Lymphocytes from children and infants mediate natural cell mediated cytotoxicity, (cytotoxicity)

Summary Lymphocytes from infants and young children were tested for natural cell mediated cytotoxicity (NCMC) against K562 and CCRF-CEM. NCMC by lymphocytes from pediatric donors of all ages was equivalent to that mediated by lymphocytes from adults. Since it has been suggested that the biological function of NCMC is to effect immunological surveillance against cancer, the appearance of NCMC effector cells early in development is consistent with early mobilization of the policing mechanism.This work was supported by Grant CA 25765 from the National Cancer InstitutePartially supported by a Grant from the Concern Foundation.     

Correlation between SERT polymorphisms and Venlafaxine response in major depression patients

Major depression (MD) has a complex multifactorial aetiology with genetic and environmental factors contributing to this disorder. As with all antidepressant treatments, there is variability in drug response because of heredity, and this leads us to focus on the genetic polymorphism of the drug’s metabolising transporter genes. The serotonin transporter (5-HTT) gene is a particularly important candidate for genetic involvement in MD disorders owing to its key role in the regulation of serotonergic transmission and is therefore considered an interesting candidate in the mechanism of antidepressant drugs. Here, we studied the associations between genetic polymorphisms in two regions of the 5-HTT gene (5-HTTLPR and VNTR) to understand venlafaxine response. Venlafaxine was found to be effective in MD patients based on their HAM-D and CGI scores (p<0.05). Although the results did not yield a significant difference between the frequencies of the SS, LS, LL, 9/9, 10/10, 12/12 and 10/12 genotypes and venlafaxine response, venlafaxine dose was increased in patients with Stin2.12 and S alleles. These alleles might have a predisposition to mood disorders. Further studies with more patients are required to confirm this clinical association.     

Functional interaction sites of OprM with MexAB in the Pseudomonas aeruginosa multidrug efflux pump

Subunit-swapping between Pseudomonas aeruginosa MexAB-OprM and MexEF-OprN efflux pumps has shown that OprM can interact with MexEF to produce a functional efflux pump, but that OprN cannot functionally interact with MexAB. Taking advantage of this subunit selectivity, we carried out experiments using chimeric proteins composed of OprM and OprN to determine which regions of OprM are necessary for functional interaction with MexAB. We constructed two types of chimeric proteins: one with the N-terminal half of OprM and the C-terminal half of OprN (OprMN), and the second with these halves reversed (OprNM). Introduction of either of the chimeric protein genes into a mutant expressing MexEF alone restored the functionality of the efflux pump. However, expression of OprMN or OprNM in the presence of MexAB did not restore the pump functionality, indicating that the both the N- and C-terminal halves of OprM are necessary for a functional interaction with MexAB.