Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 15228188 | Receptor of advanced glycation end product (RAGE) expression in the minor salivary glands | 2004 | OBJECTIVE: Receptor for advanced glycation end product (RAGE) is a cell-surface receptor with ligands capable of inducing proinflammatory responses in autoimmunity. We investigated the immunohistochemical expression and immunoblotting of RAGE in labial salivary glands from Sjögren's syndrome (SS) patients. MATERIAL AND METHODS: Ten minor salivary glands from SS and 15 from normal salivary tissue adjacent to mucocele were stained immunohistochemically using an antibody to RAGE. Immunoblotting was performed on four SS biopsies and four controls from normal gland. RESULTS: Immunohistochemistry showed all sections positive for RAGE. The SS sections did not statistically differ from controls. In immunoblotting, SS samples expressed approximately 100% more RAGE than controls [probability (p)<0.03, Student's t-test]. CONCLUSIONS: RAGE is present in the labial salivary glands of both normal and SS patients, with preliminary data suggesting over-expression in SS tissues. The role of RAGE in the pathogenesis of SS has yet to be determined. | |
| 14631283 | [Bilateral optic neuropathy in a case of primary Gougerot Sjögren's syndrome]. | 2003 Nov | INTRODUCTION: Primary Sjögren's syndrome is frequently characterized by a sicca syndrome without associated connective tissue disease. Association with an optic neuropathy is uncommon. CASE REPORT: We report a case of optic neuropathy in a 59-year-old woman known to have primary Sjögren's syndrome confirmed clinically and histologically 2 years ago. She suddenly presented an initial bilateral visual loss. The ophthalmological exam noted a visual acuity of 1/10 in the right eye and limited to light perception in the left eye, with bilateral optic ischemic neuropathy more developed in the left eye. Fluorescein angiography showed, signs of ischemic neuropathy. The diagnosis of Horton disease was suspected, but subnormal blood velocity and a negative biopsy of the temporal artery confirmed the diagnosis of optic neuropathy associated with primary Sjögren's syndrome. General steroid therapy improved optic neuropathy in the right eye but was ineffective in the left eye. CONCLUSION: Optic neuropathy associated with Sjögren's syndrome is rare but must be considered the most common ophthalmological manifestation of the disease. Visual prognosis depends on the rapidity of diagnosis and therapy. | |
| 11914666 | Decreased thyroid uptake of Tc-99m pertechnetate in patients with advanced-stage Sjögren | 2002 Apr | PURPOSE: The authors assessed the uptake of Tc-99m pertechnetate in the thyroid using salivary gland scintigraphy in patients with Sjögren syndrome and in healthy controls. MATERIALS AND METHODS: Salivary gland scintigraphy and a labial biopsy were performed in 73 patients with Sjögren syndrome. Based on the labial biopsy findings, 32 patients with a histopathologic grade of 1 or 2 were regarded as having early-stage Sjögren syndrome and 41 patients with a grade of 3 or 4 were regarded as having an advanced stage. After the administration of 370 MBq (10 mCi) Tc-99m pertechnetate, dynamic salivary gland scintigraphy was performed for 50 minutes. Lemon juice was used to stimulate the salivary glands, and the thyroid gland was included in the imaging area. Scintigraphy was also performed in an age- and sex-matched control group of 25 healthy persons. The thyroid uptake ratio was calculated for the scintigraphic images and compared among the three groups: healthy controls, patients with early-stage Sjögren syndrome, and those with advanced-stage Sjögren syndrome. RESULTS: When compared with the control group, the thyroid uptake ratio of the early-stage Sjögren syndrome group was not significantly different, whereas that of the advanced-stage group was significantly lower. CONCLUSIONS: Thyroid uptake of Tc-99m pertechnetate was less in patients with advanced-stage Sjögren syndrome than in patients with early-stage Sjögren syndrome or in healthy controls. Measuring the thyroid uptake of Tc-99m pertechnetate using salivary gland scintigraphy is an easy and useful method for assessing thyroid disorders in Sjögren syndrome and thus should be performed routinely. | |
