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ID PMID Title PublicationDate abstract
9061658 Anti-Ro(SS-A) antibody positive Sjögren's/lupus erythematosus overlap syndrome. 1997 Unlike anti-Ro(SS-A) antibody positive subacute cutaneous lupus erythematosus (SCLE) patients, anti-Ro(SS-A) antibody positive lupus patients with Sjögren's syndrome (SS/LE) appear to have a more guarded prognosis. Our studies indicate these SS/LE patients have an increased frequency of pulmonary, neurological, and renal disease compared to SCLE patients.
11905842 Autoantibodies in primary Sjögren's syndrome: new insights into mechanisms of autoantibod 2001 Characterisation of autoantibodies and their target autoantigens in primary Sjögren's syndrome (SS) is an important entry point for studying this common systemic autoimmune disease. Diversification of anti-Ro/La responses is believed to occur by a process of determinant spreading following initiation of an autoimmune response to one component, possibly 52-kD Ro (Ro52). Recent evidence supports the ER-resident chaperone Grp78 as a potential candidate in the initiation of an autoimmune response against Ro52, by binding to a Grp78 binding motif in the COOH-terminal region of Ro52. The subsequent diversification of the anti-Ro/La response is influenced by distinct HLA class II alleles. Anti-salivary duct autoantibodies have been revisited and shown to be mimicked by cross-reactive isoantibodies to AB blood group antigens. Identification of autoantibodies that act as antagonists at M3-muscarinic receptors represents an important advance. As well as contributing to the sicca symptoms, the functional effects of these autoantibodies may explain associated features of autonomic dysfunction in patients with SS. Anti-M3 receptor autoantibodies occur in both primary and secondary SS and allow Sjögren's syndrome to be viewed as a disorder of anti-receptor autoimmunity.
11315936 Treatment of chronic sialadenitis in a murine model of Sjögren's syndrome by local fasL g 2001 Apr OBJECTIVE: Infection of Fas (Fas/CD95)-mutant C57BL/6 (B6)-lpr/lpr mice with murine cytomegalovirus (MCMV) leads to a chronic sialadenitis similar to that of Sjögren's syndrome (SS). The aim of this study was to evaluate whether chronic sialadenitis would also occur in Fas ligand (FasL/CD95L)-mutant B6-gld/gld mice upon infection with MCMV and whether the expression of FasL by local gene transfer using recombinant adenoviral vectors would be an effective therapeutic strategy. METHODS: B6-gld/gld mice were infected intraperitoneally with MCMV, and salivary glands were analyzed histologically at different time points. For treatment of sialadenitis, recombinant adenoviral vectors expressing the fasL gene (AdLoxpFasL + AxCANCre) or the lacZ gene (AdCMVLacZ) were locally injected into the salivary glands of MCMV-infected B6-gld/gld mice and uninfected B6-+/+ and B6-gld/gld mice. RESULTS: Following MCMV infection, B6-gld/gld mice developed an acute and chronic sialadenitis characterized by multiple foci of infiltrating T cells. After local injection of adenoviral vectors, high levels of lacZ or fasL gene expression could be detected in acinar and ductal cells. Treatment of acute and chronic sialadenitis in B6-gld/gld mice with local fasL gene transfer resulted in a significant reduction in the number of inflammatory foci and tissue destruction in salivary glands compared with mice treated with AdCMVLacZ. Despite high levels of FasL expression after injection of recombinant vectors, <5% of ductal and acinar cells were TUNEL positive, demonstrating that, in this model of SS, acinar and ductal cells were not highly sensitive to FasL-mediated apoptosis. CONCLUSION: Chronic sialadenitis similar to that of SS developed in B6-gld/gld mice after MCMV infection. FasL expression was reconstituted by local gene transfer, resulting in significant reduction of infiltrating mononuclear cells, which indicates that local gene transfer of fasL might be a novel treatment for chronic sialadenitis.
