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ID PMID Title PublicationDate abstract
1376088 Comparative evaluation of CD5 B cells in patients with rheumatoid arthritis and essential 1992 May 4 In this study, using both a FACSCAN flow cytometer and the FACS analyzer, and two-color fluorescence, CD5 B cells have been enumerated in the peripheral blood (PB) of normal controls (NC) and patients with rheumatoid arthritis (RA) or essential mixed cryoimmunoglobulinemia (EMC). Using a FACSCAN flow cytometer, no significant difference was observed between the percentage of CD5 B cells in the NC (21.24% +/- 3.71) and RA (24.83% +/- 3.85), or EMC (21.03% +/- 6.38). Using the FACS analyzer, however, there was significant difference between the NC (9.14% +/- 3.82) and EMC (2.84% +/- 2.58) (p less than 0.05), but no significant difference between the NC and RA (7.17% +/- 2.55). Further analysis of 10,000 B cells selected by live gating showed that there were three populations of B cells, with the majority of B cells unstained, a small number of cells brightly stained for CD5 in the NC (3.78% +/- 1.09) or RA (2.80% +/- 0.96), and about 6.45% to 9.43% with intermediate staining in patients with RA and the NC, respectively. In addition, serum low molecular weight IgM (LMW IgM) from patients with RA was detected by an enhanced chemiluminescence detection system combined with a modified immunoblot technique. A significant linear correlation was observed between the percentage of CD5 B cells and the height of LMW IgM peak (r = 0.69, p less than 0.05).
8589663 Localization of viable bacteria and bacterial antigens in arthritic joints of Erysipelothr 1995 Oct Chronic polyarthritis was induced in pigs by infection with Erysipelothrix rhusiopathiae (serovar 2, strain T28). Viable bacteria could be reisolated as long as 5 months post-infection from synovial fluid, synovial tissue and from isolated chondrocytes. The number of viable bacteria could be increased by hypotonic shock of the chondrocytes indicating a substantial intracellular amount of bacteria. Bacterial antigens were shown by immunohistochemistry to be present on the surface of both chondrocytes and synovial cells in arthritic joints. Neither viable bacteria nor bacterial antigen were detected in unaffected joints.
1582125 Proliferation of peripheral blood mononuclear cells from rheumatoid arthritis patients to 1992 Mar Proliferation of rheumatoid and control peripheral blood mononuclear cells (PBMC) to an antigenic acetone-precipitable extract from mycobacterium tuberculosis (MTa) was investigated. Cells were also stimulated with the recall antigen tuberculin PPD (purified protein derivative) and the mitogen OKT3. Controls had a significantly higher response to both MTa and tuberculin PPD than RA patients. However, lymphocytes from patients who had had their disease for 3-10 years proliferated more vigorously to MTa than did PBMD from patients with longer disease duration. There was no difference in the proliferation to OKT3 between patients and controls. We were not able to confirm a previously found correlation between the HLA-DR4 phenotype and lymphocyte transformation to MTa.
8757658 Incidence and possible aetiological factors in the development of pelvic insufficiency fra 1996 Jun Five patients out of a total of 183 treated with radical radiotherapy for carcinoma of cervix at The Royal Marsden Hospital from 1991 to 1994 inclusive have developed severe pelvic fractures. Two patients had rheumatoid arthritis, one of whom died as a result of the radiation induced damage. This patient developed radiological evidence of radionecrosis within 1 month of completing radiotherapy. There are very few reports in the literature of such a rapid onset. We suggest that the presence of a connective tissue disorder in a patient with other risk factors such as steroid use, old age and osteopenia should alert the clinician to the risk of radionecrosis following radical irradiation.
