirrhosis in 2% of cases and rheumatoidal arthritis in 0,9 of cases. In the group of 80 ulcerative colitis patients, coexistence of celiac disease basing on serological histopatological investigation was found in 4 patients (5%). CONCLUSIONS: Coexistence of coeliac disease with other autoimmune diseases is quite frequent. Gluten enteropathy symptoms may be interpreted as originating from other autoimmune disease. It can delay the diagnosis of celiac disease and introduction of gluten free diet, which improves the quality of life and protects from dangerous GI complications.
19859713 The anti-malaria agent artesunate inhibits expression of vascular endothelial growth facto 2011 Jan Increasing evidence indicates that the anti-malarial agent artemisinin and its derivatives may exert anti-angiogenic effect. In the present study, we explored the effect of artesunate, a artemisinin derivative, on TNFα- and hypoxia-induced expression of hypoxia inducible factor-1α (HIF-1α) and secretion of vascular endothelial growth factor (VEGF) and inteleukin-8 (IL-8) in human rheumatoid arthritis fibroblast-like synoviocytes (RA FLS), and further investigated the signal mechanism by which this compound modulates HIF-1α, VEGF and IL-8 expression. RA FLS obtained from patients with active rheumatoid arthritis were pretreated with artesunate, and then stimulated with TNFα and hypoxia. Production of VEGF and IL-8 was measured by ELISA. Nuclear location of HIF-1α was measured by confocal fluorescence microscopy. HIF-1α and other signal transduction proteins expression was measured by Western blot. Artesunate decreased the secretion of VEGF and IL-8 from TNFα- or hypoxia-stimulated RA FLS in a dose-dependent manner. Artesunate also inhibited TNFα- or hypoxia-induced nuclear expression and translocation of HIF-1α. We also showed that artesunate prevented Akt phosphorylation, but did not find evidence that phosphorylation of p38 and ERK was affected. TNFα- or hypoxia-induced secretion of VEGF and IL-8 and expression of HIF-1α were hampered by treatment with the PI3 kinase inhibitor LY294002, suggesting that inhibition of PI3 kinase/Akt activation might inhibit VEGF and IL-8 secretion and HIF-1α expression induced by TNFα or hypoxia. Our results suggest that artesunate inhibits angiogenic factor expression in RA FLS, and provide novel evidence that, as a low-cost agent, artesunate may have therapeutic potential for RA.
19211095 Occult thyroid eye disease in patients presenting with dry eye symptoms. 2009 May PURPOSE: To describe the clinical presentation, laboratory features, and treatment outcomes in a series of patients with occult thyroid eye disease (TED). DESIGN: Retrospective observational case series. METHODS: Among 539 patients who were referred for dry eye evaluation over 2 years, 21 were diagnosed with occult TED, based on typical findings in orbital echography. Medical records of these patients were reviewed to collect information on demographics, clinical findings, laboratory studies, and treatment response. RESULTS: All patients presented with symptoms of dry eye. Median age of patients was 57 years (range, 24 to 78 years), with the majority female (86%). No patients carried prior diagnosis of TED or had typical findings of TED such as proptosis, dysmotility, or diplopia. Suspicion of TED was based on conjunctival hyperemia with or without chemosis localized to extraocular muscles (100%), and subtle widening of interpalpebral fissure (48%). Clinical findings included corneal fluorescein staining (57%), rapid tear break-up time (31%), and abnormal Schirmer test (19%). Nineteen percent of patients had other rheumatologic disorders commonly associated with dry eye: Sjögren syndrome (n = 3), and rheumatoid arthritis (n = 1). Patients were treated topically using cyclosporine 0.05% 2 to 4 times a day, with or without steroid. Other treatments were also employed as necessary including warm compresses, artificial tears, and puntal plugs. Majority of patients (76%) had improvement of their symptoms. CONCLUSION: Occult TED is a potential cause of inflammatory ocular surface disease with dry eye symptomatology and should be considered in the differential diagnosis when evaluating dry eye patients.
19759329 An environmental sensor, TRPV4 is a novel regulator of intracellular Ca2+ in human synovio 2009 Nov The activation of a vanilloid type 4 transient receptor potential channel (TRPV4) has an obligatory role in regulation of intracellular Ca(2+) (Ca(2+)(i)) in several types of cells including vascular and sensory organs. In this study, we provide evidence that TRPV4 is a functional regulator of Ca(2+)(i) in human synoviocytes. Although significant expression of TRPV4 in synoviocytes from patients with (RA) and without (CTR) rheumatoid arthritis was detected at mRNA and protein level, those in the human fibroblast-like synoviocyte line MH7A were rather lower. Consistently, the selective TRPV4 agonist 4alpha-phorbol 12,13-didecanoate (4alphaPDD) effectively elevated Ca(2+)(i) in the RA and CTR cells, which was abolished by the removal of external Ca(2+). Moreover, the elevation was inhibited by ruthenium red, a blocker of TRPVs. In MH7A cells transfected with human TRPV4 (MH7A-V4), 4alphaPDD elevated the Ca(2+)(i) in a similar manner to those in the RA and CTR cells. Electrophysiological analysis also revealed that 4alphaPDD activated nonselective cationic currents in RA cells. Application of 227 mosM solution to the RA and MH7A-V4 cells elevated their Ca(2+)(i), but this does not occur when it was applied to MH7A cells. Treatment of RA but not MH7A cells with 4alphaPDD for 24 h reduced their production of IL-8. These results suggest that an environmental sensor, TRPV4, is a novel regulator of intracellular Ca(2+) in human synoviocytes.
