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Biomedical subjects

Y M Ooi

Publications and source records attributed to Y M Ooi.

11 recordsLinked to original sources
PubMed1979

Genetic defect in secretion of complement C5 in mice.

A genetic deficiency of the fifth (C5) component of complement1-3, a serum glycoprotein of molecular weight (MW) 220,000 (ref. 4), has been found in 39% of inbred strains of mice3. Sera of deficient mice lack detectable C5 activity and protein2,3. In addition deficient mice produce antibody to mouse C5 when injected with sera from C5 sufficient (normal) strains. Levy et al.5 showed that somatic cell hybrids between C5 deficient (B10.D2/old line) macrophages and either C5 sufficient (B10.D2/new line) mouse kidney or chicken erythroblasts secreted haemolytically active mouse C5 in vitro. Several possible molecular mechanisms to account for the findings were considered, but insufficient direct data were available to choose among them. We recently reported that mouse (CD.1 strain) peritoneal cells in culture synthesise and secrete a single chain precursor, pro-C5 (MW approximately 210,000), of the two-chain (alpha chain, 125,000 and beta chain 83,000 MW) C5 protein6. Radiolabelled precursor C5 was contained within the cells and was secreted into the tissue culture media. Using similar methods, we now find that C5 deficiency in each of five different mouse strains (AKR, SWR, DBA/2J8 A/HeJ and B10.D2/old line) is due to a failure in secretion of C5 protein and not to a failure in biosynthesis of pro-C5.

Animals↗
PubMed1979

Immunofluorescent localization of fibronectin in the human kidney.

Fibronectin is a glycoprotein shown previously to be present on the surfaces of cells, connective tissue matrices, and in extracellular fluids. Its distribution in the human kidney was evaluated by immunofluorescence methods studying 65 renal biopsies with a variety of pathologic disorders. Fibronectin was found in the mesangium of the normal kidney and increased proportionately in the disease states characterized by mesangial expansion. It was visualized in glomerular capillary loops in some biopsies with membranoproliferative glomerulonephritis, diffuse proliferative glomerulonephritis, and membranous nephropathy. Additionally, fibronectin was detected in glomerular crescents, diabetic nodules, vascular thrombi, glomerular sclerosis, and variably in the interstitium.

Fibronectins↗
PubMed1979

Biosynthesis and post-synthetic modification of a precursor (pro-C5) of the fifth component of mouse complement (C5).

Mouse peritoneal macrophages synthesized and secreted a precursor (pro-C5) of the fifth component of serum complement (C5) in short-term tissue culture. Approximately 0.2% of the newly synthesized intracellular protein and 0.8% of secreted protein were precipitable with antiserum to mouse C5. The precursor is similar in size to the native serum protein (210,000 daltons), but consists of a single polypeptide chain. In contrast, serum C5 consists of two polypeptide chains (m.w. 125,000 and 83,000) linked by disulfide bridges. An electrophoretic variant of pro-C5 distinct from intracellular C5 was detected in medium from macrophage cultures.

Animals↗
PubMed1977

Serum immune complexes in membranoproliferative and other glomerulonephritides.

Immune complexes were detected in the serum of patients with membranoproliferative glomerulonephritis (MPGN) Types I and II, systemic lupus erythematosus (SLE), and acute poststreptococcal glomerulonephritis (AGN) by sucrose gradient ultracentrifugation and by measurement of Clq binding activity (Clq-BA). Clq-BA was more sensitive in detecting complexes than was gradient ultracentrifugation. By gradient ultracentrifugation, the sedimentation velocities of the complexes in the three diseases were similar, ranging from 13S to 19S. This range corresponds to that observed by others in experimental chronic serum sickness nephritis. The complexes isolated by gradient ultracentrifugation always contained C3, usually IgG and C4, and in some patients with SLE and AGN, IgM. In MPGN, IgM and IgA could be present in glomerular deposits when not present in circulating complexes. In this disease also, serum complement levels were poor predictors of the presence of complexes. With increased Clq-BA, the levels of Clq, C4, and C2 could be normal or reduced and there was no correlation with C3 levels. With few exceptions, the clinical status of the patients with MPGN correlated well with Clq-BA.

Acute Disease↗
PubMed1977

Circulating immune complexes after renal transplantation. Correlation of increased 125I-Clq binding activity with acute rejection characterized by fibrin deposition in the kidney.