8778019 The collagen-like component of the complement system, C1q, is recognized by 7 S autoantibo 1996 Mar Cross-reactivity between type II collagen (CII) and C1q, the collagen-like subunit of the first component of complement, has been demonstrated in synovial fluid (SF) from rheumatoid arthritis (RA) patients. Many authors have studied autoimmunity to CII in RA, but little work has been done on autoimmunity to C1q in RA. In the data presented here, we have been able to show that in addition to native C1q, an altered form of C1q is present in SF from RA patients. Furthermore, a low molecular weight form of C1q is present in RA SF, although its role, if any, in the pathogenesis of RA is unclear. The presence in these RA SF of C1q-specific antibodies (IgG and IgM) has been studied and we have partially characterized the antibody moieties involved. As well as binding to C1q and fragments representing the collagen-tails from C1q, 7 S IgG autoantibodies against C1q also bind to a C1q molecule altered in vitro by incubation with reactive oxygen species and to the non-apeptide KGEQGEPGA (representing residues 26-34 from the C1q A-chain), which has previously been shown to suppress the onset of CII-induced arthritis in an animal model.
7801055 Abnormal colonic microbial function in patients with rheumatoid arthritis. 1994 The aim of this study was to examine the microflora-associated characteristics (MACs) of faecal samples of patients with rheumatoid arthritis (RA) and to evaluate the actions of sulphasalazine (SASP) on these MACs. The conversion of cholesterol to coprostanol, the production of urobilinogen, the degradation of faecal tryptic activity (FTA) and of beta-aspartylglycine were measured in faecal samples from 19 patients treated with SASP and 21 patients not treated with this medication. A control group of 21 healthy subjects was sex- and age-matched with the untreated patients. The conversion of cholesterol to coprostanol showed a bimodal distribution. The frequency of high converters in patients without SASP treatment was higher than in healthy subjects (p < 0.05). Treatment with SASP markedly increased the FTA and reduced the urobilinogen values, as compared to the untreated patients (p < 0.05). Beta-aspartylglycine was not found in any faecal samples. The results indicate that patients with RA have an abnormal formation of coprostanol, which is ascribed to alterations in the function of the Eubacteria species. In patients with RA, SASP treatment induces disturbances in the metabolism of the microflora.
8572731 Associations of HLA-DRB and -DQB genes with two and five year outcome in rheumatoid arthri 1996 Jan OBJECTIVE: To evaluate the clinical usefulness of genomic HLA typing during the first five years of established rheumatoid arthritis (RA). METHODS: The HLA-DRB and -DQB alleles were determined by restriction length polymorphisms and polymerase chain reaction amplification with sequence specific primers in 99 Swedish patients with RA. Clinical features after two and five years disease duration were related to the genetic pattern. Seventy four patients were seropositive, 25 had nodules, 90 developed erosions, and 15 required joint replacements. Twelve patients were in remission after five years. Disability was assessed by health assessment questionnaire, and radiographic damage in hands and feet by the Larsen method. RESULTS: Eighty seven per cent of the patients carried the conserved third hypervariable region sequence (HVR3), 32% had DRB1*04 on one allele, and 26% had DRB1*04 on both alleles (all frequencies significantly greater than in controls). Frequencies of DRB1*04 associated DQB*0301 and *0302 were normal. Patients carrying DRB1*04 on both alleles tended to have more radiographic changes after two years, but this difference had diminished after five years. Disability did not vary with regard to the genotype. Homozygous HVR3 patients had about three times greater risk of undergoing joint replacement. Homozygosity for HVR3 and presence of DQB*0302 both tended to be associated with erosive disease. CONCLUSIONS: We confirmed a strong association of disease with the presence of the shared epitope on one or two alleles. However, genotype was not strongly associated with disease severity after two and five years disease duration, and thus the value of genomic typing to select patients for early aggressive therapy is questionable.
1464860 Detection of myeloid precursors (granulocyte/macrophage colony forming units) in the bone 1992 Oct Various cytokines were recently found to be involved in the pathogenesis of rheumatoid arthritis (RA) and particularly, cytokines with hematopoietic activity have been detected in synovial tissues. We counted the number of myeloid precursors in terms of granulocyte/macrophage colony forming units (CFU-GM) and the number of stromal cell progenitors in terms of fibroblast colony forming units (CFU-F) in the tibial bone marrow adjacent to the joints affected by RA (n = 21), osteoarthritis (OA) (n = 10), and trauma (n = 2) using the colony formation unit assay. We also quantitated the amounts of interleukin 1 beta (IL-1 beta), IL-6, and granulocyte/macrophage colony stimulating factor (GM-CSF) in the culture supernatant of synovial tissue explants of these patients by enzyme linked immunosorbent assay (ELISA). The mean number (+/- SEM) of CFU-GM in patients with RA (7.4 +/- 4.9) was greater than that in patients with OA (0.5 +/- 0.2), while CFU-GM was not detected in trauma patients. The number of CFU-GM in the tibial bone marrow of patients with RA correlated well with the amount of IL-1 beta (r = 0.64, p < 0.01), but not with GM-CSF or with IL-6 from synovial tissues. These findings suggest that active bone marrow is present adjacent to the affected joints in patients with RA and that hematopoietic activity is influenced by IL-1 beta produced in nearby synovial tissues.
