In vitro simian virus 40 large tumor antigen expression correlates with differential immune responses following DNA immunization

Simian virus 40 (SV40) contains an essential protein, large tumor antigen (Tag), which assists in viral replication and causes cell transformation and immortalization. Our laboratory has examined plasmid DNA, expressing SV40 Tag under two different promoters, for use in potential cancer vaccination strategies. One plasmid, pSV3-neo, failed to induce SV40 Tag antibody, produced a weak cell-mediated response, and only partial protection in murine experimental tumor challenge systems. The second plasmid, pCMV-Tag, induced antibodies to SV40 Tag, produced a robust cell-mediated response, and invoked complete tumor immunity in vivo. The induction of CD4+ and CD8+ T cell responses following plasmid DNA immunization and tumor cell challenge reflected a type 1 cytokine secretion profile. Our hypothesis for this differential immune response is that pCMV-Tag exhibits a higher level of transgene expression due to a more efficient promoter. We determined that pCMV-Tag levels of SV40 Tag mRNA and protein expression were higher when compared to pSV3-neo. A threshold amount of SV40 Tag may be required to stimulate antibody production and provide complete systemic tumor immunity.     

New choices for patients needing kidney transplantation across antibody barriers

Antibodies in the blood of a kidney transplant recipient can provide a barrier to transplantation, which is additional to the usual possibility of cellular rejection. The antibodies most frequently encountered are ABO (blood group) and human leucocyte antigen (HLA) (tissue-type) antibodies. About 250 living donor transplants each year in the United Kingdom have been stopped because of an antibody barrier. It is now possible to offer a choice of treatment modalities to these people, including exchange transplantation and antibody-incompatible transplantation. It is likely that both schemes will complement each other and both are available in the United Kingdom.     

A multicentre randomised clinical endpoint study of PARMA 5 computer-assisted oral anticoagulant dosage

To meet growing demand for oral anticoagulation worldwide there has been increased dependence on computer-assistance in dosage although the safety and effectiveness of any of the individual computer-assisted dosage programs has not previously been established. This randomised multicentre clinical end-point study assessed a new version of the PARMA 5 program. It compared PARMA 5 safety and effectiveness with manual dosage by experienced medical staff at 19 centres with a known interest in oral anticoagulation. Target recruitment was 8000 patient-years, randomised to medical staff or PARMA-5 assisted dosage. Safety and effectiveness of the PARMA 5 program was compared with manual dosage. A total of 10,421 patients were recruited (15,369 patient-years) in the 5-year study. International normalised ratio (INR) tests numbered 167,791 with manual and 160,078 with PARMA 5 dosage. With parma 5 there was overall a non-significant reduction in clinical events but in the 2542 patients with deep vein thrombosis/pulmonary embolism, clinical events were significantly reduced (P = 0.005). Success in achieving 'time in target INR range' was also significantly greater with PARMA 5 compared with the dosage by experienced medical staff. This study demonstrated the safety and effectiveness of PARMA 5-assisted dosage.     

Shirley Glasstone Hughes Memorial Prize for Dental Research: an evaluation of the output 15 years after the Trust's inception

In May 2005, a decision was taken by the Shirley Glasstone Hughes (SGH) Foundation trustees to suspend investments in research for one year, to allow a review of the outcomes of SGH research funding over the past 15 years. Money was instead directed to the BDA Research Unit, to employ a staff member who would conduct the evaluation under the supervision of the BDA Scientific Adviser. The evaluation focused on three aspects of the research produced: 1) relevance to primary dental care, 2) scientific quality and impact on the research community, and 3) grant recipients' feelings about SGH funding and whether the mechanisms of supporting research could be improved. The methods used included questioning BDA members about the research they found of interest and relevance, checking research outputs against standardised quality criteria, examining impact factors and citation rates (relative to the funding received) and questioning grant recipients about their experience with SGH funding. The results implied that the fund had largely been spent on research themes felt to be relevant to practice by BDA members. In addition, the publication rate, publication quality, impact and citation indices demonstrated the SGH research work to be largely of high quality. Recipients of the fund indicated several factors which might improve the experience of receiving funding and possibly also improve the research output. It can be concluded that the SGH funds have largely been well spent but that it is worth considering implementing changes which would make the research findings of greater relevance to clinical practice.