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Biomedical subjects

N Amos

Publications and source records attributed to N Amos.

At least 73 records · Page 4Linked to original sources
PubMed1993

Lymphoproliferation in primary Sjögren's syndrome. Evidence of selective expansion of a B cell subset characterized by the expression of cross-reactive idiotypes.

OBJECTIVE: To evaluate the possibility that lymphoproliferation in primary Sjögren's syndrome (SS) arises within a subset of B cells. METHODS: A panel of monoclonal antibodies (MAb) specific for rheumatoid factor (RF)-associated cross-reactive idiotypes (CRI) and anti-V kappa and anti-VH subgroup antibodies were used to define the clonality of B lymphocytes undergoing neoplastic transformation in 5 patients with primary SS. Anti-CRI antibodies were also used to study longitudinal variations in serum paraprotein levels and in vitro regulation of IgM and IgM-RF production by peripheral blood lymphocytes. The levels of CRI, IgM, and IgM-RF were quantitated in serum and culture supernatants by enzyme-linked immunosorbent assay. Heavy and light chain isotypes and VH subgroups of the paraproteins were determined by immunoelectrophoresis, immunofixation, and Western blotting. RESULTS: Paraproteins from all patients expressed an epitope associated with V kappa IIIb sub-subgroup of light chains. Three of the paraproteins were cryoglobulins with RF activity, all of which expressed the V kappa IIIb-associated CRI (detected by MAb 17-109) and the VHI-associated CRI (detected by MAb G6 and G8). None of the paraproteins expressed the VHIII-associated CRI (detected by MAb B6 and D12). The CRI were consistently expressed over a period of 5-6 years. The anti-CRI and anti-subgroup antibodies substantially inhibited spontaneous production of IgM-RF and IgM by peripheral blood B lymphocytes from 3 of the SS patients. CONCLUSION: These results suggest that lymphoproliferation in primary SS is highly selective, and that the anti-CRI antibodies can be used as an aid to early diagnosis as well as for monitoring and modulating the lymphoproliferative process in primary SS.

Adult↗
PubMed1993

Anti-P antibodies are associated with psychiatric and focal cerebral disorders in patients with systemic lupus erythematosus.

In a cross-sectional study, 62 patients with systemic lupus erythematosus were assessed using standardized psychiatric and psychological methods; systemic disease activity was scored using the British Isles Lupus Assessment Group and the Lupus Activity Criteria Count indices. IgG and IgM anti-P antibodies were measured by ELISA using a synthetic 22 amino acid peptide as the relevant antigen. IgG and IgM anti-P antibodies were significantly associated with neuropsychiatric disorders (psychiatric and neurological) but failed to distinguish patients with psychiatric disorders from those with neurological disorders. These antibodies were not associated with cognitive impairment or systemic disease activity.

Antibodies↗
PubMed1993

Antiribosomal P protein antibodies in different populations of patients with systemic lupus erythematosus.

We report a significantly increased prevalence of antiribosomal P protein antibodies in Malaysian Chinese patients (38%) with SLE compared to white Caucasian (13%) and Afro-Caribbean (20%) patients. The increased prevalence was not due to a generalized increase in autoantibody production because anti-dsDNA and anti-SSA antibodies were present in comparable frequencies in the three ethnic groups while anti-Sm and anti-SSB antibodies were rarely found in the Malaysian Chinese patients.

Antibodies, Anti-Idiotypic↗
PubMed1992

Accumulation of polyvinylpyrrolidone within the inflamed paws of adjuvant-induced arthritic rats.

125I-Labelled polyvinylpyrrolidone ([125I]PVP) of a range of molecular weights (mol. wt 10, 40 and 360 kDa) was injected i.v. into adjuvant-induced arthritic and normal rats and the blood clearance and tissue distribution of the polymers determined. The half-life of PVP in the circulation increased with increasing mol. wt; 10, 40 and 360 kDa polymers had mean terminal half-lives of 2.2, 6.9 and 16.4 h, respectively. Tissue uptake was also found to be mol. wt dependent, the largest PVP molecule accumulating to a greater extent in the spleen, liver, lungs and paws in both normal and arthritic rats (P less than 0.01) than the two lower mol. wt polymers. Accumulation of the polymer in inflamed paws (g tissue)-1 greatly exceeded that of normal paws (P less than 0.01). This difference was particularly noticeable with 360 kDa PVP, where arthritic paws amassed 7 times more PVP than normal paws.