20623491 Intra-articular electrotransfer of mouse soluble tumour necrosis factor receptor in a muri 2010 Aug BACKGROUND: Rheumatoid arthritis (RA) is a chronic autoimmune disease that causes inflammation and destruction of the joints. In the collagen-induced arthritis mouse model of RA, we developed a nonviral gene therapy method designed to block in situ the main cytokine tumour necrosis factor (TNF)-alpha METHODS: Electrotransfer was used to deliver a plasmid encoding extracellular domain of mouse soluble TNF-alpha receptor type I fused to the Fc fragment of mouse immunoglobulin (Ig)G1 (pTNFR-Is) corresponding to a dimeric TNF-alpha soluble receptor fusion protein (mTNFR-Is/Ig). RESULTS: Delivery of the plasmid into the knees at symptom onset improved the histological inflammation and destruction not only at the knees, but also at the ankles, indicating a local and a regional therapeutic effect. The plasmid was detected in synovial membrane and meniscus specimens from the injected joints. In the synovial membrane, 15 days post-injection, interleukin (IL)-17 and TNF-alpha mRNAs expression were increased, whereas IL-10 mRNA was unchanged. However, the empty plasmid exerted a pro-inflammatory effect 30 days post-injection. CONCLUSIONS: These data indicate that local nonviral gene therapy against TNF-alpha is effective, although further work is needed to decrease plasmid induced inflammation.
19890092 Evidence for a cross-talk between human neutrophils and Th17 cells. 2010 Jan 14 Interleukin-17A (IL-17A) and IL-17F are 2 of several cytokines produced by T helper 17 cells (Th17), which are able to indirectly induce the recruitment of neutrophils. Recently, human Th17 cells have been phenotypically characterized and shown to express discrete chemokine receptors, including CCR2 and CCR6. Herein, we show that highly purified neutrophils cultured with interferon-gamma plus lipopolysaccharide produce the CCL2 and CCL20 chemokines, the known ligands of CCR2 and CCR6, respectively. Accordingly, supernatants from activated neutrophils induced chemotaxis of Th17 cells, which was greatly suppressed by anti-CCL20 and anti-CCL2 antibodies. We also discovered that activated Th17 cells could directly chemoattract neutrophils via the release of biologically active CXCL8. Consistent with this reciprocal recruitment, neutrophils and Th17 cells were found in gut tissue from Crohn disease and synovial fluid from rheumatoid arthritis patients. Finally, we report that, although human Th17 cells can directly interact with freshly isolated or preactivated neutrophils via granulocyte-macrophage colony-stimulating factor, tumor necrosis factor-alpha, and interferon-gamma release, these latter cells cannot be activated by IL-17A and IL-17F, because of their lack of IL-17RC expression. Collectively, our results reveal a novel chemokine-dependent reciprocal cross-talk between neutrophils and Th17 cells, which may represent a useful target for the treatment of chronic inflammatory diseases.
20632803 Role of CXCR4 in HIV infection and its potential as a therapeutic target. 2010 Jul The chemokine receptors CCR5 and CXCR4 are the two major coreceptors for HIV entry. Numerous efforts have been made to develop a new class of anti-HIV agents that target these coreceptors as an additional or alternative therapy to standard HAART. Among the CCR5 inhibitors developed so far, maraviroc is the first drug that has been approved by the US FDA for treating patients with R5 HIV-1. Although many CXCR4 inhibitors, some of which are highly active and orally bioavailable, have also been studied, they are still at preclinical stages or have been suspended during development. Importantly, the interaction between CXCR4 and its ligand SDF-1 is involved in various disease conditions, such as cancer cell metastasis, leukemia cell proliferation, rheumatoid arthritis and pulmonary fibrosis. Therefore, CXCR4 inhibitors have potential as novel therapeutics for the treatment of these diseases as well as HIV infection.
20505937 Anti-cyclic citrullinated peptide and rheumatoid factor in HIV positive patients. 2011 Dec The aim of this study was to determine the difference of anti-CCP and RF between HIV positive patients and a healthy control group. The rheumatological complications in HIV positive patients are rather common and are recognized as a serious problem that requires more attention. Anti-CCP and RF are the only laboratory tools for rheumatoid disorder diagnostics and predictors of the course of the disease. We determined anti-CCP and RF in sera of 35 healthy volunteers and 45 HIV positive patients. Data were compared using chi-square test, Mann-Whitney test and ROC curve statistics. Both parameters were significantly higher in HIV positive patients, and significant differences between areas under the anti-CCP and RF curves were observed. Median value for anti-CCP in HIV positive patients was higher than the reference interval, and RF values were, in the reference interval, suggested by the manufacturer. Both anti-CCP and RF are significantly higher in HIV positive patients. ROC analysis showed that anti-CCP distinguishes the two groups better than RF. Because of that, it would be of a great interest to investigate the HIV positive patients after the detailed rheumatological examination.
