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ID PMID Title PublicationDate abstract
9256010 [Study of apoptosis in Sjögren's syndrome]. 1997 Jul To clarify the role of apoptosis in the pathogenesis of Sjögren's syndrome (SS), we investigated apoptosis and apoptosis-related molecules in peripheral blood lymphocytes (PBL) and salivary glands (SG) from SS patients and normal controls. In PBL, SS T lymphocytes showed accelerated in vitro apoptosis, and CD4+ T cells showed increased Fas expression compared to those in normal controls. Interestingly, SS T cells also showed increased Bcl-2 expression. The acinar epithelial cells in SS were Fas+ and FasL+, and these cells died by apoptosis. The majority of infiltrating lymphocytes in SS were Fas+ and Bcl-2+, while few lymphocytes expressed FasL. In situ detection of apoptosis showed minimal cell death among lymphocytes, particularly in dense periductal foci. Bax seemed to be expressed in apoptotic acinar cells. In conclusion, blocked apoptosis of SG infiltrating lymphocytes as well as enhanced apoptosis of peripheral T cells may be characteristics of SS. SS acinar cells may die by apoptosis, and this may ultimately lead to SG destruction in SS patients.
9190103 Primary biliary cirrhosis, sicca complex, and dysphagia. 1997 Summer We investigated symptoms suggestive of swallowing problems in patients with primary biliary cirrhosis, some of whom displayed features of sicca complex. A prospective study of 95 consecutive patients with primary biliary cirrhosis was conducted at a single teaching hospital using a questionnaire administered over the telephone. Some symptoms of sicca complex (dry mouth and/or dry eyes) were found in 65 patients (68.4%). Subjective xerostomia alone was present in 45 patients (47.4%). The questionnaire revealed an increase in incidence of dysphagia in xerostomia subjects, affecting 21 of 45 patients, compared with 6 of 50 non-xerostomia patients. Multivariate logistic regression analysis showed that confounding factors such as age, obesity, cigarette smoking, and medications associated with a dry mouth could not explain these findings. Twenty-eight patients complained of hoarseness, 23 of coughing, and 14 of wheezing, all of which were significantly more frequent than in the 50 patients without xerostomia. Heartburn affected 17 xerostomia patients and 15 non-xerostomia patients, indicating no difference in frequency between these two groups, even after age, obesity, cigarette smoking, and medications associated with heartburn were considered in the multivariate analysis. Acid regurgitation, nausea, and vomiting were also similar in frequency between patients with and without xerostomia. Swallowing problems, manifested primarily as dysphagia, are common in primary biliary cirrhosis patients who have subjective xerostomia.
10862795 Distinct roles for the NF-kappaB1 (p50) and c-Rel transcription factors in inflammatory ar 2000 Jun Rheumatoid arthritis (RA) is a complex disease, with contributions from systemic autoimmunity and local inflammation. Persistent synovial joint inflammation and invasive synovial pannus tissue lead to joint destruction. RA is characterized by the production of inflammatory mediators, many of which are regulated by the Rel/NF-kappaB transcription factors. Although an attractive target for therapeutic intervention in inflammatory diseases, Rel/NF-kappaB is involved in normal physiology, thus global inhibition could be harmful. An alternate approach is to identify and target the Rel/NF-kappaB subunits critical for components of disease. To assess this, mice with null mutations in c-rel or nfkb1 were used to examine directly the roles of c-Rel and p50 in models of acute and chronic inflammatory arthritis. We found c-Rel-deficient mice were resistant to collagen-induced arthritis but had a normal response in an acute, destructive arthritis model (methylated BSA/IL-1 induced arthritis) suggesting c-Rel is required for systemic but not local joint disease. In contrast, p50-deficient mice were refractory to induction of both the chronic and acute arthritis models, showing this subunit is essential for local joint inflammation and destruction. Our data suggest Rel/NF-kappaB subunits play distinct roles in the pathogenesis of inflammatory arthritis and may provide a rationale for more specific therapeutic blockade of Rel/NF-kappaB in RA.
