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ID PMID Title PublicationDate abstract
9566669 An immunocytochemical study of the distribution of proline-4-hydroxylase in normal, osteoa 1998 Mar The monoclonal antibody 5B5 reacts with the beta subunit of proline-4-hydroxylase, the enzyme which catalyses the formation of 4-hydroxyl proline in collagen and other proteins with collagen-like amino acid sequences. This study aims to assess the production and tissue distribution of this enzyme in normal and diseased synovia from patients with various joint diseases, on the basis that it is a putative marker of collagen-producing cells and, therefore, in this context, of fibroblasts. Sections from five normal, 10 osteoarthritic (OA) and 26 rheumatoid arthritic (RA) synovia were labelled with a mouse monoclonal antibody to proline-4-hydroxylase. The enzyme was found to be expressed by a proportion of synovial intimal cells and by fibroblasts in the underlying connective tissue in normal, OA and RA synovia. Labelling was more pronounced in OA and RA cases. The intimal cells labelling positively showed type B synoviocyte morphology, which was confirmed by subsequent double immunolabelling with 5B5 and antibody against type IV collagen using immunocytochemistry and immunoelectron microscopy.
9165372 Phorbol 12-myristate 13-acetate (PMA)-induced oxyradical production in rheumatoid synovial 1997 Apr We successfully detected the oxyradical production in human synovial A (macrophage-like) and B (fibroblast-like) cells by phorbol 12-myristate 13-acetate (PMA) using the luminol-chemiluminescence method. The PMA (0.1 microgram/ml)-induced photon generation was abolished by an O2- scavenger, superoxide dismutase, and an H2O2 scavenger, catalase, suggesting that the stimulus produced oxyradicals in synovial cells. Both of these responses were abolished by a protein kinase C (PKC) inhibitor, calphostine C, but unaffected by an intracellular Ca2+ chelator, BAPTA-AM, and Ca2+ removal from the extracellular medium. These findings suggest that synovial A and B cells produce oxyradicals through PKC-mediated and [Ca2+]i-independent mechanisms, probably through the activation of NADPH oxidase.
11508598 Seasonal symptom severity in patients with rheumatic diseases: a study of 1,424 patients. 2001 Aug OBJECTIVE: To examine the nature of seasonal symptoms, their prevalence, and differences among rheumatic disorders by examining longitudinal data over a period of up to 24 years. METHODS: We used a questionnaire assessment of seasonal symptoms using the Seasonal Pattern Assessment Questionnaire (SPAQ) in 1,424 patients with rheumatoid arthritis (RA), osteoarthritis (OA), and fibromyalgia (FM). Clinical status was evaluated with standard assessment measures, and reported symptoms were compared with actual seasonal differences measured for periods of up to 24 years. RESULTS: About 50% of patients with rheumatic disease reported exacerbation of rheumatic symptoms (pain, global severity, and fatigue) by seasonal changes. The presence of seasonal symptoms was not related to diagnosis or to seasonal affective disorder (SAD) symptoms, and symptoms were less common in older patients and in men. The number of symptoms and the severity of allied factors (depression, anxiety, pain, global severity, number of months with seasonal symptoms) were increased in persons with FM and/or complete SAD symptoms. Using circular statistics, the modal months for worse symptoms were December and January, and for best symptoms was July. Bimodal patterns of seasonality were identified for global severity, joint pain, fatigue, and socialization. Seasonal symptoms differed as to the degree at which they were dispersed around the 12 month circle. When pain and global severity measurements obtained over a 24 year period were analyzed, pain was slightly increased in the summer and global severity was not related to season at all. Even when patients who specifically reported worse symptoms in winter and best symptoms in summer were examined, no effect of season could be found. CONCLUSION: Seasonal rheumatic symptoms are commonly reported across all rheumatic diseases, but appear to reflect perception rather than reality since reported symptoms do not agree with measured clinical scores. In addition, regardless of seasonal complaints, measured pain and global severity scores are not worse in winter. Although patients with FM and Season (+) patients report more severe symptoms, their pattern of reporting and their actual scores do not differ according to season compared to persons without FM or positive seasonality.
