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Biomedical subjects

C J Elson

Publications and source records attributed to C J Elson.

At least 73 records · Page 4Linked to original sources
PubMed1994

Chondro-osseous metaplasia, bone density and patellar cartilage proteoglycan content in the osteoarthritis of STR/ORT mice.

The evolution of osteoarthritis (OA) was compared in male and female STR/ORT mice and in male CBA mice with particular emphasis on the changes in para-articular structures which occur before the classical degenerative phenomena in the articular cartilage of the knee. In male STR but not female STR mice or male CBA mice, chondro-osseous metaplasia was found in the tendinous structures which surround the joint and in the major ligamentous entheses such as the patellar ligament. This change was detectable from the age of three months. By contrast, changes in the articular surfaces of the knee were never detected before four months while the total patellar proteoglycan content in male STR animals increased from three months. Line density profile measurements on radiographs of the knees revealed that changes in the bone density of the sub-chondral zone of the articular surfaces only increased in affected animals after the development of severe OA changes in the joint. It is suggested that the model of OA which develops in male STR/ORT mice is secondary to soft tissue changes, particularly chondro-osseous metaplasia in para-articular structures.

Achilles Tendon↗
PubMed1994

Inhibitor regulation of tissue kallikrein activity in the synovial fluid of patients with rheumatoid arthritis.

Tissue kallikrein (TK) and alpha 1-antitrypsin (AT)/TK complexes can be detected in SF from patients with RA if components of the fluids which interfere with the detection of TK are removed. alpha 2-Macroglobulin (alpha 2-M) in SF was demonstrated to contain trapped proteases which were still active in amidase assays. Removal of alpha 2-M from RA SF reduced their amidase activity. However, at least some of the remaining activity was due to TK because it was soya bean trypsin inhibitor resistant and trasylol sensitive and was partly removed by affinity chromatography on anti-TK sepharose. Removal of RF from the fluids reduced the values obtained for TK levels by ELISA. Addition of SF to human urinary kallikrein (HUK) considerably reduced the levels of TK detected suggesting the presence of a TK ELISA inhibitor in the fluids. Removal of components of > 300 kDa from SF markedly reduced the TK ELISA inhibitory activity and increased the values for both the TK and alpha 1-AT/TK levels in fluids as measured by ELISA. It is considered this novel inhibitor does not bind to the active site of TK but rather binds to the site reactive with anti-TK antibodies.

Adult↗
PubMed1994

Characterisation of an oxidative response inhibitor produced by Streptococcus pneumoniae.

BACKGROUND: Pneumonia caused by infection with Streptococcus pneumoniae is still a major clinical problem. Reactive oxygen species contribute to the killing of these bacteria by polymorphonuclear leucocytes (PMNs). Defence mechanisms of Str pneumoniae which counter reactive oxygen species are characterised. METHODS: PMNs were stimulated with phorbol myristate acetate (PMA) in the presence and absence of Str pneumoniae and supernatants from them, and superoxide (O2-) production was measured by the reduction of ferricytochrome c. RESULTS: Streptococcus pneumoniae, but not Klebsiella pneumoniae or Staphylococcus aureus, inhibited PMA stimulated superoxide production by PMNs. Washed PMNs which had been preincubated with Str pneumoniae autolysis phase supernatants also exhibited depressed H2O2 production in response to PMA. The inhibitory activity was not attributable to non-specific cytotoxicity as assessed by release of the cytoplasmic enzyme lactate dehydrogenase, nor did the supernatants inhibit PMA stimulated degranulation of PMNs. Fractionation of the autolysis phase supernatants revealed inhibitory activity in both the fractions greater than and less than 10 kD. Like pneumolysin the inhibitory activity was heat sensitive. However, both a parent and pneumolysin negative mutant Str pneumoniae, and autolysis phase supernatants from them, inhibited PMN superoxide production. Antisera to pneumolysin failed to abrogate the inhibitory effect of intact Str pneumoniae or autolysis phase supernatants from types 1 or 14 Str pneumoniae. CONCLUSIONS: The inhibitory effect of Str pneumoniae on the respiratory burst of PMNs is not shared by two other common lung pathogens. The existence of a novel inhibitor of the PMN respiratory burst, distinct from pneumolysin, has been demonstrated. The inhibitor is specific for the respiratory burst and is active both in the logarithmic phase of growth and during autolysis.

Autolysis↗
PubMed1994

Tumor necrosis factor-alpha receptor expression on chondrocytes isolated from human articular cartilage.

