The use of retroviruses as pharmaceutical tools for target discovery and validation in the field of functional genomics.

Retrovirally mediated functional genomics enables identification of physiologically relevant cellular therapeutic targets. Unique properties of retroviruses make them ideal tools for the introduction of large and diverse libraries of potential genetic effectors to a variety of cell types. The identification and recovery of intracellular library elements responsible for altered disease responses establishes a direct basis for pharmaceutical development. Recent innovations in retroviral infection efficiency and expression control have broadened application of the methodology to include libraries of mutagenized cDNAs, peptides and ribozyme genetic effectors.

Validation of an automated technique for determining the mechanical characteristics of coronary arteries during balloon angioplasty: laboratory assessment with necropsy segments.

OBJECTIVES: To develop a technique for automatic inflation of a percutaneous transluminal coronary angioplasty (PTCA) balloon, with continuous measurement of the balloon pressure and volume; to validate the technique for determining the mechanical characteristics of coronary arteries. METHODS: During necropsy examination of the hearts of nine patients, 17 coronary artery samples were obtained for histological examination. A PTCA balloon was inserted into each artery, and the balloon pressure and volume were measured continuously during four repeat automatic inflations of the balloon. RESULTS: Of the 17 arteries, eight showed elastic, six plastic, and three fracture pressure-volume deformation characteristics. For the plastic deformations, the first inflation required a higher pressure than subsequent repeat inflations of 82 (61) kPa (mean (SD), range 25 to 175 kPa). For the three in the fracture group, the pressure drop because of the fracture occurred between 210 and 540 kPa. Two of these three showed a tear on visual inspection, and the other showed disruption of the intimal plaque on blinded histological examination. Of the six with plastic deformation characteristics alone, one showed a tear, and on histological examination two others showed splitting of the internal and external elastic lamina and one showed separation of intima and media. None in the elastic group showed any of these characteristics. CONCLUSIONS: Plastic and fracture deformation characteristics could be differentiated from elastic characteristics. Visual or histological evidence of fracturing was present in all three arteries identified during angioplasty as having pressure-volume fracture characteristics.