10072558 Plasma cell development in synovial germinal centers in patients with rheumatoid and react 1999 Mar 1 Plasma cells are found surrounding the inflammatory infiltrates of macrophages, T, and B cells in the synovial tissue of patients with rheumatoid and reactive arthritis. This characteristic arrangement suggests that in the synovial tissue CD20+ B cells differentiate into plasma cells. To examine clonal relationships, we have used micromanipulation to separately isolate CD20+ B cells and plasma cells from single infiltrates. DNA was extracted, and from both populations the VH/VL gene repertoires was determined. The data show that in the inflamed synovial tissue activated B cells are clonally expanded. During proliferation in the network of follicular dendritic cells, V gene variants are generated by the hypermutation mechanism. Surprisingly, we do not find identical rearrangements between CD20+ B cells and plasma cells. Nevertheless, the finding of clonally related plasma cells within single infiltrates suggests that these cells underwent terminal differentiation in the synovial tissue. These results indicate that B cell differentiation in the synovial tissue is a dynamic process. Whereas CD20+ B cells may turnover rapidly, plasma cells may well be long lived and thus accumulate in the synovial tissue. The analysis of individual B cells recovered from synovial tissue opens a new way to determine the specificity of those cells that take part in the local immune reaction. This will provide new insights into the pathogenesis of chronic inflammatory diseases like rheumatoid or reactive arthritis.
9801775 Centralization of the femoral component in cemented hip arthroplasty using guided stem ins 1998 In order to improve the positioning of the stem within the femur, to centralize it within the cement and to achieve a complete and homogeneous cement mantle, a new hip endoprosthesis with guided stem insertion was developed. The femoral component has a longitudinal channel that takes up a guidewire which directs it during insertion into the centre. The guidewire is attached to the cement stopper which is positioned in the marrow cavity before applying the bone cement. The first 100 endoprostheses of this type with an observation period of at least 6 years were assessed radiologically and clinically. The clinical evaluation according to the hip scores of Merle d'Aubigne and Harris revealed a marked improvement between preoperative and postoperative values for all criteria. On radiological assessment 94% of the stems had a neutral position within the femur; 98% of the stems were found to be ideally centred within the cement distally, 80% distally and proximally; 74% of the cement cuffs had a complete and homogeneous cement layer between 2 and 5 mm medially and laterally, while 25% had partially a dimension of more than 5 mm, predominantly proximally. In only 3 cases was one part of the cement mantle found to be less than 2 mm. The radiological follow-up was also documented according to the delineated zones of Gruen. It revealed zonal radiolucent lines in 15 cases, combined in 11 cases with reactive lines, never extending up to 4 zones out of 14. Five prostheses had subsided moderately between 2 and 3 mm, and only one 8 mm. None of these radiological signs was associated with clinical symptoms. There were five cement fractures. Two stems were symptomatic, radiologically loose and revised. Beside these two cases of aseptic loosening there was one septic case, so that in total 97% of the implants are still functioning well.
9576018 [Value of inflammation and bone scintigraphy in differential diagnosis of painful affectio 1998 It was the aim of this study to evaluate different markers of inflammation such as 99mTc-labelled human immunoglobulin G and 99mTc-nanocolloid with respect to their ability to detect inflammatory or degenerative affections of small joints of hand and fingers. While conventional bone scanning reveals good agreement with clinical findings it is not well suited for screening of inflammatory processes due to its poor specificity. In small joints conventional three-phase bone scan with information of perfusion, bloodpool and accumulation is not suitable due to the small ROI, low count rate with high statistics. Therefore we used inflammatory markers to overcome this problem. Immunoglobulin G was true positive in case of inflammatory lesions in 69%, and false positive in case of degenerative lesions in 24%, while nanocolloid was true positive in 72% and false positive in 14%, respectively. Significant differences were found between markers of inflammation and the bone scanning agent while both inflammatory markers, immunoglobulin G and nanocolloid demonstrated significant correlation. While bone scanning tracers detect all kinds of joint affections, immunoglobulin G and nanocolloid accumulate preferentially in inflammatory joints and therefore might be useful to differentiate between inflammatory and degenerative lesions.