Animals↗
PubMed1992

Antibodies to protein P in systemic lupus erythematosus.

A synthetic peptide was used to develop an enzyme linked immunosorbent assay (ELISA) to detect antibodies to the ribosomal proteins P0, P1, and P2. Significantly increased levels of IgG antibodies to protein P were found in 16% (18/116) of patients with systemic lupus erythematosus but slightly increased levels were detected in 2% (2/98) of patients with rheumatoid arthritis and one normal control subject. No association was observed between the presence of IgG antibodies to protein P and either lupus psychosis or depression. Sequential studies in individual patients failed to show an association between antibody levels and the development of psychosis.

Antibodies↗
PubMed1992

Postpartum thyroiditis: an organ specific syndrome which is not associated with a postpartum polyclonal B-cell activation.

Recent reports have detailed the presence of autoantibodies characteristic of non-organ specific autoimmune diseases in the serum of patients with autoimmune postpartum thyroiditis (PPT). These observations suggest that PPT could be part of a polyclonal B-cell activation postpartum. We have measured 4 non-organ specific autoantibodies (anti-DNA, anti-cardiolipin, anti-nuclear factor (ANF) and antibodies against extractable nuclear antigens (ENA)) together with autoantibodies against thyroglobulin and thyroid peroxidase in a group of PPT women at 4 time points during the first year postpartum (early, time of hyperthyroidism, time of hypothyroidism, late). Whilst 18/18 patients showed thyroid specific autoantibody changes there was only a low frequency of occurrence of the non-organ specific autoantibodies (ENA 2/18; ANF 1/18; anti-DNA 2/18; anti-dsDNA 0/18; anti-cardiolipin 0/18) and, when positive, the response was poor. We conclude that PPT is not associated with a polyclonal b-cell activation but is a postpartum rebound of a thyroid specific autoimmune phenomenon.

Antibodies, Antinuclear↗
PubMed1991

Terminal complement complexes and C1/C1 inhibitor complexes in rheumatoid arthritis and other arthritic conditions.

Terminal complement complex (TCC) and C1r-C1s-C1 inhibitor complex (C1/C1 INH) concentrations were measured in plasma and synovial fluid from patients with arthritis and related to other measures of disease activity. Both TCC and C1/C1 INH concentrations were significantly increased in patients with rheumatoid arthritis (RA) compared with patients with osteoarthritis (plasma and synovial fluid, P less than 0.05) and normal subjects (plasma only, P less than 0.001). In the patients with RA, there was no correlation between plasma or synovial fluid TCC concentrations and IgM rheumatoid factor, immune complex or C1/C1 INH levels. However, in 10 patients with seronegative RA, C1/C1 INH and immune complex levels correlated significantly in synovial fluid (r = 0.69, P less than 0.05) although not in plasma (r = 0.52). Plasma and synovial fluid TCC and C1/C1 INH concentrations did not differ in rheumatoid patients with severe compared with mild joint disease (categorized by the Ritchie score). These results confirm a role for complement activation in RA but suggest that several mechanisms are involved in its pathogenesis.

Adult↗
PubMed1990

Complement-mediated inhibition of immune precipitation in rheumatoid vasculitis.

Complement-mediated inhibition of immune precipitation (CMIP) was measured in patients with rheumatoid arthritis (RA), rheumatoid vasculitis (RA VASC), patients with skin vasculitis not associated with a systemic connective tissue disease and normal healthy controls. CMIP was impaired in 100% (14/14) of the RA vasculitic patients, 60% (12/20) of the RA patients and 22% (2/9) of the dermovasculitic patients. The degree of impairment of CMIP was significantly greater in the RA vasculitic patients compared to the non-vasculitic patients. This difference was due to the significantly lower complement levels and the presence of higher concentrations of an inhibitor of CMIP in the RA vasculitic sera. The levels of this inhibitory activity correlated significantly with IgM rheumatoid factor concentration. Serial studies in three patients with RA vasculitis treated with corticosteroids and immunosuppressive drugs showed significant clinical improvement in two patients, which was associated with improvement in CMIP, reduction in circulating immune complex levels and reduction in IgM rheumatoid factor concentrations.

Adrenal Cortex Hormones↗
PubMed1990

Specific accumulation of cholesterol-rich liposomes in the inflammatory tissue of rats with adjuvant arthritis.