20186515 Increased occurrence of cardiovascular events and comorbidities in a general rheumatology 2010 Jun BACKGROUND: To identify cardiovascular and other comorbidities in a general rheumatology cohort. METHODS: Interviews/retrospective chart audits were conducted on 1,000 patients attending rheumatology outpatient clinics of a university teaching hospital. Comorbidities were classified using the Charlson comorbidity index (Ambrose et al. in Ir J Med Sci 178(1):53-55, 2009). RESULTS: Mean age 58 +/- 15.3 years, mean BMI 26. Of the patients, 400 (40%) were diagnosed with dyslipidemia and hypertension (p = 0.002), 160 (16%) with obesity and 80 (8%) with hypothyroidism. Overall 160 (16%) patients were diagnosed with coronary heart disease (CHD). Of these, 120 (75%) had RA (p = 0.001), 100 (63%) were male, mean age 60 +/- 15.8 years, 120 (75%) had dyslipidemia and BMI > 30 (p = 0.002), 112 (70%) were smokers (p = 0.002), 40 (25%) were diagnosed with diabetes mellitus and 20 (12%) with hypothyroidism. CONCLUSIONS: The increased prevalence of these comorbidities may serve as a reminder to the rheumatologists that many of their patients will have coexistent disease of which they need to be aware to properly plan their management.
20496042 Leflunomide in the treatment of patients with early rheumatoid arthritis--results of a pro 2010 Aug Leflunomide is effective and well tolerated in the treatment of rheumatoid arthritis (RA), however, data on its use in early RA are scarce. This study seeks to evaluate effectiveness and safety of leflunomide in the treatment of early RA in daily practice. This prospective, open-label, non-interventional, multi-center study was carried out over 24 weeks including adults with early RA (< or =1 year since diagnosis). Leflunomide treatment was according to label instructions. Three hundred thirty-four patients were included. Disease activity score in 28 joints (DAS28) response (reduction in DAS28 of >1.2 or reduction of >0.6 and a DAS28 of < or =5.1) was 71.9% at week 12 and 84.6% at week 24. 25.0% of patients achieved clinical remission (DAS28 < or = 2.6). Most frequently reported adverse drug reactions (ADR) were diarrhea (3.0%), nausea (2.4%), hypertension (1.8%), and headache (1.5%). Serious ADR were reported in four patients (1.2%). Leflunomide showed the effectiveness which was to be expected from controlled studies without revealing any new or hitherto unknown side effects. Onset of action was quick and significant improvement of disease was seen after 12 weeks of therapy and at even higher rates after 24 weeks irrespective of the use of a loading dose. Interestingly, the DAS28-remission rate achieved was similar to the rate seen with methotrexate or biologic therapy in other studies.
19013427 Adiponectin stimulates IL-8 production by rheumatoid synovial fibroblasts. 2009 Jan 9 The adipokines are linked not only to metabolic regulation, but also to immune responses. Adiponectin, but not leptin or resistin induced interleukin-8 production from rheumatoid synovial fibroblasts (RSF). The culture supernatant of RSF treated with adiponectin induced chemotaxis, although adiponectin itself had no such effect. Addition of antibody against adiponectin, and inhibition of adiponectin receptor gene decreased adiponectin-induced IL-8 production. Nuclear translocation of nuclear factor-kappa B was increased by adiponectin. The induction of interleukin-8 was inhibited by mitogen-activated protein kinase inhibitors. These findings suggest that adiponectin contributes to the pathogenesis of rheumatoid arthritis.
20817139 BOOST: A fast approach to detecting gene-gene interactions in genome-wide case-control stu 2010 Sep 10 Gene-gene interactions have long been recognized to be fundamentally important for understanding genetic causes of complex disease traits. At present, identifying gene-gene interactions from genome-wide case-control studies is computationally and methodologically challenging. In this paper, we introduce a simple but powerful method, named "BOolean Operation-based Screening and Testing" (BOOST). For the discovery of unknown gene-gene interactions that underlie complex diseases, BOOST allows examination of all pairwise interactions in genome-wide case-control studies in a remarkably fast manner. We have carried out interaction analyses on seven data sets from the Wellcome Trust Case Control Consortium (WTCCC). Each analysis took less than 60 hr to completely evaluate all pairs of roughly 360,000 SNPs on a standard 3.0 GHz desktop with 4G memory running the Windows XP system. The interaction patterns identified from the type 1 diabetes data set display significant difference from those identified from the rheumatoid arthritis data set, although both data sets share a very similar hit region in the WTCCC report. BOOST has also identified some disease-associated interactions between genes in the major histocompatibility complex region in the type 1 diabetes data set. We believe that our method can serve as a computationally and statistically useful tool in the coming era of large-scale interaction mapping in genome-wide case-control studies.