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H Stolte

Publications and source records attributed to H Stolte.

At least 91 records · Page 5Linked to original sources

Functional and morphological study on the onset of proteinuria in experimental diabetes mellitus.

In latent hereditary diabetes mellitus increased protein excretion has been found in male diabetic mice compared to controls. This proteinuria is partly due to an increased excretion of higher molecular weight proteins, which could be identified as deriving from plasma. The suggested glomerular proteinuria has been verified by an increase in the renal excretion of high molecular weight PVP. No changes in GFR occurred in this early stage of diabetic glomerulopathy. No changes in morphology could be detected, suggesting some changes in the biochemical membrane structure that cause the findings of increased permeability of the diabetic basement membrane for plasma proteins.

Albuminuria↗

Glomerular protein filtration in normal and nephritic rats. A micropuncture study.

The acute heterologous phase of anti-basement membrane glomerulonephritis in rats was studied morphologically and functionally at the single nephron level. In samples drawn from Bowman's space or from the very early segment of the proximal tubule the protein content was measured by ultra micro-disc-electrophoresis. Morphologically, in rats which were treated with anti-glomerular basement-membrane serum (AGBM) no significant changes could be seen in light microscopy whereas in immunohistology the typical, linear, subendothelial fluorescent staining for IgG could be seen. In controls, small amounts of albumin were filtered (7.57 +/- 0.66 mug/min X 100 g body weight, n = 14) but in nephritic animals the filtered load of albumin increased significantly to 58.33 +/- 4.10 mug/min X 100 g body weight, (n = 8). Besides this increased albumin filtration also several serum globulins could be detected, whereas in controls they were missing. Total GFR and proximal passage time did not change significantly. It is concluded that the glomerulus is an effective barrier for protein under control conditions and that it becomes permeable for albumin and higher molecular weight serum proteins following the antigen antibody reaction at the glomerular basement membrane in the AGBM-treated animals.

Albuminuria↗

Fibronectin turnover in human mesangial cell cultures as affected by adriamycin.

Fibronectin (FN) turnover and turnover changes induced by the anticancer drug Adriamycin (ADR) were measured in human mesangial cells (HMC) in vitro. HMC cultures synthesize cellular FN (2.2 +/- 0.3% of total protein synthesis; n = 12) which is secreted and incorporated into a fibrillar extracellular matrix (ECM). A 24 hr incubation of HMC with ADR (0.5-5 micrograms/ml) resulted in an accumulation of FN in the culture medium, with a maximum increase following 5 micrograms/ml (7.3 +/- 2.3 pg/cell vs. controls: 4.4 +/- 1.9 pg/cell; n = 10). Correspondingly, radioactively labeled immunoprecipitable FN was increased in a dosage-dependent manner in the culture medium up to 50% vs. controls. The incorporation of radioactively labeled FN into ECM was significantly increased following 2 micrograms ADR/ml. In accordance, immunofluorescence staining revealed an expansion of pericellular FN fibers in cultures exposed to 2 micrograms ADR/ml. Concomitant with the accumulation of extracellular FN, radioactively labeled FN in the cells was reduced by 22%. Qualitative characterization of FN patterns revealed a diminished number of degradation products in the culture medium of ADR-treated HMC. These data suggest that ADR interferes with the turnover of FN secreted by HMC in vitro in such a way that FN accumulates extracellularly. This in turn leads to a reduced FN synthesis. These findings are compatible with a loss of urinary FN degradation products accompanying the onset of proteinuria in ADR-treated rats.

Cells, Cultured↗

The "fixed" charge of glomerular capillary wall as determinant of permselectivity.

The determinants of glomerular capillary wall (GCW) permeability to proteins have been subject of controversial discussion. To study this question we have developed a modified isolated perfused rat kidney model in which tubular transport processes are completely blocked by perfusion fixation with glutaraldehyde. This model allows to directly titrate the charge density of the GCW using albumin solutions buffered over a wide pH-range, a manipulation that cannot be performed in the intact kidney. Analyzing the results of these experiments helped to determine a fixed charge density of the GCW of 43 mEq/L. In the present work, we used the isolated perfused fixed rat kidney model to study the influence of this fixed charge on the transglomerular passage of proteins. To do this, the fixed kidney was perfused with albumin solutions containing different isoforms of horseradish peroxidase. The lowest sieving coefficient was obtained with the acidic isoform (0.035+/-0.008, n = 7), while the isoforms at pI 6.85 and 8.45 showed higher sieving coefficients (0.059+/-0.008, n = 7 and 0.090+/-0.008, n = 4, respectively). The highest sieving coefficient (0.59+/-0.031, n = 6) was observed in perfusion experiments of the fixed kidney with cationic HRP (pI > or = 9.30). However, when comparing the sieving coefficients, the highly cationic isoform was excluded because it has a lower molecular weight than the other isoforms. The sieving coefficients of the other isoforms were significantly different (p < 0.05. ANOVA, Scheffé test). In conclusion, the presence of a discrete (even if lower than previously thought) "fixed" charge on the GCW of 43 mEq/L restricts the transglomerular passage of isoforms of horseradish peroxidase by a factor 2-3. These results imply that the influence of charge selectivity has been overstated in the literature.

Albumins↗

On the glomerular mechanism of the renal protein excretion. Studies in the isolated perfused rat kidney.

The glomerular permeability of the isolated perfused kidney is manifold higher than in vivo, although structural changes at the glomerular filtration barrier are not described. It has been proposed that in vivo high molecular weight plasma proteins are concentrated at the glomerular endothelium forming an additional filtration barrier ('concentration polarization'). To test this hypothesis, isolated rat kidneys were perfused with substrate-enriched Krebs-Henseleit solutions containing albumin (50 g/l) or albumin/globulin (40/10 g/l), or with plasma. The pO2 was 675 mm Hg. Furthermore, experiments were carried out with the addition of erythrocytes with and without a reduced O2 supply (pO2 35 mm Hg). Independent of the composition of the perfusate a continuously increasing glomerular permeability was observed immediately after perfusion was started. After about 10 min, a steady state value for the glomerular permeability was reached. The addition of globulin to the perfusate or perfusion with plasma did not prevent the initial increase of the permeability. However, after addition of 5% erythrocytes to the perfusate the increase of permeability was much less pronounced. Neither the reduction of the O2 supply nor the addition of erythrocytes to a higher concentration than 5% had any further effect on the glomerular permeability. These data show that concentration polarization of high molecular weight proteins does not take place at the endothelium of the glomerulus. Independent of their ability to carry O2 erythrocytes play an important role in the glomerular filtration process.

Albumins↗