Browse

Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
11256140 [Pharma-clinics. The drug of the month. Celecoxib (Celebrex)]. 2001 Jan Celecoxib (Celebrex, Pharmacia) is a potent and selective inhibitor of the COX-2 isoform of cyclooxygenase which is used as nonsteroidal anti-inflammatory drug (NSAID). Its current indications are osteoarthritis and rheumatoid arthritis. The usual recommended daily dosage of celecoxib is 200 mg (in one or two intakes per day), to be increased up to 400 mg (two intakes per day) if necessary. Its clinical efficacy seems to be similar to that of other NSAIDs. However, its safety profile, especially gastro-intestinal tolerance and perhaps renal safety, is much better because of the COX-2 selectivity.
11361220 Zymosan modulates CD44 isoform expression in a murine model of inflammation resembling rhe 2001 May OBJECTIVE: To study local inflammation induced by zymosan in the murine air pouch, considered a model of synovial-like tissue inflammation, we investigated the time-course synthesis of CD44 and tumor necrosis factor-alpha (TNF-alpha) mRNA and established a relationship with leukocyte migration into the air pouch and CD44 expression on the leukocyte membrane. METHODS: Leukocytes from the air pouch exudate were collected and counted at 1, 4, 12, 24, 48, and 72 h after zymosan or saline injection. CD44 and TNF-alpha mRNA were studied by RT-PCR. CD44 variable exon analysis was assessed by Southern blot and CD44 membrane expression by flow cytometry. RESULTS: Leukocyte accumulation after zymosan injection was significantly higher than in saline injected controls. CD44 standard and variable isoforms including at least variable exons v6 and v9 were highly expressed in leukocytes from the zymosan air pouch exudate. In contrast, only the CD44 mRNA standard isoform was present in leukocytes from saline air pouch. Maximal TNF-alpha mRNA level was observed at 48 h after zymosan injection, whereas CD44 mRNA was constantly expressed throughout the whole term of the experiment, although variations in leukocyte count and relative formula were observed. CONCLUSION: Expression of CD44 variable isoform in leukocytes was specifically induced by zymosan, since none was detected in saline controls. TNF-alpha mRNA expression and leukocyte count at every time point served as markers for local inflammation. The presence of variable isoforms, including at least exons v6 and v9, consistently expressed throughout the assay suggests that they could play a role in this arthritis-like inflammation induced under zymosan stimulus.
9141551 Heterogeneity of the human corticotropin-releasing factor-binding protein. 1997 May Human corticotropin-releasing factor (hCRF), secreted by the placenta, principally in the third trimester, is specifically bound in the peripheral circulation to a 37-kDa binding protein (CRF-BP). This complex is cleared from the circulation. We postulate that the protein may be returned to the blood in a form that is immunologically altered and not well recognized by the reported RIAs. We report that a stable isoform can result from temporary denaturation of recombinant CRF-BP by 8 mol/L urea. This isoform, urea-treated binding protein, which can bind CRF, has been found to bind to an antibody raised against a synthetic peptide comprising the first 24 amino acid residues of CRF-BP, but not to a second similar N-terminal antibody, although it was closely matched in titer. Urea-treated binding protein also cross-reacts poorly in the RIA with CRF-BP. It is proposed that as a result of in vivo post-ligand binding events, isoforms may be susceptible to cleavage. After affinity purification, which involves denaturation, recombinant CRF-BP was often found to be cleaved after storage in the presence of protease inhibitors. Here we present evidence for a C-terminally truncated form of the native binding protein in the plasma of subjects suffering from rheumatoid arthritis, which may parallel the in vitro truncation.
