Search PubMed⌕ Search

Biomedical subjects

S Ruddy

Publications and source records attributed to S Ruddy.

105 records · Page 6Linked to original sources
PubMed1969

Complement metabolism in man: hypercatabolism of the fourth (C4) and third (C3) components in patients with renal allograft rejection and hereditary, angioedema (HAE).

Highly purified and radioiodinated human C4 and (or) C3 were administered to patients with renal allografts in rejection, with hereditary angioedema (HAE), with chronic glomerulonephritis, and to control subjects. The latter group included normal individuals, anephric patients before transplantation, and stable renal allograft recipients. The catabolic rates of these complement proteins were determined by analysis of the disappearance of plasma protein-bound radioactivity (k(m)), and by direct measurement of urinary excretion of radioactivity (k(u)). The correlation coefficient between these two methods was 0.96. The mean +/-2 SD for catabolic rates in the control subjects was 0.9-2.7% plasma pool/hr for C4 and 0.9-2.0% plasma pool/hr for C3. Patients experiencing renal allograft rejection had unstable levels of C4 and C3, and exhibited moderate hypercatabolism of both proteins. One patient with chronic glomerulonephritis had hypercatabolism of C4 and C3 in the presence of stable normal serum levels. In patients with HAE who had extremely low levels of C4, catabolic rates for C4 were markedly elevated (3.7, 5.8, 7.0 and 8.8%/hr). Analysis of plasma curves in HAE revealed a three component disappearance curve instead of the two component curve in control subjects receiving the same preparation. Even though C3 levels were normal, moderate hypercatabolism of C3 was also present in HAE (2.6, 2.8, 2.8, and 3.2% of pool/hr). The marked hypercatabolism of C4 in HAE constitutes the first direct evidence for the in vivo destruction by uninhibited C1 esterase of its natural substrate C4. The moderate hypercatabolism of C3 is consistent with the in vivo formation of C3-convertase.

Adolescent↗
PubMed1969

Structural polymorphism of the fourth component of human complement.

The fourth component of human complement (C4) in 102 individual plasma samples has been examined by the technique of antigen-antibody crossed electrophoresis (AACE). Electrophoretic heterogeneity of C4 was manifested by the repeated occurrence of seven different precipitin patterns. These patterns were formed by varying combinations of three subtypes of C4, differing in electrophoretic mobility. The subtypes were designated C, A, and A(1), in order of increasing electrophoretic mobility toward the anode. The evidence that the observed electrophoretic heterogeneity of the C4 molecule represents structural polymorphism rests on five points: the pattern obtained from the plasma of a given individual was reproducible in different runs and with different bleedings; all seven patterns could be demonstrated on the same electrophoretic run; C4 of a given subtype retained its characteristic mobility after purification, when run alone or mixed with plasma containing C4 of other subtypes; the subtypes A(1) and C comprising pattern 6 could be separated chromatographically as well as electrophoretically; and the characteristic relative mobilities of different C4 subtypes, in plasma or after purification, were retained even after the rather large shift in mobility associated with conversion to C4i. The ratio of C4 hemolytic activity to protein concentration varied according to the subtype composition of individual samples, with highest ratios occurring with patterns composed of subtype C alone, intermediate values with patterns consisting of A and C, and lower values occurring with patterns containing subtype A alone. Although the mechanism of inheritance of this polymorphism is not yet clear, the data suggest that subtypes A and A(1) are inherited as autosomal codominant characteristics, independent of the inheritance of subtype C.

Animals↗
PubMedDate not supplied

Depressed synovial fluid levels of properdin and properdin factor B in patients with rheumatoid arthritis.

Two proteins in the properdin system, properdin and factor B, and complement components C4 and C3 were measured by radial immunodiffusion in serums and synovial fluids from 21 patients with rheumatoid arthritis (RA) and positive tests for rheumatoid factor, 9 patients with seronegative RA, and 10 with degenerative joint disease. In addition to depressions of synovial fluid C4 which correlated with lowered C3 in seropositive RA, consistent with activation of the classic pathway, low synovial fluid levels of factor B and properdin in seropositive RA indicate intraarticular activation of the properdin pathway as well.

Arthritis, Rheumatoid↗
PubMedDate not supplied

Intraarticular activation of the complement system in patients with juvenile rheumatoid arthritis.

Analyses of CH50, complement components, properdin factors, and kininogen in synovial fluid of patients with juvenile rheumatoid arthritis revealed evidence of activation of the classic complement pathway in all clinical subgroups. Juveniles with the adult pattern of disease had the greatest incidence of complement abnormalities. Evaluation of individual components by both activity determination and protein measurement showed decreased synovial fluid specific functional activity (activity per microgram protein) to the more marked in synovial fluids with profound depressions of complement activity. These findings provide further evidence that nonfunctional, antigenically intact component protein may remain after complement activation. Radial immunodiffusion measurements of properdin factors and kininogen failed to support their involvement in joint inflammation. Serum complement component measurements by activity but not protein concentration correlated with other parameters or inflammation. Four patients had isolated depressions of serum C2 activity. Immunoglobulin levels, particularly IgA, correlated with some complement measurements and with the sedimentation rate.

Adolescent↗