11741631 Subcellular distribution of aquaporin 5 in salivary glands in primary Sjögren's syndrome. 2001 Dec 1 Secretions from salivary and lacrimal glands are reduced in patients with primary Sjögren's syndrome (PSS). Since aquaporin 5 is involved in transport of water and is present in salivary and lacrimal glands, this protein was thought to have a major role in the pathogenesis of PSS. We used indirect immunofluorescence and an immunoperoxidase technique to assess expression and subcellular localisation of aquaporin 5 in patients and controls. Our results suggest that the distribution and density of aquaporin 5 in salivary glands does not differ between patients with PSS and those without. Thus, the role of aquaporin 5 in the pathogenesis of PSS needs to be reassessed and alternative pathogenetic mechanisms investigated.
11263777 Immunoglobulin Vkappa light chain gene analysis in patients with Sjögren's syndrome. 2001 Mar OBJECTIVE: Patients with Sjögren's syndrome (SS) have characteristic lymphocytic infiltration of the salivary glands with a previously reported predominance of Vkappa-bearing B cells and produce a variety of autoantibodies, indicating that there is a humoral autoimmune component in this syndrome. This study was undertaken to determine whether there are primary deviations of immunoglobulin V gene usage, differences in somatic hypermutation, defects of selection, or indications for perturbances of B cell maturation in SS. METHODS: Individual peripheral B cells from patients with SS were analyzed for their Ig V gene usage, and the findings were compared with results in normal controls. RESULTS: Molecular differences, as reflected by findings in the nonproductive Vkappa repertoire of the patients, were identified by an enhanced usage of Jkappa2 gene segments and a lack of mutational targeting toward RGYW/WRCY sequences compared with controls. A greater usage of Vkappa1 family members and a reduced frequency of Vkappa3 gene segments in the productive repertoire suggested differences in selection, possibly driven by antigen. Overall positive selection for mutations, especially for replacements in the complementarity-determining region and for mutations in RGYW/WRCY, similar to that found in controls, was detected. CONCLUSION: Disturbances of strictly regulated B cell maturation, during early B cell development as indicated by prominent Jkappa2 gene usage and during germinal center reactions as indicated by a lack of targeting of the hypermutation mechanism, might contribute to the emergence of autoimmunity in SS.
11246665 Sympathetic dysfunction in patients with primary Sjögren's syndrome. 2001 Feb OBJECTIVE: To investigate autonomic nervous system function in patients with primary Sjögren's syndrome (SS) and relate the findings to clinical variables. METHODS: Autonomic nervous system function was determined in 30 patients with primary SS using the finger skin blood flow test [vasoconstrictory (VAC) index], deep-breathing test [expiration/inspiration (E/I) ratio], and the tilt table (orthostatic) test [acceleration index (AI), brake index (BI), and orthostatic blood pressure]. The results were compared with age matched control materials (finger skin blood flow test, n = 80, and deep-breathing and tilt table tests, n = 56). RESULTS: The VAC index was found to be significantly increased and the E/I ratio significantly decreased in patients compared to controls, indicating both a sympathetic and a parasympathetic dysfunction. Further, the patients, especially the anti-SSA and anti-SSB antibody seropositives, were found to have an abnormal blood pressure reaction to tilt compared to controls. No correlations were found between autonomic nerve function variables measured and the clinical ophthalmologic or the oral tests, performed at the time of diagnosis. CONCLUSION: Patients with primary SS show signs of both sympathetic and parasympathetic dysfunction. Further, immunological mechanisms seem to influence blood pressure in patients with primary SS.