OBJECTIVE: To determine whether the previously observed enhanced susceptibility of osteoarthritic (OA) cartilage to tumor necrosis factor-alpha (TNF-alpha) induced degradation could be due to differences in receptor expression. METHODS: Using specific monoclonal antibodies flow cytometry was used to identify and quantify 2 TNF-alpha receptors on the surface of chondrocytes isolated from human articular cartilage. RESULTS: The proportion of chondrocytes expressing p55 TNF-alpha receptor was significantly higher in populations from OA cartilage (p < 0.01) when compared with similar populations from non-arthritic cartilage. The number of p55 receptors/chondrocyte was also significantly higher (p < 0.01) in OA. A significant correlation (r = 0.72, p < 0.18) was found in OA between the numbers of chondrocytes expressing p75 receptor and the number of receptors/chondrocyte. CONCLUSION: p55 TNF-alpha receptor expression is significantly increased on OA chondrocytes ex vivo. Enhanced expression of p55, purported to be the biologically active receptor, could contribute to OA cartilage degradation.

Aged↗
PubMed1994

The functional activity of human monocytes passively sensitized with monoclonal anti-D suggests a novel role for Fc gamma RI in the immune destruction of blood cells.

The role of Fc gamma RI in the immune destruction of blood cells is uncertain as serum IgG levels are sufficient to competitively inhibit interactions between this high-affinity receptor and sensitized red cells. In the current study, it is proposed that, rather than functioning as a receptor for opsonized red cells, Fc gamma RI might, under appropriate conditions, mediate the passive sensitization (or 'arming') of human macrophages with IgG antibodies resulting in the in vivo destruction of unsensitized cells expressing the corresponding antigen. To examine this hypothesis, Fc gamma RI-bearing human monocytes and U937 cells were first passively sensitized by incubation in vitro with human monoclonal anti-D, and then incubated with D-positive red cells. The uptake of monoclonal anti-D by U937 cells was rapid and, in the presence of 2.5 micrograms/ml IgG1 or IgG3 anti-D, was almost complete after 5 min at 37 degrees. Subsequent incubation of passively sensitized U937 cells in an IgG-free medium for 1 hr at 37 degrees resulted in the loss from the cell surface of approximately 50% cell-bound IgG; the remaining cell-bound IgG was lost more slowly despite repeated washing. In functional assays, passively sensitized monocytes (M-IgG) mediated adherent, phagocytic and chemiluminescent (CL) responses to D-positive red cells. After incubation of M-IgG in 50% v/v fresh normal human serum (FNHS) for 2 hr, sufficient anti-D remained bound to monocytes to promote the adherence of red cells. The adherence and phagocytosis of red cells by M-IgG was enhanced by the simultaneous addition of 50% FNHS, probably owing to the binding of low levels of C3bi to red cells. In contrast, phagocytic and CL responses of unsensitized monocytes to anti-D-sensitized red cells (E-IgG) were abrogated in the presence of 0.25% v/v FNHS, presumably owing to blocking of Fc gamma RI by IgG. It is considered that in vivo, Fc gamma RI may mediate the passive sensitization of macrophages in close proximity with antibody-secreting cells in the reticular network of the splenic cords. Once 'armed' in this way, macrophages may destroy cells expressing the appropriate antigen.

Antibodies, Monoclonal↗
PubMed1993

The separation and identification by monoclonal antibodies of dog IgG fractions.

Four fractions of IgG from normal dog serum have been successfully isolated by gel filtration followed by protein A and protein G affinity chromatography using the fast protein liquid chromatography (FPLC) system. Protein A chromatography produced three peaks: peak 1 was fallthrough material consisting of components which did not bind to protein A, peak 2 consisted of bound material eluting at pH 6, and peak 3 contained bound material eluting at pH 3.5. The three peaks were then subjected individually to protein G affinity chromatography. Peak 1 from protein A chromatography produced a fallthrough peak followed by a weakly binding component which eluted at pH 8, and was called peak w. Peak 2 from protein A chromatography bound to protein G and eluted as a single peak at pH 3.8, and was called peak x. Peak 3 from protein A chromatography emerged as two separate peaks (y and z) off the protein G column; peak y bound and eluted at pH 4.1, and peak z bound weakly to protein G and emerged as a broad band at pH 8. Peaks w, x, y and z have been named gamma w, gamma x, gamma y and gamma z, respectively, and there purified IgG fractions were used to immunize mice for the preparation of monoclonal antibodies (McAbs). To date, two sets of McAbs have been produced: one which recognizes an epitope present in both gamma w and gamma z fractions and another set of McAbs which recognizes an epitope in the gamma x and gamma y fractions.

