Medical Research Council

About: Medical Research Council is a government organization based out in London, United Kingdom. It is known for research contribution in the topics: Population & Malaria. The organization has 16430 authors who have published 19150 publications receiving 1475494 citations.

Integration of high-risk human papillomavirus: a key event in cervical carcinogenesis?

Abstract: An important occurrence in cervical carcinogenesis is deregulated expression of the high-risk human papillomavirus (HR-HPV) oncogenes E6 and E7. Several risk factors for cervical neoplastic progression are likely to contribute to viral oncogene deregulation, particularly integration of HR-HPV into the host genome. Integration represents a by-product of viral infection that is detected in almost 90% of cervical carcinomas. The mechanism of integration is not fully understood, although there is a clear predilection for chromosomal common fragile sites, most likely due to their accessibility for insertion of foreign DNA. Recent work has suggested that an important intermediate stage in cervical carcinogenesis is characterized by transcriptionally silent HR-HPV integrants, which co-exist with viral episomes in infected cells. As episome-derived E2 protein inhibits integrant transcription, clearance of episomes (eg by host innate immunity) is associated with loss of integrant silencing and integrant selection. The process of integration and subsequent clonal selection of integrants can therefore be considered as two independent and biologically distinct events. Indeed, integrated HPV may be viewed as selectable because it represents a form of the virus that is resistant to host mechanisms of viral clearance, enabling infected cells to maintain viral oncogene expression and avoid cell death. Care should be taken in interpreting studies of HPV integration frequency in clinical samples, as the techniques used have assessed either the presence of integrated viral DNA or evidence of transcriptional activity from integrants, but not both.

Newborns Develop a Th1-Type Immune Response to Mycobacterium bovis Bacillus Calmette-Guérin Vaccination

Abstract: Data obtained in animals indicate that neonatal immune responses are biased toward Th2. This could reduce the efficacy of vaccines against viral and mycobacterial diseases. The ability of human newborns to develop a Th1 immune response upon immunization has not been studied. Since the vaccine Mycobacterium bovis bacillus Calmette-Guerin (BCG) triggers a Th1-type response in adults, we investigated whether it induces a similar response in newborns and whether age at vaccination influences immunogenicity. We found that BCG vaccination at birth induces a memory Th1-type response of similar magnitude to that when given later in life. This study demonstrates that human newborns can be immunized against pathogens controlled by a Th1 immune response.

Frontotemporal dementia and corticobasal degeneration in a family with a P301S mutation in tau.

Abstract: The tau gene has been found to be the locus of dementia with rigidity linked to chromosome 17. Exonic and intronic mutations have been described in a number of families. Here we describe a P301S mutation in exon 10 of the tau gene in a new family. Two members of this family were affected. One individual presented with frontotemporal dementia, whereas his son has corticobasal degeneration, demonstrating that the same primary gene defect in tau can lead to 2 distinct clinical phenotypes. Both individuals developed rapidly progressive disease in the third decade. Neuropathologically, the father presented with an extensive filamentous pathology made of hyperphosphorylated tau protein. Biochemically, recombinant tau protein with the P301S mutation showed a greatly reduced ability to promote microtubule assembly.