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ID PMID Title PublicationDate abstract
8608635 A synthetic 10-kD heat shock protein (hsp10) from Mycobacterium tuberculosis modulates adj 1996 Mar The heat shock protein, hsp10, is an abundant protein in Mycobacterium tuberculosis (Mtb), its nucleotide sequence encoding a protein of 99 amino acids with a molecular mass of 10.7 kD. This sequence is phylogenetically conserved, being represented by the GroES homologue of Escherichia coli. Hsp10 and GroES are members of the chaperonin 10 family of molecular chaperones, and GroEs is necessary for the optimal activity of GroEL, a member of the chaperonin 60 family and the E. coli homologue of mycobacterial hsp65. Since hsp65 has been implicated in both experimental and human rheumatoid arthritis, we aimed to assess the immunomodulatory effects of its co-chaperonin, hsp10, in experimental arthritis. Our results show that an aqueous solution of a mycobacterial hsp10 delayed the onset and severity of adjuvant-induced arthritis in rodents when administered after disease induction but before joint involvement occurred. This biological activity was specific for the hsp10 of Mtb, since neither GroES not the rat homologue was effective. Using synthetic hsp10 fragments, the activity was localized to the N-terminal region of the molecule. Assessment of circulating antibody levels to mycobacterial hsp10 and hsp65 indicated that all arthritic rats had increased titres to both hsp10 and hsp65: hsp10-treated rats showed further elevation of this humoral response not only to hsp10 but also to hsp65 when compared with the untreated arthritic control. This is the first report of the immunomodulatory activity of mycobacterial hsp10 in experimental arthritis, and exhibits a potential role for this co-chaperonin in pathophysiological situations.
8586488 Effect of a novel anti-rheumatic drug, TA-383, on type II collagen-induced arthritis. 1995 Jul The effects of Ta-383 (0.016, 0.08, 0.4, 2 and 10 mg/kg) and anti-rheumatic drugs (lobenzarit 10 and 50 mg/kg, dexamethasone 0.25 mg/kg) were evaluated on type II collagen-induced arthritis in DBA/1J mice. The arthritis score was markedly suppressed in the groups treated with dexamethasone and TA-383. Serum anti-type II collagen IgG was significantly suppressed in the groups treated with dexamethasone and 0.4 mg/kg TA-383. Histopathological evaluation of the knee joints revealed suppression of the inflammatory changes in the groups treated with dexamethasone and TA-383. These findings suggest that the histopathological examination of the joints of the animal model is useful for the evaluation of anti-rheumatic drugs, and that TA-383 has suppressive effects on type II collagen-induced arthritis, an animal model for human rheumatoid arthritis.
1496165 Pulmonary and gastrointestinal manifestations of Sjögren's syndrome. 1992 Aug The respiratory system is frequently involved in primary SS but this involvement is rarely clinically significant. Its manifestations are secondary to desiccation of the tracheobronchial tree and lymphocytic infiltration of the lung parenchyma. The desiccation of the tracheobronchial tree gives rise to the most important clinical manifestation, dry cough (xerotrachea), but is rarely a cause of infection and obstructive airways disease. The lymphocytic infiltration of the lung parenchyma starts as lymphocytic alveolitis in a very large number of SS patients but rarely evolves into frank lymphocytic interstitial pneumonitis and fibrosis. Even more rare is the evolution of pseudolymphoma into malignant lymphoma. Pleurisy with or without effusion is not a frequent manifestation of primary SS. It occurs often in secondary SS and is due to the underlying rheumatic disorder. In general, secondary SS rarely has significant pulmonary manifestations other than those of the disorder it accompanies. The manifestations from the gastrointestinal system in patients with SS include mucosal dryness, accelerated dental decay, and enlargement of the major salivary glands, as well as dysphagia, nausea, epigastric pain, and dyspepsia. The dysphagia is probably secondary to esophageal dysfunction, and the gastric symptoms might be attributable to chronic atrophic gastritis. Whether the small bowel is affected in SS patients is not clear. Pancreatic involvement usually is being expressed as subclinical acute or chronic pancreatitis. Finally, the liver could be involved in SS patients, and some studies indicate that the pathogenic process responsible for the hepatic damage and for the salivary gland destruction could be similar.