Animals↗
PubMed1993

Pathogenic autoantibodies in the NZB mouse are specific for erythrocyte band 3 protein.

NZB mice spontaneously develop autoimmune hemolytic anemia (AIHA). The red blood cell (RBC) autoantigen bound by pathogenic IgG autoantibodies, previously designated "X", was identified by immunoprecipitation. Autoantibody eluted from the RBC of AIHA-positive NZB mice precipitated a 105-kDa antigen that was identical in apparent molecular mass to Band 3, the RBC anion channel protein. Furthermore, the immunoblotted antigen also reacted specifically with BRIC 132, a monoclonal antibody against Band 3. The results, therefore, demonstrate that Band 3 bears autoantigenic epitopes that are important in the pathogenesis of AIHA in the NZB mouse.

Animals↗
PubMed1993

Red cell-bound immunoglobulins and complement measured by an enzyme-linked antiglobulin test in dogs with autoimmune haemolysis or other anaemias.

A direct enzyme-linked antiglobulin test (DELAT) was used to measure IgG, IgM, IgA and C3 bound to the red blood cells (RBC) of anaemic dogs. One or more of these parameters was raised in 78 per cent of the cases tested, and elevated levels of bound IgG, IgM, IgA and C3 was the most common pattern recorded. When the DELAT-positive animals were divided into two groups on the basis of clinical findings, the two categories differed serologically. Cases diagnosed clinically as primary autoimmune haemolytic anaemia (AIHA) were typified by the demonstration of specific antibody binding to RBC, had significantly higher levels of RBC-bound IgG (P < 0.001) and IgM (P < 0.02) and included a significantly (P < 0.01) higher proportion of the dogs with at least three DELAT parameters raised. The second group comprised the DELAT-positive dogs with other diseases. In most of these cases, RBC-specific antibody was not detectable and there was a significant (rs = 0.62, P < 0.001) relationship between RBC-bound and serum IgG levels, suggesting that the immunoglobulin was reacting with the RBC non-specifically in a concentration-dependent manner. It is concluded that elevated levels of RBC-bound immunoglobulin and, or, complement are detectable with the DELAT in most anaemic dogs, but that this finding is not necessarily associated with autoimmune haemolysis.

Anemia↗
PubMed1993

Red cell-reactive non-specific immunoglobulins and autoantibodies in the sera of normal and anaemic dogs.

The levels of red blood cell (RBC) membrane-reactive IgG were measured in sera from normal and anaemic dogs using an enzyme-linked immunosorbent assay with erythrocyte ghosts as the target antigen (g-ELISA). The anaemic dogs were classified as cases of primary autoimmune haemolytic anaemia (AIHA), other anaemias with elevated levels of RBC-bound immunoglobulin detected by a direct enzyme-linked antiglobulin test (DELAT), or DELAT-negative anaemias. The g-ELISA detected IgG capable of binding RBC membranes in all the serum samples tested, and the levels were significantly higher (P < 0.05) in dogs with AIHA than in cases of DELAT-negative anaemia or in healthy animals. When sera were preabsorbed with RBC ghosts, g-ELISA readings were reduced in two of three AIHA cases that were tested, but not in dogs from any other group. There was no correlation between g-ELISA results and serum IgG levels in the cases of AIHA, but there was a significant relationship (rs = 0.74, P < 0.001) between these parameters in the dogs with other DELAT-positive anaemias. When spectrin(s) from the internal RBC membrane skeleton was used as the target antigen in the s-ELISA, sera from all groups of anaemic dogs yielded a wide range of values. Although the levels of spectrin-reactive IgG were significantly higher (P < 0.05) in AIHA cases than normal dogs, suggesting that haemolysis provoked production of anti-membrane skeleton antibodies, the highest reading was recorded in a healthy animal. It is concluded that all canine sera contain IgG non-specifically reactive with RBC membranes and that serum antibodies against the erythrocyte surface can also be detected in some dogs with primary AIHA. Distinct spectrin-reactive serum IgG antibodies can also be demonstrated in normal and AIHA positive dogs.

Anemia, Hemolytic, Autoimmune↗
PubMed1993

Susceptibility to pristane-induced arthritis is altered with changes in bowel flora.