10220831 Increased salivary interleukin-6 levels in patients with primary Sjögren's syndrome. 1999 This study's purpose was to evaluate salivary interleukin-6 (IL-6) levels in patients with primary Sjögren's syndrome (SS). Salivary and serum IL-6 concentrations were evaluated by ELISA in 36 patients with SS and compared with 19 patients complaining of dry mouth and with normal controls. Salivary IL-6 levels were significantly elevated (P < 0.01) in the 36 patients with SS as compared to the 19 patients with dry mouth (200.5 +/- 43.6 and 12.6 +/- 6.8 pg/ml, respectively). No significant differences were noted in the serum IL-6 levels between these two groups (105.8 +/- 17.1 and 84.8 +/- 17.1 pg/ml, respectively). Both salivary and serum IL-6 levels in the normal controls were below the level of detection of the assay. Positive correlation (r = 0.8613, P < 0.0001) was found between salivary IL-6 levels and the focus score of labial biopsies in SS patients. Elevated salivary IL-6 levels appear to be a consequence of local production and may reflect the component of salivary gland inflammation in SS.
10096321 Air trapping in primary Sjögren syndrome: correlation of expiratory CT with pulmonary fun 1999 Mar PURPOSE: The purpose of our study was to correlate the extent of air trapping on expiratory CT scans with results of pulmonary function tests (PFTs) in a large group of patients with primary Sjögren syndrome and to determine whether these techniques may be complementary in assessing small airways obstruction. METHOD: Thirty-four nonsmoking patients with proven primary Sjögren syndrome and 10 healthy nonsmokers underwent paired inspiratory-expiratory thin section CT and PFTs. Expiratory scans were scored for the presence and extent of areas of air trapping. Extent of air trapping was assessed visually and given a score. The functional significance of the extent of air trapping was evaluated in both groups and then correlated with the results of PFTs. RESULTS: Bronchiolar abnormalities were seen in 11 (32%) of 34 patients with primary Sjögren syndrome. On the expiratory CT scans, a mosaic pattern of lung attenuation was identified in 17 patients. Air trapping was found in 44 of 204 lobar observations on the expiratory scans. The median point scale score at end-expiration was 3.6 (20%, Grade 1), ranging from 1 (5.5%, Grade 1) to 9 (50%, Grade 2). The mean total score of air trapping was more prevalent in lower (46/68) lobes (22.4%) than in upper (22/136) lobes (5.3%) (p < 0.001). PFTs were normal in the primary Sjögren syndrome patients as well as the healthy subjects. Air trapping was found more frequently in patients with primary Sjögren syndrome than in the healthy group. Only during exhalation was there evidence of minimal lobular-sized areas or air trapping (Grade 1) in three of the healthy subjects. We did not find any correlation between air trapping and PFTs including the forced expiratory flow rate between 25 and 75% of the forced vital capacity (FEF25-75). CONCLUSION: Expiratory high resolution CT revealed the extent of bronchiolar disease in patients with primary Sjögren syndrome. We also found that the extent of air trapping did not correlate with PFTs, which suggests the existence of a subclinical bronchiolar inflammatory process that may precede detectable abnormalities in lung function tests.
9575679 Recurrent annular erythema in a case of seronegative Sjögren's syndrome. 1998 Mar We describe a case of Sjögren's syndrome who repeatedly developed annular erythema on her extremities. Her anti-nuclear antibody, anti-SSA/Ro antibody, and anti-SSB/La antibody were all negative. Characteristics of the annular erythema included a tendency to appear on the extremities especially in summer, spontaneous regression after 1-2 weeks, and residual slight pigmentation. The histological findings revealed dermal perivascular lymphocytic infiltration admixed with some neutrophils. Slight exsudative changes were found in the upper dermis. There were no epidermal changes. This case suggests the existence of annular erythema which may not be related to the anti-SSA/Ro or anti-SSB/La antibody. Unknown factors other than those antibodies may be involved in the pathogenesis of the annular erythema.
10665745 AV-block III in a patient with sarcoidosis mimicking Sjögren's syndrome. 1999 A 55-year old woman with a diagnosis of primary Sjögren's Syndrome suddenly developed AV-block III. A diagnostic procedure finally revealed sarcoidosis with multiorgan involvement.