9090648 Rhenium-188 labeled hydroxyapatite and rhenium-188 sulfur colloid. In vitro comparison of 1997 Mar AIM: One therapeutic approach to rheumatoid arthritis and other inflammatory arthropathies besides surgical removal of inflamed synovium is radiation synovectomy using beta-emitting radionuclides to destroy the affected synovial tissue. Up to now the major problem associated with the use of labeled particles or colloids has been considerable leakage of radionuclides from the injected joint coupled with high radiation doses to liver and other non target organs. In this study we compared 188Re labeled hydroxyapatite particles and 188Re rhenium sulfur colloid for their potential use in radiation synovectomy. METHODS: To this end we varied the labeling conditions (concentrations, pH-value, heating procedural and analyzed the labeling yield, radiochemical purity, and in vitro stability of the resulting radiopharmaceutical. RESULTS: After optimizing labeling conditions we achieved a labeling yield of more than 80% for 188Re hydroxyapatite and more than 90% for the rhenium sulfur colloid. Both of the radiopharmaceuticals can be prepared under aseptic conditions using an autoclave for heating without loss of activity. In vitro stability studies using various challenge solutions (water, normal saline, diluted synovial fluid) showed that 188Re labeled hydroxyapatite particles lost about 80% of their activity within 5 d in synovial fluid. Rhenium sulfur colloid on the other hand proved to be very stable with a remaining activity of more than 93% after 5 d in diluted synovial fluid. CONCLUSION: These in vitro results suggest that 188Re labeled rhenium sulfur colloid expects to be more suitable for therapeutic use in radiation synovectomy than the labeled hydroxyapatite particles.
11580755 NF-kappaB and the MAP kinases/AP-1 pathways are both involved in interleukin-6 and interle 2001 Oct As in rheumatoid arthritis (RA), it was demonstrated recently that bacterial fragments of DNA or rRNA are present in the joint and therefore could play a role in inducing or perpetuating the disease, this work was initiated to define mechanisms that account for the stimulatory activities of the oral streptococcal modulin, protein I/II, on fibroblast-like synoviocytes (FLSs) from RA patients. FLSs from RA patients were stimulated with protein I/II, and expression of interleukin (IL)-6 and IL-8 mRNA was evaluated by reverse transcription-polymerase chain reaction (RT-PCR). Immunoblotting by antibodies specific for activated forms of MAPKs and electrophoretic mobility shift assays (EMSAs) were performed to study downstream signalling, which allowed the synthesis of IL-6 and IL-8. We reported that protein I/II interactions with FLSs from RA patients trigger the synthesis and release of IL-6 and IL-8. We also demonstrated that protein I/II enhances the phosphorylation of ERK 1/2, p38 and JNKs and that ERK 1/2 and JNK MAPKs seem to play a more important role than p38 in protein I/II-mediated synthesis of IL-6 and IL-8. Our experiments also indicated that stimulation of FLSs with protein I/II induces nuclear translocation of NF-kappaB, AP-1-binding activity and that NF-kappaB plays a major role in IL-6 and IL-8 secretion from activated cells.
11329148 The angiogenic pathway "vascular endothelial growth factor/flk-1(KDR)-receptor" in rheumat 2001 May Active angiogenesis, together with an up-regulation of angiogenic factors, is evident in the synovium of both rheumatoid arthritis (RA) and osteoarthritis (OA). The present study assessed, by immunohistochemistry, the microvessel density in the synovium of these arthritides and in normal controls, in relation to the expression of the angiogenic factors vascular endothelial growth factor (VEGF) and platelet-derived endothelial cell growth factor (PD-ECGF) and the apoptosis-related proteins bcl-2 and p53. More importantly, using the novel 11B5 MAb, the activated "VEGF/flk-1(KDR)-receptor" microvessel density was assessed. VEGF expression in fibroblasts was diffuse in both RA and OA. Diffuse PD-ECGF expression of fibroblasts was noted in all cases of RA, while fibroblast reactivity was focal in the OA material. The standard microvessel density (sMVD), as assessed with the anti-CD31 monoclonal antibody (MAb), was higher in RA (64+/-12) and in OA (65+/-16) than in normal tissues (52+/-8; p=0.008 and 0.0004, respectively). The activated microvessel density (aMVD), assessed with the 11B5 MAb, was significantly higher in RA (29+/-10) than in OA (17+/-4; p<0.0001) and than in normal tissues (14+/-2; p<0.0001). The "activation ratio" (aMVD/sMVD) was statistically higher in RA (0.46+/-0.17) than in OA and normal synovial tissues, the latter two having a similar ratio (0.28+/-0.08 and 0.26+/-0.03, respectively). Cytoplasmic bcl-2 expression was frequent in the synovial cells of OA, but rare in RA. Nuclear p53 protein accumulation was never observed. It is suggested that the angiogenic pathway VEGF/flk-1(KDR) may play an important role in the pathogenesis of RA and OA. Thus, failure of VEGF/flk-1(KDR) activation, in the presence of increased VEGF expression, may indicate a synovium with an impaired capacity to establish a viable vasculature, consistent with the degenerative nature of OA. On the other hand, the activated angiogenesis in RA shows a functional, still pathologically up-regulated VEGF/flk-1(KDR) pathway. Whether restoration of an impaired VEGF/flk-1(KDR) pathway in OA, or inhibition of this in RA, would prove of therapeutic importance requires further investigation.