1603203 Neuro-musculo-skeletal manifestations in primary Sjögren's syndrome. 1992 Apr Primary Sjögren's syndrome is a systemic autoimmune disorder whose main characteristics are dryness of the eyes and mouth, caused by lymphocytic infiltration of the exocrine glands. Patients may also show signs of extraglandular involvement of lung, liver, kidney and vessel walls, as well as of the central and peripheral nervous systems, muscles and joints. This article presents a review of the literature on extraglandular involvement of the peripheral and central nervous systems, muscles and joints. Several data support the hypothesis that vasculitis is the underlying mechanism. The need for an extended inventory of the extraglandular manifestations, preferentially linked to immunoserological and -histological investigations to gain more insight into the aetiology and pathogenesis is stressed. As far as the clinical picture is concerned, myalgia and arthralgia are often reported, but myositis and arthritis are rare. Data about the prevalence of peripheral and central nervous system involvement are conflicting: factors contributing to these differences are discussed. As insight into prognosis and therapy will strongly depend on the diagnostic criteria used, the need for international agreement on these is emphasized.
8250993 Sjögren's syndrome presenting as hypokalemic periodic paralysis. 1993 Dec We describe a 21-year-old Hispanic woman who presented with hypokalemic paralysis as the initial manifestation of Sjögren's syndrome (SS). Our review of the English literature revealed 12 previously reported cases of SS and renal tubular acidosis (RTA). Paralysis often preceded the sicca complex in those patients. Renal function in the patients with hypokalemic paralysis was reduced compared with that in patients who had primary SS and RTA but no history of hypokalemic paralysis (P < 0.002). Hypokalemic periodic paralysis is a rare manifestation of SS. It is seen more often in patients with primary SS, may precede the classic sicca complex, and may serve as a clinical marker for more severe renal disease in patients who have primary SS and RTA.
8607899 Interleukin-10 inhibition of the progression of established collagen-induced arthritis. 1996 Mar OBJECTIVE: Interleukin-10 (IL-10) is a potent inhibitor of the proinflammatory cytokines, including tumor necrosis factor alpha and IL-1, which are considered important in the pathogenesis of rheumatoid arthritis (RA). The study was undertaken to establish whether IL-10 can ameliorate arthritis in the collagen-induced arthritis (CIA) model of RA. METHODS: DBA/1 mice were immunized with bovine type II collagen in adjuvant, and treated daily after disease onset with recombinant murine IL-10 or with saline as a control. Mice were monitored for paw swelling and clinical score. Histologic analysis was also performed. RESULTS: IL-10 treatment of established CIA inhibited paw swelling (P < 0.0001), as well as disease progression as defined by clinical score (P < 0.0002). Cartilage destruction, as assessed histologically, was reduced in IL-10-treated mice compared with controls (P < 0.01). CONCLUSION: IL-10 suppresses established CIA, probably by inhibiting proinflammatory cytokine production. Our results, taken together with previously reported findings, indicate a potential therapeutic role for IL-10 in RA.
8184320 Correlations between education and arthritis in the 1971-1975 NHANES I. 1994 Feb Data from the National Health and Nutrition Examination Survey I, 1971-1975 (NHANES I) were used to analyze associations among highest education level and arthritis. The dependent variables indicated whether the respondent had ever been diagnosed with any form of arthritis by a physician (10,678 women and 7243 men) or whether physician X-ray readings suggested arthritis of the knee (3491 women and 3119 men). These variables did not distinguish between osteo- and rheumatoid arthritis. It is likely that the great majority of the sample reporting or diagnosed with arthritis had osteoarthritis. There were strong univariate correlations between answers to the general arthritis question and the knee question on the one hand and gender, age, body mass, schooling, income and employment on the other. Respondents' education level was found to be strongly and negatively associated with self-reported arthritis in the larger samples both before and after controls were entered for employment, income and potential biological risk factors. The association between self-reported arthritis or arthritis of the knees and education was weaker for men, but not for women after employment and income were accounted for. When body mass was accounted for, the association between self-reported arthritis or arthritis of the knees and education was weaker among women but not men. Long-run preventive strategies to combat osteoarthritis ought to consider investments in education.
8482852 A synthetic peptide analogue of a determinant of type II collagen prevents the onset of co 1993 May 15 The immunization of genetically susceptible strains of mice with type II collagen (CII) elicits a collagen-induced arthritis that resembles rheumatoid arthritis. Our laboratory previously identified a region of CII, CII-245-270, that contains a T cell epitope that is prominent in the immune response to CII. Residues critical to the I-Aq-restricted presentation of this determinant have been characterized. To produce synthetic peptides with the potential of disrupting I-Aq-restricted Ag presentation, synthetic analogue peptides were developed that contain site-directed substitutions in critical positions. One analogue peptide was found to be an efficient competitor for binding to I-Aq and to be capable of inhibiting T cell responses in vitro. When DBA/1 mice were coimmunized with CII and the analogue peptide, the incidence and severity of arthritis were greatly reduced, concordant with the humoral immune responses to CII.