| 12625896 | Bilateral parotid cysts as presentation of Sjögren's syndrome. | 2003 Feb | We present a case of a 40-year woman with bilateral parotid salivary gland enlargement as presentation of primary Sjögren's syndrome. Computed tomography (CT) and magnetic resonance imaging (MRI) showed parotid cysts, suggestive of cystic benign lymphoepithelial lesions. A sub-labial biopsy confirmed the syndrome. After 24-month follow-up, the left parotid cysts remain the same, whereas other cysts have appeared in the right parotid gland. Parotid involvement in Sjögren's syndrome is discussed. | |
| 12003095 | Surface activity of tear fluid in patients with primary Sjögren's syndrome. | 2002 Jan | Rupture of the preocular tear film leads to formation of a dry spot on the cornea with ocular irritation and symptoms of dry eye. One of the factors determining the stability of the tear film is its surface activity. The purpose of this study was to examine the surface activity of tear fluid from patients with Sjögren's syndrome. Tear fluid was sampled from the eyes of 16 patients with primary Sjogren's syndrome. The surface activity of the sample was measured on a Wilhelmy balance. Maximum and minimum surface tension was 72.2+/-1.7 and 52.9+/-7.4 mN m(-1), respectively. Corresponding values in a previously studied group of normal subjects were 71.5+/-1.3 and 46.6+/-3.8 mN m(-1), respectively. The difference in minimal surface tension was statistically significant (P<0.001). Reduced surface activity may be caused by dysfunction of the Meibomian glands and suggests a mechanism for causing the symptoms of dry eyes. | |
| 12823858 | DEK binding to class II MHC Y-box sequences is gene- and allele-specific. | 2003 | Using electrophoretic mobility shift assays, we examined sequence-specific binding of DEK, a potential autoantigen in juvenile rheumatoid arthritis, to conserved Y-box regulatory sequences in class II MHC gene promoters. Nuclear extracts from several cell lines of different phenotypes contained sequence-specific binding activity recognizing DRA, DQA1*0101, and DQA1*0501 Y-box sequences. Participation of both DEK and NF-Y in the DQA1 Y-box binding complex was confirmed by 'supershifting' with anti-DEK and anti-NF-Y antibodies. Recombinant DEK also bound specifically to the DQA1*0101 Y box and to the polymorphic DQA1*0501 Y box, but not to the consensus DRA Y box. Measurement of the apparent dissociation constants demonstrated a two- to fivefold difference in DEK binding to the DQA1 Y-box sequence in comparison with other class II MHC Y-box sequences. Residues that are crucial for DEK binding to the DQA1*0101 Y box were identified by DNase I footprinting. The specific characteristics of DEK binding to these related sequences suggests a potential role for DEK in differential regulation of class II MHC expression, and thus in the pathogenesis of juvenile rheumatoid arthritis and other autoimmune diseases. | |
| 12006317 | Multicentric reticulohistiocytosis: a rare cause of erosive arthropathy of the distal inte | 2002 Jun | BACKGROUND: Multicentric reticulohistiocytosis (MRH) is a rare systemic disease, presenting with typical skin abnormalities and erosive polyarthritis, which is often associated with malignancy. CASE REPORT: A case of MRH arthropathy, in which the typical nodular skin manifestation of the disease was absent, is described in a patient with a past history of breast cancer and no evidence of recurrent or new malignancy. RESULTS: Careful clinical and roentgenological evaluation disclosed important clues to differentiate this condition from other more common distal interphalangeal arthritides--namely, osteoarthritis and its "erosive" variant, rheumatoid arthritis, psoriatic arthritis, tophaceous gout, dialysis related hand arthropathy, and from the rarer fibroblastic rheumatism, all of which can be mimicked by MRH. Histopathology showed the characteristic histiocytic and multinucleated giant cell infiltrate with ground glass cytoplasm, and immunohistochemical analysis showed markers evocative of a monocyte/macrophage origin of MRH. | |
