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ID PMID Title PublicationDate abstract
1378495 Phenotypic analysis of peripheral blood monocytes isolated from patients with rheumatoid a 1992 Feb The expression of CD14, Fc gamma receptor I (Fc gamma RI), Fc gamma RII, and HLA-DR on peripheral blood monocytes from patients with rheumatoid arthritis (RA) was studied to investigate their nature and their role in the pathogenesis of rheumatoid synovitis. Peripheral blood mononuclear cells obtained from 9 patients with active RA, 8 patients with RA in complete remission, and 14 healthy individuals, were stained with various monoclonal antibodies and analyzed on a fluorescence activated cell sorter. The expression of CD14 as well as Fc gamma RI and Fc gamma RII was upregulated on peripheral blood monocytes from patients with active RA, although the expression of HLA-DR was not increased. In addition, the expression of Fc gamma RI and Fc gamma RII on monocytes was still upregulated in patients with RA in complete remission, whereas the expression of CD14 on monocytes was normalized in these patients. These results indicate that peripheral blood monocytes in patients with active RA are already activated to express higher densities of CD14. In addition, our observation that CD14 density was increased on a subset of circulating blood monocytes in active RA, that HLA-DR was not significantly altered and that Fc gamma RI and Fc gamma RII were increased in both active and inactive RA is not compatible with the expected actions of interferon gamma. Finally, it is suggested that peripheral blood monocytes in patients with RA may have intrinsic abnormalities as evidenced by the enhanced expression of Fc gamma R, which is repeatedly observed regardless of the disease activity of RA.
8144128 The association of myasthenia gravis and connective tissue diseases--the role of Sjøgren' 1994 Feb The symptoms of myasthenia gravis (MG) reflect the loss of neuromuscular transmission due to the functional loss of the acetylcholine receptor. We reviewed the reported association of MG and connective tissue diseases including rheumatoid arthritis, systemic lupus erythematosus, progressive systemic sclerosis (PSS), polymyositis and dermatomyositis, mixed connective tissue disease (MCTD) and Sjøgren's syndrome (SjS). We found that the association of MG and MCTD or PSS is rare. We also reviewed the role of D-penicillamine, thymus abnormalities and the coexistence of SjS as one of the underlying pathological conditions for the association of MG and various connective tissue diseases.
7481486 Expression of a multidrug resistance gene in human rheumatoid synovium. 1995 The objective of this study was to assess the expression of a multidrug resistance (MDR) phenotype, implicated in the cellular resistance of tumor to chemotherapy, in rheumatoid synovial membrane. Synovial membrane from 16 rheumatoid (RA) patients was studied. Six patients with osteoarthritis constituted the control group. The cell membrane expression of the glycoprotein Pgp 170, encoded by the MDR 1 gene, was determined by an immunoperoxidase technique using two different monoclonal antibodies (JSB 1, C 219). The polymerase chain reaction (PCR) methods were used in parallel to detect the presence of the MDR 1 gene mRNA in the synovial cells. Pgp 170 was expressed on the cell membrane of five RA patients and MDR 1 cellular transcription was detected in one other RA patient. We did not observe any association between synovial glycoprotein expression and age, disease activity, and a specific treatment with a long-acting drug. However, MDR protein expression was associated with the successive treatment with more than three disease-modifying antirheumatic drugs (DMARDs). We concluded that the synovial membrane expresses a glycoprotein recognized by the antibodies JSB 1 and C 219. The absence of concomitant MDR 1 transcription suggests the expression of an atypical MDR phenotype in the synovial membrane, distinct from the Pgp 170 encoded by the MDR 1 gene. The implications of the MDR phenotype and the resistance of RA to DMARDs is further discussed.