To assess the role of circulating immune complexes in the pathogenesis of acute rejection, sera were measured for such complexes by the (125)I-C1(q) binding assay in 45 normal subjects, 24 allografted patients undergoing acute rejection, and in 11 allografted patients in a quiescent phase. Increased C1(q)-binding activity (C1(q)-BA) was detected in 14 patients with acute rejection, 9 of whom had renal biopsies showing fibrin deposition in the vasculature together with cellular infiltrates in the tubulo-interstitial structures; renal histology was not available in the other 5 patients. The other 10 patients with acute rejection, whose biopsies showed only cellular infiltrates, and the 11 patients in a quiescent phase posttransplantation did not have increased levels of serum C1(q)-BA. Of the group with increased serum C1(q)-BA, serial studies in eight patients showed a correlation between increased serum C1(q)-BA and the occurrence of rejection; with reversal by therapy, serum C1(q)-BA returned to within normal levels. Complexes from six patients were analyzed by sucrose density gradient ultracentrifugation to have sedimentation coefficients ranging from 15S to 18.4S. After acid dissociation and analysis by double-diffusion techniques, C1(q)-reactive complexes were shown to contain IgG. Immunofluorescent studies done in five renal biopsies from this group revealed granular deposits of immunoglobulin, and (or) less frequently, of complement in the glomeruli or the tubular basement membranes. The findings suggest that circulating immune complexes may mediate the type of acute rejection characterized by fibrin deposition in the kidney. The role of circulating immune complexes arising from the recipient's original kidney disease could be excluded in 10 patients with humoral rejection, inasmuch as the underlying renal pathology was of a "nonimmunologic" nature; this was corroborated by sequential studies in six patients in whom circulating immune complexes could not be demonstrated before rejection. The participation of administered antilymphocyte globulin (ALG) as an antigen also appears to be excluded in four patients, two who were not given ALG, and in two of whom episodes of rejection occurred unrelated temporally to ALG administration.

Antigen-Antibody Complex↗
PubMed1977

Relationship of levels of circulating immune complexes to histologic patterns of nephritis: a comparative study of membranous glomerulonephropathy and diffuse proliferative glomerulonephritis.

Immunofluorescent studies have suggested that immune complex deposition is the pathogenetic mechanism responsible for MGN and diffuse PGN. Despite this common mechanism, both renal disorders show considerable differences in the rate of progression of renal functional deterioration. To examine whether differences in the amounts of circulating immune complexes may in part be responsible for these differences, such complexes were assayed for in the sera of the two patient populations by a 1251-C1q binding assay, which has a lower limit of sensitivity for 75 microgram of aggregated human gamma globulin per milliliter of serum. Circulating complexes were found in sera from 11 of 14 patients with diffuse PGN but were undetectable in sera from 13 patients with MGN. Additional evidence for existing differences in the amounts of circulating immune complexes in the two groups was provided by serum C3 measurements. Serum C3 concentrations were below normal limits in nine of 14 sera from patients with diffuse PGN but were within normal limits for sera from all patients with MGN. Sucrose density gradient ultracentrifugation analysis of C1q reactive complexes showed them to have sedimentation coefficients ranging from 14.6S to 18.2S. The sizes of the complexes are consistent with those analyzed in animal models as being capable of inducing nephritis.

Antigen-Antibody Complex↗
PubMed1976

Classical complement pathway activation in membranoproliferative glomerulonephritis.

Levels of components of the classical and alternative complement pathways and the activity of the C3 nephritic factor (C3NeF) were measured in serum specimens from patients with type I (subendothelial deposits) and type II (intramembranous dense deposits) membranoproliferative glomerulonephritis (MPGN) and the results compared with the levels in normal subjects. Although C3 and C5 concentrations were comparably depressed in type I and type II, the levels of Clq and C4 were lower in type I and the correlation coefficients between Clq vs. C4 and C4 vs. C3 were higher than in type II. The profile was highly suggestive of classical pathway activation. In contrast, in type II MPGN, factor B levels were lower and C3NeF activity was more frequently detectable and higher. A feature of interest was that type I, as compared to type II, was characterized by significantly lower serum concentrations of properdin, higher and more significant correlation coefficients between serum properdin concentrations and those of Clq, C4 and C3, and consistent glomerular deposition of properdin. The involvement of properdin in type I may reflect recruitment of a pathway resembling the C1 bypass mechanism, said to involve C1, properdin, factor B and C3-9.

Adult↗