1449942 Radiolunate and radioscapholunate arthrodesis. 1992 Eleven patients underwent radiocarpal arthrodesis for a wrist disease other than rheumatoid arthritis. Operations included seven radiolunate fusions and four radioscapholunate fusions. The indication for surgery was posttraumatic changes secondary to radius fracture (five), Kienböck's disease (three), localized arthritis secondary to sepsis (two) and acute comminuted fracture of the distal radius (one). All patients had arthritis or post-traumatic changes limited to the articulation between the radius and carpus. Follow-up ranged from 24 months to 7 years, with an average of 41 months. Postoperatively, average range of motion of the wrist was 30.9 degrees of extension, 22.7 degrees of flexion, 10 degrees of radial deviation, and 19.3 degrees of ulnar deviation, and grip strength averaged 81.8% of that for the uninvolved hand. Pain relief was achieved in all patients, and they were able to return to their previous occupation. Bony union was achieved in all cases. Degenerative changes in the midcarpal joint were not seen.
8937683 Nerve growth factor (NGF) autoantibodies and NGF in the synovial fluid: implications in sp 1996 We investigated the presence of nerve growth factor (NGF) autoantibodies and NGF in the synovial fluid (SF) of patients with different forms of chronic arthritis such as spondylarthropathy (SpA), rheumatoid arthritis (RA), calcium pyrophosphate dihydrate crystal deposition disease (CPPD) and osteoarthritis (OA) and compared them to their levels in serum. NGF autoantibodies were detected by ELISA and by their capacity to immunoprecipitate NGF and to inhibit its biological activity. NGF was measured with a two-site enzyme-linked immunosorbent assay. Significantly high NGF autoantibody levels (p < 10(-4)) and high frequency of detectable NGF (p < 0.01) were observed in the SF of SpA patients and to a lesser degree in RA patients as compared to CPPD and OA patients. In the serum high frequency of detectable NGF was observed only in RA patients. These results suggest a role of NGF autoantibodies and NGF in joint inflammation especially in spondylarthropathies.
7547116 Gout, uric acid metabolism, and crystal-induced inflammation. 1995 Jul Serum triglyceride levels are significantly higher and serum high-density lipoprotein cholesterol levels are lower in patients with gout compared with healthy individuals. Whereas increased serum triglyceride levels exist intrinsically in gout, serum uric acid concentration correlates inversely with insulin sensitivity and positively with serum triglycerides. Interaction of monosodium urate crystals with granulocyte-macrophage colony-stimulating factor and with tumor necrosis factor-activated neutrophils favored the production of interleukin-1 over that of interleukin-1-Ra, resulting in a proinflammatory imbalance. Interaction of the crystals with iron or tyrosine kinase may modify their inflammatory response and can be an important modulating mechanism in gouty arthritis. E-selectin is a specific marker for synovial fluid soluble endothelial activity and is increased in the synovial fluid of patients with gouty arthritis, as well as in that of patients with other inflammatory arthritides. Similarly, E-selectin was found to be high in joints with monosodium urate crystal-induced synovitis. In addition, synovial fluid levels of interleukin-8 were found to be high in gout, rheumatoid arthritis, and osteoarthritis.
7788153 Symptomatic enlarged iliopsoas bursae in the presence of a normal plain hip radiograph. 1995 Apr The clinical and radiological features of seven cases of enlarged iliopsoas bursae are presented, all of which had normal plain hip radiographs. Two cases had rheumatoid arthritis, one had septic arthritis diagnosed by synovial biopsy and the remaining four cases occurred as isolated findings, in the absence of any recognized hip pathology. A communication with the hip joint was demonstrated in one case associated with septic arthritis. All patients presented with symptoms of hip pain and limitation of movement. Two patients had a groin mass, one of which produced localized pressure symptoms and retroperitoneal extension. All patients had an arthrogram or bursogram performed. In the two cases where a mass was palpable, ultrasound and computed tomography were performed. We conclude that, in the presence of persistent hip pain or reduced range of movement, an enlarged iliopsoas bursa should be considered as a potential diagnosis, even in cases where the plain hip radiograph is normal.