8064731 Serum ferritin and isoferritins are tools for diagnosis of active adult Still's disease. 1994 May OBJECTIVE: Still's disease is an acute systemic inflammatory disorder. There are no pathognomonic symptoms or specific laboratory abnormalities. Serum ferritin concentration in rheumatoid arthritis together with some plasma glycoproteins such as alpha 2-glycoprotein and C-reactive protein are part of the response to inflammation. Ferritin in plasma is glycosylated and the sialoglycosylated forms increase its microheterogeneity. Our purpose was to confirm in a large series that high values of ferritin can be found in adult Still's disease (ASD) and to see if a specific isoferritin can be isolated in this disease compared with the other systemic diseases. METHOD: Thirty-one sera were investigated from 11 men and 9 women with ASD and compared with 27 sera from 27 patients with systemic diseases. We studied the course of one case of ASD for 15 months. Serum ferritin was determined by immunoenzymology (Abbott Ferrizin). The isoferritins were investigated by isoelectric focussing and the percentage of glycosylation by affinity for concanavalin A (Con-A). RESULTS: In patients with active ASD, the ferritin levels were higher than in patients with inactive ASD or other systemic diseases: p < 0.001. The glycoforms of ferritin were basic and the proportion of ferritin bound to Con-A was lower than other ASD: p < 0.001. CONCLUSIONS: Serum ferritin levels have a diagnostic value for acute ASD. The study of sialylation and abnormalities in the glycosylation of ferritin helps to discriminate ASD from arthritis or other systemic diseases. In conclusion, the glycoform of isoferritins and the percentage of glycosylation offers an additional tool for the diagnosis of Still's disease.
8724289 CD4+ T cell inducible immunoregulatory cytokine response in rheumatoid arthritis. 1996 May OBJECTIVE: Monocytes and CD4+/CD8+ T cells produce immunoregulatory cytokines that participate in the pathogenesis of various immune disorders. We investigated the secretion of Th1-Th2 cell response cytokine production of CD4+/CD8+ T cells from the synovial fluid (SF) and blood of patients with rheumatoid arthritis (RA). METHODS: Blood and SF purified monocytes, CD4+ and CD8+ T cells were stimulated with bacterial lipopolysaccharides or anti-CD3 antibody, and secretion of various cytokines was determined by bioassay or ELISA: RESULTS: Monocytes from SF and blood of patients with RA produced highly elevated levels of interleukin-1 alpha (IL-1 alpha), IL-6, tumor necrosis factor-alpha (TNF-alpha), and granulocyte macrophage colony stimulating factor (GMCSF), the leading mediators of inflammation. However, CD4+ T cells secreted deficient levels of IL-2 and interferon-gamma (IFN-gamma), but higher levels of IL-4 and IL-10, the typical immunoregulatory Th2 cell response cytokines. CD8+ T cells also produce elevated levels of IL-4 and IL-10 but almost normal levels of IFN-gamma in this disease. CONCLUSION: The cytokine produced by monocytes (IL-alpha, IL-6, TNF-alpha, and GMCSF) and by CD4+ T cells Th2 cell responses (IL-4 and IL-10) may exert immunopathologic and immunoregulatory effects in SF and thus mediate some of the clinical manifestations of RA.
1371472 T cell receptor diversity and activation markers in the V delta 1 subset of rheumatoid syn 1992 Feb In the present study we have characterized the gamma/delta T cell receptor (TcR) population in synovial fluid (SF) and peripheral blood (PB) of patients with chronic inflammatory arthritis. By double staining we have shown that (a) synovial V delta 1+ cells have a high expression of activation markers CD45R0 ("memory cells") and HLA-DR as compared to PB, indicating a preactivated population of V delta 1-carrying T cells in vivo and (b) interleukin 2-induced expansion of synovial cells yields a high proportion of gamma/delta in most samples expressing predominantly the V delta 1 TcR. Junctional sequence analysis of the TcR delta chain from interleukin 2-expanded PB cell lines demonstrated a polyclonal V delta 1 population in three out of three samples. In SF cell lines three out of four samples were polyclonally expanded. In SF from one patient, however, a limited repertoire of expressed V delta 1 genes was found. Altogether, our data demonstrate the presence of preactivated V delta 1-expressing cells in the synovial compartment. This V delta 1 population is predominantly polyclonal, except in one patient where oligoclonally expanded V delta 1 cells were detected.