High performance liquid chromatography has shown that after intravenous injection cholesterol-poor liposomes (100 nm) are unstable and their phospholipid is redistributed. Under identical conditions cholesterol-rich liposomes remain structurally intact within the circulation. When injected intravenously cholesterol-rich liposomes accumulate within the inflamed paws of rats with adjuvant induced arthritis to the same extent as cholesterol-poor liposomes. Uptake in inflamed tissue of three cholesterol-rich liposome preparations was always significantly greater than the uptake noted in normal tissue. The degree of accumulation in inflamed tissue was found to depend on the size of the liposome, with the greatest uptake, 7% of the injected dose, achieved by the smallest vesicle (100 nm). These results indicate that intact liposomes accumulate at inflamed joint tissue sites. Therefore the passive targeting of anti-inflammatory drugs encapsulated within these liposomes could be contemplated.

Animals↗
PubMed1989

Specific accumulation of technetium-99m radiolabelled, negative liposomes in the inflamed paws of rats with adjuvant induced arthritis: effect of liposome size.

Technetium-99m labelled, negatively charged liposomes accumulate in the inflamed tissue of rats with adjuvant induced arthritis. Up to 10 times more liposome accumulation was seen in inflamed paws than in paws of control rats, and this represented 5.3% of the injected liposome dose. The accumulation of liposomes in inflamed tissue was directly related to the liposome size, the maximal accumulation occurring with liposomes less than 100 nm in diameter.

Animals↗
PubMed1989

Autoantibody analysis in chronic graft-versus-host disease.

Chronic graft-versus-host disease (cGVHD) bears clinical similarities to connective tissue diseases which are characterized by a spectrum of autoantibody formation. A wide range of autoantibody analyses in 19 allogeneic and 16 autologous bone marrow transplant (BMT) patients has determined that the most commonly detected antibody is IgM anti-cytoplasmic factor (ACF) occurring in 37% and 20% of allogeneic and autologous group respectively and of a type not normally seen in connective tissue disease. The antigen is as yet unidentified. These results suggest that autoantibody formation post-BMT is unrelated to the graft-versus-host process. Ophthalmic examination revealed evidence of a Sjögren-like syndrome in 20% autologous and 47% allogeneic patients, suggesting that the development of dry eyes post-BMT is not uniquely a feature of cGVHD.

Adult↗
PubMed1988

Complement mediated inhibition of immune precipitation in rheumatoid arthritis: studies on interaction of heat aggregated IgG with IgM rheumatoid factor.

Serum samples from patients with seropositive rheumatoid arthritis contain an inhibitor of complement mediated inhibition of immune precipitation (CMIP). This inhibitory effect can be produced by the addition of either purified monoclonal or polyclonal IgM rheumatoid factor (RF) to human serum. The specificity of the rheumatoid factor influences the degree of inhibition, and when precipitation occurs the rheumatoid factor coprecipitates with the antigen-antibody complex. In rheumatoid sera there was a significant positive correlation between IgM RF concentration and inhibitory activity, though the range of inhibitory activity seen for the same concentration of rheumatoid factor was considerable. Small quantities of heat aggregated IgG (HAGG) had a much greater effect on the measurement in an enzyme linked immunosorbent assay (ELISA) of IgM RF than they did on the inhibitory activity of IgM RF in the CMIP assay. Larger quantities of HAGG initiated complement activation and increased the precipitation of immune complexes. IgM RF reduced the complement activating properties of HAGG by reducing the amount of Clq which bound to the aggregate. The mechanisms by which IgM RF overcomes CMIP in rheumatoid sera may involve its inhibitory effects on the binding of Cl to the antigen-antibody complex.

Antigen-Antibody Complex↗
PubMed1987

Monoclonal antibodies to restricted and cross-reactive idiotopes on monoclonal rheumatoid factors and their recognition of idiotope-positive cells.

Four human monoclonal rheumatoid factors (MRF) were used to raise a panel of mouse monoclonal antibodies (mAb) which were selected in a solid-phase radioimmunoassay for binding to MRF but not normal IgM. Three mAb, each raised against a different MRF, bound to the majority of MRF and also to most polyclonal RF. Four other mAb bound selectively to the MRF against which they were raised and to no other MRF, and rarely to any polyclonal RF. Competition studies using cold and radiolabeled mAb further indicated that these mAb recognize distinct and different epitopes on MRF. RF activity of MRF was inhibited by 3 of the 4 mAb binding to a single MRF and 2 of the 3 mAb binding to multiple RF. It was thus concluded that of this panel of mAb 3 recognized cross-reactive idiotopes and the remainder demonstrated highly restricted idiotopes on MRF. These mAb identified MRF idiotope-bearing cells in the peripheral blood of 3 of the MRF donors (and a further subject with type II essential cryoglobulinemia), with a frequency ranging from 0.3-10% of all mononuclear cells with the mAb to restricted idiotopes or 1.5-17% with mAb to cross-reactive idiotopes. These anti-idiotopic mAb should thus provide a highly specific means of identifying and monitoring MRF-producing cells in vivo.