10753017 Different airway responsiveness profiles in atopic asthma, nonatopic asthma, and Sjögren' 2000 Mar BACKGROUND: Different mechanisms may underlie bronchial hyperresponsiveness (BHR) in different diseases. The aim of this study was to investigate the bronchial responsiveness profile produced by three different challenge tests, methacholine, a direct stimulus, and two indirect stimuli, adenosine 5'-monophosphate (AMP) and cold air, in subjects with asthma and patients with Sjögren's syndrome. METHODS: The study population comprised 40 adult patients with asthma, 18 subjects with Sjögren's syndrome, and 20 controls. Blood samples were collected before each challenge for measurements of serum eosinophil peroxidase (S-EPO) and eosinophil cationic protein (S-ECP). The investigated subjects recorded peak expiratory flow and kept a symptom diary. RESULTS: Atopic subjects with asthma were significantly more hyperresponsive to AMP than nonatopic subjects with asthma (P=0.01) and subjects with Sjögren's syndrome (P=0.02). No difference was seen between atopic and nonatopic subjects with asthma in the case of challenges with methacholine or cold air. In atopic subjects with asthma, a significant correlation was found between challenges with methacholine and AMP (r=0.91, P=0.0001) and methacholine and cold air (r=0.83, P=0.004), but, in nonatopic subjects with asthma, no significant correlation was seen between methacholine and AMP or cold air challenges. In atopic subjects with asthma, the dose-response slope for AMP was correlated to S-EPO (r= -0.56; P = 0.01) and S-ECP (r= -0.51, P = 0.02), while no correlation between BHR and inflammation markers was found in the two other patient groups. CONCLUSIONS: The results of this study suggest that patients with asthma and subjects with Sjögren's syndrome display different bronchial responsiveness profiles for different challenge agents. Atopic subjects with asthma are more hyperresponsive to AMP than nonatopic subjects and patients with Sjögren's syndrome. More than one challenge may be required to detect different aspects of bronchial responsiveness.
10845583 Mikulicz's disease and Sjögren's syndrome. 2000 Jun PURPOSE: To characterize lacrimal gland function and lymphocyte infiltration in patients with Mikulicz's disease (MD) and Sjögren's syndrome (SS). METHODS: Four patients with MD and 5 with SS were recruited, on whom were performed Schirmer test I (Schirmer test without anesthesia), Schirmer test with nasal stimulation, and vital staining of the ocular surface. The lacrimal gland was then biopsied and the tissues stained with CD3, CD4, CD8, B220, APO2.7, Fas, and Fas ligand (Fas-L) antibodies. RESULTS: Although regular Schirmer test results in the MD group were less than 10 mm, those with nasal stimulation, 38.1 +/- 3.4 mm, were significantly greater than the SS group. There were minimal ocular surface changes in MD. Morphologic staining with hematoxylin and eosin was identical in both groups, but the acinar cells were stained with APO2.7 only in the SS group. There was strong Fas and Fas-L staining in SS patients but not in those with MD. CONCLUSIONS: Lacrimal gland acinar cells in those with MD maintained their function and were not programmed for cell death. The sicca syndrome was not observed in MD patients. Although the pathology is similar for MD and SS, the difference in acinar cell apoptosis and function can explain clinical differences.
10836524 Mast cell derangement in salivary glands in patients with Sjögren's syndrome. 2000 Mast cells (MCs) have been implicated in many immune-inflammatory disorders. Deranged mast cell distribution and function may contribute to the local pathomechanisms in the labial salivary glands (LSG) in Sjogren's syndrome (SS). Evidence for MC presence, localization, frequency, subtype, and degree of activation was sought by using reverse transcriptase-polymerase chain reaction (RT-PCR), immunohistochemistry (IHC)/image analysis, transmission electron microscopy, Western blotting, spectrophotometric activity assay, and radioimmunoassay. The overall expression (densitometric units) of MC tryptase mRNA (1483 +/- 228 vs 1044 +/- 308) did not differ between SS and control LSGs. However, IHC disclosed an uneven distribution of MCs in SS with an absence in lymphocyte foci and increased numbers (cells/mm2 77 +/- 7 vs 38 +/- 4, P < 0.01) elsewhere. Absence of MCs in the lymphocyte foci was not a fixation artefact and was not explained by the presence of "phantom" MCs in these areas. In both SS and controls, 80% of all MCs were chymase containing, but the typical lattices/gratings characteristic for connective tissue MCs (CTMCs) were not found. Instead, MC granules had mostly a homogeneous, finely granular substructure characteristic of "new" granules subjected to a continuous, low-grade release. 32 kDa MC tryptase was found in saliva and its activity/concentration was comparable to that found in controls. However, tryptase output was low in SS (1.30 +/- 0.30 microg/min vs 3.49 +/- 0.66 microg/min, P < 0.001). Normal LSGs contain mostly CTMCs, in close contact with various resident and immigrant cells, characterized by a low-grade release of MC mediators. In SS this normal pattern is disturbed so that MCs are absent in lymphocyte foci (but increased elsewhere in the glands). The net salivary output of MC mediators is low in SS. This derangement of MCs may contribute to the pathogenesis of SS via multiple mechanisms.
