Transthyretin Arg-83 mutation in vitreous amyloidosis.

Both of the patients in the report had floaters and progressive vision loss for years. Two cases of familial vitreous amyloidosis occurred in three generations with typical white fibrilar opacities in the vitreous body. Pars plana vitrectomy was performed in the two patients. The vitreous specimens were subjected to histopathological examination. The specimens showed typical microscopic features of amyloidosis with Congo red stain and non-branching fibrils were seen randomly distributed with 5-10nm in diameter on a transmission electron microscope. All of the exons of the transthyretin gene were amplified with DNA isolated from the peripheral blood cells. Bi-directional sequencing of the transthyretin gene revealed a single base-pair substitution, which results in an amino acid substitution at position83, glycine to arginine (transthyretin Arg-83).

EphB4 overexpression in B16 melanoma cells affects arterial-venous patterning in tumor angiogenesis.

EphB4 receptor and its ligand ephrinB2 play an important role in vascular development during embryogenesis. In blood vessels, ephrinB2 is expressed in arterial endothelial cells (EC) and mesenchymal supporting cells, whereas EphB4 is only expressed in venous ECs. Previously, we reported that OP9 stromal cells, which support the development of both arterial and venous ECs, in which EphB4 was overexpressed, could inhibit ephrinB2-positive (ephrinB2+) EC development in an embryonic tissue organ culture system. Although the EphB4 receptor is expressed in a variety of tumor cells, its exact function in regulating tumor progression has not been clearly shown. Here we found that overexpression of EphB4 in B16 melanoma cells suppressed tumor growth in a s.c. transplantation tumor model. Histologic examination of these tumors revealed that EphB4 overexpression in B16 cells selectively suppressed arterial ephrinB2+ EC development. By coculturing ephrinB2-expressing SV40-transformed mouse ECs (SVEC) with EphB4-overexpressing B16 cells, we found that EphB4 induced the apoptosis of SVECs. However, ephrinB2 did not induce the apoptosis of EphB4-overexpressing B16 cells. Based on results from these experiments, we concluded that EphB4 overexpression in B16 tumor cells suppresses the survival of arterial ECs in tumors by a reverse signaling via ephrinB2.