11441114 Tissue-type plasminogen activator deficiency exacerbates arthritis. 2001 Jul 15 Fibrin deposition, cell migration, and tissue remodeling are key components in the lesions of inflammatory joint diseases, such as rheumatoid arthritis. The plasminogen activators (PAs), namely, tissue-type PA (t-PA) and urokinase PA, are implicated in these aspects of an inflammatory response, although their precise roles are yet to be defined. We therefore used gene-deficient mice to explore their role in a two-stage arthritis model involving intraarticular methylated BSA injection, followed by systemic IL-1 treatment. We report in this study that both t-PA and urokinase PA are protective for the mild arthritis induced by intraarticular methylated BSA injection alone, since absence of either of them exacerbates the response; following s.c. IL-1 injection, t-PA(-/-) mice had particularly severe disease. Fibrin deposition appeared to parallel disease severity under the various conditions, suggesting that PA-mediated fibrinolysis may be normally playing a protective role in inflammatory joint disease.
9067525 Dynamics of proinflammatory cytokine expression in the joints of mice with collagen-induce 1997 Mar This report contains a description of the cellular localization and kinetics of proinflammatory cytokine expression in murine CIA, a model for rheumatoid arthritis. Tissue cryostat sections of undecalcified paws from type II collagen-immunized DBA/1 mice, taken 1-10 days after the onset of clinical arthritis, were examined for the presence of tumour necrosis factor-alpha (TNF-alpha), IL-1beta and IL-6 using an indirect immunoperoxidase technique. In parallel, interferon-gamma (IFN-gamma) production by lymph node cells, stimulated in vitro with type II collagen, was assessed as a marker of T cell activity. The main areas of TNF-alpha, IL-1beta and IL-6 expression were in the synovial lining layer and in tissue contiguous with cartilage and bone (the marginal zone), in particular at sites of pannus formation and joint erosion. There was a progressive increase in the number of TNF-alpha-, IL-1beta- and IL-6-positive cells from day 1 to day 10 of arthritis, during which time IFN-gamma production by CD4+ T cells from draining lymph nodes declined sharply. A further finding of potential significance was that TNF-alpha was consistently detected at day 1 of arthritis, whereas IL- 1beta-positive cells were not found until day 3, suggesting that the expression of TNF-alpha precedes that of IL-1beta.
12903452 [Apoptosis of chondrocytes in cartilage]. 2000 Aug OBJECTIVE: To observe apoptosis of chondrocytes in cartilage and arthritis. METHODS: Apoptosis was detected by light and electron microscope and DNA electrophoresis, while [Ca2+]i was detected by confocal laser scanning microscope. RESULTS: Cartilage cells from osteoarthritis (OA) and rheumatoid arthritis (RA) could be seen to undergo normal differentiation after cultured for 3 days under light or electron microscope, while some chondrocytes directly isolated without culturing could give early changes of apoptosis, and normal chondrocytes in vitro after treatment with IL-1, TNF-alpha also underwent apoptosis. IL-1, TNF-alpha could induce increase of [Ca2+]i in chondrocytes. CONCLUSIONS: Our data showed that apoptosis might present in the normal cartilage as well as in OA and RA cells. IL-1, TNF-alpha could induce apoptosis of chondrocytes and [Ca2+]i increase during apoptosis.