9375888 Preliminary core sets for endpoints in ankylosing spondylitis. Assessments in Ankylosing S 1997 Nov An international working group was formed to select core sets to be used as endpoints in clinical trials in ankylosing spondylitis (AS). The results of the first steps of the selection of these core sets are described. The definition of the settings for which the core set will be intended are defined. The methods used to select the core sets were a combination of literature search, nominal group discussions, and plenary discussions. The following settings were defined: disease controlling antirheumatic therapy (DC-ART), symptom modifying antirheumatic drugs (SMARD)/physical therapy, and clinical record keeping. Over 110 variables used as endpoints in AS were found in the literature. The preliminary core set for DC-ART consists of physical function, pain, spinal mobility, patient global assessment, peripheral joints/entheses, x-ray spine. The selected core set for SMARD/physical therapy includes physical function, pain, spinal mobility, spinal stiffness, and patient global assessment. The core set for clinical record keeping includes all measures of the SMARD/physical therapy core set completed by peripheral joints/entheses, and acute phase reactants. Three preliminary core sets for AS have been defined. Further research will be performed to select specific measures for all domains.
11714978 Circulating tumour necrosis factor-alpha and interferon-gamma are detectable during acute 2001 Dec To investigate whether cytokine responses may have a bearing on the symptoms and outcome of parvovirus B19 infection, circulating cytokines were measured during acute infection (n=51), follow-up of acute infection (n=39) and in normal healthy controls (n=50). At acute B19 virus infection (serum anti-B19 IgM-positive), patients ranged in age from 4 to 54 years, with a mean age of 28.2 years. The male:female ratio was 1:4.1 and symptoms were rash (n=15), arthralgia (n=31), fatigue (n=8), lymphadenopathy (n=4), foetal hydrops (n=3), transient aplastic crisis (n=2), neutropenia (n=2), myelodysplasia (n=1), thrombocytopenia (n=1) and pancytopenia (n=1). Of these patients, 39 were contacted after a follow-up period of 2-37 months (mean of 22.5 months). In comparison with normal controls, detectable IL-6 was associated with acute B19 virus infection (26%; P=0.0003), but not with follow-up (6%; P=0.16). Detection of interferon (IFN)-gamma was associated with acute B19 virus infection (67%; P<0.0001) and follow-up (67%; P<0.0001). Detection of tumour necrosis factor (TNF)-alpha was associated with acute B19 virus infection (49%; P<0.0001) and follow-up (56%; P<0.0001). IL-1beta was detected in acute infection (20%), but not at follow-up. At acute B19 virus infection, detection of serum/plasma IL-6 was associated with rheumatoid factor (P=0.038) and IFN-gamma (> or =7 pg/ml) was associated with fatigue in those patients of > or =15 years of age (P=0.022). At follow-up, fatigue was associated with IFN-gamma (> or =7 pg/ml) and/or TNF-alpha (> or =40 pg/ml) (P=0.0275). Prolonged upregulation of serum IFN-gamma and TNF-alpha appears to represent a consistent host response to symptomatic B19 virus infection.