1304408 IgG subclasses in systemic lupus erythematosus and other autoimmune rheumatic diseases. 1992 Dec In this study the concentration of the different subclasses of IgG in sera from patients with a range of autoimmune rheumatic diseases (ARD) was detected by radial immunodiffusion. In the second part the IgG subclasses of autoantibodies that recognize single-stranded DNA (ssDNA), double-stranded DNA (dsDNA), Ro, La, Sm and RNP in patients with ARD were measured by enzyme-linked immunosorbent assay. We studied 15 patients with lupus, 20 patients each with primary and secondary Sjögren's syndrome (SS) and 10 each with rheumatoid arthritis (RA), scleroderma and myositis. Twenty healthy controls were also measured. The serum concentration of IgG2 in ARD patients was generally reduced. In contrast, the concentrations of IgG1, IgG3 and IgG4 subclasses were normal or raised. A high degree of correspondence in the IgG1, IgG2 and IgG3 responses to dsDNA and ssDNA in SLE was found. Notable differences in the IgG1 anti-Ro and ssDNA responses compared to the other subclasses were seen in 1 degree and 2 degrees SS. In addition, an unexpected high level of IgG4 antibodies to ssDNA in 1 degree SS (65%) and IgG4 antibodies to Sm/RNP in RA was observed.
8129789 A cost-utility analysis of misoprostol prophylaxis for rheumatoid arthritis patients recei 1994 Mar OBJECTIVE: To determine the cost-utility of low-dose misoprostol prophylaxis in rheumatoid arthritis (RA) patients treated with nonsteroidal antiinflammatory drugs (NSAIDs). METHODS: Prospectively collected, population-based data on 57 RA patients' preferences (obtained using the category scaling and time trade-off techniques), charge data from a consecutive, population-based cohort of 36 RA patients with NSAID-related gastric ulcer, and literature-derived probability estimates were incorporated into a decision analysis model. RESULTS: Probabilistic sensitivity analysis using 10,000 Monte Carlo simulations demonstrated that, on average, prophylaxis resulted in modest additional costs and no additional quality-of-life benefits. At best, the incremental cost per quality-adjusted life year gained was $9,333. At worst, prophylaxis reduced quality of life. Prophylaxis was cost-saving if the ulcer complication rate was > 1.5%, or if the 3-month price of misoprostol was < or = $95. CONCLUSION: Whereas prophylaxis may be cost-saving among high-risk NSAID users, from some patients' perspective, it reduces quality of life. Although these data may not be generalizable to other clinical populations, they illustrate the importance of incorporating patient preferences into economic evaluations.
8906749 Inhibition of human B cell activation by gold compounds. 1996 Nov The mechanism of action of gold compounds, which are effective in the treatment of rheumatoid arthritis (RA), has not been clearly identified. Although one of the characteristic features of RA is chronic stimulation of B cells, the effects of gold compounds on B cells have not been precisely assessed. We therefore examined the effects of gold sodium thiomalate (GST) on human B cells. IgM production was induced from highly purified B cells obtained from healthy donors by stimulation with Staphylococcus aureus Cowan 1 (SA) plus IL-2. T cell proliferation and IFN-gamma production were induced from highly purified T cells by stimulation with immobilized mAb to CD3. As little as 0.1 microg/ml (0.25 microM) GST almost completely suppressed B cell IgM production, whereas it did not suppress T cell proliferation or IFN-gamma production. The inhibition of IgM production by GST is not due to its thiomalate, but is most likely due to its gold components, since thiomalate alone did not inhibit IgM production. GST was required at the initiation of cultures to exert optimal suppressive effects on IgM production. Moreover, GST suppressed the expression of IL-2R (CD25) and transferrin receptor (CD71) on SA-stimulated B cells. These results indicate that GST preferentially inhibits the function of B cells at concentrations much lower than those which inhibit the function of T cells by interfering with the initial activation of B cells. The direct inhibitory effects of GST on human B cell activation described here may contribute at least in part to its therapeutic effect in RA.