7553058 [A case of Felty's syndrome with marked thrombocytopenia and severe hypocomplementemia]. 1995 Apr Felty's syndrome is diagnosed when a patient shows both splenomegaly and leukocytopenia of various degree during the course of rheumatoid arthritis (RA). The accompanying immunologic abnormalities (e.g., antinuclear antibody, antiplatelet antibody, and hypocomplementemia) also characterize Felty's syndrome, but some authors may regard these abnormalities as a transitional form into overlap syndrome [RA + systemic lupus erythematosus (SLE)]. Here we reported a female case of Felty's syndrome who showed marked thrombocytopenia and severe hypocomplementemia. Thrombocytopenia had been refractory against several forms of therapies including high-dose methylprednisolone. Simultaneously, she had various autoantibodies (i.e., antiplatelet antibody, positive Coombs' test, antithyroglobulin antibody, antimicrosome antibody and anti-RNP antibody). Although she did not fulfill the ARA diagnostic criteria for SLE, the degree of thrombocytopenia as well as that of hypocomplementemia argued in favor of the overlap of SLE in this patient. Low-dose cyclosporin A (CsA) combined with small dose of prednisolone could increase both platelet count and level of complement. Notably, the titers of several autoantibodies dropped after CsA was started. These findings might suggest that CsA could normalize the underlying immunologic abnormalities in this patient. However, the disease activity of RA could not be decreased without a help of low-dose methotrexate.
8803912 The use of antimalarials in combination with other disease modifying agents in RA--the Bri 1996 Jun Antimalarial drugs are effective disease modifying agents in RA with a low incidence of serious toxic effects. Recently, combinations of second-line agents have been used in RA in attempts to treat patients with no response to a number of single agents, or suboptimal response to a single agent. Combinations of drugs have been selected for maximum efficacy and minimum toxicity, but clinical trials are difficult to design and interpret. In particular, ensuring adequate power to detect small differences in response poses a major problem. Antimalarials are an attractive choice for combination therapy due to their efficacy, mechanisms of action and toxicity profile. In this review, the evidence for the use of antimalarials in combination in RA is examined. No advantage has been shown in combining antimalarials with gold, penicillamine or sulphasalazine compared with monotherapeutic regimens. There is some evidence to suggest a beneficial combination of antimalarials with methotrexate, but this is as yet inconclusive. Open non-randomised uncontrolled studies have shown that antimalarials combined with cytotoxic agents are effective but highly toxic. The authors conclude that there is little good evidence to support the introduction of combination second-line drug therapy for RA into widespread therapeutic use.
8286292 The compressible silicone rubber prosthesis in temporomandibular joint disease. 1993 Dec An alternative technique for temporomandibular joint arthroplasty is described, in which the mandibular condyle is replaced by a soft compressible silicone rubber prosthesis. A modified Nicolle-Calnan metacarpo-phalangeal joint prosthesis was used to reconstruct 31 joints in 24 patients. Results suggest that in those patients where there has been no loss of the prosthesis, function continues to be markedly improved when compared with the pre-operative condition. Painful symptoms were relieved in cases of specific joint pathology but the technique was of little value in the management of dysfunctional pain when radiographic evidence of joint pathology was absent. A specifically designed TMJ prosthesis of this type may be a useful addition to the surgeon's armamentarium.