10728442 Synovial fluid lymphocyte proliferation in response to crude microbial antigens is not use 2000 Jan OBJECTIVE: To determine the role of lymphocyte proliferation assay of synovial fluid mononuclear cells (SFMC) with whole fraction bacteria in the diagnosis of reactive arthritis (ReA) or arthritis of unknown origin. METHODS: We stimulated SFMC of 52 unselected patients who consecutively presented in our rheumatology outpatient clinic with the following diagnoses: ReA (n = 8), rheumatoid arthritis (RA) (n = 16), ankylosing spondylitis (AS) (n = 6), osteoarthritis (OA) (n = 5), psoriatic arthritis (PsA) (n = 5) and arthritis of varying origin (AVO) (n = 12) and peripheral blood MC (PBMC) of 10 healthy controls with arthritogenic (Y. entero-colitica, S. enteritidis, C. trachomatis) and non-arthritogenic (E. coli, K. pneumoniae, S. pyogenes, C. albicans) bacteria/mitogens and Tetanus toxoid. T cell proliferation was measured in a standard [3H] Thymidine uptake assay. RESULTS: In all groups of patients tested, SFMC could be stimulated both by arthritogenic and non-arthritogenic bacteria. So-called specific responses were observed in patients with ReA, but also in RA and AS. CONCLUSION: Our findings show that a lymphocyte proliferation assay with SFMC with whole fraction bacteria is not an adequate diagnostic tool to confirm bacterial involvement in inflammatory arthritis.
10343526 Destruction of articular cartilage by alpha 2 macroglobulin elastase complexes: role in rh 1999 Feb OBJECTIVE: Neutrophil elastase accounts for the ability of some fresh rheumatoid synovial fluids to degrade cartilage matrix in vitro. The aim of this study was to determine if enzyme activity could result from depletion of synovial fluid inhibitors or protection of the enzyme from inhibition. METHODS: The ability of synovial fluids to inhibit porcine pancreatic elastase was investigated together with chemical pretreatments capable of inactivating alpha 1 protease inhibitor (alpha 1PI) or preventing formation of alpha 2 macroglobulin (alpha 2M) elastase complexes. Subsequently, complexes of human neutrophil elastase with alpha 2M were prepared and applied to frozen sections of cartilage. Proteoglycan loss was quantified by alcian blue staining and scanning and integrating microdensitometry. Parallel studies were carried out using a low molecular weight chromogenic elastase substrate. The effects of alpha 1PI and SF on these systems were investigated. Finally, synovial fluids were subjected to gel filtration and the fractions assayed for elastase activity. High molecular weight fractions were pooled, concentrated, and tested for their ability to degrade cartilage sections. RESULTS: All synovial fluids reduced the activity of porcine pancreatic elastase, the inhibition mainly being attributable to alpha 1PI, whereas remaining activity resulted from complexes of elastase with alpha 2M. Complexes of human neutrophil elastase with alpha 2M were shown to cause proteoglycan degradation in frozen sections of human articular cartilage. Alpha 1PI prevented alpha 2M elastase complexes from degrading cartilage but not the chromogenic substrate. The data suggested that alpha 1PI does not inhibit elastase bound to alpha 2M but sterically hinders the complex. However, only one of five synovial fluids was able to completely block the actions of alpha 2M elastase complexes against cartilage. Gel filtration of rheumatoid synovial fluids showed elastase and cartilage degrading activity to be associated with fractions that contained alpha 2M, and not with fractions expected to contain free enzyme. CONCLUSIONS: The data suggest that synovial fluid alpha 2M elastase complexes can degrade cartilage matrix in rheumatoid arthritis.
11186254 Adrenal androgen and glucocorticoid dissociation in premenopausal rheumatoid arthritis: a 2000 Controlled studies of adrenal steroids in premenopausal women with rheumatoid arthritis (RA) have revealed subtle and inconsistent decreases in glucocorticosteroid (GCS) function, but prominent deficiencies of adrenal androgens (AA). Such findings have suggested that hypoandrogenicity may predispose to RA in younger women. However, recent prospective studies of serum cortisol and dehydroepiandrosterone sulfate (DHEAS) levels before (x = 12 yrs) the onset of the disease (pre-RA) offer an alternative perspective. Significant dissociation of serum cortisol and DHEAS levels was found only in the subgroup of premenopausal women who developed RA before age 50. This subgroup alone had significant deficiency in serum DHEAS levels. Aggregate data imply that the documented deficits of DHEAS (and other AA) in such young females are a correlate of relative adrenal insufficiency, and that subtle GCS dysfunction may either contribute to development of RA in such young women as well as pubertal girls or may predispose to earlier onset of disease.
