PubMed Health⌕ Search

Biomedical subjects

P Mumford

Publications and source records attributed to P Mumford.

At least 19 recordsLinked to original sources
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↗
PubMed1987

MRL-lpr/lpr mice show an impairment of IgG aggregate removal which relates to parameters of disease activity.

MRL-lpr/lpr mice show an age-related impairment in the removal of heat-aggregated IgG (HAGG) from the circulation. The female mice, which have an earlier mortality than their male counterparts, clear HAGG more slowly than the male animals. Delay in clearance of this probe of mononuclear phagocytic system (MPS) function relates directly to high levels of circulating immune complexes (CIC) and to significant renal damage. In addition it relates indirectly to hepatic and splenic uptake of HAGG. MPS saturation plays a significant role in the pathogenesis of the disease seen in MRL-lpr/lpr mice.

Aging↗
PubMed1985

The production of small IgG aggregates by glutaraldehyde cross-linking.

Reaction conditions have been determined for the production of soluble IgG polymers in the size range 10 S to 30 S by covalent cross-linking with glutaraldehyde. This size range is comparable with that of the immune complexes which are frequently found in the circulation of patients with certain autoimmune diseases such as rheumatoid arthritis and systemic lupus erythematosus. The yield of IgG aggregates in this size range is far greater than has been reported for cross-linking by other bifunctional reagents or for aggregation by heating. Glutaraldehyde cross-linked IgG polymers are stable and biologically reactive. They can also be labelled with fluorescein and freeze-dried with minimal loss of integrity or reactivity.

Aldehydes↗
PubMed1985

Soluble IgG aggregates produced by heating remain stable on freeze-drying.

IgG aggregates produced by heating gamma globulin solutions were freeze-dried, kept at 4 degrees C and reconstituted up to 4 months later. By comparison with frozen (-20 degrees C) preparations, only minimal changes in biological reactivity and in physical integrity occurred during this period. These results demonstrate that freeze-dried preparations of heat-aggregated IgG are potentially useful as a reference reagent for the comparative evaluation and standardisation of immune complex assays.

Antigen-Antibody Complex↗
PubMed1985

IgG antibodies to SS-B (La), RNP/Sm and DNA are produced by PWM-stimulated normal human lymphocytes in culture.

Peripheral blood lymphocytes from five healthy subjects and three patients with Sjögrens syndrome and systemic lupus erythematosus were stimulated with pokeweed mitogen to examine the effects of polyclonal activation on the secretion of autoantibodies in health and disease. Antibodies to SS-B (La), RNP/Sm and DNA were detected in supernatants from cultures from healthy controls, in some cases approaching levels secreted by the patients. All secreted autoantibodies were of IgG class and the antigen specificity of the secreted anti-SS-B was proven by cross-adsorption experiments. Our results extend the range of defined specificities of autoreactive B cells in healthy individuals. These data argue against a case for physiological deletion of autoreactive B cell clones and support theories of their active recruitment in autoimmunity.

Adult↗
PubMed1985

MRL mice show an age-related impairment of IgG aggregate removal from the circulation.

The fate of heat-aggregated human IgG (HAGG) was examined in young and old autoimmune MRL-lpr/lpr and MRL-+/+ mice and compared to BALB/c mice of different ages. Following iv injection of [125I] HAGG the older MRL-lpr/lpr and MRL-+/+ mice showed impaired hepatic and splenic uptake of this material. In addition the clearance rate of HAGG was significantly slower in the older MRL-lpr/lpr mice (t1/2 = 50 min) when compared to younger controls (t1/2 = 13 min) although this age-related retardation of clearance was not observed in the MRL-+/+ mice. No difference was seen in the clearance rate or organ uptake studies of the two age groups of BALB/c mice. Catabolic studies using trichloracetic acid suggested that the HAGG was catabolized to smaller fragments with time but not to such a great extent in the older diseased animals, again no age-related difference was seen in the BALB/c mice. Our studies suggest that with age both autoimmune strains of MRL mice show some saturation of the mononuclear phagocytic system (MPS) and that this process is more obvious in the MRL-lpr/lpr mice. MPS saturation may play a role in the pathogenesis of autoimmune disease in these mice.

Aging↗
PubMed1984

Differences in immunochemical characteristics of cryoglobulins in rheumatoid arthritis and systemic lupus erythematosus and their complement binding properties.

Cryoglobulins isolated from sera of patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) were analysed for their immunoglobulin, antibody, and complement components. In both disease categories the cryoglobulins contained predominantly IgG with lesser amounts of IgM and IgA, but relative to serum more IgM was concentrated in the cryoglobulins. IgM rheumatoid factor was found in 65% of RA cryoglobulins but in only 17% of SLE cryoglobulins (p less than 0.02), whereas SLE cryoglobulins contained more DNA binding activity than RA cryoglobulins (p less than 0.01). C1q binding activity was detectable in the majority of SLE and RA sera and SLE cryoglobulins. Paradoxically only two out of 34 RA cryoglobulins bound C1q, although rheumatoid factor activity was present in both cryoglobulins and sera. When isolated from serum the rheumatoid factor fraction strongly bound C1q. Both RA and SLE cryoglobulins contained similar small amounts of C3 and C4. Differences in antibody composition and complement binding activity of cryoglobulins from RA and SLE sera may reflect properties of immune complexes which affect their tissue localisation and pathogenicity.

Antibodies, Antinuclear↗
PubMed1982

The complement fixing ability of putative circulating immune complexes in rheumatoid arthritis and its relationship to extra-articular disease.

