[Connections of the laterodorsal nucleus of the thalamus in the monkey. Study of efferents]. / Connexions du noyau latéro-dorsal du thalamus chez le singe. Etude des efférences.

Efferent pathways of the LD nucleus of the thalamus were studied in 6 Papio-papio baboons with the retrograde transport technique utilizing HRP. Injections were made in cingular and parietal cortex and hippocampal formation. Large projection from the LD to the cingular and subicular cortex were visualized as reciprocal connections. No pathway to parietal area 7 was found. The course of the fibers is via the fornix, the cingular bundle and the retro-lenticular portion of the internal capsule. The result of this study make it necessary to reconsider neuropathological hypotheses on memory.

A new case of Pick's disease. Anatomical and ultrastructural studies.

The fine structure of a cortical frontal biopsy of Pick's disease is described. Pic bodies appear made of unbranched 120 A neurofilaments, sometimes clustered in geometrical pattern. Post-mortem examination, performed 8 years later, reveals typical lesions. The characteristics of Pick bodies are discussed.

Effects of epidermal growth factor on calf renal glomerular cells in vitro.

Epidermal growth factor (EGF) stimulates the mitosis and differentiation of a variety of cellular types. It also delays the cell senescence in vitro. Because of its multiple functions, the effects of EGF on cells from isolated, explanted calf renal glomeruli have been studied. The cell types emerging from glomeruli cultured with and without EGF were compared and identified by morphological, immunofluorescence and electron microscopy criteria. Two cell types: visceral epithelial cells or podocytes (type I) and mesangial cells (type II) emerged from glomeruli cultivated without EGF. A third cell type, called type III cells, appeared only in the presence of EGF. These cells divided, were mobile and had prolonged lifespan in culture. They appeared pavement-like, and acquired progressively the morphological features and cytoskeletal components of type I cells. They also showed certain characteristics of podocytes in vivo. We suggest that type III epithelial-like cells are precursor cells of podocytes, that EGF triggers their emergence from glomeruli and their subsequent proliferation and differentiation in vitro. EGF also prolongs their lifetime in culture.

Glomerular expression of type IV collagen chains in normal and X-linked Alport syndrome kidneys.

Alport syndrome is an inherited nephropathy characterized by alterations of the glomerular basement membrane because of mutations in type IV collagen genes. COL4A5 mutations, causing X-linked Alport syndrome, frequently result in the loss of the alpha5 chains of type IV collagen in basement membranes. This is associated with the absence of the alpha3(IV) and alpha4(IV) chains and increased amounts of alpha1(IV) and alpha2(IV) in glomerular basement membranes. The mechanisms resulting in such a configuration are still controversial and are of fundamental importance for understanding the pathology of the disease and for considering gene therapy. In this article we studied, for the first time, type IV collagen expression in kidneys from X-linked Alport syndrome patients, using in situ hybridization and immunohistochemistry. We show that, independent of the type of mutation and of the level of COL4A5 transcription, both COL4A3 and COL4A4 genes are actively transcribed in podocytes. Moreover, using immunofluorescence amplification, we were able to demonstrate that the alpha3 chain of type IV collagen was present in the podocytes of all patients. Finally, the alpha1(IV) chain, which accumulates within glomerular basement membranes, was found to be synthesized by mesangial/endothelial cells. These results strongly suggest that, contrary to what has been found in dogs affected with X-linked Alport syndrome, there is no transcriptional co-regulation of COL4A3, COL4A4, and COL4A5 genes in humans, and that the absence of alpha3(IV) to alpha5(IV) in glomerular basement membranes in the patients results from events downstream of transcription, RNA processing, and protein synthesis.

Diffuse leiomyomatosis associated with X-linked Alport syndrome: extracellular matrix study using immunohistochemistry and in situ hybridization.

Inherited diffuse esophageal leiomyomatosis a benign tumor involving smooth muscle cells of the whole esophagus, is frequently associated with X-linked Alport syndrome, a hereditary disease of type IV collagen. Families with this condition are consistently found to have deletions encompassing the 5' ends of both the alpha 5 chain of type IV collagen (COL4A5) and the alpha 6 chain of type IV collagen (COL4A6) genes, always limited in COL4A6 to exons 1', 1, and 2. On the contrary, patients with COL4A5/COL4A6 deletions extending further into COL4A6 display no such tumors. Despite the deletion, a COL4A6 transcript including exon 4, but not exon 3, was found in a tumor sample, raising the possibility of the involvement of a truncated alpha 6(IV) chain in the tumorous process. Using immunohistochemistry and in situ hybridization methods, we analyzed the expression and distribution of the alpha 6 chain of type IV collagen in tumors in comparison with that of normal, fetal, and mature esophagus. We also studied associated changes in tumor basement membrane composition and in tumor-cell integrin subunit distribution. No labeling with alpha 6(IV) antibodies was detected in tumors, ruling out the hypothesis of a stably integrated truncated alpha 6(IV) chain in tumor basement membranes. In contrast, despite the deletions of the first two exons of the gene and its 5' end, a COL4A6 transcript is clearly expressed by tumor cells. This finding raises the question of a potential role for this RNA in the tumor process. The absence of the alpha 6(IV) chain is associated with the absence of the alpha 5(IV) chain, as was suggested by the COL4A5 deletion. An additional striking feature is the absence of the beta 1 chain of laminin in tumor basement membranes and the lack of or uneven expression of the alpha 5 integrin subunit. These findings show that dramatic changes in the composition of the matrix and the expression of integrin receptors also occur in this benign tumorous process.