8556465 Current trends in temporomandibular joint imaging. 1995 Nov Diagnostic imaging of the temporomandibular joint has undergone a revolutionary development during the last two decades. With advanced modalities we have been able to differentiate between different articular entities in patients with temporomandibular joint disorders. The purpose of this article is to review and discuss these modalities and their contribution to our present knowledge, with emphasis made on current trends in diagnostic temporomandibular joint imaging. The main section deals with diagnostic imaging of the subgroup of disorders with internal derangement caused by disk displacement including posttreatment imaging. Imaging of pathologic entities characterized by chronic inflammation such as rheumatoid arthritis are discussed in the second section. Finally, the potential of diagnostic imaging of infrequent conditions such as tumors is briefly reviewed. Magnetic resonance imaging has surpassed arthrography and computed tomography for the evaluation of most patients in these three subgroups. In patients who have various forms of disk displacements with or without accompanying bone abnormalities, a diagnostic accuracy of at least 90% may be achieved by oblique sagittal and coronal magnetic resonance imaging. In addition, alterations in the condylar marrow may be detected. T2-weighted magnetic resonance imaging can make a significant diagnostic contribution by demonstrating inflammatory reactions such as joint effusion and marrow edema. In the subgroup of patients with chronic inflammatory diseases, magnetic resonance imaging may also demonstrate abnormalities not shown with other imaging modalities. Disk deformation, fragmentation, and destruction may indirectly suggest the presence of synovial proliferation/pannus formation, which in selected cases may be directly depicted with intravenous gadopentetate dimeglumine. For more detailed evaluation of the bone condition and of soft tissue calcifications in joints with inflammatory diseases, tumors, or other disorders, computed tomography is the preferable imaging modality.
8390334 Correlative studies of rheumatoid factors and anti-viral antibodies in patients with rheum 1993 Jun An analysis of the relationship between the immune response to ubiquitous herpes family viruses, namely Epstein-Barr virus (EBV), cytomegalovirus (CMV), and varicella-zoster virus (VZV) and the presence of rheumatoid factors (RF), which are autoantibodies characteristic of patients with rheumatoid arthritis (RA), was conducted. Antibody profiles (RF, anti-viral antibodies) were monitored in the serum of the RA patients, and in normal individuals. No patient was found to have circulating RF in the absence of anti-viral antibodies. When the patients and normal controls were subdivided according to the presence of serum RF, it was found that when RF were present, the frequency of anti-CMV antibodies, but not anti-EBV or anti-VZV antibodies, was significantly higher (P = 0.02) when compared with RF-negative individuals. The titres of anti-CMV but not anti-VZV antibodies were found to increase in the RA patients with disease duration. To see if these viruses could stimulate RF production in vitro, peripheral blood mononuclear cells (PBMC) isolated from the patients and normal controls were stimulated with viral antigens. PBMC from normal controls, but not from RA patients, appeared to be responsive to viral antigen stimulation and produced RF. These data suggest that the immune response to CMV, to a greater extent than to EBV or VZV, correlates with the presence of RF.
1575573 Leucocyte integrin and CR1 expression on peripheral blood leucocytes of patients with rheu 1992 Mar Expression of the leucocyte integrins (CD11a, b, c/CD18) and of CD35 (CR1) on leucocytes from the peripheral blood of patients with rheumatoid arthritis (RA) (n = 14) and control subjects (n = 12) was measured by flow cytometry using a rapid fixation and leucocyte preparation procedure. The mean (SE) percentages of lymphocytes expressing CD11a (RA 93.4 (1.7)%; controls 97.2 (1.8)%) and CD18 (RA 91.3 (2.3)%; controls 97.0 (2.6)%) were lower and the percentage of monocytes expressing CD11b (RA 86.9 (11.4)%; controls 78.4 (11.9)%) and CR1 (RA 62.6 (15.5)%; controls 36.6 (17.6)%) were higher in patients with RA than in controls. In addition, the mean fluorescence intensity of CD18 (RA 22.1 (2.3); controls 30.7 (2.5)) on lymphocytes was decreased and that of CD11b (RA 4.5 (0.8); controls 2.9 (0.9)) and CR1 (RA 2.4 (0.4); controls 1.5 (0.5)) on monocytes was increased in patients with RA compared with controls. The functional importance (if any) of the altered expression of the antigens on lymphocytes is not yet known. Altered expression on monocytes is consistent with activation within the circulation.