9415648 Acute gouty synovitis associated with "urate milk". 1997 Dec OBJECTIVE: To analyze the clinical features of acute gouty synovitis associated with thick, milky white, "chalky," urate laden synovial effusions, and to investigate the effects on synovial white blood cell (WBC) counts when leukocyte-rich rheumatoid effusions are incubated with a urate packed milky synovial fluid. METHODS: Five patients (all men, mean age 70.8 years) with acute gouty synovitis (acute arthritis in 3, acute bursitis in 2) associated with "urate milk" were studied between 1993 and 1996. RESULTS: Synovial effusions were thick, "chalky," and appeared "milky" white. The fluids were packed with monosodium urate (MSU) crystals, which sedimented upon standing, leaving a clear supernatant containing a few MSU crystals. The presence of massive amounts of MSU crystals and crystal clumps interfered with accurate determination of synovial WBC counts. Four fluids showed "a few leukocytes," and one a WBC count of 6750/mm3 with 91% neutrophils and several intraleukocytic crystals. Four patients had subcutaneous tophi. Of the risk factors associated with development of gout, the most frequent was ethanol abuse, in 4 and possibly all 5 patients. Incubation of leukocyte-rich rheumatoid synovial effusions with urate laden knee fluid from Patient 5 produced a greater reduction in synovial WBC counts compared to controls. CONCLUSION: Milky white synovial effusions containing massive quantities of urate crystals (referred to as "urate milk") may rarely occur in the setting of acute gouty arthritis or bursitis. Ethanol abuse appears to be a risk factor associated with the development of hyperuricemia and gout in these patients.
11094441 Immune ablation and stem-cell therapy in autoimmune disease. Clinical experience. 2000 In the past 5 years, around 350 patients have received haematopoietic stem cell (HSC) transplantation for an autoimmune disease, with 275 of these registered in an international data base in Basel under the auspices of the European League Against Rheumatism (EULAR) and the European Group for Blood and Marrow Transplantation(EBMT). Most patients had either a progressive form of multiple sclerosis (MS; n = 88) or scleroderma (now called systemic sclerosis; n = 55). Other diseases were rheumatoid arthritis (Ra n = 40), juvenile idiopathic arthritis (JIA; n = 30), systemic lupus erythematosus (SLE; n = 20), idiopathic thrombocytopenic purpura (ITP; n = 7) and others. The procedure-related mortality was around 9%, with between-disease differences, being higher in systemic sclerosis and JIA and lower in RA (one death only). Benefit has been seen in around two-thirds of cases. No one regimen was clearly superior to another, with a trend toward more infectious complications with more intense regimens. Prospective, controlled randomized trials are indicated and being planned.
17009177 Modified Burton and Pellegrini procedure for trapezium excision, ligament reconstruction a 1997 Mar GOAL OF SURGERY: Relieve of pain and increased stability at the base of 1st metacarpal. INDICATIONS: Painful degenerative and inflammatory arthritis in trapeziometacarpal joint (TMCJ). CONTRAINDICATIONS: Patients not willing to undergo lengthy intensive postoperative rehabilitation. Rheumatoid arthritis (relative). POSITIONING AND ANAESTHESIA: Supine. Hand table. General or regional anaesthesia. SURGICAL TECHNIQUE: Modification of the Burton-Pelligrini operation by using half of the flexor carpi radialis for interposition between base of 1st metacarpal and scaphoid. Stabilization with a Kirschner wire. In the presence of scaphotrapezoid arthritis an arthrodesis of this joint is performed for better pain control. POSTOPERATIVE MANAGEMENT: Immobilization in a below elbow cast for 6 weeks. Then active physiotherapy, night splint for another 6 weeks. POSSIBLE COMPLICATIONS: Fracture while drilling the base of the 1st metacarpus, migration of Kirschner wires, injury to the radial artery and cutaneous nerves. RESULTS: Out of 15 patients 12 (14 thumbs) were followed for at least 6 months. In 11 patients the shape of the hand was normal and 10 patients were satisfied with the result of the operation. Complications included: twice postoperative migration of Kirschner wires, and once intraoperative tearing of the tendon which had to be sutured.
11829791 [Reinfusion of autologous shed blood after joint replacement]. 1999 Feb OBJECTIVE: To evaluate the results of reinfusion of autologous shed blood after joint replacement. METHODS: From February 1996 to March 1998, we selected 36 patients for 56 joint replacements. Apart from preoperative donation of autologous blood, all patients received transfusion of unwashed autologous drained blood from hips and knees after arthroplasty. The CBCIIConstaVac blood conservation system was used to salvage shed blood. Among the patients, 8 hips and 48 knees were involved. 12 patients had rheumatoid arthritis, 16 osteoarthritis, 5 ankylosing spondylitis, and 3 other arthritis. RESULTS: 36 patients received 24 260 ml (50%) autologous shed blood, 9 700 ml (20%) reserved autologous blood, and 14 600 ml (30%) allogenic blood. 15 patients experienced transient febrile reaction at the time of reinfusion, no other clinic abnormalities were discovered after reinfusion. CONCLUSIONS: Reinfusion of autologous shed blood is a safe and effective to decrease the use of allogenic blood and avoid the complications of its transfusion.