Pristane-induced arthritis (PIA) is unique among the animal arthritides in that a non-infectious, non-antigenic oil induces a chronic immune based arthritis with a prolonged delay between exposure to the inciting agent and development of the disease. Mice with pristane-induced arthritis have elevated T cell and humoral responses to the 65 kDa heat shock protein derived from Mycobacterium bovis (hsp65) and in common with several other models of autoimmune diseases the incidence of PIA is markedly suppressed by preimmunisation with hsp65 in Freund's incomplete adjuvant (Thompson et al. (1990) Eur. J. Immunol. 20, 2479). Recent studies have investigated how autoimmune reactions to heat shock proteins are involved in the development of arthritis. Arthritic CBA/Igb mice given pristane alone develop antibodies to both hsp65 and GroEl (bacterial 60 kDa heat shock proteins) and to hsp58 (the mammalian equivalent). Moreover, the splenic T cells of such mice proliferate vigorously in response to both bacterial and mammalian 60 kDa heat shock proteins. Remarkably, the anti-hsp65 antibody response in normal mice rises rapidly with age, directly correlating with the age related incidence of PIA. In addition, specific pathogen free mice (SPF) maintained in an isolator have negligible anti-hsp65 responses but these convert to positive responses if the animals are exposed to the open part of the animal facility (Thompson et al. (1992) Arthritis Rheum. 35, 139).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Comparison between the protective effects of mycobacterial 65-kD heat shock protein and ovomucoid in pristane-induced arthritis: relationship with agalactosyl IgG.

The IgG of patients with rheumatoid arthritis and mice with pristane induced arthritis (PIA) tends to lack the terminal galactose normally on the conserved N-acetylglucosamine linked beta 1-2 to mannose in IgG. The terminal N-acetylglucosamine (GlcNAc) residues of oligosaccharides on agalactosyl IgG may be an important component of the action of these glycoforms. Here, administration of ovomucoid, a glycoprotein rich in terminal GlcNAc, before pristane injection was found to reduce the incidence of PIA. This observation is the second report of an intraperitoneally administered antigen that reduces the incidence of PIA, mycobacterial 65-kD heat shock protein (hsp65) being the first. The suppressive effect of ovomucoid was not transferred from protected to naive recipients by spleen cells at the dose tested. By contrast, transfer of spleen cells from hsp65-protected mice to naive recipients conferred protection and this protection may be antibody-mediated. It is considered that ovomucoid and hsp65 protect against the development of PIA by different mechanisms.

Animals↗
PubMed1993

Control of human thyroid autoantibody production in SCID mice.

In order to determine the phenotype of the cells required for thyroid autoantibody production, peripheral blood mononuclear cells (PBMC) from patients with autoimmune thyroid disease (AITD) were transferred to severe combined immunodeficient (SCID) mice. The production of human IgG, thyroglobulin (Tg) antibody and thyroid peroxidase (TPO) antibody in the SCID recipients was monitored for up to 4 months. PBMC from 10 of 13 AITD patients produced substantial IgG (> or = 100 micrograms/ml) and detectable Tg and TPO antibodies in recipient mice. PBMC pretreated to deplete or enrich T cells produced low or undetectable thyroid-specific antibody in SCID mice. Depletion of CD4+ T cells resulted in much lower or undetectable IgG, Tg and TPO antibodies compared with levels seen in recipients of control PBMC. By contrast, depletion of CD8+ T cells from the PBMC had no overall effect on autoantibody production, although with PBMC from some patients CD8+ depletion possibly enhanced both IgG and autoantibody production. In eight of 10 experiments, autoantibody levels reached maximal titres before total IgG levels peaked. It is considered that thyroid autoantibodies are produced from memory B cells activated in SCID mice and that this activation is T cell- and CD4+ T cell-dependent.

Adult↗
PubMed1993

Inhibition of interleukin 1 beta induced rat and human cartilage degradation in vitro by the metalloproteinase inhibitor U27391.

Interleukin 1 induced proteoglycan loss from cartilage in vitro was prevented by a biochemical inhibitor of metalloproteinase activity. The inhibitor also partially relieved the inhibition of proteoglycan synthesis caused by interleukin 1. The loss of glycosaminoglycan by rat and human femoral head cartilage in response to human recombinant interleukin 1 beta (rhIL-1 beta) was established, and the modulation of this loss by the metalloproteinase inhibitor U27391 was investigated. Rat femoral head cartilage consistently lost glycosaminoglycan in response to rhIL-1 beta whereas only a proportion (30%) of normal human femoral head cartilage did so. Concentrations of 10-100 mumol/l U27391 inhibited the action of rhIL-1 beta on rat femoral head cartilage, reversing both the loss of glycosaminoglycan and the inhibition of glycosaminoglycan synthesis. U27391 also prevented the reduction in glycosaminoglycan content of those human femoral head cartilage explants responsive to rhIL-1 beta. Metalloproteinase inhibition therefore prevents rhIL-1 beta induced glycosaminoglycan loss by rat and human femoral head cartilage, suggesting that inhibitors of such enzymes may prove to be of therapeutic benefit in erosive diseases in humans.