8647206 HLA-associated inverse correlation between T cell and antibody responsiveness to islet aut 1996 Jun Insulin-dependent diabetes mellitus (IDDM) is a T cell-dependent immune-mediated disease. Recently, a novel islet cell antigen (ICA69) recognized by autoantibodies was described. We tested T cell responsiveness to ICA69 in peripheral blood of patients with recent onset IDDM (n = 46), patients with long-standing IDDM (n = 44), non-diabetic age-matched, islet cell autoantibody- and glutamic acid decarboxylase (GAD)65 antibody-negative first-degree relatives of IDDM patients (n = 15) and rheumatoid arthritis patients (n = 22). T cell responsiveness was significantly higher in recent onset IDDM patients, compared to IDDM patients post-disease onset, non-diabetic first degree relatives and rheumatoid arthritis patients (p < 0.001). In responding IDDM patients a significant inverse correlation between T cell and autoantibody responsiveness to ICA69 was observed (p < 0.0005). Immunogenetic evaluation revealed an association of HLA-DR3 with T cell responsiveness to ICA69 (p < 0.02) and absence of ICA69-reactive autoantibodies (p < 0.04). The increased T cell reactivity to ICA69 in the absence of antibody reactivity at onset of IDMM is associated with an HLA class II immune response gene, and therefore suggestive of a genetically controlled selective activation of T helper subsets to a specific autoantigen in humans.
8579722 Purification of recombinant human Hsp60: use of a GroEL-free preparation to assess autoimm 1995 Oct A 65 kDa mycobacterial heat shock protein has been implicated in the development or perpetuation of the inflammatory diseases rheumatoid arthritis (RA) and insulin dependent diabetes mellitus (IDDM). An homology of the mycobacterial hsp65 with human hsp60 (HuHsp60) has been thought to constitute a cross reactive autoimmunizing pathogenetic potential. Study of this cross reactivity with recombinant reagents has been complicated by the fact that recombinant HuHsp60 might be contaminated by the E. coli homologue of HuHsp60, groEL. GroEL and HuHsp60 are very similar in isoelectric point and molecular weight and therefore difficult to separate by classical physicochemical means. Therefore, the HuHsp60 gene was subcloned into the vector, pRSET-B, which resulted in recombinant HuHsp60 protein fused to a 4.5 kDa peptide containing a polyhistidine hexamer. Metal ion affinity for the polyhistidine allowed the rapid and efficient chromatographic separation of the HuHsp60 from groEI. Rabbit antisera were developed to linear peptide epitopes unique to either HuHsp60 or groEL and utilized to discriminate between these proteins during their separation. With the newly prepared HuHsp60 we show that the amount of anti-HuHsp60 autoantibody in both RA and normal sera was too great to be accounted for by cross reacting anti-MbHsp65.
8069012 Effect of daily subcutaneous administration of recombinant erythropoietin on chronic anemi 1994 Apr Mean (+/- SD) serum erythropoietin (EPO) levels were 18.6 +/- 5.6 mU/ml in 180 normal Japanese subjects. Serum EPO levels were elevated with a negative correlation on a log scale (r = -0.864, P < 0.005) to hematocrit (Ht) values in anemic patients not associated with rheumatoid arthritis (RA) or chronic renal failure (CRF). Serum EPO levels in patients with RA (31.6 +/- 16.4 mU/ml) were relatively lower than those in normal subjects and anemic patients without RA or CRF when matched for comparative Ht values. Seven anemic patients with RA were treated by daily subcutaneous (sc) injection of recombinant EPO (rEPO, 500-1,000 U/day) for 4 weeks. The patients had initial Ht values of 25.1% or less and maintained stable clinical status. The treatment with rEPO raised serum EPO levels (53.8 +/- 15.2 mU/ml, P < 0.05), which resulted in an increase in Ht values (more than 3%) in 6 out of 7 patients with RA. The mean (+/- SD) Ht values at the end of the treatment with rEPO (500-1,000 U/day) were greater than those before the treatment in the 7 patients with RA (28.5 +/- 4.6 vs. 22.7 +/- 2.5%, P < 0.05). These findings suggest that chronic anemia associated with RA may be corrected by daily sc injection of a small dose of rEPO.