10606366 Increased in vitro production of interleukin 6 in response to trimethoprim among persons w 1999 Dec OBJECTIVE: Trimethoprim occasionally triggers a systemic adverse reaction including fever, malaise, head and backache, and even overt meningeal irritation, particularly in women with an autoimmune rheumatic disease. To study the unknown pathogenesis of the reaction we measured the effect of trimethoprim upon the cytokine [interleukin (IL) 2, 6, 10, and tumor necrosis factor-alpha] production of trimethoprim reactive and tolerant persons' peripheral blood mononuclear cells in vitro. METHODS: Peripheral blood mononuclear cells from 12 women reactive to trimethoprim (3 with primary Sjögren's syndrome, 3 with systemic lupus erythematosus, 1 with systemic scleroderma, 5 with no rheumatic disease) were cultured in the presence of trimethoprim, and the cytokine production was measured. Eleven women who tolerated trimethoprim (6 with Sjögren's syndrome and 5 with no rheumatic disease) served as controls. RESULTS: Therapeutic trimethoprim concentration induced in the mononuclear cells of the trimethoprim reactive patients significantly higher IL-6 production [mean +/- SD (median), 2034+/-2965 (572) pg/ml] versus cells of the trimethoprim tolerant subjects [954+/-2552 (89) pg/ml; p = 0.036]. No significant differences in the production of other cytokines were detected. CONCLUSION: Trimethoprim induces IL-6 production in the peripheral blood mononuclear cells of trimethoprim reactive persons. We suggest that IL-6 production is the probable trigger leading to the clinical reaction.
10522209 Primary Sjögren's syndrome: salivary gland function and clinical oral findings. 1999 Apr OBJECTIVE: To evaluate salivary gland function, saliva composition and oral findings in patients with primary Sjögren's syndrome (pSS) subdivided into patients with and without focus score > or = 1 (FS) and/or antibodies to SSA/SSB (AB) as well as in healthy controls. SUBJECTS AND METHODS: Unstimulated (UWS) and chewing stimulated (SWS) whole saliva, and stimulated parotid saliva (SPS) were collected in 16 patients fulfilling the European classification criteria for pSS subdivided into those with FS and/or AB (n = 8) and those without FS and AB (n = 8), and in age-matched (n = 14) and young healthy controls (n = 13). UWS and SWS were analysed for Na+ and K+. SPS was analysed for Na+, K+, statherin, and proline-rich proteins (PRPs). Sicca symptoms, DMFT/DMFS, plaque (PI) and gingival (GI) scores, periodontal pocket depth (PPD), and mucosal status were recorded. RESULTS: The young healthy controls had lower UWS as compared to the aged controls (P = 0.03). However, the aged controls had higher DMFT/DMFS (P < 0.001) and PI, GI and PPD (P < 0.01). Patients with FS and/or AB generally had lower saliva secretory rates than patients without FS and/or AB (P = 0.01 for UWS and SPS) and age-matched healthy controls (P = 0.001). There was no significant difference in the content of Na+ and K+, statherin and PRPs between groups. Patients with FS and/or AB had the highest frequency of oral mucosal changes and higher DMFT/DMFS than patients without FS and/or AB and healthy controls (P < 0.01). However, PI, GI, and PPD did not differ significantly. CONCLUSION: Patients with FS and/or AB had lower salivary secretory rates, higher DMFT/DMFS, and more oral mucosal changes than patients without FS and/or AB. Additionally, data suggest that salivary gland function in healthy individuals do not decrease with age.
