The epidemic form of the hemolytic uremic syndrome (HUS), beginning with an acute gastroenteritis, has been associated with a verocytotoxin- producing Escherichia coli infection. The endothelial cell is believed to play an important role in the pathogenesis of HUS. Endothelial cell damage by verocytotoxin-1 (VT-1) in vitro is potentiated by the additional exposure of inflammatory mediators, such as tumor necrosis factor-alpha (TNF-alpha). Preincubation of human umbilical vein endothelial cells (HUVEC) with TNF-alpha resulted in a 10- to 100-fold increase of specific binding sites for 125I-VT-1. Furthermore, interleukin-1 (IL-1), lymphotoxin (TNF-beta), and lipopolysaccharide (LPS) also markedly increase VT-1 binding. Several hours' exposure to TNF-alpha was enough to enhance the number of VT-1 receptors on the endothelial cells for 2 days. The TNF-alpha-induced increase in VT-1 binding could be inhibited by simultaneous addition of the protein synthesis inhibitor cycloheximide. Glycolipid extracts of TNF-alpha- treated cells tested on thin-layer chromatography demonstrated an increase of globotriaosylceramide (GbOse3cer), a functional receptor for VT-1, which suggests that preincubation of human endothelial cells with TNF-alpha leads to an increase in GbOse3cer synthesis in these cells. We conclude from this study that TNF-alpha and IL-1 induce one (or more) enzyme(s) that is (are) rate-limiting in the synthesis of the glycolipid VT-1 receptor, GbOse3cer. These in vitro studies suggest that, in addition to VT-1, inflammatory mediators play an important role in the pathogenesis of HUS.

Pairs of glomerular and tubular basement membrane preparations were obtained from kidneys of individuals of premature age up to 80 years. The purity of the preparations was established with light and electron microscopy and by estimating the total phosphorus content. The amino acid and carbohydrate composition was determined and statistically evaluated for 33 to 38 preparations divided over five age groups. Comparison of glomerular and tubular basement membranes from the same kidneys showed that regardless of age glomerular basement membranes contain more 3-hydroxyproline and more of the heteropolysaccharide constituents neuraminic acids and mannose. These differences cannot be ascribed solely to the presence of a minor amount of interstitial collagen. The chemical composition of the two types of basement membranes changes with age. For the first few years after birth the contents of glycine and total imino acids increase and those of collagen-nonspecific amino acids decrease, whereas constituents of the heteropolysaccharide units do not change markedly. These results suggest that proportions of collagenous and noncollagenous peptide moieties gradually change with age in both glomerular and tubular basement membranes. In addition, the extent of hydroxylation of proline and lysine increases significantly with age, reaching an adult level for glomerular basement membranes after 4 to 7 months of age and for tubular basement membranes during late childhood. The contents of glucose and galactose rise with age to an extent comparable with that of hydroxylysine. The age-related changes in basement membrane composition may influence functional properties of these extracellular renal structures.

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Hyporeninemic hypoaldosteronism was observed in an infant at the age of 3 months. Persistent hyperkalemia, hyperchloremic acidosis and salt wasting were present. All abnormal electrolyte values were corrected by the administration of fludrocortisone. Both active and inactive renin were lowered. This infant had also an unexplained spastic quadriplegia and psychomotor retardation. Hyporeninemic hypoaldosteronism should be considered to be one of the causes of salt-losing in infancy.

Sera from 45 patients from The Netherlands, Germany and Belgium who had a clinical diagnosis of haemolytic uraemic syndrome (HUS) were screened for antibodies to the lipopolysaccharide (LPS) of Escherichia coli producing Verocytotoxin (VTEC). Sera from 43 family contacts and 34 control patients were also examined. Using the techniques of EIA and immunoblotting, antibodies to the LPS of Escherichia coli O157 were found in 28 patients, and to the LPS of serogroups O115 and O145 in one patient and one family member respectively. The results of our study suggest that VTEC, and in particular Escherichia coli O157, might be a significant cause of HUS in Western Europe.