9433404 A retrospective study of treating RA patients with various combinations of slow-acting ant 1997 During the period 1/1990-9/1995 a total of 311 RA patients were challenged 458 times with 52 different COMBOs. As the first COMBO methotrexate (MTX), sulphasalazine (SSZ), im gold (GOLD), and hydroxychoroquine (HCQ) were combined with each other in 272/311 cases. The respective six and 12 months survivals of these COMBOs were 68.6% (95% CI 63.0% to 74.3%) and 53.6% (95% CI 47.4% to 59.9%). Inefficacy (27.9%), rather than adverse events (23.5%) or other causes (16.9%) was the leading reason for the discontinuations. Only in five cases (1.8%) these COMBOs were discontinued due to a remission. Not a single adverse event related to a COMBO treatment was judged as serious. The mean survival time for COMBOs including MTX (24.0 months; 95% CI 20.6 to 27.4) was statistically significantly longer than the respective time for COMBOs without MTX (14.5 months; 95% CI 11.2 to 17.7). We conclude that, when meticulously monitored, the treatment with COMBOs is safe. However, their efficacy on patients with advanced RA is modest. The survival time for COMBOs including MTX is longer than COMBOs without MTX.
10437061 [Repair of large articular cartilage defect of hip with allograft of skull periosteum]. 1998 May It is very difficult to repair large articular cartilage defect of the hip. From May 1990 to April 1994, 47 hips in 42 patients of large articuler cartilage defects were repaired by allograft of skull periosteum. Among them, 14 cases, whose femoral heads were grade. IV necrosis, were given deep iliac circumflex artery pedicled iliac bone graft simultaneously. The skull periosteum had been treated by low tempreturel (-40 degrees C) before and kept in Nitrogen (-196 degrees C) till use. During the operation, the skull periosteum was sutured tightly to the femoral head and sticked to the accetabulum by medical ZT glue. Thirty eight hips in 34 patients were followed up for 2-6 years with an average of 3.4 years. According to the hip postoperative criteria of Wu Zhi-kang, 25 cases were excellent, 5 cases very good, 3 cases good and 1 case fair. The mean score increased from 6.4 before operation to 15.8 after operation. The results showed, in compare with autograft of periosteum for biological resurface of large articular defect, this method is free of donor-site morbidity. Skull periosteum allograft was effective for the treatment of large articular cartilage defects in hip.
9584378 Immediate weightbearing after uncemented total hip arthroplasty. 1998 Apr Radiographic subsidence of the femoral prosthesis and clinical results after unilateral and simultaneous bilateral uncemented total hip arthroplasty were compared. Patients who had bilateral total hip arthroplasty began weight-bearing as tolerated on both lower extremities the day after surgery. Patients who had undergone unilateral total hip arthroplasty were maintained at 10% weightbearing on the operative limb for 6 weeks after surgery. Patients in both groups were matched for age, gender, and weight. Minimal followup was 2 years. There was no difference between the two groups in terms of clinical results. Radiographic assessments were performed immediately after surgery, 6 weeks after surgery, and again at 2 years after surgery. Radiographs were reviewed by a single observer and analyzed with a digitized data recorder. Increased subsidence of the femoral prosthesis within the bilateral group was found at 6 weeks. The mean subsidence of the femoral prosthesis at 6 weeks for the bilateral total hip arthroplasty group was 0.86 mm (range, 0.18-2.60 mm) and for the unilateral group was 0.39 mm (range, 0.07-1.46 mm). However, subsidence occurring between 6 weeks and 2 years averaged 0.50 mm (range, 0.09-1.10 mm) for the bilateral group and 0.54 mm (range, 0.03-0.99 mm) for the unilateral group. This difference was not significant. At the 2-year followup, all femoral prostheses in both groups appeared radiographically stable with evidence of bone ingrowth and no indications of loosening. Thus, immediate weightbearing after bilateral total hip arthroplasty in this study resulted in more initial subsidence (during the first 6 weeks after surgery) of the femoral prosthesis but did not preclude the prosthesis from becoming stable and achieving bone ingrowth. Patients in both groups obtained satisfactory clinical results. Because initial stability and bone ingrowth are factors influenced by prosthesis design, the results of this study may not be applicable to all implants.