9598888 Primary Sjögren's syndrome: role of the HLA-DRB1*0301-*1501 heterozygotes. 1998 May OBJECTIVE: To examine the respective role of the DRB1*, DQB1*, and DPB1* HLA alleles in primary Sjögren's syndrome (SS) and in the clinical and autoantibody profile of primary SS. METHODS: HLA-DRB1*, DQB1*, and DPB1* alleles were analyzed in 42 patients with primary SS and 200 controls by reverse dot blot hybridization for DRB1* and DPB1* and by polymerase chain reaction-restriction fragment length polymorphism for DQB1*. RESULTS: We found a significant increase of the HLA-DRB1*15-*03 heterozygote genotype frequency (19% primary SS vs 3.5% controls; p<0.0006, OR=6.49) and especially for the HLA-DRBI*1501-*0301 genotype (16.7% primary SS vs 3% controls; p<0.002, OR=6.47). The DQB1*0201-*0602 genotype was also significantly increased in primary SS (17.1% primary SS vs 4% controls; p<0.006, OR=4.86). However, the higher risk to primary SS development was associated with the DRB1*1501-*0301 genotype (OR=6.47 vs 4.86). There were no differences between patients and controls in DPB1* allele frequencies. The HLA-DRB1*15-*03 heterozygote genotype was also associated with systemic features such as hematologic manifestations and Raynaud's phenomenon (RP) and with autoantibody production such as antinuclear, anti-Ro(SSA) or La(SSB) autoantibodies and rheumatoid factor. CONCLUSION: Our data suggest a role of the HLA-DRB1*1501-*0301 heterozygote genotype in susceptibility to primary SS. Moreover, the HLA-DRB1*1501-*0301 genotype was also found to be associated with a particular form of the disease characterized by RP, hematologic manifestations, and autoantibody production.
9433880 A novel NOD-derived murine model of primary Sjögren's syndrome. 1998 Jan OBJECTIVE: The appearance of autoimmune diabetes prior to autoimmune exocrinopathy in the NOD mouse suggests that it is an excellent model of secondary, but not primary, autoimmune sicca complications. Since the unique major histocompatibility complex (MHC) I-A(g7) expression in NOD mice is essential for the development of insulitis and diabetes in these animals, we investigated exocrine gland function in NOD.B10.H2b mice, which have an MHC congenic to NOD, as a potential model for primary Sjögren's syndrome (SS). METHODS: Histopathologic manifestations of lymphocytic infiltrates into the pancreas and exocrine tissues were examined by light microscopy. Sera were evaluated for the presence of antinuclear antibodies. Saliva, tears, and gland lysates were evaluated for total volume and protein concentration, the aberrant expression and processing of parotid secretory protein, and cysteine protease activity. RESULTS: NOD.B10.H2b mice exhibited the exocrine gland lymphocytic infiltration typical of the SS-like disease and dysfunction observed in NOD mice, but without the insulitis and diabetes. These mice additionally expressed elevated levels of cysteine protease activity (a measure of apoptotic activity) and abnormal expression and cleavage of parotid secretory protein in the submandibular tissues. CONCLUSION: The results of this study suggest that the unique NOD MHC I-A(g7) is not essential for exocrine tissue autoimmunity. Furthermore, the findings indicate that sicca syndrome occurs independently of autoimmune diabetes and that the congenic NOD.B10.H2b mouse represents a novel murine model of primary SS.
