Antibodies to beta 2 microglobulin in the sera of patients with systemic lupus erythematosus.
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Biomedical subjects
Publications and source records attributed to V E Pollak.
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With the use of a highly sensitive radioimmunoassay for rat albumin, urine albumin excretion rate (UalbV) was measured under baseline conditions and following saline-induced volume expansion. Volume expansion was associated with a significant increase in glomerular filtration rate (GFR), urine volume (V), fractional excretion of sodium (FEna), and UalbV (p less than 0.002). The increase in UalbV correlated far better with the increase in GFR than the increase in F and FEna, which suggests that volume expansion results in an increased albumin filtration with saturation of the tubular reabsorptive capacity.
The present study examined intrarenal blood flow distribution and possible involvement of tubular elements in rats with aminonucleoside (AMN)-induced nephrotic syndrome. Tubular maxima of para-aminohippurate (T M PAH) were determined during mild saline expansion in control rats and in rats on days 4, 5, 6, and 14 following a single intravenous injection of AMN (10 mg/100 gm of body weight). T M PAH and glomerular filtration rates (GFR's), unchanged from controls on day 4, were equally depressed on days 5, 6, and 14; minimum values were reached on day 6. Composite linear regression analysis of controls and AMN-treated rats showed that T M PAH and GFR's were significantly correlated (r = 0.704, p less than 0.001). Microsphere studies in animals with chronic carotid catheters demonstrated a decrease in the ratio of outer to inner cortical blood flow 6 days following AMN. The data suggest that AMN produces primarily glomerular lesions and that outer cortical blood flow is more susceptible to AMN than is inner cortical blood flow.
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.
We combined the use of a concentrating device (Minicon) and polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate to semi-quantitate the concentration of (a) the collective low-molecular-weight proteins and (b) of albumin excreted in the urine of patients after renal transplantation. Analytical recovery of many serum proteins from samples concentrated 100-fold in the Minicon apparatus was about 70%. It was possible to examine many urine samples by polyacrylamide gel electrophoresis after concentration with this device. The reproducibility (CV) of the technique was on the order of 20% when albumin and low-molecular-weight protein were in about equal concentration. The method was adequate to differntiate glomerular and tubular proteinuria, because in glomerular proteinuria the ratio of albumin to low-molecular-weight proteins is about 20/1, whereas in tubular proteinuria the ratio is about 1/1.
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To define interstitial nephritis without preselection bias, 25 consecutive renal biopsy specimens from patients with tubular damage, interstitial damage and interstitial inflammation were analyzed in detail. In four patients (all with acute renal failure), tubulitis, and interstitial eosinophil and lymphocyte infiltration were found, but no glomerular abnormalities. In four others, the findings were similar but some glomerular abnormalities were noted. Two patients had probable healed interstitial nephritis. The clinical presentation varied from transient renal insufficincy to oliguric renal failure. Three of the patients with glomerular abnormalities had significant proteinuria. When the 10 patients with interstitial nephritis were compared with the other 15 serving as controls, striking features in the former group were skin rash, eosinophilia, the absence of hypertension and the frequency of administration of penicillin and its analogs. Serum immunoglobulin E (IgE) levels were elevated in three of the patients. The striking eosinophilia, interstitial eosinophil infiltration and increased IgE levels suggest that allergen-reaginic complexes may be involved in the pathogenesis of the lesion.
A most unusual case of chronic membranoproliferative glomerulonephritis with nodule formation is reported in an elderly man in whom it was possible to document many episodes of acute oilguric and hemorrhagic glomerulonephritis and a syndrome resembling acute rheumatic fever. Severe renal failure necessitating peritoneal dialysis occurred on three occasions. Renal function returned to near preexacerbation levels in each episode. Although there was strong clinical evidence for streptococcal hypersensitivity, convincing laboratory documentation was lacking. The histologic and immunopathologic findings changed comparatively little during the several exacerbations. Impairment in fibrinolytic and coagulation activities by circulating macromolecular complexes is postulated for the induction and perpetuation of the glomerular injury.
Experiments were done to investigate whether molecular discrimination occurred in the renal handling of two species of serum albumin. Human albumin, 40 mg, was infused into rats; it was removed from serum (t1/2 equal to 15.8 hr) more rapidly than previously reported measurements of removal of endogenous rat albumin (t1/2 equal to 46 hr). Human albumin was cleared by the rat kidney at a constant rate of 0.0026 mul/min--a value virtually identical to that of rat albumin (0.0020 mul/min). In rats with proteinuria following the single iv injection of puromycin aminonucleoside, human albumin was removed from serum with a half-life of 17.6 hr. During the development of the nephrotic syndrome, the renal clearances of human and rat albumin increased proportionately. Despite the difference in the serum concentration and rates of removal of the two species of albumin, renal handling of the two species was similar. Thus the kidney did not appear to discriminate in its handling of these two proteins.
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