10897233 Rheumatic fever in the Nazareth area during the last decade. 2000 Jun BACKGROUND: Acute rheumatic fever is considered a relatively uncommon disease in developed countries. Although cases are encountered in the Nazareth area in Israel, no systematic study of this disease has been done in the last 20 years. OBJECTIVE: To study the incidence and characteristics of acute rheumatic fever cases in the Nazareth area during the last decade. METHODS: Cases of acute rheumatic fever diagnosed according to the modified Jones criteria were identified in two hospitals in the Nazareth area during the 10 years. These two hospitals receive about 75% of non-obstetric referrals to the emergency room. Clinical, laboratory and treatment data of these patients were documented and the incidence of disease calculated. The population census in the Nazareth area was obtained from the Central Bureau of Statistics. RESULTS: Forty-four patients, with a mean age of 18 years, were identified. The mean annual incidence was 5 cases/100,000 population. Arthritis was found in 98% of the patients (migratory in 52%) and carditis in 34%, but only one patient had a subcutaneous nodule, and none had either erythema marginatum or chorea. Only one patient with carditis developed heart failure a few months later due to severe mitral stenosis. CONCLUSION: Rheumatic fever in the Nazareth area is still manifest. The mean age of the patients was higher than found previously. In only half of the patients was the arthritis migratory, with other major manifestations of rheumatic fever found only rarely.
10070273 Altered leucocyte trafficking and suppressed tumour necrosis factor alpha release from per 1998 Dec OBJECTIVES: A generalised transient improvement may follow intra-articular administration of glucocorticoids to patients with inflammatory arthropathy. This may represent a systemic anti-inflammatory effect of glucocorticoid released from the joint, mediated through processes such as altered leucocyte trafficking or suppressed release of pro-inflammatory cytokines. Patients, who had received intra-articular injections of glucocorticoids were therefore studied for evidence of these two systemic effects. METHODS: Patients with rheumatoid arthritis were studied. Peripheral blood leucocyte counts, tumour necrosis factor alpha (TNF alpha) release by peripheral blood monocytes, blood cortisol concentrations, and blood methylprednisolone concentration were measured for 96 hours after intra-articular injection of methylprednisolone acetate. RESULTS: Measurable concentrations of methylprednisolone were present in blood for up to 96 hours after injection. Significant suppression of the hypothalamic-pituitary-adrenal axis persisted throughout this time. Altered monocyte and lymphocyte trafficking, as evidenced by peripheral blood monocytopenia and lymphopenia, was apparent by four hours after injection and resolved in concordance with the elimination of methylprednisolone. Granulocytosis was observed at 24 and 48 hours. Release of TNF alpha by endotoxin stimulated peripheral blood monocytes was suppressed at four hours and thereafter. Suppression was maximal at eight hours and was largely reversed by the glucocorticoid antagonist, mifepristone. CONCLUSIONS: After intra-articular injection of methylprednisolone, blood concentrations of glucocorticoid are sufficient to suppress monocyte TNF alpha release for at least four days and to transiently alter leucocyte trafficking. These effects help to explain the transient systemic response to intra-articular glucocorticoids. Suppression of TNF alpha is principally a direct glucocorticoid effect, rather than a consequence of other methylprednisolone induced changes to blood composition.