8760745 Use of oral corticosteroids in the community and the prevention of secondary osteoporosis: 1996 Aug 10 OBJECTIVE: To determine the prevalence of continuous use of oral steroids in the general population, the conditions for which they are prescribed, and the extent to which patients taking oral steroids are taking treatment to prevent osteoporosis. DESIGN: A cross sectional study with a four year retrospective review of drug treatment. SETTING: Eight large general practices in central and southern Nottinghamshire. SUBJECTS: A population of 65,786 patients (52% women) registered with a general practitioner during 1995. RESULTS: 303 patients (65% (197) women) aged 12-94 years were currently taking "continuous" (for at least three months) oral corticosteroid treatment. This figure represents 0.5% of the total population and 1.4% (245/17 114) of patients aged 55 years or more (1.7% (166/9601) of women). The usual steroid was prednisolone (97% (294/303)), the mean dose was 8.0 mg/day, and the median duration of oral steroid treatment determined in 149 patients was three years. The most common conditions for which continuous oral steroids were prescribed were rheumatoid arthritis (23% (70)), polymyalgia rheumatica (22% (66)), and asthma or chronic obstructive airways disease (19% (59)). Only 41 (14%) of the 303 patients taking oral steroids had received treatment for the prevention of osteoporosis over the past four years. Although 37 of the 41 patients were women, only 10% (18/181) of the women over 45 years taking continuous oral corticosteroids were currently taking hormone replacement therapy. CONCLUSIONS: If our figures are typical then they suggest that over 250,000 people in the United Kingdom are taking continuous oral steroids and that most of these are taking no prophylaxis against osteoporosis.
7984836 [Silicosis and primary Gougerot-Sjögren syndrome]. 1994 We report three cases of primary Sjögren's syndrome in silicotic coal miners. All patients fulfilled the diagnostic criteria for Sjögren's syndrome recently established by the European Community study group. One patient had cryoglobulinemia and polynevritis. Another had Raynaud's phenomenon, arthralgia, purpura and polynevritis. Capillary microscopy was normal in all the three patients. Antinuclear antibodies were detected only in one patient, who had also anti-SSa and anti-SSb antibodies. The prevalence of systemic sclerosis, rheumatoid arthritis and probably systemic lupus erythematosus is significantly higher after longstanding occupational exposure to silica. On the contrary, any case of Sjögren's syndrome was till now described in the course of pulmonary silicosis. The physiopathological mechanisms of these associations are misunderstood.
8513048 Disseminated infection with rapidly growing mycobacteria. 1993 Apr Disseminated infection with the rapidly growing mycobacteria Mycobacterium chelonae and Mycobacterium fortuitum is uncommon. Only eight cases were diagnosed at Duke University Medical Center (Durham, NC) over the last 14 years. We identified 46 other cases by review of the medical literature since 1960. We categorized these 54 cases into three groups according to underlying disease and outcome. Group 1 comprised patients with no identified immune defect, a kidney transplant, collagen vascular disease, or chronic renal failure; these patients usually presented with skin involvement and responded well to antimicrobial therapy (survival rate, 90%). Group 2 comprised patients with cell-mediated immune deficiency, lymphoma, or leukemia; they presented with widespread, multiorgan involvement and severe illness. The survival rate in this group was only 10%. Patients in group 3 (who had other underlying diseases) had intermediately severe illnesses and intermediate responses to therapy. These groups provide the basis for an understanding of disseminated infection secondary to rapidly growing mycobacteria and of the profound effect that unresolved immunosuppression has on survival.
1284061 T-cell receptor beta usage by 35 different antigen-specific T-cell clones restricted by HL 1992 Nov We studied whether antigen-specific T cells being restricted by the very similar HLA-Dw4 and/or -Dw14.1 molecules might demonstrate homogeneities in parts of their TCR. TCCs were generated from three individuals who were all HLA-Dw4/Dw14.1 heterozygous. Thirty-five TCCs specific for PPD or TT and restricted by HLA-Dw4 and/or -Dw14.1 were selected for TCR beta gene sequencing. We found that 19 different V beta genes from 13 V beta families were expressed by these TCCs. Thus, it seems that many different TCRV beta genes may be used by TCCs restricted by these HLA molecules. For PPD-specific TCCs, a possible biased usage of V beta 8, as well as possible preferential usage of a CDR3 motif, were found.