Antibodies, Monoclonal↗
PubMed1987

Absence of circulating IgG immune complexes in minor recurrent aphthous ulceration.

A monoclonal rheumatoid factor binding assay has been employed to detect IgG type immune complexes in sera from 21 patients with minor recurrent aphthous ulceration and 31 control subjects. In only one of the ulcer group patients was there a marginal elevation of immune complexes above the normal range, with no statistically significant difference between the patient and control groups. Assays of intrinsic serum rheumatoid factor and serum IgG, IgM and IgA levels also showed no significant differences between patient and control groups, with all mean values falling within the normal ranges.

Adolescent↗
PubMed1985

Meningococcal endocarditis with profound acquired hypocomplementaemia.

A patient is described who presented with chronic endocarditis, due to Neisseria meningitidis, affecting a previously normal mitral valve. The illness was associated with glomerulonephritis that caused renal impairment and the nephrotic syndrome. Despite antibiotic treatment and replacement of the mitral valve, serum complement values remained very low, only returning to normal when immune complexes and a type III cryoglobulin disappeared from the circulation three months after resection of the valve vegetation. Such acquired hypocomplementaemia may have contributed to the chronicity of the disease process in this patient.

Adult↗
PubMed1985

Proteinuria in autoimmune thyroid disease.

We have investigated the prevalence of proteinuria in patients with Graves' disease and chronic autoimmune thyroiditis attending a routine thyroid clinic. Using the urine protein creatinine index, proteinuria was found in 29.8% of patients with autoimmune thyroid disease and in 9.5% of patients attending the same clinic but without these conditions. When patients with Graves' disease were treated with 131I, proteinuria measured by 24 h collections developed in 9 of 14 patients without pre-existing proteinuria and appeared to diminish in 4 patients in whom proteinuria had been present before treatment. The prevalence and fluctuation of proteinuria was independent of thyroglobulin and microsomal antibody levels. We were unable to confirm previous reports of a high prevalence of circulating immune complexes in autoimmune thyroid disease; complexes were detected in only 7.9% of patients and did not correlate with proteinuria. The causes of mild proteinuria in autoimmune thyroid disease are not apparent, but previous case reports suggesting that membranous glomerulonephritis is associated with Graves' disease, albeit rarely, indicate that immunological mechanisms may be implicated.

Adult↗
PubMed1985

Simultaneous turnover of normal and dysfunctional C1 inhibitor as a probe of in vivo activation of C1 and contact activatable proteases.

Simultaneous turnover of normal and dysfunctional C1-inhibitor (C1-INH) was carried out in 10 normal subjects and 13 patients with rheumatoid arthritis as a measure of the in vivo activation of C1 and the contact activatable enzymes. In the first series of experiments, dysfunctional protein We was used in simultaneous turnover studies in five normal subjects and nine patients. The fractional catabolic rate of the dysfunctional C1-INH, We, (FCR(d)) was unchanged in both groups but the fractional catabolic rate of the normal C1-INH (FCR(n)) was faster in the patients compared to the controls, in particular patients with vasculitis. The enzyme-dependent catabolism defined as FCR(n-d) X concentration of C1-INH X plasma volume, was raised in the patient group, and correlated with disease activity score (r = 0.83, P less than 0.05). Neither FCR(n) nor FCR(d) was dependent on C1-INH concentration. The latter was higher in the patients (206 mg/l compared with 155 mg/l) indicating a very high synthetic rate in the patients (280.81 micrograms/kg/h compared with 179.77 micrograms/kg). In the second series of turnovers in six patients and five normal subjects, another dysfunctional C1-INH, at, was used. The FCR of C1-INH was slower than C1-INH (We) (1.88%/h compared with 2.7%/h). Enzyme-dependent catabolism of C1-INH in these patients were raised and also correlated with disease activity score (r = 0.82, P less than 0.05).

Adult↗