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Systemic lupus erythematosus is an autoimmune disease characterized by multi-system involvement and autoantibody production. Abnormal T cell DNA methylation and type-I interferon play an important role in the pathogenesis of lupus. We performed a genome-wide DNA methylation study in two independent sets of lupus patients and matched healthy controls to(More)
Systemic lupus erythematosus is a chronic-relapsing autoimmune disease of incompletely understood etiology. Recent evidence strongly supports an epigenetic contribution to the pathogenesis of lupus. To understand the extent and nature of dysregulated DNA methylation in lupus T cells, we performed a genome-wide DNA methylation study in CD4 (+) T cells in(More)
Sjögren's syndrome is a common autoimmune disease (affecting ∼0.7% of European Americans) that typically presents as keratoconjunctivitis sicca and xerostomia. Here we report results of a large-scale association study of Sjögren's syndrome. In addition to strong association within the human leukocyte antigen (HLA) region at 6p21 (Pmeta = 7.65 × 10(-114)),(More)
PURPOSE Expression of the proteoglycan core proteins biglycan, decorin, perlecan and syndecan-1, and differentiation related markers of keratins 18 and 20 were examined to determine the origins of the loss of the glycosaminoglycan layer and investigate more fully the altered differentiation of the urothelium in interstitial cystitis. MATERIALS AND METHODS(More)
Glutamate-releasing synapses are essential in fast neuronal signalling. Plasticity at these synapses is important for learning and memory as well as for the activity-dependent control of neuronal development. We have evaluated the trial-to-trial fluctuations of excitatory postsynaptic currents mediated by glutamate receptors of the AMPA and NMDA types in(More)
NMDA receptor dependent synaptic plasticity was examined in hippocampal slices using a novel pharmacological pairing procedure. Field excitatory postsynaptic potentials (EPSPs) were recorded from the CA1 area of slices maintained in a low Mg(2+) solution using a stimulus rate of 0.1-0.2 Hz. The NMDA receptor antagonist 2-amino-5-phosphonovalerate (AP5) was(More)
The involvement of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) vs. N-methyl-d-aspartate (NMDA) receptor mediated changes in NMDA-induced long-term depression (LTD) was assessed by monitoring isolated AMPA, isolated NMDA and composite field excitatory postsynaptic potentials (EPSP) in the CA1 area of acute rat hippocampal slices.(More)
Systemic lupus erythematosus (SLE) has a strong but incompletely understood genetic architecture. We conducted an association study with replication in 4,478 SLE cases and 12,656 controls from six East Asian cohorts to identify new SLE susceptibility loci and better localize known loci. We identified ten new loci and confirmed 20 known loci with genome-wide(More)
Fibrosis is a common disease process in which profibrotic cells disturb organ function by secreting disorganized extracellular matrix (ECM). Adipose tissue fibrosis occurs during obesity and is associated with metabolic dysfunction, but how profibrotic cells originate is still being elucidated. Here, we use a developmental model to investigate perivascular(More)
OBJECTIVES To perform fine mapping of the autoimmunity susceptibility gene BLK and identify functional variants involved in systemic lupus erythematosus (SLE). METHODS Genotyping of 1163 European SLE patients and 1482 controls and imputation were performed covering the BLK gene with 158 single-nucleotide polymorphisms. Logistic regression analysis was(More)