Percutaneous angioscopy. Work in progress

The cardiovascular applications of flexible fiber-optic technology are imminent because of recent advances in miniaturization. In the work described here, angioscopy, or vascular endoscopy, was performed in the cadaveric aorta and in the systemic and pulmonary circulations of the canine model and selected human patients. Subsequent to our development of percutaneous techniques, clinical trials have ranged from lower-extremity venoscopy to aortic-root arterioscopy. Angioscopy could be clinically useful because of relative or absolute contraindications to iodinated contrast material. The ability to see in color and three dimensions may afford some other advantages to angioscopy over conventional angiography.     

Age-specific regulation of clotting factor IX gene expression in normal and transgenic mice

Factor IX (FIX), a circulating serine protease that serves as an essential component of the blood coagulation pathway, has been shown to increase with age in humans. We show here that murine FIX mRNA and activity levels also increase with age. Furthermore, one form of hemophilia B, hemophilia B Leyden, which is caused by mutations within the promoter region of the FIX gene, has a distinct age-dependent phenotype. To determine the source of the age-related increases in FIX gene expression, we have analyzed the regulation of the normal FIX gene promoter and FIX Leyden gene promoter with the +13 mutation during aging by generating transgenic mice that contain the -189 to +21 bp promoter segment ligated to a chloramphenicol acetyltransferase reporter gene. We have established that the normal FIX promoter and the Leyden promoter transgenes are expressed in a tissue-specific manner in vivo. The normal FIX promoter transgene does not show any differences in the pattern of expression with age or sex of the organism, whereas the Leyden promoter transgene showed age-dependent male-specific expression. This is the first demonstration of the FIX Leyden phenotype in a transgenic mouse model.