1384113 Autoantibodies to the nuclear Sp100 protein in primary biliary cirrhosis and associated di 1992 Oct Sp100, a protein with a dot-like intranuclear localization in immunofluorescence microscopy, is a major target for patient autoantibodies in primary biliary cirrhosis (PBC) and occasionally in rheumatic disorders. The human Sp100 cDNA has recently been cloned, and the deduced amino acid sequence was found to contain sequence similarities with an MHC class I domain and several transacting regulatory proteins, including HIV-1 nef proteins. In this study, recombinant Sp100 fusion proteins were used to differentiate the immunoglobulin isotypes and to map the epitopes involved in the anti-Sp100 autoimmune response. PBC patients developed IgG as well as IgM and/or IgA class anti-Sp100 autoantibodies whereas most patients with rheumatic diseases developed IgG class autoantibodies only. For epitope mapping, truncated versions of the Sp100 protein were probed for immunoreactivity in ELISA and immunoblotting. With 55 sera, 17 different reaction patterns were obtained, and at least three non-overlapping major autoantigenic domains were recognized by the majority of sera. One domain, which contains the sequence similarity with HIV nef proteins, was recognized by all anti-Sp100 sera and harbours multiple, in part discontinuous, epitopes. These data demonstrate a heterogeneous and patient-specific anti-Sp100 autoimmune response which is antigen-driven and, at least in terms of isotype composition, different in PBC and non-PBC patients.
8579291 Evaluation of an enzyme-immunometric assay for serum alpha-glutathione S-transferase. 1995 Nov A commercially available enzyme-immunometric assay for serum alpha-glutathione S-transferase (GST) was evaluated. Endogenous serum alpha-GST diluted linearly within the calibration range. However, we recommend that the sample and second antibody reagent are always added sequentially in the assay to avoid hook effect. Between-assay variability was below 7% across the calibration range and the upper limit of the reference range in adults (n = 219) was 11.4 micrograms/L. Within-individual variability in serum alpha-GST concentrations measured over a 4-6 week period in 4 healthy adults was small. Serum alpha-GST concentrations did not change significantly 6 h after a therapeutic dose of paracetamol. Studies in two patients after liver transplantation showed that serum alpha-GST is a better discriminant of acute changes in liver function than conventional tests. Serum alpha-GST concentrations were unaffected by gross muscle damage, extrahepatic inflammation, or haemolysis and thus appear to be more liver specific than transaminase activities. The effect of renal impairment on serum alpha-GST concentrations requires further investigation.
8655398 Distribution in human tissues of the synovial lining-associated epitope recognised by mono 1996 Feb Murine monoclonal antibody Mab 67 was originally shown on histochemical screening to bind to synovial intimal fibroblasts (SIF), cells in lymphoid follicles and elastic fibres. As part of a programme to isolate the antigen recognised by Mab 67 and determine its function, a wider histochemical study was performed. Cryostat sections were prepared from normal human adult synovium, skin, placenta, amnion, kidney, tonsil, breast, thyroid, colon and pericardium, fetal limb tissues and rheumatoid arthritic synovium. Sections were stained with Mab 67, anti-CD3, as isotype matched control, and anti-VCAM-1 using alkaline phosphatase -anti-alkaline phosphatase. Selected sections were double labelled for nonspecific esterase activity. Staining by Mab 67 of SIF, identified as NSE-negative intimal cells, and follicle centre cells was confirmed. Staining with Mab 67 was also seen on Bowman's capsule and juxtaglomerular apparatus, stratum granulosum of skin, pulmonary alveolar cells, amniotic epithelium, chorionic villi, fetal synovium, bone marrow stromal cells and epidermis, and interstitial elastic fibres in most tissues, but not at other sites in these tissues or in pericardium, muscle, colon, breast, thyroid, salivary gland or vein. The staining pattern with Mab 67 suggests that the antigen is pericellular. Its distribution does not match any molecule known to us but overlaps at several sites with VCAM-1 (SIF, follicle centres, Bowman's capsule and bone marrow stroma). We suggest that the antigen involved may possible by similarly involved in cell-matrix interaction.