| 14526341 | The treatment of Sjögren's syndrome with tibolone: a case report. | 2003 Sep | We report the successful treatment with tibolone of a postmenopausal woman affected by primary Sjögren's syndrome. One year after the beginning of treatment, the woman does not need artificial tears and vaginal lubricants. This is the first report of an effective pharmacologic treatment for primary Sjögren's syndrome in humans. | |
| 12425151 | [Cevimeline hydrochloride hydrate (Saligren capsule 30 mg): a review of its pharmacologica | 2002 Oct | Cevimeline hydrochloride hydrate is a muscarinic receptor agonist with a chemical structure of a quinuclidine. Intraduodenal administration of cevimeline hydrochloride hydrate dose-dependently increased salivary secretion in normal mice and rats, two strains of autoimmune disease mice, and X-irradiated rats. The clinical efficacy of the cevimeline hydrochlide hydrate at 30 mg t.i.d. during 4 weeks has been demonstrated in double blind comparative study with placebo. In addition, its treatments in 52 weeks have increased salivary flow and improved subjective and objective symptoms of patients with xerostomia in Sjögren's syndrome. | |
| 15187433 | Suppressive effect of Dai-bofu-to on collagen-induced arthritis. | 2004 Jun | Dai-bofu-to (DBT) is a traditional Japanese herbal medicine (Kampo medicine) used for the treatment of rheumatoid arthritis (RA). In the present study, to establish the usefulness of DBT, we examined the effect of DBT on collagen-induced arthritis (CIA). DBT (1.72 g/kg/d) significantly reduced the severity of arthritis throughout the experiment and significantly delayed the onset of arthritis. The induction of CIA decreased T cells and increased B cells in popliteal lymph nodes close to the affected joints, while the treatment of CIA with DBT counteracted the changes in T and B cells. In pX transgenic mice as a spontaneously developed arthritis model, a decrease in T cells and increase in B cells in popliteal lymph nodes were observed, as compared to BALB/c mice, the littermates of pX transgenic mice. In contrast, DBT returned the cell number of T and B cells to the level of BALB/c mice. As osteoclastogenesis is regulated by some T cell cytokines and osteotropic factors, we examined the effect of DBT on the receptor activator of NF-kappa B (RANK), RANK ligand (RANKL), osteoprotegerin (OPG) and M-CSF mRNAs, which were induced by arthritis induction. Although DBT had no effect on RNAK or RANKL mRNA levels, DBT stimulated an increase in OPG mRNA levels and suppressed an increase in M-CSF mRNA level. These results suggest that DBT may possess an anti-osteoclastogenetic effect, which is brought by reducing the ratio of RANKL/OPG and by decreasing M-CSF mRNA levels. In conclusion, immunomodulatory and anti-osteoclastogenetic effects might be involved in the suppression of arthritis by DBT. | |
| 12508385 | Synergistic effect on the attenuation of collagen induced arthritis in tumor necrosis fact | 2003 Jan | OBJECTIVE: To evaluate any additive effect on attenuation of collagen induced arthritis (CIA) in tumor necrosis factor receptor I (TNFRI) and interleukin 6 (IL-6) double knockout (DKO) mice. METHODS: CIA was induced in wild-type (Wt), TNFRI knockout (TNFRIKO), IL-6 knockout (IL-6KO), and DKO mice. Comparative studies were performed among these different mouse genotypes observing clinical (incidence, arthritis score), histological, radiologic, and immunological aspects. RESULTS: More than 90% of the Wt, TNFRIKO, and IL-6KO mice developed definite CIA, while only 20% of the DKO mice did so. Severity of arthritis, indicated by the arthritis score, was significantly reduced in both the TNFRIKO and IL-6KO mice compared with the Wt mice. Moreover, the severity of arthritis in the DKO mice was significantly reduced compared with each single KO mouse (by arthritis scores; DKO vs TNFRIKO, IL-6KO mice, p < 0.05). In addition, histological