10089139 High expression of macrophage migration inhibitory factor in the synovial tissues of rheum 1999 Feb Macrophage migration inhibitory factor (MIF) plays an important role in inflammation and immunity via autocrine/paracrine and endocrine routes. We examined the presence of MIF in the synovial fluids of rheumatoid arthritis (RA) patients. The content of MIF in the synovial fluid was quantitated by enzyme-linked immunosorbent assay which revealed that the concentration of MIF for RA patients was 85. 7+/-35.2 ng/ml (mean+/-SD) (n=25). In comparison, the concentrations for osteoarthritis patients and normal volunteers were 19.5+/-5.3 ng/ml (n=12) and 10.4+/-1.1 ng/ml (n=5), respectively. The expression of MIF mRNA and presence of MIF protein in the synovial tissues of RA were demonstrated by Northern blot and Western blot analyses, respectively. Immunohistochemical analysis revealed that positive staining was largely observed in the cytoplasm of infiltrating T lymphocytes, which might be the major source of MIF detected in the synovial fluids. The pathophysiological role of MIF in RA remains to be elucidated; however, the present results for the first time suggest the possibility that MIF is involved in the potentiation of inflammatory and immunological responses in rheumatoid joints.
9361161 Methotrexate pulmonary toxicity. 1997 Nov Drug-induced pulmonary disease is a well-recognized complication of MTX treatment of rheumatic diseases. Physicians involved in the management of patients receiving MTX should be aware of this potentially life-threatening complication. The prompt evaluation of new pulmonary symptoms in patients receiving MTX is important in the early recognition of this drug-induced complication. The characteristic symptoms are shortness of breath, nonproductive cough, fatigue, and fever. If an MTX-induced pulmonary reaction is suspected and abnormalities are noted on lung examination, chest radiography should be performed. In the presence of an abnormal chest radiograph, MTX should be discontinued, supportive measures instituted, and the diagnosis of the patient's pulmonary complaints investigated by specifically looking for features of the underlying rheumatic process, infection, and other medical conditions. Patients with severe pulmonary compromise should be hospitalized and given supplemental oxygen and high-dose corticosteroids. Most patients recover from their illness. No risk factors have been identified that consistently identify patients at the greatest risk for MTX-induced pulmonary toxicity. All patients receiving MTX should be educated concerning this potentially life-threatening drug toxicity and instructed to contact their physician immediately if significant pulmonary symptoms develop.
10826953 Amidase and peptidase activities of polyclonal immunoglobulin G present in the sera of pat 2000 Jan Polyclonal Immunoglobulin (Ig) G from patients with rheumatoid arthritis (RA) and healthy subjects hydrolyzed carbobenzoxy-Val-Gly-Arg p-nitroanilide and D-Pro-Phe-Arg p-nitroanilide. RA IgG exhibited higher activity against the former substrate, but not the latter. On the other hand, RA IgG showed reduced activity against D-Pro-Phe-Arg methylcoumarinamide, when compared with those of the healthy controls. These results suggest that RA IgGs differ from normal IgGs in the substrate specificity of amidase activity. Preliminary studies have shown that two out of three RA IgG samples cleaved a pentapeptide--Gln-Arg-Arg-Ala-Ala--which is assumed to be associated with the risk of developing RA (Gregersen, P. K. et al. (1987), Arthritis Rheum. 30, 1205-1213). By contrast, virtually no cleavage of the same peptide was observed with IgG from healthy controls. A peptide analog, Gln-Arg-Arg-Trp-Ala, was not cleaved at all by any IgGs examined either from RA patients or healthy controls.