7575692 Antibodies to synovial antigens in recent-onset rheumatoid arthritis. 1995 Oct OBJECTIVE: To identify synovial antigens that bind to serum antibodies from subjects with recent-onset rheumatoid arthritis (RA) (< 6 months of synovitis). METHODS: Soluble and insoluble fractions of Triton X-100 extracts of RA and normal synovial tissue, and normal spleen and placenta, were immunoblotted with sera from 27 patients with recent-onset RA, 13 autoimmune disease control subjects, and 13 blood bank control donors. Bound immunoglobulin was probed with 125I-labeled protein A. RESULTS: Antibodies in the sera of 20 (74%) patients with recent-onset RA recognized at least 1 of 5 antigens in both a disease- and tissue-specific and nonspecific manner. Anti-La antibodies, usually associated with primary Sjögren's syndrome, were detected in 2 sera. Eight sera had increased reactivity to an IgG heavy and light chain dimer. There was strong binding of 8 sera with a 35-kd doublet and of 3 sera with a 55-kd species in RA and normal synovial lysates (insoluble fractions). Two sera uniquely recognized a 45-kd protein only in the RA synovial lysate (soluble fraction). CONCLUSION: IgG antibodies in the sera of patients with recent-onset RA show positive immunoblots for 3 novel synovial antigens of 35-kd, 55-kd, and 45-kd, as well as for 2 previously characterized antigens (La and IgG). Thus, a variety of synovial antigens appear to be recognized by B cells even early in the clinical course of RA.
7780391 Forefoot postoperative continuous pain control by nonelectronic device. 1995 Jan The authors present a system against postoperative pain in forefoot operations, which functions by continuous infusion of anesthetic in the malleolar internal space. The system (Single-Day Baxter Infusor) was utilized in 145 patients who had undergone forefoot surgery. The effectiveness of the method was evaluated by means of a numeric scale (0 to 5) reflecting pain level. The method was effective in controlling postoperative pain in 110 cases (score 0 to 1); 25 cases (score 2) reported pain in the dorsal hallux, in the deep peroneal area, whereas in 10 cases (score 4 to 5 on the scale), nonsteroidal anti-inflammatory drugs had to be administered.
8572734 Synovial fluid and serum concentrations of aminoterminal propeptide of type III procollage 1996 Jan OBJECTIVES: To analyse synovial fluid and serum concentrations of the amino-propeptide of the type III procollagen (PIIINP) in normal individuals and patients with joint disease, and to explore the relationship between synovial fluid PIIINP concentrations and the rheumatological diagnosis, local inflammation, and joint disease. METHODS: A radioimmunoassay was used to measure the PIIINP concentrations in serum and knee joint synovial fluid from 16 healthy volunteers and patients with osteoarthritis (OA) (n = 40), rheumatoid arthritis (RA) (n = 30), and psoriatic arthritis (PsA) (n = 12). The PIIINP measurements were related to demographic data, synovial fluid leucocyte counts, and radiographic changes at the knee. RESULTS: Serum PIIINP concentrations were greater in each of the disease groups than in control subjects, but there were no differences between the disease groups. Synovial fluid concentrations of PIIINP were much greater than those in serum, indicating local production, and were significantly greater in RA than in other disease groups (p < 0.001). There was only a weak positive correlation between synovial fluid leucocyte counts, some radiographic changes, and synovial fluid PIIINP concentrations. CONCLUSIONS: These data suggest that synovial fluid PIIINP concentrations may reflect local synovial proliferative processes in joint disease, and that they could be of diagnostic and prognostic value in inflammatory arthropathies.