and radiologic changes were also significantly reduced in the DKO mice compared with each single KO mouse (by histological and radiologic scores; DKO vs TNFRIKO, IL-6KO mice, p < 0.05 and p < 0.01 respectively). In immunological studies, serum anti-type II collagen (anti-CII) antibody concentrations were significantly decreased in the DKO mice compared with each single KO mouse (DKO vs TNFRIKO, IL-6KO mice, p < 0.01). CONCLUSION: Simultaneous blockade of TNFRI and IL-6 showed synergistic rather than additive effects on the attenuation of CIA. Combinations of anti-TNF-a and anti-IL-6 therapy may provide clinical benefits for treatment of rheumatoid arthritis compared with therapy against each single cytokine. | |
| 15213234 | A potential role of 15-deoxy-delta(12,14)-prostaglandin J2 for induction of human articula | 2004 Sep 3 | The cyclopentenone prostaglandin (PG) J2 is formed within the cyclopentenone ring of the endogenous prostaglandin PG D2 by a nonenzymatic reaction. The PG J family is involved in mediating various biological effects including the regulation of cell cycle progression and inflammatory responses. Here we demonstrate the potential role of 15-deoxy-Delta(12,14)-prostaglandin J2 (15d-PG J2) in human articular chondrocyte apoptosis. 15d-PG J2 was released by human articular chondrocytes and found in joint synovial fluids taken from osteoarthritis or rheumatoid arthritis patients. Proinflammatory cytokines such as interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) up-regulated chondrocyte release of 15d-PG J2. PG D2 synthase mRNA expression was up-regulated by IL-1beta, TNF-alpha, or nitric oxide. 15d-PG J2 induced apoptosis of chondrocytes from osteoarthritis or rheumatoid arthritis patients as well as control nonarthritic subjects in a time- and dose-dependent manner and in a peroxisome proliferator-activated receptor gamma-dependent manner. Peroxisome proliferator-activated receptor gamma expression was up-regulated by IL-1beta and TNF-alpha. Inhibition of NF-kappaB, and the activation of p38 MAPK were also found to be involved in 15d-PG J2-induced chondrocyte apoptosis. Such signal pathways led to the activation of the downstream pro-apoptotic molecule p53 and caspase cascades. Together, these results suggest that 15d-PGJ2 may play an important role in the pathogenesis of arthritic joint destruction via a regulation of chondrocyte apoptosis. | |
| 15161337 | Etanercept: in ankylosing spondylitis. | 2004 | Etanercept is a dimeric fusion protein based on the p75 tumor necrosis factor (TNF) receptor. It binds to TNFalpha and blocks its biological activity. Subcutaneous etanercept is effective in the treatment of rheumatoid arthritis, psoriatic arthritis, and polyarticular-course juvenile rheumatoid arthritis. More recently, etanercept has shown efficacy in the treatment of adults with ankylosing spondylitis. In randomized, double-blind, placebo-controlled trials, subcutaneous etanercept 25mg twice weekly for 6-24 weeks significantly reduced disease activity in patients with active ankylosing spondylitis. In the largest trial, etanercept produced a response rate of 57% compared with 22% for placebo after 24 weeks (response was determined via the validated ASAS 20 response criteria developed by the Assessments in Ankylosing Spondylitis [ASAS] Working Group). Etanercept therapy significantly improved health-related quality of life in patients with ankylosing spondylitis compared with placebo. The greatest improvements in a 16-week study were seen in the domains of physical functioning, physical role, bodily pain, vitality, and social functioning. Etanercept was generally well tolerated, with few serious adverse events or treatment withdrawals. The most common adverse events were injection-site reactions and minor upper respiratory tract infections. | |