9987950 [Institute of Rheumatology and progress of antirheumatic therapy]. 1998 The paper deals with the achievements of the Institute of Rheumatology in antirheumatic therapy, among them there are methods of objective assessment of antirheumatic drugs, the first use of antimalarials in the treatment of chronic rheumatic fever, discovery of immunodepressive properties of these drugs, specification of the mechanism of action of several NSAIDs. Antilymphocytic globulin, salazopyridazine and the alkylating drug dopan were used for the first time in therapy of rheumatic diseases. Administration of the most potent NSAIDs diclofenac or indomethacin to patients with acute rheumatic fever proved to be as effective as prednizolone. Special attention is paid to the combination treatment of rheumatoid arthritis with NSAIDs. The concurrent administration of aurannofin and methotrexate was shown to cause a more rapid development of clinical improvement than monotherapy with either drug. A combination of gold aurothiomalate and hydroxychloroquine and that of low doses of D-penicillamine and cyclophosphamide had no advantages over monotherapy. Revealing the therapeutical potential of antibodies to interferon-gamma in the treatment of rheumatic arthritis and psoriatic arthritis was the most important achievement of recent years. These studies open new vistas for anticytokine treatment of rheumatic diseases.
9435395 [Aminotransferase levels in rheumatoid arthritis patients treated with methotrexate]. 1997 Mar Increase of the aminotransferase levels in 53 patients treated with methotrexate (MTX) were analysed in a retrospective study. The mean dose of MTX was 7.46 mg/week (range 2.5-15 mg) during at least 30 weeks (mean time of MTX use 124 weeks). The aminotransferase levels were transitorily increased in 13 patients, always less than three times the upper limit of normal. Only in three patients the AST and ALT levels were persistently increased and lead to the drug discontinuation in two cases. These results showed that increase of aminotransferases was a frequent observation (24.5%) during the first two-three years of follow-up, without interference in the overall clinical management.
9690133 Induction of abundant osteoclast-like multinucleated giant cells in adjuvant arthritic rat 1998 Jul The development of an in vivo system for investigating osteoclast differentiation is important because molecular events occurring in vivo can be observed during the differentiation of the authentic osteoclasts. In adjuvant arthritic rats, an experimental model of human rheumatoid arthritis, extensive bone resorption is observed in the distal diaphysis of the tibia. In the area of extensive bone resorption, it is always accompanied with clusters of numerous multinucleated giant cells (MGCs) as well as bone-resorbing osteoclasts. Here we characterized the morphological properties of these MGCs with the use of enzymehistochemical and immunohistochemical techniques. Extensive destruction but also a marked formation of the inner and outer bone surfaces were the predominant features in the tibiae of such arthritic rats 4 weeks after the adjuvant injection. Numerous MGCs were frequently clustered in the bone marrow spaces located apart from the bone matrices. Although the MGCs lacked ruffled borders, these cells were rich in mitochondria and vacuoles. These multinucleated cells revealed a positive reaction for tartrate-resistant acid phosphatase but a negative reaction for non-specific esterase staining. Most of these MGCs expressed the Kat 1-antigen, an immunological marker specifically expressed on the cell surface of rat osteoclasts. In a dentin resorption experiment using a cluster of MGCs excised from the bone marrow tissues of the tibial distal diaphyses of rats with adjuvant arthritis, many resorption lacunae were formed on dentin slices after a 3-day culture. These results suggest that the majority of the MGCs are osteoclasts but not macrophage polykaryons.