Publications

Renal plasma filtration is a critical physiologic function that depends upon the precise composition and arrangement of the constituent extracellular matrix proteins within the glomerular basement membrane (GBM). The GBM develops during renal embryogenesis by the fusion of discrete basement membranes produced independently by endothelial and visceral epithelial cells, and, possibly from matrix secreted by the mesangial cells. In the mature animal, however, the epithelial cell has generally been accepted as the sole source of all GBM constituent proteins. Although the final structures and distributions of the component proteins have been defined by histochemical techniques, the individual contributions of the three resident glomerular cell types to the maintenance and turnover of the mature GBM remain uncertain. We report the application of a new technique, in situ reverse transcription (ISRT), for the localization of RNA transcripts of nine major GBM protein components within the closely apposed cells of the glomerulus. Using this technique, we demonstrate that in normal adult rat glomeruli the RNA transcripts for heparan sulfate proteoglycan and the laminin-S chain are primarily expressed by visceral epithelial cells, while Type IV alpha-1 and alpha-2 collagen transcripts were restricted to the endothelial cells in a heterogeneous pattern. RNA transcripts for entactin and the laminin-A and -B2 chains were expressed by all three glomerular cell types, while laminin-B1 and fibronectin transcripts were limited to the mesangium. These findings demonstrate that GBM synthesis in the mature animal is not restricted to the epithelial cell and that all intrinsic glomerular cells contribute to the production of GBM protein components. The ISRT technique also provided the additional, and unexpected, finding that appreciable synthetic heterogeneity exists within individual glomerular cell types.

Nonulcer dyspepsia (NUD) is an enigmatic disorder which likely has heterogeneous etiologies. Helicobacter pylori-associated gastritis has been identified in a large number of patients with NUD, raising speculation that chronic infection with this organism may cause dyspepsia in some patients. Prospective case-control and cohort studies however do not suggest that H. pylori prevalence is greater in NUD than in asymptomatic controls. Limited therapeutic trials of H. pylori-eradication therapy have not shown a convincing symptomatic improvement compared with placebo treatment. Definition of the role of H. pylori in NUD awaits further well-designed, well-controlled epidemiologic and therapeutic studies. Until such information is available, routine endoscopic gastric biopsies looking for H. pylori in patients with NUD should be abandoned.