Stable gene expression occurs from a minority of integrated HIV-1-based vectors: transcriptional silencing is present in the majority.

Human immunodeficiency virus (HIV)-based vectors are being increasingly used in vitro for gene transfer and in vivo for gene therapy. The proportion of integrated retroviral vectors that are silenced or remain transcriptionally active, and the stability of gene expression in the latter remains poorly explored. To study this, T cells were infected with an HIV-1-based vector construct containing a long terminal repeat-driven reporter gene. Only a small percentage of detectable integrated vector expressed gene product. In clones derived from cells with transcriptionally active vector, gene expression was remarkably stable with more than 80% continuing to express for greater than 18 months. Failure to continue expressing the vector was associated with epigenetic changes. Our data suggest that there are two forms of vector silencing: one occurring immediately after integration affecting the majority of the vectors, and one occurring in the much longer term affecting a small minority of vectors which had previously established expression.

Managing aging men in Asia: a strategic approach.

We have established a comprehensive diagnostic paradigm for the management of aging men which seeks to evaluate the various determinants of the aging process in five major health areas: cardio-health, bone health, sex health, general health and endocrine state. This paradigm appears to be useful for the management of the problem of aging in our local population. It could be used for the management of individuals as well as for population research. When combined with the establishment of evidence-based management modalities, it will provide a useful tool for the holistic management of aging in Asia.