| 15758426 | Early closure of growth plate causes poor growth of long bones in collagen-induced arthrit | 2002 Jun | Abnormalities of the epiphyseal growth plate that occur in collagen-induced arthritis (CIA) were studied. CIA was induced in 6-week-old Lewis rats by immunization with type II collagen. Radiographic examination revealed the early closure of the epiphyseal growth plate with growth retardation of the femur and tibia. Histological evaluation confirmed the early closure of the epiphyseal growth plate accompanied by decreased intensity of safranin-O staining indicating decreased amounts of proteoglycans in the extracellular matrix (ECM) of the cartilage. Immunohistochemical methods showed that the number of chondrocytes expressing matrix metalloproteinase (MMP)-3 and/or vascular endothelial growth factor (VEGF) increased in the growth plates of CIA rats. This study confirmed that disturbances of long bone growth with early closure of the epiphyseal growth plates occur in CIA. There appeared to be overexpression of MMP-3, which may be involved with proteoglycan degradation. Additionally, VEGF, which is associated with cartilage ossification and angiogenesis, might also play a role in this event. Further clarification of the mechanism of the growth disturbance in CIA may yield clinical benefits, especially in prevention of the premature closure of growth plate that is seen in juvenile rheumatoid arthritis and other diseases. | |
| 15366399 | Health benefits of omega-3 fatty acids. | 2004 Aug 11 | Evidence suggests that omega-3 polyunsaturated fatty acids play an integral role in cell membrane function and development of the brain and eyes. Optimising intake appears to confer many benefits, including reduced risk of heart disease and possibly a reduced likelihood of behavioural problems, depression and inflammatory conditions such as rheumatoid arthritis. Although there is some disagreement on what level of intake is optimal, British diets are low in omega-3 fatty acids. Good sources include oily fish and novel sources include fortified eggs and oils derived from microalgae. | |
| 15775137 | [Inflammatory cytokines and bone diseases]. | 2003 Jun | The abnomalities in cytokines may be an pathogenetic factor in human diseases as diverse as rheumatoid arthritis (RA), some bone diseases, multiple myeloma, metastatic bone tumors. A cytokine imbalance in favour of pro-inflammatory mediators may be a central pathogenic mechanism in RA. Pro-inflammatory mediators include the cytokines TNF-alpha and IL-1, which activate osteoclasts to resorb subchondral bone. A further important mediator is the recently described osteoclast differentiation factor (ODF) (also reffered to as TNF-related activation-induced cytokine [TRANCE], receptor activator of nuclear factor kappaB ligand [RANKL], or osteoprotegerin ligand). | |
| 11783976 | Intratendinous rupture of flexor digitorum profundus caused by non-specific synovitis. | 2002 Jan | Closed ruptures of flexor tendons in the hands of patients without rheumatoid arthritis are rare. We report a case of closed rupture of the flexor digitorum profundus of the middle finger in zone II, secondary to acute florid synovitis forming a tumour-like mass. No similar case has been reported to our knowledge. The management of this unexpected finding at surgical exploration is discussed. | |
| 12610753 | The association of myasthenia gravis and connective tissue diseases. Effects of thymectomy | 2003 Mar | OBJECTIVES: To describe the effects of thymectomy in a group of patients with myasthenia gravis (MG) with associated connective tissue diseases (CTD). PATIENTS AND METHODS: We analyzed six patients with CTD and myasthenia. They were followed-up for at least 3 years. RESULTS: Records of a cohort of 132 patients with established diagnosis of MG undergoing thymectomy in our institution between 1987-1999 were reviewed. The percentage of patients with CTD was 5 % (6/132). Five patients had rheumatoid arthritis (RA) and one patient systemic lupus erythematosus (SLE). All patients were women, and the mean age was 38.5 years old (SD 13.7). Mean time of MG diagnosis to operation was 16 months (range from 1 to 144 months). Preoperative Osserman classification was the following: stage IIb, four patients; stage III, one patient; and stage IV, one patient. Before surgery all patients were on anticholinesterase agent (pyridostigmine), and four patients were on corticosteroids. An extended transsternal thymectomy was practiced on five patients and a transcervical thymectomy was performed in the remaining patient. Pathologic findings were as follows: thymic hyperplasia in four patients and thymic atrophy in the other two. Good response (remission or improvement) was present in three patients (50 %) and poor response (no change or worse) in the other three (50 %). CONCLUSIONS: A low response to the thymectomy is observed in patients with MG and associated CTD (RA and an SLE). | |
