Search PubMed⌕ Search

Biomedical subjects

R N Maini

Publications and source records attributed to R N Maini.

At least 181 records · Page 10Linked to original sources
PubMed1991

Correlation of histopathological features of pannus with patterns of damage in different joints in rheumatoid arthritis.

The cartilage-pannus junction has been studied in multiple sections from 23 rheumatoid joints. Changes suggesting a metaplastic reaction of the articular cartilage, termed transitional fibroblastic zone, were commonly found in hips and knees, but were rarely present in metatarsophalangeal joints, in which an invasive pannus with cartilage degradation in close association with inflammatory cells was seen. Thus when multiple sections from rheumatoid joints were examined a transitional fibroblastic zone was found in 1/15 (7%) sections from metatarsophalangeal joints compared with 29/57 (51%) and 15/48 (31%) sections from knee and hip joints respectively. In contrast, an invasive pannus occurred in 11/15 (73%) sections from metatarsophalangeal joints compared with 22/57 (39%) sections from knees and 19/48 (40%) sections from hips. These findings led to the suggestion that this pathological variation between different joints may explain the predominance of erosive change in small joints as compared with joint space narrowing with secondary osteoarthritis found in large joints in rheumatoid arthritis. Inappropriate comparisons between different joints may in part explain the variation in findings of previous histopathological studies.

Arthritis, Rheumatoid↗
PubMed1990

The synovium-cartilage junction of the normal human knee. Implications for joint destruction and repair.

The immunohistology of the synovium-cartilage junction was studied in 8 normal human knees, using monoclonal antibodies. In all joints at the junction with synovium, a vascular, wedge-shaped tongue of tissue was found to cover the cartilage surface. This marginal tissue overlying cartilage was in continuity with and was immunohistochemically similar to the adjacent synovial tissue, and contained cells possessing class II HLA antigens and antigens present on macrophages and type B synoviocytes. Periosteal tissue adjacent to the synovium-cartilage junction contained not only macrophages and other class II-positive cells, but also cells and matrix that stained with monoclonal antibodies specific for articular cartilage (keratan sulfate and type II collagen). This study demonstrates the presence of immunocompetent cells in tissue overlying the cartilage surface and adjacent to bone in normal human joints. It is likely that pannus in chronic inflammatory rheumatic disease develops by the recruitment of inflammatory cells augmenting this normal marginal tissue. Furthermore, overgrowth of tissue onto the cartilage surface may not be necessary in the pathogenesis of joint destruction in rheumatoid arthritis. In addition, our findings suggest that cells in the periosteum, rather than those in the marginal synovium, may be involved in attempted "repair" mechanisms, such as osteophyte formation.

Adolescent↗
PubMed1990

Detection of interleukin 8 biological activity in synovial fluids from patients with rheumatoid arthritis and production of interleukin 8 mRNA by isolated synovial cells.

The presence of neutrophils in the synovial joint of patients with rheumatoid arthritis (RA) is thought to be due to the activity of chemotactic factors released by activated cells in the joint. We have shown in this report, for the first time, the abundance of one such factor, interleukin 8 (IL 8), in the synovial fluid of patients both with RA and other non-RA joint diseases, and the spontaneous production of IL 8 mRNA by RA synovial cells in culture. There was no correlation between the levels of chemotactic activity and IL 8 protein, suggesting that other factors with similar neutrophil chemotactic activity are also present in the synovial fluid exudate. In support of this concept neither the level of chemotactic activity nor IL 8 protein levels correlated with neutrophil or leukocyte infiltration, indicating that the mechanism of migration into the inflammatory environment of the joint is complex. Such migration is likely to be due to a number of chemotactic signals in addition to IL 8, which may either synergize with, or inhibit, the action of IL 8.

Adult↗
PubMed1990

Antinuclear antibody determination methods.