11369699 Suppression of arthritis by forced expression of cyclin-dependent kinase inhibitor p21(Cip 2001 Jun Rheumatoid synovial fibroblasts (RSF) express cyclin-dependent kinase (CDK) inhibitors p16(INK4a) and p21(Cip1) when they are growth-inhibited in vitro. The induction of p16(INK4a) is characteristic of RSF and intra-articular p16(INK4a) gene therapy has been shown to suppress adjuvant arthritis (AA) of rats. The other inducible CDK inhibitor, p21(Cip1), has multiple functions depending on the cell type. They include inhibition of CDK as well as promotion of active CDK complex formation and induction of apoptosis. This study is to discern the biological effects of p21(Cip1) gene transfer into RSF and its therapeutic effects on AA. A recombinant adenovirus containing a human p21(Cip1) gene and control adenoviruses were prepared. RSF infected with these viruses were examined for their cell growth. Apoptotic cell death was evaluated by nuclear staining and DNA fragmentation analysis. In vivo gene therapy of rat AA was carried out by intra-articular injection of the viruses. Severity of the arthritis was clinically scored. The treated joints were examined histologically and proliferating cell nuclear antigens (PCNA) were detected immunohistochemically. The adenoviral p21(Cip1) gene transfer inhibited growth of RSF without inducing apoptosis. p21(Cip1) gene therapy suppressed AA clinically and histologically. The effects were comparable to p16(INK4a) gene therapy. PCNA expression was reduced in the p21(Cip1)-treated joints. The adenoviral gene transfer of p21(Cip1) ameliorated rat AA. The effect was attributable to inhibition of proliferation. Because p21(Cip1) is induced more easily by many chemicals than p16(INK4a), it also appears to be a feasible target in developing anti-rheumatic drugs.
11785594 Community-acquired pneumonia--implementation of a prediction rule to guide selection of pa 2001 Dec The aim of this study was to determine the outcomes of outpatient treatment of community-acquired pneumonia (CAP) when a prediction rule was followed by emergency physicians to guide the selection of patients. This was a prospective observational study conducted at the emergency department of a university-affiliated hospital in Hong Kong, China. A clinical prediction rule was implemented to guide the selection of patients with CAP for outpatient treatment. All subsequent hospitalizations gial presentation were recorded, and the reasons were assessed. The utilization of the observation unit was incorporated into the treatment algorithm. Of 72 patients with CAP followed up as outpatients, 60 (83.3%) were treated successfully, nine (12.5%) required subsequent hospitalization within 30 days, and three (4.2%) were lost to follow-up. None of the patients died, and none required admission to the intensive care unit. Factors associated with subsequent hospitalization include: tuberculosis, underlying malignancy, persistent fever, comorbidity (rheumatoid arthritis and severe osteoporosis), intravenous drug addiction and alcoholism. The observation ward was utilized in 10 (16.7%) patients successfully treated as outpatients. It is concluded that the prediction rule can be safely implemented as a guide for emergency physicians. The short-stay observation unit may be usefully employed for treating low-risk CAP.
9427067 Pharmacological profile of JTE-522, a novel prostaglandin H synthase-2 inhibitor, in rats. 1997 Nov OBJECTIVE AND DESIGN: The antinociceptive, antipyretic, and anti-inflammatory effects of JTE-522, a novel selective prostaglandin H synthase (PGHS)-2 inhibitor, were examined in rats. MATERIALS: Sheep seminal vesicle PGHS-1 and placenta PGHS-2 were used for in vitro assay, while for in vivo experiments, male rats (4-8 weeks old) were used. TREATMENT: JTE-522 and reference compounds (0.01-100 microM) were subjected to enzyme assay. JTE-522 (0.3-30 mg/kg) and indomethacin (0.3-10 mg/kg) were administered orally. RESULTS: JTE-522 inhibited PGHS-2 (IC50: 0.64 microM) without affecting PGHS-1 activity at 100 microM. In rats with yeast-induced hyperalgesia, JTE-522 showed a dose-dependent antinociceptive effect (ED50: 4.4 mg/kg). In rats with yeast-induced pyrexia, JTE-522 significantly reversed the pyrexic response (ED50: 3.9 mg/kg). Orally administered JTE-522 dose-dependently inhibited carrageenin-induced rat paw edema (ED30: 4.7 mg/kg). In rats with adjuvant-induced arthritis, JTE-522 showed a significant inhibitory effect at daily doses of 0.3-3 mg/kg. JTE-522 did not cause severe gastric lesions at oral doses up to 300 mg/kg. CONCLUSIONS: Our results indicate that the selective PGHS-2 inhibitor JTE-522 may represent a novel type of anti-inflammatory drug without adverse effects on the gastrointestinal tract. JTE-522 may thus be a promising agent for treating both acute inflammatory disease and chronic inflammatory diseases such as rheumatoid arthritis.