10520896 A rheumatoid factor specific mimotope identified by a peptide display library. 1999 We screened a 10 amino acid peptide display library in filamentous phage with B'20, a monoclonal high affinity IgM rheumatoid factor (RF) expressing the VkIIIa-dependent 4C9 idiotype. Using direct and indirect selection techniques, 12 B'20 reactive peptides were identified, 9 of which belonged to one of two motifs. Binding of B'20 to phage-bearing peptides was inhibited by both IgG and 4C9 antiidiotype. Synthetic peptides corresponding to the two motifs inhibited the Fc binding of a low avidity IgA B'20 construct. Purified IgM from 6/8 RF-positive RA patients and 8/11 monoclonal RFs with VkIII-encoded light chains bound to the phage, whereas none of the four monoclonal RFs with VkI or VkII encoded light chains bound. Phage binding appeared to be RF specific. Three 4C9 positive/RF negative cell lines from RA patients did not bind to phage nor did three B'20 mutants that had lost RF specificity, whereas two mutants that retained RF specificity also retained phage binding. We propose that there is a common epitope(s) recognized by VkIII encoded RFs that is mimicked by the structure of these peptides. Such mimotopes might be exploited to design novel agents that interfere with autoantibody binding.
11708406 A human glucocorticoid receptor gene variant that increases the stability of the glucocort 2001 Nov OBJECTIVE: To study the occurrence and function of polymorphism in the human glucocorticoid receptor (hGR) gene in rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). METHODS: We used single stranded conformation polymorphism (SSCP) and direct sequencing to study the hGR gene in 30 patients with RA, 40 with SLE, and 24 controls. A newly identified polymorphism was transfected in COS-1 cells and the stability of the mRNA containing the polymorphism was tested using real-time PCR. RESULTS: A polymorphism in the hGR gene in exon9beta, in an "ATTTA" motif, was found to be significantly associated with RA. Introduction of this polymorphism in the hGRb mRNA was found to significantly increase stability in vitro compared to the wild-type sequence. CONCLUSION: Our findings show an association between RA and a previously unreported polymorphism in the hGR gene. This polymorphism increased stability of hGRbeta mRNA, which could contribute to an altered glucocorticoid sensitivity since the hGRbeta is thought to function as an inhibitor of hGRalpha activity.
11155809 Relationship between interleukin-6 (IL-6) and hypothalamic-pituitary-adrenal axis hormones 2000 Systemic symptoms in rheumatoid arthritis (RA) are mediated, at least in part, by elevated levels of circulating interleukin 6 (IL-6), which is a potent activator of the human hypothalamic-pituitary-adrenal (HPA) axis. In a recent study, we observed that the 24 h time-integrated plasma ACTH and cortisol, as well as urinary free cortisol levels of untreated RA patients were not significantly different from control subjects, in spite of their active disease. However, an earlier morning surge of plasma ACTH and cortisol in RA patients was found. Plasma ACTH and cortisol responses to oCRH were similar between RA patients and controls. Plasma IL-6 levels showed a pronounced circadian variation and were significantly increased in the RA patients, compared to control subjects. In the RA patients, we detected a positive temporal correlation between plasma levels of IL-6 and ACTH/cortisol, with IL-6 preceding ACTH and cortisol by 1 and 2 h, respectively. In the same patients, we detected a negative effect of cortisol upon IL-6 exerted with a delay of 5 h. In patients with early untreated RA--although endogenous IL-6 stimulates the ACTH and cortisol secretion--the overall secretory activity of the HPA axis remains "inappropriately" normal despite elevated plasma IL-6 levels. The resulting "inappropriately" normal cortisol levels are apparently insufficient to satisfactorily limit the inflammation in these patients. In patients with Sjögren's syndrome the ACTH and cortisol response after CRH stimulation has been found to be blunted. On the other hand, patients suffering from systemic lupus erythematosus, when subjected to insulin tolerance testing, showed a lower cortisol response compared to healthy controls. These data indicate a direct and/or indirect involvement of a defective HPA axis in the pathogenesis of certain autoimmune-related pathologic entities.