Biomedical subjects

N Amos

Publications and source records attributed to N Amos.

11 recordsLinked to original sources

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↗

PubMed1978

The immunogloblin nature of nephritic factor (NeF).

NeF was shown to be antigenically and structurally similar to IgG by the following experiments: (1) NeF activity in serum was absorbed by and, under acid conditions, could be eluted from (a) anti-myeloma IgG antibody coupled to Sepharose and (b) protein A-Sepharose. (2) Purified NeF could bind to anit-myeloma IgG-Sepharose and could be eluted with acid, and this binding was blocked by myeloma IgG. (3) An antibody to beta2, microglobulin, showing strong cross-reactivity with normal IgG, bound NeF activity before, but not after, absorption of the antiserum with IgG. (4) Sepharose-coupled antibodies to NeF could bind activity which was recovered in the acid eluate. This binding capacity was lost after absorption of the antibody with normal and myeloma IgG. (5) Structural similarity was demonstrated by pepsin and papain digestion, which resulted in NeF activity eluting with F(ab')2 and Fab fragments from protein A-Sepharose and Sephadex G-150. (6) Autoradiography of PAGE-SDS of 125I-labelled NeF eluted from EA43bBb cells showed that NeF had a larger H chain than normal IgG, suggesting that NeF might be an abnormal IgG molecule.

Chemical Phenomena↗

PubMed1977

Metabolism of the fifth component of complement, and its relation to metabolism of the third component, in patients with complement activation.

The metabolism of the fifth component of complement (C5), and its relatonship to metabolism of the third component of complement (C3), has been studied in normal subjects and patients by simultaneous administration of radioiodine labeled C5 and C3. In seven normal subjects the fractional catabolic rate of C5 ranged from 1.5 to 2.1% of the plasma pool/h and extravascular/intravascular distribution ratio from 0.22 to 0.78, these values being similar to those obtained for C3, and synthesis rate from 71 to 134 mug/kg per h, In patients with complement activation the increase in fractional catabolic rate of C5 was nearly always less than that of C3. The data also showed that there was increased extravascular distribution of C3 and C5 in most patients and considerable extravascular catabolism of both proteins in some. However, there were differences in metabolic parameters between patients with different types of complement activation. In patients with systemic lupus erythematosus, fractional catabolism and extravascular distribution of C3 and C5 were both increased, and there was marked extravascular catabolism of both proteins. There was increased fractional catabolism and extravascular distribution of C3 in patients with mesangiocapillary nephritis and (or) partial lipodystrophy, and fractional catabolism of C5 was also increased in three of six studies although distribution of C5 was always within the normal range; however, in two patients with nephritic factor in their serum fractional catabolism of C5 was normal despite markedly increased C3 turnover, suggesting that in patients with alternative pathway activation by nephritic factor little or no C5 convertase is generated.

Adolescent↗

PubMed1977

C3b receptors in glomerular disease.

Using two indicator systems--sheep erythrocytes or fluoresceinated S. typhi coated with C3b the presence of a receptor for C3b (but not C3d) in the normal human glomerulus is confirmed. No receptor could be detected in other species tested (mouse, rat, guinea-pig, rabbit and rhesus monkey). Binding of indicator particles was reduced or lost in diseases associated with glomerular capillary deposition of C3, but not in those with mesangial deposition alone. However in some cases the receptor was lost in the absence of detectable C3 deposition. No receptors were detected in proliferating cells in glomerular crescents.

Animals↗

PubMed1977

Guinea-pig nephrotoxic nephritis II. Autologous phase: complement activation without detectable injury.

In the autologous phase of nephrotoxic induced by sheep antibody to glomerular basement membrane (GBM) in Dunkin-Hartley and C4 deficient strain guinea-pigs, less than 50% of animals developed proteinuria at the height of the autologous antibody response despite high anti-sheep immunolglobulin tetres and fixation of guinea-pig IgG and complement in the kidney. tonly two of thirty-sdven animals (5-4%) developed progressive. In a passive model of autologous phase injury using high titres rabbit antibody to sheep IgG, proteinuria failed to occur despite fixation of up to 95 microng rabbit antibody per kidney. Repeated injection of sheep nephrotoxic antibody (NTab) caused a persisting nephrotic syndrome but not the characteristic proliferative lesion of anti GBM diseases in other species.

Animals↗

PubMed1976

The complement abnormalities of lipodystrophy.

Investigation of the serum complement system in 25 patients with various forms of lipodystrophy showed no abnormality in three patients with total lipodystrophy; a single patient with limb lipodystrophy had evidence of activation of the classical complement pathway. However, of the 21 patients with partial lipodystrophy, 17 had low serum C3, with normal C4 and C2, concentrations, accompanied in 14 by a serum C3 splitting factor indistinguishable from nephritic factor, suggesting activation of the alternative pathway. These abnormalities occurred in 10 patients without clinically overt renal disease. Seven patients had overt nephritis; renal biopsies obtained in six showed mesangiocapillary (membranoproliferative) nephritis in all. Thus, the majority of patients with partial lipodystrophy have hypocomplementemia. Although nephritis may not invariably develop, the high rate of mesangiocapillary nephritis in these patients suggests that complement activation via the alternative pathway predisposes to the development of this form of glomerular disease.

Adolescent↗

PubMed1976

The cofactors required by C3 nephritic factor to generate a C3 convertase in vitro.

The mechanisms by which a C3 convertase is generated by C3 nephritic factor (NeF) were investigated using purified NeF, C3, C3b, factor B and factor D of the alternative pathway of complement activation. NeF could generate a C3 convertase with C3 and B in the absence of D, and without cleavage of B. At lower concentrations of NeF the addition of D was required to generate a C3 convertase, and B cleavage now occurred. The generation of both the D-independent and D-dependent C3 convertases with NeF was inhibited by preincubation of the C3 source with C3b inactivator (KAF); isolated C3b was more efficient than the C3 preparations used in generating the D-independent C3 convertase with NeF. These experiments indicate that C3b is required for the formation of both convertases, and that the reaction occurring with apparently native C3 is due to trace amounts of C3b. It is concluded that the C3 convertase generated by NeF in the absence of D is C3bB (NeF), and that generated in the presence of D is the feedback convertase C3bBb. The relevance of these experiments to reactions which may occur in vivo is discussed.

Biological Products↗

PubMed1975

Guinea-pig nephrotoxic nephritis. I. The role of complement and polymorphonuclear leucocytes and the effect of antibody subclass and fragments in the heterologous phase.

In guinea-pig nephrotoxic nephritis induced by a sheep antibody there was minimal glomerular capillary deposition of C3 and accumulation of polymorphonuclear leucocytes (PMN) in the heterologous phase. The C4-deficient strain developed the same injury as normal Duncan-Hartley animals. Complement depletion with cobra venom factor, polymorph depletion with nitrogen mustard or anti-PMN serum and treatment with antihistamines provided no protection. The relationship between the dose of nephrotoxic antibody and the proteinuria was similar for gamma1 and gamma2 subclasses and the F(ab')2 fragment of gamma1 antibody. However, the F(ab') and F(ab) antibody fragments, though fixing on the glomerular basement membrane, did not cause proteinuria. It is concluded that the development of proteinuria in this system: is largely independent of the complement-polymorph system; is due to the fixation of the F(ab')2 fragment of the antibody molecule; and does not depend on an intact Fc piece.

Animals↗