Animals↗
PubMed1993

Interference with the oxidative response of neutrophils by Streptococcus pneumoniae.

BACKGROUND: Pneumococcal infections are still a major clinical problem. Polymorphonuclear leucocytes (neutrophils) are considered to have a key role in the host's defence against Streptococcus pneumoniae but the mechanisms by which they kill the pneumococcus remain unclear. As reactive oxygen species are regarded as a major antimicrobial defence of phagocytes an attempt has been made to establish their role in the response of neutrophils to S pneumoniae. METHODS: S pneumoniae isolated from patients with bacteraemic pneumococcal pneumonia were incubated with neutrophils in suspension and superoxide production was measured by reduction of ferricytochrome c. RESULTS: S pneumoniae did not stimulate superoxide production alone or in the presence of normal human serum. Spontaneous superoxide production by neutrophils was actually abrogated by S pneumoniae, as was the powerful respiratory burst stimulated by phorbol myristate acetate. This phenomenon depended on both the dose and the viability of the bacteria. With S pneumoniae in the logarithmic phase of growth inhibitory activity was confined to the organisms themselves but with organisms undergoing autolysis it was also present in filtered supernatants, suggesting that the inhibitory activity can be attributed to a factor released during autolysis. CONCLUSIONS: S pneumoniae can interfere with the respiratory burst of neutrophils. This property may help to explain the pathogenicity of the organism.

Humans↗
PubMed1993

Hypothesis: cartilage catabolic cofactors in human arthritis.

Cartilage degradation in rheumatoid arthritis (RA) and osteoarthritis (OA) is commonly thought to be mediated by interleukin 1 (IL-1) and tumor necrosis factor (TNF). However, recent new evidence suggests that IL-1 and TNF on their own do not mediate all the cartilage changes seen in RA and OA. We propose that cartilage degradation is mediated by a complex network of cytokines, including IL-1, TNF and at least one cofactor present in synovial fluid.

Arthritis, Rheumatoid↗
PubMed1993

Identification of murine erythrocyte autoantigens and cross-reactive rat antigens.

Autoimmune haemolytic anaemia (AIHA) can be induced in mice by repeated injections with rat red blood cells (RBC). Here we describe the identification of murine RBC autoantigens and cross-reactive rat antigens. Sera and RBC eluates from the AIHA-positive mice immunoprecipitated a murine RBC autoantigen of 42,000 MW that comigrates with a zone of glycophorin in PAS-stained polyacrylamide gels. In addition, the eluates immunoprecipitated a 105,000 MW protein corresponding to band 3, the erythrocyte anion channel, and two further components of 34,000 and 29,000 MW within the glycophorin zone. The 42,000 MW band was not detected by immunoblotting, indicating that it bears autoantigenic epitope(s) that are denatured during electrophoresis. Cross-reactive autoantibody in the eluates immunoprecipitated a rat RBC protein that comigrated with band 3, together with two bands of 36,000 MW and 34,000 MW that may represent minor rat glycophorins. In contrast, rat-specific serum IgG from mice with AIHA reacted predominantly with major rat glycophorins of 75,000 MW and 38,000 MW. Immunoblotting revealed that normal murine sera contain IgG that binds autologous spectrin from the RBC membrane skeleton, and that this activity is increased in mice with AIHA. Sera from AIHA-positive mice also reacted with other internal murine RBC components that are not exposed on the surface of intact cells. It is evident from the data that immunization of mice with rat RBC results in the generation of multiple autoantibodies with a complex range of specificities.

Anemia, Hemolytic, Autoimmune↗
PubMed1993

Prevention of pristane-induced arthritis by the oral administration of type II collagen.

This is the first demonstration of a role for type II collagen in pristane-induced arthritis. Pretreatment with soluble type II collagen either lowers or raises the subsequent incidence and severity of pristane-induced arthritis. These effects are dependent upon both the dose and route of administration of the soluble type II collagen. Increasing doses of orally administered type II collagen lowered both the incidence and severity of pristane-induced arthritis. Conversely, increasing doses of intraperitoneally administered type II collagen increased both the incidence and severity of arthritis. This exacerbation of pristane-induced arthritis was accompanied by elevated B- and T-cell responses to type II collagen. These findings highlight the importance of the site at which antigen is encountered in influencing subsequent immune responses and extend the observations of the use of orally administered antigens to ameliorate experimental autoimmunity.

Administration, Oral↗