Electron microscopy of nephropathia epidemica. Renal tubular basement membrane.

Tubular basement membranes in kidney biopsies from 18 patients with nephropathia epidemica were studied by electron microscopy. Both in the cortex and in the medulla there was splitting of the basement membrane. Thickened basement membrane around occasional tubules contained membrane vesicles, usually empty but also with a core and a diameter of approximately 180 nm. Membranous convoluted structures and light finely fibrillar areas in the basement membranes were seen. Splitting of the basement membrane was most prominent in the medulla, and the membrane was filled with round to oval particles 55 to 470 nm in diameter. Of the possible mechanisms of damage at the basement membrane level in this disease, the findings suggest liberation of antigen from the tubular cells and reaction of circulating antibodies with the antigen in the basement membrane.     

Scanning electron microscopy of the acellular glomerular basement membranes in idiopathic membranous glomerulopathy

After using a cellular digestion technique to extract cells from the basement membranes of frozen kidney tissue, we employed scanning electron microscopy to examine the acellular glomerular basement membranes (AGBM) from normal kidneys and from kidneys of patients with idiopathic membranous glomerulopathy (MGN). This method revealed, in the AGBM, previously unrecognized three-dimensional patterns of pathologic changes. These patterns correlated with increasing MGN stage as defined by Ehrenreich and Churg. On the epimembranous AGBM surface these patterns were composed of ridge-like trabeculae, irregular plaques, and reticulated crater-like deformities. The endothelial AGBM surfaces were smooth in stages I and II MGN, but in stage III MGN the endothelial surfaces were irregular and perforated. In contrast to lupus-related MGN, where some immune-complex-like material remained after cellular extraction, epimembranous immune-complex-like material in idiopathic MGN was extracted.     

Disease of dense basement membranes

In the disease of dense basal membranes, typical membrane lesions of the immune complex origin were found both in the kidneys and the spleen. On this basis the disease of dense basal membranes is considered to be a distinct entity of systemic nature.     

Silver impregnation of the glomerular basement membranes

A method based on the periodic acid-produced (secondary) argentaffinity of the basement membranes is described. Sodium tetraborate is used for alkalizing of the silver nitrate solution.     

Laminin M is found in placental basement membranes, but not in basement membranes of neoplastic origin

Laminin is a high molecular weight glycoprotein found in all basement membranes studied to date. Two subunits of laminin, A and B, have been isolated and characterized from a variety of tumor matrices. Recently we have reported the finding, in human placenta, of a new laminin subunit which we termed M. In the present study we report on the presence of laminin M in placentae of other species such as bovine, rat and mouse. In addition, we have examined laminin extracted from mouse EHS-tumor, rat ED-PYS carcinoma and three human carcinoma cell lines. The laminin subunits were detected by the electroimmunoblot technique using antibodies against mouse, rat and human laminin. Laminin M could not be demonstrated either in the two murine tumors, or in the three different human neoplastic cell lines studied. If the absence of laminin M is the consequence of neoplastic transformation, then studies of the metabolism of this subunit may provide new information on neoplastic transformation and invasion, and a useful marker in tumor diagnosis.     

Microvascular basement membranes in diabetes mellitus

The alterations in the microvascular system of diabetes mellitus patients are responsible for the most devastating complications of this widespread disease. In the kidney, the microangiopathy leads to thickening of the glomerular capillary basement membrane but also to the expansion of the mesangial matrix and thickening of the tubular basement membrane. Several mechanisms are implicated in the pathogenesis of diabetic renal microangiopathy. These include increased synthesis of type IV collagen following hyperglycaemia-induced alteration of the pattern of podocyte-integrin expression, decreased expression of matrix metalloproteinases (MMP-2 and 3), and increased expression of tissue inhibitor of metalloproteinase (TIMP). An altered morphology of podocytes accompanies these basement membrane alterations. Other factors which may contribute to renal matrix accumulation include vascular endothelial growth factor (VEGF), since treatment with anti-VEGF antibodies attenuates glomerular basement membrane thickening, platelet-derived growth factor (PDGF) (B chain) and its receptor, which appear to be highly expressed in mesangial and visceral epithelial cells and might play a role in the development of diabetic nephropathy. Also oxygen radicals/oxidative stress may play a role in matrix accumulation in diabetic nephropathy as aminoguanidine, an inhibitor of the formation of advanced glycation end-products but with antioxidant properties, attenuates diabetic nephropathy. Retinal diabetic microangiopathy follows much the same principles, be it that microvascular proliferation is a distinctive element in the retina. Nephropathy and retinopathy occur frequently but not always together, indicating that in their multifactorial pathogenesis much remains to be clarified.     

Mucopolysaccharide heterogeneity of the reptilian kidney basement membranes.

The kidney basement membranes of fifteen different reptiles from marine, terrestrial, desert, amphibious and fresh-water habitats have been analysed for their mucopolysaccharide contents histochemically, employing well-known and recent techniques. Capsular and tubular basement membranes possess only neutral mucopolysaccharides; on the other hand glomerular basement membrane possesses both neutral and acidic (sialic acid) mucopolysaccharides. The concentration of different mucopolysaccharides seems to be dependent on the type of habitat. Their possible physiological significance in the kidney function is discussed in great details.     

Hereditary abnormalities of renal basement membranes.

The glomerular and tubular basement membranes are the principal barriers to filtration and re-absorption of water and molecules in the nephron. They are composed primarily of type IV collagen, laminin, fibronectin, sulphated proteoglycans and collagen type I. Three common inherited diseases are associated with abnormalities of basement membrane proteins: Alport's syndrome, thin basement membrane disease (TBMD) and adult polycystic kidney disease. In this review we describe the application of molecular biological techniques to the study of these conditions. Classic Alport's syndrome is an X-linked disorder with a lamellated glomerular basement membrane (GBM) which typically results in renal failure in males. Studies with sera from patients with Goodpasture's syndrome, or monoclonal antibodies specific for the Goodpasture antigen, show that the Goodpasture antigen is absent or masked in the kidneys of individuals with Alport's syndrome. There is some evidence to suggest that the Goodpasture antigen is best represented by the non-collagenous domain of the alpha 3 chain of type IV collagen, but that other non-collagenous regions may also contribute to the antigen. It is through these non-collagenous regions that the type IV collagen chains form the typical network, and the abnormality in Alport's syndrome interferes with this network formation. However, we have recently demonstrated that the gene for the non-collagenous domain of the alpha 3 collagen chain is present in individuals with Alport's syndrome. Furthermore, other groups have shown a defect in a novel type IV collagen chain, the alpha 5 chain, in 3 unrelated cases of Alport's syndrome.(ABSTRACT TRUNCATED AT 250 WORDS)