Screening rheumatology patients for anti-nuclear and anti-cytoplasmic antibodies is easily done in a qualitative manner using the IF, CIE and ID assays. The immunoblot is of use for anti-La and anti-RNP assays but gives anomalous results for Sm binding by anti-RNP sera and is not easily quantitated. These deficiencies of the immunoblot do not apply to the ELISA. Advances in cloning of autoantigens will enable standardisation of antigen preparations used for these ELISAs. The quantitation of autoantibody appears significant since disease flares occur together with elevations in specific autoantibody. IgM anti-Sm autoantibody was detected with a different disease distribution to IgG anti-Sm but the prognostic implications for this remain to be determined.

Antibodies, Antinuclear↗
PubMed1990

Lack of natural antibodies in rheumatic diseases.

The prevalence and Ig class of natural antibodies in the sera of healthy individuals and of patients with rheumatic diseases were studied. The presence, even in high concentrations, of natural antibodies in normals was confirmed. In the rheumatic diseases tested, however, a discordance in the levels and Ig class of anti-actin, anti-myosin and anti-ssDNA antibodies was noted. IgM anti-actin antibodies occur infrequently, whereas IgM anti-myosin and anti-ssDNA are increased in these diseases. IgG anti-actin antibodies are increased in the sera of patients with RA, but not in patients with SLE, polymyositis or mixed connective tissue disease (MCTD). IgG anti-myosin as well as anti-ssDNA antibodies were increased in patients with RA and SLE, but not in patients with polymyositis or MCTD. These findings suggest that these natural antibodies are unlike the multispecific autoantibodies produced by lymphocytes from the CD5+ B cell lineage and that they may have undergone affinity maturation. Perhaps natural antibodies are a feature of health rather than of disease.

Actins↗
PubMed1990

Expression of intercellular adhesion molecule-1 and lymphocyte function-associated antigen-3 on human thyroid epithelial cells in Graves' and Hashimoto's diseases.

Human endocrine thyroid epithelial cells (TEC) from autoimmune thyroiditis which express HLA Class II antigens have been shown to present autoantigens to T cells for a TEC-specific immune response. Since the initiation of a specific immune response also involves antigen-receptor independent interactions between accessory molecules, such as lymphocyte function-associated antigen-1 (LFA-1) with intercellular adhesion molecule-1 (ICAM-1) and lymphocyte function-associated antigen-3 (LFA-3) with CD2, it was of interest to determine whether TEC can express the adhesion molecules (ICAM-1 and LFA-3) which augment the efficiency of antigen presentation. Cultured TEC were studied for their expression of ICAM-1 and LFA-3 by immunofluorescence. Those derived from Graves' disease expressed these molecules after stimulation with recombinant human interferon-gamma (IFN gamma) or with recombinant human tumour necrosis factor-alpha (TNF alpha). However, using the same stimuli, TEC from non-toxic goitre were induced to express ICAM-1, but not LFA-3. To establish whether ICAM-1 and LFA-3 on TEC were expressed in vivo during the disease process, antibodies against these molecules were incubated with frozen sections of autoimmune thyroiditis, including Graves' and Hashimoto's diseases, and non-toxic goitre. Both ICAM-1 and LFA-3 were highly expressed in the autoimmune diseases, but not in non-toxic goitre. These findings establish that TEC are able to express adhesion molecules and suggest the possible involvement of these adhesion molecules in the TEC-specific immune response in autoimmune thyroiditis.

Antigens, Surface↗
PubMed1990

Dialysis arthropathy: a clinical, biochemical, radiological and histological study of 36 patients.

