Cholera toxin stimulates human B-cell DR antigen biosynthesis at the level of translation.

Cholera toxin (CT) exerts many diverse regulatory effects on cells of the immune system and is considered a potent adjuvant on gut mucosal immune responses to orally presented antigens. It has been previously described that CT induces surface DR expression in human resting B-cells. As a further step toward understanding this phenomenon, the molecular mechanisms underlying the regulation of DR expression were investigated. By the use of Western analysis, it is shown that CT increases the total levels of DR protein in highly purified human tonsillar cells. [35S]Methionine incorporation studies show that the aforementioned increase is due to de novo biosynthesis of DR protein at as early as 6 hr after CT stimulation and is completed by 24 hr. [3H]Uridine uptake experiments, nuclear transcription runoff assays, and Northern analysis show that CT does not exert its effect at a transcriptional level, indicating translational regulation. Anti-IgM, which mimics B-cell antigen binding, behaves in a manner similar to CT. The B subunit of CT (B-CT) and prostaglandin E2, either alone or in combination, do not induce DR protein biosynthesis nor do they exert any effect on the transcription of DR beta 1 gene. These results show that cAMP elevation as well as binding of B-CT to GM-1 ganglioside, by themselves, do not lead to DR protein biosynthesis suggesting that other activation pathways may be involved.

Alpha 1-antitrypsin and survival in pancreatic cancer.

The association between serum levels of alpha 1-antitrypsin (a1AT) at the time of diagnosis and survival was studied in a group of 44 patients with confirmed pancreas cancer. All 44 patients were followed until time of death, which occurred in all cases from pancreas cancer, with a median time of 3 months and a range of 0.5 to 16 months. Cox's proportional hazards model was utilized in the analysis controlling for sex, age and tobacco smoking. Males, older patients and smokers have higher fatality rates, but none of these relations was statistically significant. By contrast, there was a statistically highly significant association of increased levels of serum a1AT, at the time of diagnosis of the cancer of pancreas, with shorter survival; patients with serum a1AT higher by 100mg/100ml had a 57% higher fatality rate. These results indicate that serum a1AT represents a clinically interesting prognostic factor in pancreas cancer.