11062605 Active synovial matrix metalloproteinase-2 is associated with radiographic erosions in pat 2000 INTRODUCTION: In cancer the gelatinases [matrix metalloproteinase (MMP)-2 and MMP-9] have been shown to be associated with tissue invasion and metastatic disease. In patients with inflammatory arthritis the gelatinases are expressed in the synovial membrane, and have been implicated in synovial tissue invasion into adjacent cartilage and bone. It is hypothesized that an imbalance between the activators and inhibitors of the gelatinases results in higher levels of activity, enhanced local proteolysis, and bone erosion. OBJECTIVES: To determine whether the expression and activity levels of MMP-2 and MMP-9, and their regulators MMP-14 and tissue inhibitor of metalloproteinase (TIMP), are associated with early erosion formation in patients with synovitis of recent onset. PATIENTS AND METHOD: A subset of 66 patients was selected from a larger early synovitis cohort on the basis of tissue availability for the study of synovial tissue and serum gelatinase expression. Patients with peripheral joint synovitis of less than 1 years' duration were evaluated clinically and serologically on four visits over a period of 12 months. At the initial visit, patients underwent a synovial tissue biopsy of one swollen joint, and patients had radiographic evaluation of hands and feet initially and at 1year. Serum MMP-1, MMP-2, MMP-9, MMP-14, and TIMP-1 and TIMP-2 levels were determined, and synovial tissue was examined by immunohistology for the expression of MMP-2 and MMP-9, and their molecular regulators. Gelatinolytic activity for MMP-2 and MMP-9 was quantified using a sensitive, tissue-based gel zymography technique. Four healthy individuals underwent closed synovial biopsy and their synovial tissues were similarly analyzed. RESULTS: Of the 66 patients studied, 45 fulfilled American College of Rheumatology criteria for rheumatoid arthritis (RA), with 32 (71%) being rheumatoid factor positive. Of the 21 non-RA patients, seven had a spondylarthropathy and 14 had undifferentiated arthritis. Radiographically, 12 of the RA patients had erosions at multiple sites by 1 year, whereas none of the non-RA patients had developed erosive disease of this extent. In the tissue, latent MMP-2 was widely expressed in the synovial lining layer and in areas of stromal proliferation in the sublining layer and stroma, whereas MMP-9 was expressed more sparsely and focally. MMP-14, TIMP-2, and MMP-2 were all detected in similar areas of the lining layer on consecutive histologic sections. Tissue expression of MMP-14, the activator for pro-MMP-2, was significantly higher in RA than in non-RA patients (8.4 +/- 5 versus 3.7 +/- 4 cells/high-power field; P = 0.009). In contrast, the expression of TIMP-2, an inhibitor of MMP-2, was lower in the RA than in the non-RA samples (25 +/- 12 versus 39 +/- 9 cells/high-power field; P = 0.01). Synovial tissue expressions of MMP-2, MMP-14, and TIMP-2 were virtually undetectable in normal synovial tissue samples. The synovial tissue samples of patients with erosive disease had significantly higher levels of active MMP-2 than did those of patients without erosions (Fig. 1). Tissue expression of MMP-2 and MMP-9, however, did not correlate with the serum levels of these enzymes. With the exception of serum MMP-2, which was not elevated over normal, serum levels of all of the other MMPs and TIMPs were elevated to varying degrees, and were not predictive of erosive disease. Interestingly, MMP-1 and C-reactive protein, both of which were associated with the presence of erosions, were positively correlated with each other (r = 0.42; P < 0.001). DISCUSSION: MMP-2 and MMP-9 are thought to play an important role in the evolution of joint erosions in patients with an inflammatory arthritis. Most studies have concentrated on the contribution of MMP-9 to the synovitis, because synovial fluid and serum MMP-9 levels are markedly increased in inflammatory arthropathies. Previously reported serum levels of MMP-9 have varied widely. In the present sample of patients with synovitis of recent onset, serum MMP-9 levels were elevated in only 21%. Moreover, these elevations were not specific for RA, the tissue expression of MMP-9 was focal, and the levels of MMP-9 activity were not well correlated with early erosions. Although serum MMP-2 levels were not of prognostic value, high synovial tissue levels of MMP-2 activity were significantly correlated with the presence of early erosions. This may reflect augmented activation of MMP-2 by the relatively high levels of MMP-14 and low levels of TIMP-2 seen in these tissues. We were able to localize the components of this trimolecular complex to the synovial lining layer in consecutive tissue sections, a finding that is consistent with their colocalization. In conclusion, we have provided evidence that active MMP-2 complexes are detectable in the inflamed RA synovium and may be involved in the development of early bony erosions. These results suggest that strategies to inhibit the activation of MMP-2 may have the potential for retarding or preventing early erosions in patients with inflammatory arthritis.