18472950 Cytokine reduction in the treatment of joint conditions. 1994 The destruction of joints caused by rheumatoid arthritis and osteoarthritis is characterized by an imbalance of enzyme catalysed cartilage breakdown and regeneration. A complex cytokine network perpetuates joint conditions by direct regulation of metalloproteases, by indirect recruitment of cells that secrete degradative enzymes, and by inhibition of reparative processes. The destructive action of cytokines such as interleukin-1, interleukin-6 and tumour necrosis factor-alpha can be modulated at multiple points associated either with cytokine production or with cytokine action. Potential agents for cytokine reduction include selective anti-cytokine antibodies, anticytokine receptor antibodies, cytokine receptor antagonist proteins, and soluble and chimeric cytokine receptor molecules. Pharmacologic regulation of IL-1 and TNFalpha remain primary targets for treatment of arthritis, and results of early clinical trials are promising. However, the results of long-term clinical trials will be required to support the value of anti-cytokine therapy in treatment of arthritis.
7940346 [The DNA typing of the HLA-B27 gene among individuals with joint lesions]. 1994 To determine the HLA-B27 gene subtypes associated with joint diseases we examined 55 patients (35 with ankylosing spondylarthritis (AS), 13 with rheumatoid arthritis (RA), 5 with Reiter's syndrome, 2 with psoriatic arthritis). DNA amplification combined with sequence specific oligonucleotide hybridization were used to identify six HLA-B27 gene alleles. In the AS patients group the frequency of HLA-B2705 variant was found to be different significantly from that in healthy West Siberia Caucasians and distribution of HLA-B27 gene allele variants among AS patients in East Russia differed from that in West regions of Russia. DNA typing data can be useful together with other criteria for diagnosis of AS in a early onset.
1417126 Dependence of proteoglycan induced arthritis in BALB/c mice on the development of autoanti 1992 Aug BALB/c mice were immunised with high or low density native human cartilage proteoglycans, or the respective core proteins obtained from chondroitin ABC lyase digestion. Mice injected with high density native proteoglycans developed arthritis whereas mice injected with low density proteoglycans or with core proteins did not. Analysis of the immune response by enzyme linked immunosorbent assay (ELISA) and western blot showed a stronger and more polyspecific response in animals injected with low density proteoglycans compared with mice with arthritis which had been injected with high density proteoglycans. Autoantibodies to mouse high density proteoglycans were only present in mice injected with native human high density proteoglycans, however. The data suggest that an arthritogenic epitope lies within the glycosaminoglycan rich region of the native proteoglycan molecule, which may induce an autoantibody response and subsequently arthritis in BALB/c mice.
8857991 Synovial chondromatosis of the metacarpophalangeal joint: case report and review of the li 1996 Oct Intra-articular synovial chondromatosis in the hand is rare but should be considered in the differential diagnosis of a swollen, stiff or painful joint. Other possible diagnoses include osteoarthritis, rheumatoid arthritis, gout, trauma and chronic infection, and unless enchondral ossification of loose bodies is seen the diagnosis of synovial chondromatosis may not be made preoperatively. A 69-year-old man with synovial chondromatosis of the metacarpophalangeal joint is reported. The joint was swollen and tender. He had not sustained trauma and there was no evidence of arthritis, involvement of other joints or infection. Complete synovectomy with removal of all loose bodies was successful and his symptoms resolved. Intra-articular synovial chondromatosis is a benign condition, but spontaneous resolution is the exception and surgical synovectomy remains the most effective treatment.
8526184 [Type III polyglandular autoimmune syndrome. Report of a case]. 1995 Sep Type III polyglandular syndrome is defines as the association of insulin dependent Diabetes mellitus, thyroid gland affection (hyper or hypothyroidism) and a non endocrinological disease, rheumatological or not. Less common manifestations include pernicious anemia, vitiligo and alopecia. Circulating organ-specific auto antibodies are detected in blood smear and a lymphocyte infiltrate in the affected glands. We report a patient with insulin dependent Diabetes mellitus since the age of 3, who developed hypothyroidism at the age of 14 and severe rheumatoid arthritis at 16. Moderate anemia with positive auto antibodies against parital gastric cells was detected. Treatment with methotrexate and indomethacin was indicated with excellent results regarding her arthritis and after 2 weeks of treatment she began to walk normally again.