The hypothesis that the pathogenicity of putative circulating immune complexes (CIC) in rheumatoid arthritis (RA) is related to their ability to fix complement was investigated. Three assays for CIC were employed; (a) the 125I C1q binding assay (C1q BA), (b) the C1q solid phase assay (C1q SP) and (c) the Raji cell assay (RCA). Evidence for hypercatabolism of complement was obtained by using a highly sensitive quantitative assay for C3d (a breakdown product of C3) by rocket immunoelectrophoresis. One hundred and fifty-two patients with classical or definite RA were studied; 54 had clinical evidence of extra-articular disease including vasculitis, nodules, scleritis, neuropathy and lung disease; 98 patients had clinical evidence of joint disease alone. Plasma levels of C3d were significantly elevated in the RA group as a whole 16.7 +/- 4.4 mg/l (mean +/- 1 s.d.) compared with 13.1 +/- 3.25 mg/l in a group of 55 normal controls (P less than 0.01). Elevated levels of C3d were found in 26% of all patients but occurred significantly more often in the extra-articular disease group (P less than 0.05). Fifty-four percent of patients had at least one positive assay for CIC although no individual assay was positive in more than 36% of the group as a whole. The prevalence of positive CIC was significantly greater in those patients with extra-articular disease than in those with joint disease alone (P less than 0.005). Of the total of 82 patients with putative CIC, 30 (37%) had a raised C3d level. The coincident finding of positive tests for CIC and an elevated C3d level was very significantly correlated with the presence of extra-articular disease (chi 2 = 12.7 P = 10(-3)). Whilst putative CIC are frequent in RA (54%) these findings in contrast to previous work, suggest that the majority are not associated with abnormal complement activation and may account for the relative infrequency of clinically detectable active extra-articular disease.

Adolescent↗
PubMed1982

A longitudinal study of nutrition and growth of infants initially on the upper and lower centile for weight and age.

Twenty-four infants, initially either above the 90th centile or below the 10th centile weight for age for sex, were enrolled in an 18-month-longitudinal study. They were all under one year of age at the first survey. On four consecutive occasions, separated by six month intervals, 7-d weighed food intakes were measured together with random duplicate samples of a 24-h food intake. In addition, various anthropometric data were collected at each survey. Although the two groups of children remained different in terms of body size and skinfold measurements throughout the study, there were no differences in energy or protein intakes (per caput or per kg body weight) at any survey. We conclude that factors other than simple food intake are more important in determining the body size of pre-school children and suggest that these factors could include components of energy expenditure.

Body Weight↗
PubMed1981

Preliminary studies of energy expenditure in infants under six months of age.

In the study energy expenditure measurements have been made by open circuit calorimetry on a number of occasions on four infants, with special reference to the energy cost of resting metabolism, activity and diet-induced thermogenesis. In addition, for two subjects the energy cost of growth was determined. The energy expended with respect to activity was highly variable among all subjects and it was postulated that this was a factor of great importance in the energy balance of young infants; indeed, the effect of diet-induced thermogenesis was enhanced by activity. A calculation of the total energy required to gain 1 g of wet tissue in two infants was found to be different. As their intakes were 'low' and 'high' though their weight gains were accelerated and slow respectively, the difference in the energy cost of growth has been discussed as a reason for this paradox.

Age Factors↗
PubMed1979

Nutrient intake.

Explore the source record for details and available documents.

Body Weight↗
PubMed1979

The association of cryoglobulinaemia with nodules, vasculitis and fibrosing alveolitis in rheumatoid arthritis and their relationship to serum C1q binding activity and rheumatoid factor.

Two measurements of serum immune complexes, cryoglobulinaemia and 125I-C1q binding, have been performed in patients with severe rheumatoid arthritis (RA) and compared with normal levels. Cryoglobulinaemia was present in 20 out of 28 patients (71%) with extra-articular disease (mean level 17 micrograms/ml) including nodules, digital vasculitis, cutaneous ulcers, rash, neuropathy, lung disease and scleritis, but in none of 32 patients with joint disease alone (uncomplicated RA) (mean level 3 micrograms/ml). Cryoglobulinaemia correlates with, but probably does not antedate, extra-articular disease, and may be useful in predicting morbidity and mortailty in this group of patients. In contrast, serum 125I-Clq binding was raised in patients with uncomplicated RA and those with extra-articular disease, although levels were higher in the latter group. Both tests showed a negative correlation with serum haemolytic complement and a positive correlation with IgM rheumatoid factor although there were some sera with raised levels of rheumatoid factor without cryoglobulinaemia. These results suggest that cryoglobulinaemia is a better test than Clq-binding for demonstrating the presence of circulating immune complexes involved in the pathogenesis of extra-articular lesions.

Antigen-Antibody Complex↗
PubMed1976

Sustained release procainamide in patients with myocardial infarction.

Sustained release procainamide tablets were administered to 34 patients 48 hours after the onset of an acute myocardial infarct. Therapeutic blood levels of procainamide in the range of 4 to 8 mug/ml were consistently achieved using an 8-hourly maintenance dose of 1.5g after an initial loading dose of 2g. In contrast conventional procainamide capsules administered to 21 comparable patients repeatedly failed to produce plasma concentrations in the therapeutic range, despite the administration of a maintenance dose of 375 mg 3 hourly, after a loading dose of 1g. It is suggested that when the oral administration of procainamide is indicated for the management of ventricular arrhythmias after myocardial infarction, a sustained release preparation should be used.

Delayed-Action Preparations↗