11676176 [Changes in ulcerogenic response to non-steroidal anti-inflammatory drugs (NSAIDs) in adju 2001 Oct Gastroenteropathy is the most common among patients who use non-steroidal anti-inflammatory drugs (NSAIDs) for the treatment of inflammatory disorders. It is known that rheumatoid arthritic (RA) patients are more susceptible to NSAID-induced gastropathy than other NSAID users. This article reviewed our recent studies concerning the influence of arthritis on gastric mucosal integrity in adjuvant-induced arthritic rats. The gastric mucosal lesions induced by indomethacin, one of conventional NSAIDs, were markedly aggravated in arthritic rats. Likewise, the healing of chronic gastric ulcers induced by thermal cauterization was significantly delayed in arthritic rats. The underlying mechanisms of these phenomena observed in arthritic rats may be attributable to the enhancement of iNOS/NO pathway in the former and the less expression of various growth factors in the ulcerated mucosa, such as basic fibroblast growth factors (bFGF) or insulin-like growth factors (IGF-1) in the latter. In addition, we recently found that cyclooxygenase-2 (COX-2) selective inhibitors, such as rofecoxib or celecoxib, induced apparent gastric lesions in arthritic rats, suggesting that a caution should be paid on the use of COX-2 selective inhibitors in RA patients.
11172377 Long-term results of cemented Steffee arthroplasty of the thumb metacarpophalangeal joint. 2001 Jan A retrospective evaluation of the Steffee metacarpophalangeal (MCP) thumb joint prostheses was performed to determine the long-term outcome and survivorship of the prosthesis. Fifty-four primary thumb arthroplasties (49 patients) were performed for pain, weakness, or instability involving the thumb MCP joint secondary to arthritis. Underlying etiology included rheumatoid (49 thumbs), psoriatic (1 thumb), scleroderma (2 thumbs), and degenerative (2 thumbs) arthritis. Thirty-one thumbs had concomitant interphalangeal joint instability and underwent interphalangeal joint fusions. At an average follow-up period of 57 months, the average motion of the MCP joint was 21 degrees (range, 0 degrees to 40 degrees ), with a significant improvement in position and stability. Thumb axis length was maintained or increased in 98%. Although there was not a consistent long-term improvement in grip or pinch strength, 87% of the patients reported subjective improvement in strength and function as a result of surgery. Pain was relieved in all thumbs with preoperative pain. Complications included a periprosthetic fracture, 2 late infections, and 1 gross loosening of the implant. The survivorship of the implant was 93% survivorship at 5 years and 89% survivorship at 10 years, with only 4 failures in 54 thumbs. The Steffee thumb MCP arthroplasty resulted in excellent long-term survivorship, patient satisfaction, and functional outcome.