10534552 Effect of methotrexate on blood purine and pyrimidine levels in patients with rheumatoid a 1999 Oct OBJECTIVE: The mechanism of anti-inflammatory effects of methotrexate (MTX) at low dose may relate to a decrease in availability of the purine precursor or it may depend on accumulation of 5-aminoimidazole-4-carboxamide (AICAR) and the anti-inflammatory nucleoside adenosine. The aim of this study was to evaluate the possible mechanism of action by analysis of changes in blood concentrations of purine and pyrimidine metabolites during MTX treatment. METHODS: Venous blood samples were collected from rheumatoid arthritis patients before and at different times for up to 7 days after the start of MTX treatment. Whole blood concentrations of adenosine, uridine, hypoxanthine, uric acid and erythrocyte nucleotides were measured by HPLC. RESULTS: The initial blood adenosine concentration was 0.073 +/- 0.013 microM and no differences were observed during MTX treatment. However, a decrease in uric acid concentration was observed from 205.5+/-13.5 to 160. 9+/-13.5 microM (P<0.05) within 24 h after MTX administration. The hypoxanthine concentration decreased in parallel with uric acid, while the uridine concentration decreased 48 h after MTX administration. No accumulation of AICAR-triphosphate (ZTP) was observed in the erythrocytes. CONCLUSIONS: MTX decreases circulating purine and pyrimidine concentrations, and their availability for DNA and RNA synthesis, which may affect immune cell proliferation and protein (cytokine) expression. The absence of adenosine concentration changes and lack of ZTP formation is evidence against an AICAR/adenosine mechanism, although localized adenosine concentration changes cannot be excluded.
9485087 Treatment of rheumatoid arthritis with oral type II collagen. Results of a multicenter, do 1998 Feb OBJECTIVE: Oral administration of cartilage-derived type II collagen (CII) has been shown to ameliorate arthritis in animal models of joint inflammation, and preliminary studies have suggested that this novel therapy is clinically beneficial and safe in patients with rheumatoid arthritis (RA). The present study was undertaken to test the safety and efficacy of 4 different dosages of orally administered CII in patients with RA. METHODS: Two hundred seventy-four patients with active RA were enrolled at 6 different sites and randomized to receive placebo or 1 of 4 dosages (20, 100, 500, or 2,500 microg/day) of oral CII for 24 weeks. Efficacy parameters were assessed monthly. Cumulative response rates (percentage of patients meeting the criteria for response at any time during the study) were analyzed utilizing 3 sets of composite criteria: the Paulus criteria, the American College of Rheumatology criteria for improvement in RA, and a requirement for > or = 30% reduction in both swollen and tender joint counts. RESULTS: Eighty-three percent of patients completed 24 weeks of treatment. Numeric trends in favor of the 20 microg/day treatment group were seen with all 3 cumulative composite measures. However, a statistically significant increase (P = 0.035) in response rate for the 20 microg/day group versus placebo was detected using only the Paulus criteria. The presence of serum antibodies to CII at baseline was significantly associated with an increased likelihood of responding to treatment. No treatment-related adverse events were detected. The efficacy seen with the lowest dosage is consistent with the findings of animal studies and with known mechanisms of oral tolerance in which lower doses of orally administered autoantigens preferentially induce disease-suppressing regulatory cells. CONCLUSION: Positive effects were observed with CII at the lowest dosage tested, and the presence of serum antibodies to CII at baseline may predict response to therapy. No side effects were associated with this novel therapeutic agent. Further controlled studies are required to assess the efficacy of this treatment approach.
11273473 Doxycycline in the treatment of rheumatoid arthritis--a pilot study. 2000 Aug OBJECTIVE: To assess the efficacy and safety of doxycycline as a disease modifying anti-rheumatic drug (DMARD) in rheumatoid arthritis (RA) and compare it with methotrexate, a standard DMARD. MATERIAL AND METHODS: A single (assessor) blind prospective study with 15 patients of RA randomized to doxycycline and 14 to methotrexate. Baseline disease characteristics were similar in both groups. RESULTS: All disease activity measures studied viz. tender and swollen joint counts, physician and patient global assessment, visual analogue pain scale, health assessment questionnaire and ESR improved in both the treatment groups after six months of treatment. The difference between doxycycline and methotrexate was not statistically significant. No major side effects necessitating drug withdrawal were reported from either group. The side effects were few and mostly gastrointestinal. CONCLUSION: Doxycycline is a safe disease modifying drug in RA whose effect is sustained at six months. It compared favourably with methotrexate over a six month follow up.