8225682 Efficacy of misoprostol in controlling indomethacin induced fecal blood loss in arthritic 1993 Aug Indomethacin, a nonsteroidal anti-inflammatory drug, may cause gastric mucosal damage as shown by fecal blood loss. A randomized, double-blind, placebo-controlled, parallel group study was conducted to determine the effects of 400 mcg b.i.d. misoprostol, a synthetic prostaglandin E1 analog, on intestinal blood loss caused by 50 mg t.i.d. indomethacin. Forty-two arthritic patients, mean age 59 years, received indomethacin for 14 days. Those with baseline blood loss of at least 1.5 ml/day during the first 7 days were randomized to 400 mcg of misoprostol or placebo (days 8 to 14). Fecal blood loss was measured using 51Cr labelled red blood cell technique. Success was defined as a reduction in mean daily blood loss of at least 50% during the treatment period compared to mean daily blood loss during the baseline (pre-treatment) phase. The mean daily blood loss on treatment days 9-15 was not significantly reduced from baseline in either group. These data neither confirm nor deny the effectiveness of misoprostol in reducing fecal blood loss caused by indomethacin. The results may have been confounded by the administration of misoprostol twice daily while indomethacin was administered three times daily. In addition, fecal blood loss as an indicator of gastrointestinal mucosal damage is not a sensitive measure; it is characterized by poor reproducibility and wide fluctuations within individual responses. Inappropriate laboratory techniques may have further reduced the sensitivity and reliability of this procedure.
7849973 Treatment of the atypical lesser toe deformity with basal hemiphalangectomy. 1994 Nov Eighty-six lesser toe basal hemiphalangectomies were performed in 52 patients. The surgical technique included an oblique dorsal incision, resection of 8 mm of bone, and an extensor tenotomy. Minimum follow-up was 2 years (range 2-6/1/2 years). Sixty percent of the patients had total relief of pain. Twenty-nine percent stated that they would not have the surgery again, and we categorized these patients as dissatisfied. An extensor tenotomy increased the satisfaction rate and was found to decrease the radiographic sagittal angulation of the toe. The preoperative diagnosis was significant to the outcome of the surgery. Patients with metatarsophalangeal joint synovitis and rheumatoid toe deformities had high rates of satisfaction; those with transverse deviation, metatarsalgia, and hammertoes with metatarsophalangeal joint subluxation/dislocation had lower rates of satisfaction. Seventy percent of the dissatisfied patients were dissatisfied because of persistent flexion deformity of the PIP joint or pain under the metatarsal head. We now add a PIP fusion if any flexion deformity, even a mild deformity, is present at the PIP joint and a plantar metatarsal condylectomy for metatarsalgia.
8820681 [The differentiation of the antigens making up the circulating immune complexes]. 1996 Jan A simple method for the detection and analysis of circulating immune complexes (CIC) in specimens of biological fluids is proposed. The method was approved in the examination of patients with chronic infections caused by mycoplasmas and Streptococcus pyogenes L-forms. The method made it possible to diagnose infectious diseases accompanied by the formation of immune complexes and to study the dynamics of the processes of the accumulation and elimination of CIC in the course of the disease. Thus, the detection rate of specific antigens (Ag) incorporated into CIC in patients with mycoplasmal pneumonia exceeded 90 %. In children aged up to 1 year this rate decreased to 40 %. The diagnostic value of the determination of specific Ag incorporated into CIC was shown in streptococcal infections caused by S.pyogenes L-forms, viz. in frequently relapsing erysipelas, as well as in subacute rheumatism and in infectious allergic myocarditis.
7600245 Synovectomy and diskectomy of the temporomandibular joint in patients with chronic arthrit 1995 Feb Twenty-five temporomandibular joints (TMJs) in 15 patients with chronic arthritic disease were treated with synovectomy and diskectomy. Twenty patients with internal derangement of 27 TMJs treated with diskectomy served as a control group. A response in pain relief was seen in 73% of the patients with chronic arthritic disease and in 80% of the patients with internal derangement 3 yr postoperatively. In both groups of patients a significant increase in mouth opening capacity and lateral movement of the mandible was seen postoperatively, with no significant difference in the improvement between the two groups. Four patients with chronic arthritic disease were reoperated within the 3-yr observation period. This study indicates that synovectomy and diskectomy of the TMJ may reduce pain and improve mandibular function in patients with severe chronic arthritic TMJ disease.