Vascular toxicity in dogs associated with overdoses of a novel benzodiazepine receptor partial agonist.

Necrotizing arteritis and periarteritis were found in Beagle and German Shepherd dogs treated for 13 or 52 weeks with the novel benzodiazepine receptor (BZR) partial agonist Ro 16-6028 (generic name bretazenil). Eight male and one female out of a total of 20 dogs treated with 40-60 mg/kg/day Ro 16-6028 developed the arteritis, predominantly in the heart or the epididymis. Two of these animals died prematurely following treatment at the initial dosing levels of 80 and 55 mg/kg/day; one of these two dogs was asymptomatic and in good general condition until death.

Promoter activity and expression of sequences from Ti-plasmid stably maintained in mammalian cells.

Sequences of the plant-pathogenic Ti-plasmid were found to be constitutively expressed in LTK- and in HeLa-cells. Activity of the nopaline-synthase (nos) promoter in these cells was demonstrated by directing expression of G418 resistance from a connected neomycin-phosphotransferase II (NPT II) gene. Control transfections with the widely used thymidine-kinase (TK) promoter gave comparable transfection rates as found for the nos-promoter with NPT II.

The HBV X-ORF encodes a transactivator: a potential factor in viral hepatocarcinogenesis.

We report here on a transactivating function of HBV DNA. The effect is shown by stimulation of transient expression of pSV2cat DNA in cotransfected human liver CCL13 cells. Transfection experiments with plasmid constructs containing different HBV DNA fragments and Northern analyses of RNA from cells transfected with these recombinant plasmids indicate that a transactivating function is encoded within the X-ORF.