10072546 The human T cell leukemia virus type I-tax gene is responsible for the development of both 1999 Mar 1 We previously reported that inflammatory arthropathy resembling rheumatoid arthritis (RA) develops among transgenic mice carrying the long terminal repeat (LTR)-env-pX-LTR region of human T cell leukemia virus type I (LTR-pX-Tg mice). Because four genes are encoded in this region, we produced transgenic mice that only express the tax gene to examine its role in the development of arthritis. Transgenic mice were produced by constructing DNAs that express the tax gene alone under the control of either its own LTR or CD4 enhancer/promoter and by microinjecting them into C3H/HeN-fertilized ova. We produced seven transgenic mice carrying the LTR-tax gene and nine mice carrying the CD4-tax and found that one of the LTR-tax-Tg mice and five of CD4-tax-Tg mice developed RA-like inflammatory arthropathy similar to LTR-pX-Tg mice, indicating that the tax gene is arthritogenic. On the other hand, the other two LTR-tax-Tg mice had ankylotic changes caused by new bone formation without inflammation. In these ankylotic mice, tax mRNA, inflammatory cytokine mRNA, and autoantibody levels except for TGF-beta1 level were lower than those in LTR-pX- or CD4-tax-Tg mice. These results show that Tax is responsible for the development of inflammatory arthropathy resembling RA and that this protein also causes ankylotic arthropathy.
10617997 n-3 polyunsaturated fatty acids inhibit the antigen-presenting function of human monocytes 2000 Jan Diets rich in n-3 polyunsaturated fatty acids (PUFAs) are associated with suppression of cell-mediated immune responses, but the mechanisms are unclear. We hypothesized that n-3 PUFAs can inhibit the function of human antigen-presenting cells. A prerequisite for this role of blood monocytes is the cell surface expression of major histocompatibility complex (MHC) class II molecules [human leukocyte antigen (HLA)-DR, -DP, and -DQ], aided by the presence of intercellular adhesion molecule-1 (ICAM-1) and leukocyte function associated antigens 1 and 3. We showed previously that the n-3 PUFA eicosapentaenoic acid (EPA) inhibits the expression of HLA-DR on unstimulated human monocytes in vitro, but that docosahexaenoic acid (DHA) enhances its expression. However, both n-3 PUFAs suppress the expression of HLA-DR, HLA-DP, and ICAM-1 on interferon-gamma-activated monocytes. We also established that dietary fish-oil supplementation can inhibit the expression of these surface molecules on circulating human monocytes. We subsequently showed that when EPA and DHA were combined in the same ratio as is commonly found in fish-oil-supplement capsules (3:2), there was no significant effect in vitro on the expression of HLA-DR on unstimulated monocytes, but the expression on activated monocytes remained significantly inhibited. In the same in vitro system, the ability of activated monocytes to present antigen to autologous lymphocytes was significantly reduced after culture with the combined n-3 PUFAs. These findings provide one potential mechanism for the beneficial effect of fish oil in the treatment of rheumatoid arthritis, a disorder associated with elevated expression of MHC class II and adhesion molecules on monocytes present within affected joints.