Out of a population of 97 haemodialysis patients, 36 patients with dialysis arthropathy were identified. Dialysis arthropathy is a chronic symmetrical polyarthritis which affected 97 per cent of the patients who had been undergoing cuprophane haemodialysis for more than 10 years. It commonly affected the shoulders, hips, hands, knees and wrists, worsening with time and extending to other joints. Fifty-eight per cent of the patients complained of morning stiffness and 47 per cent complained of exacerbation of shoulder pain during or after haemodialysis. Half of the patients also suffered from carpal tunnel syndrome, which recurred and was associated with a long-lasting disability. The most common radiological abnormality was periarticular bone cysts, followed by articular erosions and a destructive spondyloarthropathy, but clinical symptoms were more common than radiological signs. Patients with dialysis arthropathy had a higher C-reactive protein level than patients without arthropathy (18.6 mg/l versus 11.4 mg/l), indicative of an inflammatory process. Some of the clinical manifestations of the disease correlated with levels of C-reactive protein and ferritin. Serum ferritin levels correlated strongly with the units of blood transfused in the past five years (RS = 0.83), and the logarithm of ferritin level correlated weakly with C-reactive protein (r = 0.32). Haemarthroses were documented in 19 per cent of patients. Mean serum beta 2-microglobulin was elevated in the patients with (57.3 mg/l) and without arthropathy (50.7 mg/l), and there was no difference in the parathormone or aluminium levels between these groups. Articular tissue was obtained in 25 patients; beta 2-microglobulin amyloid was present in 24. Larger deposits were present in the capsular tissue, and these appeared to replace collagen bundles in eight cases. Amyloid deposits replaced the lining layer in six cases. It is likely therefore that amyloid disrupts normal joint function by replacing normal joint tissue. Mild chronic synovitis with haemosiderin deposition were found in approximately 60 per cent of cases. These findings suggest that amyloid derived from beta 2-microglobulin has a primary role in the pathogenesis of dialysis arthropathy, but there was also evidence of inflammatory processes. It is suggested that iron overload or haemarthroses might contribute to the inflammation, but other factors, such as dialysis-related bioincompatibility reactions, may also have a role.

Adult↗
PubMed1990

Analysis of immunoglobulins secreted by hybridomas derived from rheumatoid synovia.

Twenty-six IgG-secreting and eight IgM-secreting hybridomas were derived from the synovia of two patients with rheumatoid arthritis (RA). Hybridomas were obtained by fusing a heteromyeloma cell line, SPAZ-4 with synovial mononuclear cells that were not deliberately stimulated in vitro. Over 96% of the IgG-secreting hybridomas produced antibodies which belonged to the IgG1 subclass and showed lambda light chain predominance; the latter was not seen in IgM antibodies, where kappa light chains dominated by 3:1. All IgG antibodies were cationic. Synovial B cells were not exposed to extrinsic stimuli prior to fusion, therefore these results reflect the state of B cell activation and differentiation in vivo. Our results indicate that IgG-secreting B cells in the RA joint are under a selective influence which is, as yet, unidentified. One out of eight IgM-secreting and two out of 26 IgG-secreting hybridomas produced rheumatoid factors (RF). The IgM-RF specificity for IgG heavy chain subclasses was determined and showed that the monoclonal bound to IgG1, IgG2 and IgG4 but not IgG3 with exception of IgG3 Goe of the G3m (st) allotype, a profile typical of specificity for the Ga epitope. This monoclonal also distinguished a determinant in the Fc region of human IgG which was not present in rabbit IgG. The overall frequency of RF-secreting hybridomas we observed indicates that B cells committed to RF production in the synovium of a seropositive and a seronegative RA patient is below 10%.

Adult↗
PubMed1990

Cells with dendritic morphology and bright interleukin-1 alpha staining circulate in the blood of patients with rheumatoid arthritis.

Freshly isolated peripheral blood mononuclear cells (PBMC) from 10 healthy volunteers, 28 patients with rheumatoid arthritis (RA), eight patients with osteoarthritis, and five patients with ankylosing spondylitis were examined for interleukin-1 alpha (IL-1 alpha) and interleukin-1 beta (IL-1 beta) production using monoclonal antibodies and an indirect immunofluorescent method. In freshly isolated PBMC from healthy controls very few cells were stained for either IL-1 type. All 20 RA patients who were not receiving parenteral gold therapy had PBMC staining for IL-1 alpha. In these patients, up to 7.5% of PBMC showed bright IL-1 alpha staining (range 1.2-7.5%). No IL-1 beta staining was seen. These IL-1 alpha-staining cells had a dendritic morphology and the percentage of cells staining correlated well with levels of C-reactive protein, an index of disease activity in these RA patients. Significantly fewer IL-1 alpha-staining cells were present in the peripheral blood of RA patients receiving gold therapy and in the blood of patients with osteoarthritis and ankylosing spondylitis. These IL-1 alpha-containing cells, circulating in the blood of RA patients and correlating with disease activity have not been previously described. These results support the idea that IL-1 alpha plays an important role in the pathogenesis of rheumatoid inflammation.