8005860 Sex as a determining factor in the effect of exercise on in vivo autoimmune response adjuv 1994 Mar The present study was conducted to examine the effect of physical exercise on the development of adjuvant arthritis (AA), an animal model of the human rheumatoid arthritis, which is a T-cell-dependent autoimmune response. AA was inducted on day 0 in 8-wk-old Lewis rats of both sexes. Between postinjection days 1 and 12, two groups of rats (male and female) were trained on a treadmill every day (45-120 min/day and 15-30 m/min) before the onset of arthritic disease. Trained female (n = 27) and male (n = 22) rats and control female (n = 29) and male (n = 17) rats were observed every 2 days for the following clinical signs of AA: number of arthritic joints (swelling and redness), paw thickness, and weight gain during the disease. The results show that the incidence of arthritis (% of arthritic rats) was significantly higher in trained female rats (74%; P < 0.03) and significantly lower in trained male rats (27%; P < 0.05) compared with control rats of both sexes (female, 45%; male, 59%). There was no difference in the severity and development of the disease between trained rats and control rats of both sexes (P > 0.05). The present study indicates that the effect of exercise on the incidence of AA, an in vivo autoimmune response, depends on the sex of the animal.
7518663 Increased IgA antibodies to cytokeratins in the spondyloarthropathies. 1994 Jun OBJECTIVES: Increased levels of IgA antibodies to cytokeratin-18 (CK-18) and epidermal keratins (EpK) in the sera of patients with rheumatoid arthritis (RA) have been demonstrated previously. In the present study investigations were carried out to determine whether levels of these autoantibodies were also raised in the spondyloarthropathies, and whether there was any association with particular disease manifestations. METHODS: Using specific enzyme linked immunosorbent assays (ELISA) measurements were taken of IgA, IgG and IgM antibodies to EpK and to CK-18 in the sera of patients with psoriatic arthropathy, ankylosing spondylitis (AS), Reiter's syndrome, psoriasis and in normal subjects. RESULTS: IgA antibodies to both EpK and CK-18 were significantly increased in sera from patients with psoriasis and psoriatic arthropathy but not in the sera from the patients with AS or Reiter's syndrome, or in the controls. In psoriatic arthritis, however, these levels were significantly higher only in those patients with peripheral joint disease and not in those with axial arthritis alone. There was no significant increase in antibody levels in patients with AS or Reiter's syndrome. There were no differences in the levels of IgG or IgM antibodies to CK-18 or EpK between the patient groups and controls. CONCLUSIONS: Raised levels of IgA antibodies to CK-18 and EpK in psoriatic arthropathy and psoriasis probably reflect exposure of intracellular cytokeratin antigens to the immune system after damage to cytokeratin containing cells, and suggests a common pathogenic mechanism in these conditions which involves production of cytokeratin autoantibodies. In patients with psoriatic arthropathy, such a mechanism appears only to be operating in patients with peripheral joint involvement and not in those with axial arthritis.
8436167 T cell regulation of collagen-induced arthritis in mice. II. Immunomodulation of arthritis 1993 Feb Injection of native type II collagen (CII) to susceptible strains of mice (H-2q) induces a rheumatoid arthritis-like disease. To study the role of CD8+ T cells in the collagen-induced arthritis (CIA), we generated CII-specific T cell hybridomas by fusion of cells from arthritic C3H. Q mice and an AKR thymoma. Two hybrid clones (P3G8 and P2D9) were selected for their ability to lyse syngeneic CII-pulsed macrophages and recognize different antigenic epitopes in association with Kq molecules. When these T cell clones were irradiated and inoculated into (C3H.Q x AKR)F1 mice 21 days prior to priming with native CII/complete Freund's adjuvant, the incidence and the duration of CIA were significantly reduced in comparison to groups receiving saline or control T cell hybridoma. Furthermore, both anti-CII T cell hybridomas were able to attenuate CIA in highly susceptible inbred strains of mice and this suppression was antigen and disease specific. The protective activity seems to require intact cells as neither membrane fractions nor cytosolic preparations of the hybridoma T cells retained the vaccinating activity. Most importantly, one of the hybrid clones (P3G8) had a therapeutic effect on CIA since its administration to arthritic DBA/1 mice on day 30 after priming down-regulated the ongoing disease. Taken together, these findings suggest that anti-CII cytotoxic T cell clones can vaccinate against CIA and even reverse the disease.