| 12442911 | Polyunsaturated fatty acids and inflammatory diseases. | 2002 Oct | Inflammation is overall a protective response, whose main goal is to liberate the human being of cellular lesions caused by micro-organisms, toxins, allergens, etc., as well as its consequences, and of death cells and necrotic tissues. Chronic inflammation, which is detrimental to tissues, is the basic pathogenic mechanism of hypersensitivity reactions against xenobiotics. Other frequent pathologies, for instance atherosclerosis, chronic hepatitis, inflammatory bowel disease (IBD), liver cirrhosis, lung fibrosis, psoriasis, and rheumatoid arthritis are also chronic inflammatory diseases. Chemical mediators of inflammation are derived from blood plasma or different cell-type activity. Biogenic amines, eicosanoids and cytokines are within the most important mediators of inflammatory processes. The different activities of eicosanoids derived from arachidonic acid (20:4 n-6) versus those derived from eicosapentaenoic acid (20:5 n-3) are one of the most important mechanisms to explain why n-3, or omega-3, polyunsaturated fatty acids (PUFA) exhibit anti-inflammatory properties in many inflammatory diseases. Dietary supplements ranging 1-8 g per day of n-3 PUFA have been reportedly beneficial in the treatment of IBD, eczema, psoriasis and rheumatoid arthritis. In addition, recent experimental studies in rats with experimental ulcerative colitis, induced by intrarectal injection of trinitrobenzene sulphonic acid, have documented that treatment with n-3 long-chain PUFA reduces mucosal damage as assessed by biochemical and histological markers of inflammation. Moreover, the defence antioxidant system in this model is enhanced in treated animals, provided that the n-3 PUFA supply is adequately preserved from oxidation. | |
| 15566969 | Stimulation of inducible nitric oxide synthase by monosodium urate crystals in macrophages | 2004 Nov | From the studies on the involvement of iNOS in arthritis, it is clear that attention has focused primarily on rheumatoid arthritis (RA) and osteoarthritis (OA). To date, little is known about the role of iNOS in the pathophysiology of gouty arthritis (GA). Here, we investigated the significance of iNOS expression in cell culture system as well as in GA patients. Gouty crystals monosodium urate (MSU) appeared to up-regulate inducible nitric oxide synthase (iNOS) mRNA and protein expression in a concentration- and time-dependent manner in RAW264.7 macrophages. This increase of iNOS expression is attributable to the activation of multiple signaling pathways. Evidence for this was initially established by inhibitor treatment of cells in the presence of MSU. While the JAK inhibitor AG490, the PI3K inhibitor LY294002, and the NFkappaB inhibitor PDTC abrogated almost completely the expression of iNOS induced by MSU, the ERK1/2 inhibitor PD98059 was only partially effective. Furthermore, the effect of MSU on the activation of PI3K/Akt, JAK/STAT, ERK1/2, and NFkappaB signaling molecules was carefully examined. Moreover, it was shown that GAS and NFkappaB motifs are required for iNOS expression mediated by MSU. In addition, synovial tissues obtained from GA patients displayed enhanced expression of iNOS when compared with normal synovium. Taken together, these findings provide the first evidence for the potential importance of iNOS in the pathogenesis of GA as well as RA and OA, and in turn raise the possibility that iNOS may be an ideal target for preventive therapy in human arthritis. |