10651393 Leflunomide: a review of its use in active rheumatoid arthritis. 1999 Dec A77 1726, the active metabolite of leflunomide, is an immunomodulator which inhibits cell proliferation in activated lymphocytes in patients with active rheumatoid arthritis. Because A77 1726 has a long half-life (approximately 2 weeks), treatment with oral leflunomide is initiated with a loading dose of 100mg once daily for 3 days and continued with 20mg once daily. Results of large randomised, double-blind, multicentre trials of up to 24 months' duration have shown that leflunomide is significantly superior to placebo and at least as effective as sulfasalazine in improving primary outcome measures, such as tender joint counts, swollen joint counts and physicians' and patients' global assessment, in adult patients with active rheumatoid arthritis. Whereas improvement in all primary outcome measures with leflunomide was similar to or significantly less than that with methotrexate after 12 months, the efficacy of both agents was similar after 24 months. The therapeutic effect of leflunomide appears earlier (at 4 weeks) than that of sulfasalazine or methotrexate, and reduction from baseline values in functional disability was significantly greater with leflunomide than with sulfasalazine, methotrexate or placebo at end-point. Leflunomide was at least as effective as sulfasalazine or methotrexate in delaying the rate of radiological progression of disease. The most common adverse events reported in patients receiving leflunomide in randomised double-blind, placebo-controlled trials were diarrhoea (27%), respiratory infections (21%), nausea (13%), headache (13%), rash (12%), increased serum hepatic aminotransferases (10%), dyspepsia (10%) and alopecia (9%). Leflunomide was as well tolerated as sulfasalazine or methotrexate in clinical trials. Monitoring of serum hepatic enzyme levels is recommended in patients receiving leflunomide. The drug is not recommended in female patients who are or may become pregnant. Drug treatment should be discontinued, and hastened drug elimination procedure should be considered, in male patients wishing to father a child. 16 potential cases of pancytopenia and 9 cases of serious skin reactions have been associated with the use of leflunomide in 76,000 patients to date. CONCLUSIONS: Leflunomide is a disease-modifying antirheumatic drug which reduces the signs and symptoms of inflammatory arthritis and delays the radiological progression of disease in adult patients with active rheumatoid arthritis. The drug appears to be as effective and as well tolerated as sulfasalazine or methotrexate, and represents a suitable alternative to these agents in adult patients with active rheumatoid arthritis. Benefits with leflunomide are evident within 4 weeks and efficacy is maintained for durations of up to 24 months.
10408070 [An unusual case of Heberden arthrosis in a young man]. 1999 Apr Heberden nodes affect mainly middle-aged women. Inheritance is autosomal dominant in female and autosomal recessive in male patients. We report the case of a young man who presented already with 12 years of age with pain in the distal finger joints. There were no other clinical or serological signs for other rheumatoid diseases, like psoriatic or rheumatoid arthritis. Radiologic findings were consistent with Heberden's osteoarthritis of the finger joints. The joint changes remained clinically and radiologically stable during a time period of more than 15 years. The HLA typing revealed the haplotype HLA A1, B8 and DR4, in accordance with former studies which reported a higher frequency of HLA A1, B8 in families with primary osteoarthritis (early onset osteoarthritis of the large joints in combination with Heberden nodes).
10810693 Total elbow replacement with the GSB III prosthesis. 2000 Mar Fourteen consecutive elbows have been treated for rheumatoid arthritis (9 elbows) and for post-traumatic osteoarthrosis (5 elbows) by total elbow replacement with the GSB III implant. The elbows were reviewed retrospectively after a mean follow-up of 6 years (2 to 9 years). Ten of 14 elbows had a functioning GSB III implant at follow-up; 7 of them were rated satisfactory and 3 unsatisfactory with the Mayo elbow performance score. In 5 of these 10 cases, the patients had significant pain relief with no or only mild pain at follow-up, whereas 5 had moderate to severe pain. With a functioning implant the range of motion averaged 140 degrees of flexion, 19 degrees of lack of extension, 65 degrees of pronation, and 84 degrees of supination. Six (43%) elbows had major complications requiring 1 to 8 additional operations. Aseptic loosening requiring revision occurred in 4 (29%) elbows. Two of them were treated by a resection arthroplasty, and 2 were revised with another hinged semiconstrained device. Three further elbows had radiolucent lines involving more than 50% of the cement-bone interface of either the humeral or the ulnar component. However, in 8 elbows the cementing technique was considered marginal or inadequate. Poor cementing (marginal or inadequate) was associated with loosening (P = .008). The GSB III total elbow prosthesis can restore function and reduce pain. The rate of aseptic loosening in this series was higher than previously reported. Based on this observation, we conclude that the GSB III implant seems to be sensitive to the insertion technique and does not tolerate suboptimal cementing.
