SUMMARYComplement activation in 73 renal transplant biopsies was investigated by indirect immunoperoxidasc staining using MoAbs rcacEivc with complement-splil products. Intense deposition of complement fragments C4d and C3d in pcritubulur capillaries, indicating activation of the classical pathway, eould be detected in the majority of transplanted kidneys wilh cell-mediated rejections. Abundant deposition of complement-split products was observed in 22 early biop.sies from patients with high 'immunological risk* (i.e. previous, rejected transplants and/or circulating antibodies against HLA-antigens). Despite negative results in the crossmatch before transplantation and paueity of immunoglobulins in transplant biopsies, antibodies directed against endothelial eell antigens should be eonsidered as a possible cause of elassical complement activation.
Molecular genetic analysis of the cases described here suggests that the observed occurrence of cowpox virus infection among human beings and pet rats in multiple geographical areas represents a unitary epidemiological event that has not yet come under control. Further cases can be expected.
The present experiments were performed to examine the effect of variation in protein intake on renal function and morphology in the non-clipped kidneys of Goldblatt hypertensive rats. After renal artery clipping, rats were put on diets containing 5 (LP), 17.5 (NP), or 51% (HP) protein. After 4 to 5 weeks, all rats had developed hypertension. GFR was directly correlated with protein intake (1.47 +/- 0.15 in HP, 1.19 +/- 0.14 in NP, and 0.93 +/- 0.08 ml/min in LP), as was SNGFR (44.2 +/- 1.89, 39.1 +/- 2.23, and 27.9 +/- 0.86 nl/min in HP, NP, and LP rats). The response of SNGFR to changes in loop of Henle flow rate was attenuated in NP and HP rats: the maximum decrease was reduced (30.0 +/- 5.2% in NP, 22.1 +/- 4.2% in HP) and higher tubular flow rates were required to elicit responses (V1/2, the flow rate at which the response is half-maximum, was 28.9 +/- 2.6 nl/min in NP and 28.2 +/- 1.4 nl/min in HP). In LP rats, the maximum response was a decrease of 47.7 +/- 2.5%, and V1/2 was 18.1 +/- 1.2 nl/min, values similar to those found in normal control rats. The weights of the non-clipped kidneys were 0.96 +/- 0.04 g (LP), 1.06 +/- 0.05 g (NP), and 1.36 +/- 0.06 g (HP). In the LP rats there was no difference between the non-clipped and clipped kidneys. Light microscopic evaluation showed a high incidence of focal glomerulosclerosis in non-clipped kidneys of HP rats, but no glomerular lesions in the non-clipped kidneys of LP rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Monoclonal antibodies reactive against the complement C4A and C4B isotypic components were used in an immunoperoxidase technique for the histological study of normal human renal tissue. Prominent staining with both antibodies was seen in the mesangial areas of all normal kidney sections investigated. Occasional staining of arteriolar walls of the same tissues, however, was also observed. In contrast, no mesangial staining was seen using monoclonal antibodies reactive against other 'early' complement components, such as C1q and C3. Specificity of the glomerular staining with the anti-C4 reagents was demonstrated in two patients possessing only the C4A serum component but lacking genetically the C4B locus products. As would be predicted, glomerular staining with the anti-C4A reagent, but not anti-C4B, was clearly demonstrable. It is concluded that both isotypes of complement C4 are present in normal human glomeruli and thus might be operative for normal mesangial function.
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