9453917 [Unusual diagnosis in recurrent arthritis, erythema nodosum and arrhythmia]. 1997 Dec 5 HISTORY AND ADMISSION FINDINGS: A 42-year-old woman, with recurrent arthritis of the large joints and erythema nodosum for 7 years, was admitted because of recent onset of bouts of rapid heart rate. A 2/6 systolic murmur at Erb's point was the only contributory finding on physical examination. INVESTIGATIONS: The transaminases and gamma-GT were elevated, as were total cholesterol, LDL fraction, IgM, total protein, gamma-globulin and IgM. Antimitochondrial antibodies, especially anti-M2, were positive, while rheumatoid factor and C-reactive protein were negative. ANA, ANCA and antibodies against double-strand DNA were not demonstrated. ENA screening was negative. Abdominal computed tomography showed discrete intrahepatic cholestasis. Liver biopsy revealed chronic destructive cholangitis, i.e. the early stage of primary biliary cirrhosis. TREATMENT AND COURSE: On treatment with ursodeoxycholic acid (10 mg/kg daily) the patient has remained free of symptoms for 3 years and laboratory tests no longer showed evidence of impaired liver function. CONCLUSION: Primary biliary cirrhosis should be included in the differential diagnosis of recurrent arthritis and erythema nodosum, as early treatment with ursodeoxycholic acid can favourably influence its course.
11479590 Mutation of DNASE1 in people with systemic lupus erythematosus. 2001 Aug Systemic lupus erythematosus (SLE) is a highly prevalent human autoimmune diseases that causes progressive glomerulonephritis, arthritis and an erythematoid rash. Mice deficient in deoxyribonuclease I (Dnase1) develop an SLE-like syndrome. Here we describe two patients with a heterozygous nonsense mutation in exon 2 of DNASE1, decreased DNASE1 activity and an extremely high immunoglobulin G titer against nucleosomal antigens. These data are consistent with the hypothesis that a direct connection exists between low activity of DNASE1 and progression of human SLE.
9699544 Use of topical cyclosporin A in a primary Sjögren's syndrome mouse model. 1998 Aug PURPOSE: A new animal model, the NFS/sld mutant mouse, was used for primary Sjögren's syndrome to investigate the efficacy of topical and systemic cyclosporin A (CyA) in preventing inflammation of the exocrine glands. METHODS: Cyclosporin A was applied topically (0.01% and 0.1%, three times a day) or administered orally (10 mg/kg and 100 mg/kg, once a day) to mice from 6 to 16 weeks of age, after which the mice were killed. RESULTS: Topical CyA reduced lacrimal gland and submandibular gland inflammation without causing pathologic changes in other organs. Flow cytometry showed that CD44 expression of CD4 T cells from the submandibular lymph nodes was downregulated, whereas that of Mel14+ was upregulated. Using a reverse transcription-polymerase chain reaction assay, we determined that topical CyA significantly decreased the expression of mRNA of IL-2 and T-cell receptor-constant beta-chain. CONCLUSIONS: Topical CyA may be clinically useful in reducing the lymphocyte infiltration of lacrimal glands associated with Sjögren's syndrome.
9933439 Hypoxia augments cytokine (transforming growth factor-beta (TGF-beta) and IL-1)-induced va 1999 Jan Vascular endothelial growth factor (VEGF) is abundant in synovium and synovial fluids, where it probably contributes to vascular permeability and angiogenesis in arthritic joints. To investigate the probable sources of VEGF in synovium, we compared the ability of several cytokines (TGF-beta, platelet-derived growth factor (PDGF), IL-1, tumour necrosis factor (TNF), basic fibroblast growth factor (bFGF) that are associated with arthritis and angiogenesis, to stimulate secretion of VEGF protein by human synovial fibroblasts. TGF-beta was the strongest inducer of VEGF secretion; six times more VEGF was secreted when cells were stimulated by TGF-beta than when stimulated by PDGF or IL-1 for 24 h. TNF-alpha and bFGF did not stimulate any secretion of VEGF. The stimulatory effects of TGF-beta and IL-1 on VEGF secretion were additive. Hypoxic culture alone also stimulated VEGF secretion, but more importantly, hypoxic culture conditions doubled the rate of VEGF secretion stimulated by the cytokines TGF-beta and IL-1. When dermal and synovial fibroblasts were stimulated identically by hypoxia and cytokines (TGF-beta and IL-1), synovial fibroblasts secreted four times more VEGF than did dermal fibroblasts. Thus in rheumatoid arthritis, the capacity of synovial fibroblasts in the hypoxic environment to secrete large amounts of VEGF in response to cytokines such as TGF-beta probably contributes significantly to angiogenesis in the synovium.