11145035 Linkage of rheumatoid arthritis to insulin-dependent diabetes mellitus loci: evidence supp 2000 Dec OBJECTIVE: To seek potential autoimmune disease susceptibility loci by testing for linkage and linkage disequilibrium between insulin-dependent diabetes mellitus (IDDM) susceptibility loci and rheumatoid arthritis (RA). METHODS: Five IDDM susceptibility loci map to 2 chromosomal regions, chromosome 2q31-34 (IDDM7, 12, and 13) and chromosome 6q25-27 (IDDM5 and 8). Microsatellite markers within these regions were genotyped in 255 RA families, by fluorescence-based genotyping technology. Evidence for linkage disequilibrium was assessed using the extended transmission disequilibrium test (ETDT) program. RESULTS: With the ETDT, we found evidence for linkage disequilibrium of the marker D6S446, at IDDM8, with RA (P < 0.0001). There was additional evidence for linkage disequilibrium with 2 markers at IDDMS (D6S311 and D6S440) (P = 0.016 and P = 0.017, respectively). There was no evidence for significant linkage disequilibrium of RA with any markers at IDDM7, 12, or 13. CONCLUSION: These results support the hypothesis that there are autoimmune disease genes at IDDM5 and IDDM8.
10952748 Reliability and sensitivity to change of various measures of hand function in relation to 2000 Aug OBJECTIVES: The reliability and discriminative capacity of hand function tests were studied in order to obtain tests suitable for the evaluation of local treatment of an arthritic metacarpophalangeal (MCP) joint. METHODS: To assess reliability, hand function tests were measured twice without local treatment of the MCP in 25 patients with rheumatoid arthritis (RA). The discriminative capacity of the hand function tests with respect to the results of intra-articular corticosteroid injection was assessed in 28 RA patients with synovitis of an MCP joint. Thereafter, a randomized, observer-blind treatment study was performed in 21 RA patients with synovitis of an MCP joint; 10 of the patients were treated. Results/Conclusions. This study showed that the efficacy of treatment of an MCP joint can be measured by several reliable and discriminative parameters: passive flexion, the Ritchie pain score, swelling, the Arthritis Impact Measurements Scales question about buttoning clothes, and visual analogue scale questions about the activity of the disease and swelling of the joint.
10769438 Transplantation osteoporosis and corticosteroid-induced osteoporosis in autoimmune disease 2000 The effect of alfacalcidol therapy on bone mineral density at the spine and proximal femur was evaluated in 112 transplant recipients (59 heart, 26 liver and 27 lung); 45 transplant cases served as controls (included in a randomised way in a placebo group) and in 42 rheumatoid arthritis cases. Liver and lung transplantation cases had before transplantation a lower bone density at the spine and femur compared to heart transplant cases. Heart transplant cases lost considerably more bone immediately after transplantation than liver and lung transplant recipients. A positive effect of 2 years alfacalcidol treatment (0.5-1 microgram/day) on bone loss was observed in all treated groups. Alfacalcidol was particularly effective against trabecular bone loss at the spine in rheumatoid arthritis patients and transplant recipients. There is a manifest difference in evolution between organ transplant groups and bone sites measured. Liver and lung transplant recipients respond better to therapy than cardiac recipients.
10025914 Overexpression of human homologs of the bacterial DnaJ chaperone in the synovial tissue of 1999 Feb OBJECTIVE: To study the expression of the chaperone family of J proteins in the synovial tissue of patients with rheumatoid arthritis (RA) or osteoarthritis. METHODS: Rabbit antibodies specific for a synthetic peptide (pHSJ1: EAYEVLSDKHKREIYD), representing the most conserved part of all J domains thus far identified--among them the Drosophila tumor suppressor Tid56--were used in immunohistochemical analyses of frozen sections of synovial tissue and immunoblotting of protein extracts of adherent synovial cells. IgG specific for Tid56 was also used. RESULTS: Both antisera predominantly and intensely stained synovial lining cells from RA patients; other cells did not stain or stained only faintly. In immunoblots, anti-pHSJ1 specifically detected several bands with molecular weights of >74 kd (type I), 57-64 kd (type II), 41-48 kd (type III), and < or =36 kd (type IV). The strongest band detected in RA adherent synovial cells was the type II band, whereas in a B cell line, a type I band was prominent. CONCLUSION: Several potentially new members of the J family are described. The type II band represents the human homolog of the Drosophila Tid56 protein and is strongly expressed in RA synovial tissue.