Regulation of p53 levels by the E1B 55-kilodalton protein and E4orf6 in adenovirus-infected cells

The adenovirus type 5 243R E1A protein induces p53-dependent apoptosis in the absence of the 19- and 55-kDa E1B polypeptides. This effect appears to result from an accumulation of p53 protein and is unrelated to expression of E1B products. We now report that in the presence of the E1B 55-kDa polypeptide, the 289R E1A protein does not induce such p53 accumulation and, in fact, is able to block that induced by E1A 243R. This inhibition also requires the 289R-dependent transactivation of E4orf6 expression. E4orf6 is known to form complexes with the E1B 55-kDa protein and to function both in the transport and stabilization of viral mRNA and in shutoff of host cell protein synthesis. We demonstrated that the block in p53 accumulation is not due to the generalized shutoff of host cell metabolism. Rather, it appears to result from a mechanism targeted specifically to p53, most likely involving a decrease in the stability of p53 protein. The E1B 55-kDa protein is known to interact with both E4orf6 and p53, and as demonstrated recently by others, we showed that E4orf6 also binds directly to p53. Thus, multiple interactions between all three proteins may regulate p53 stability, resulting in the maintenance of low levels of p53 following virus infection.     

A closer look at vitamin E. Can this antioxidant prevent chronic diseases?

Vitamin E, the most effective natural free radical scavenger identified to date, is taking America by storm-and apparently for good reason. Reports of benefits ranging from Improved Immunity to prevention of cancer and cardiovascular disease are appearing regularly. In this article, the authors review the scientific literature to help you evaluate whether patients might benefit from supplemental vitamin E.     

Saccharide-assisted delivery of cytotoxic liposomes to human malignant cells

The overexpression of lectins by malignant cells was applied for in vitro targeting of liposomes equipped with a saccharide vector and loaded in the lipid phase with a lipid derivative of anticancer agent sarcolysine. The lectin specificity of human leukemia HL-60 and human lung adenocarcinoma ACL cells was revealed by tests with fluorescein-labeled sugar probes. With the help of fluorescent lipid dye it was shown that active saccharide ligands increased the level of the vectored liposome binding to malignant cells by 50-80% as compared to liposomes without vector or with inactive one. The degree of liposome/cell membrane fusion was monitored fluorometrically and was shown to be complete and independent of the vectors. The targeted drug-loaded liposomes had the cytotoxic activity 2-4 times higher as compared to the vector-free ones.     

Prevalence of teaching apical patency and various instrumentation and obturation techniques in United States dental schools

Maintaining an open apex beyond the apical constriction with an endodontic file during canal instrumentation is a concept that has been advocated by several authors and clinicians. To ascertain the prevalence of teaching the patency concept as well as various instrumentation and obturation techniques in the United States dental schools, a survey was conducted. Forty-eight out of a total of 53 dental schools (91%) responded to the survey. Results indicate that 50% of the schools surveyed teach the concept of patency to their undergraduates or graduates or both; 83% teach a step-back instrumentation technique; and 89.6% teach lateral condensation of gutta percha as their primary obturation technique.