Adult↗
PubMed1990

Measurement of the chemotactic complement fragment C5a in rheumatoid synovial fluids by radioimmunoassay: role of C5a in the acute inflammatory phase.

Evidence suggests that complement is activated in rheumatoid joints. A sensitive radioimmunoassay for the activation fragment of C5, C5a, which is a potent chemoattractant for neutrophils, was therefore developed. A mean C5a concentration in 22 rheumatoid joint fluids of about 2.5 x 10(-9) mol/l was found. This concentration of C5a is sufficient to induce two of the characteristic features of the acute inflammatory phases of rheumatoid arthritis: neutrophil accumulation and microvascular plasma protein leakage. In animal models it has been shown that C5a is a potent inducer of inflammatory oedema by a neutrophil dependent mechanism. A striking feature of the acute inflammatory phases of rheumatoid arthritis is the appearance of high numbers of neutrophils in the synovial fluid. It is suggested that C5a might have a role in mediating neutrophil accumulation and, as a consequence, may be important in acute joint swelling and pain.

Adult↗
PubMed1990

CD5 (Ly-1)-negative, conventional splenic B cells make a substantial contribution to the bromelain plaque-forming cell response in CBA and BW mice.

CD5 (Ly-1) B cells are a minor subpopulation in mouse spleen and are thought to be responsible for the production of natural autoantibodies to bromelain-treated autologous erythrocytes (Br-RBC). Here it is shown that substantial numbers of conventional, CD5-negative, splenic B cells also secrete these antibodies in CBA and (NZB x NZW)F1 mice, whereas in NZB and BALB/c mice they are all produced by the CD5 B-cell population. However, stimulation with bacterial lipopolysaccharide in vivo preferentially activates the CD5 B-cell group to anti-Br-RBC antibody secretion.

Animals↗
PubMed1990

Antibodies to the mycobacterial 65-kd heat-shock protein are reactive with synovial tissue of adjuvant arthritic rats and patients with rheumatoid arthritis and osteoarthritis.

The expression of 65-kd mycobacterial heat-shock protein (HSP)-related antigens in synovial membrane from rats and humans with arthritis was studied using three monoclonal antibodies and one polyclonal antiserum directed to antigens of mycobacteria. The antibodies labeled synovial tissue sections from both adjuvant arthritis (AA) rats and from patients with either rheumatoid arthritis (RA) or osteoarthritis (OA); especially the synovial lining cells appeared to be positive. The cytoplasmic staining patterns in rats and humans were essentially the same and were not related to the extent of inflammation ie, the size of lymphoid infiltration. In control tissues no cytoplasmic staining was observed. The results suggest a role for a 65-kd HSP or a cross-reactive molecule in the immunopathologic process of arthritic disease.

Animals↗
PubMed1990

Immunoglobulin V genes expression and mRNA sequencing in rheumatoid arthritis.

Antibodies to exogenous antigen and to self antigen--that is, autoantibodies, are both encoded by the combining of V, D, and J genetic elements in the heavy chain, and V and J in the light chain immunoglobulins. The mechanism which generates autoantibodies does not seem to differ from that which generates the immune response to foreign antigen, and analysis of DNA from normal and autoimmune strains of mice appears similar with no appreciable defects in the immunoglobulin germline genes. Although there is restricted use of particular gene families in murine antibodies to exogenous antigen, the preferential use of particular V genes in murine autoantibodies remains controversial. Until recently, because of the obvious limitations on human experimentation, there was little information about the genetics of the human autoimmune response. Recent developments in molecular cloning techniques, however, some of which are discussed here, have shown that the germline arrangement of the human immunoglobulin variable genes differs from that found in the mouse. Furthermore, there is increasing evidence that human autoantibodies make restricted use of the V gene repertoire, and this indicates that the human autoimmune response is less polymorphic than the murine autoimmune response.

Animals↗