Breast cancer incidence highest in the range of one species of house mouse, Mus domesticus

Incidence of human breast cancer (HBC) varies geographically, but to date no environmental factor has explained this variation. Previously, we reported a 44% reduction in the incidence of breast cancer in women fully immunosuppressed following organ transplantation (Stewart et al (1995) Lancet346: 796–798). In mice infected with the mouse mammary tumour virus (MMTV), immunosuppression also reduces the incidence of mammary tumours. DNA with 95% identity to MMTV is detected in 40% of human breast tumours (Wang et al (1995) Cancer Res55: 5173–5179). These findings led us to ask whether the incidence of HBC could be correlated with the natural ranges of different species of wild mice. We found that the highest incidence of HBC worldwide occurs in lands where Mus domesticus is thse resident native or introduced species of house mouse. Given the similar responses of humans and mice to immunosuppression, the near identity between human and mouse MTV DNA sequences, and the close association between HBC incidence and mouse ranges, we propose that humans acquire MMTV from mice. This zoonotic theory for a mouse-viral cause of HBC allows testable predictions and has potential importance in prevention. © 2000 Cancer Research Campaig

ESC Working Group Cellular Biology of the Heart: Position Paper: Improving the pre-clinical assessment of novel cardioprotective therapies

Ischemic heart disease (IHD) remains the leading cause of death and disability worldwide. As a result, novel therapies are still needed to protect the heart from the detrimental effects of acute ischemia-reperfusion injury, in order to improve clinical outcomes in IHD patients. In this regard, although a large number of novel cardioprotective therapies discovered in the research laboratory have been investigated in the clinical setting, only a few of these have been demonstrated to improve clinical outcomes. One potential reason for this lack of success may have been the failure to thoroughly assess the cardioprotective efficacy of these novel therapies in suitably designed pre-clinical experimental animal models. Therefore, the aim of this Position Paper by the European Society of Cardiology Working Group Cellular Biology of the Heart is to provide recommendations for improving the pre-clinical assessment of novel cardioprotective therapies discovered in the research laboratory, with the aim of increasing the likelihood of success in translating these new treatments into improved clinical outcomes

Persistence of Simian Varicella Virus DNA in CD4+ and CD8+ Blood Mononuclear Cells for Years after Intratracheal Inoculation of African Green Monkeys

AbstractSimian varicella virus (SVV) DNA was detected in blood mononuclear cells (MNCs) of adult African green monkeys 7 days to 23 months after intratracheal inoculation with 103 plaque forming units. Infectious virus was not detected in MNCs at 14 months postinfection (p.i.), and electron microscopic (EM) analysis of MNCs from two monkeys 21 months p.i. did not reveal virus particles. Real-time quantitative PCR analysis of DNA from blood MNCs taken at multiple intervals from SVV-infected monkeys M7 and M8 revealed a 10- to 100-fold decrease, but not clearance of SVV DNA in MNCs between 11 and 17 months p.i. Thereafter, the SVV DNA copy number did not decrease further between 17 and 23 months p.i. PCR analysis of MNCs sorted by flow cytometry revealed SVV DNA in T cells (CD4+, CD8+) and B cells (CD20+), but not in monocyte-macrophages (CD14+), 10 days p.i. At 11 and 23 months p.i., SVV DNA was found exclusively in CD4+ and CD8+ T cells. Whether the detection of SVV DNA in CD4+ and CD8+ MNCs many months after the resolution of acute varicella reflects continued infection of these cells that began at the time of acute varicella or represents infection acquired by MNCs trafficking through infected tissues is unknown

Naturally Acquired Simian Varicella Virus Infection in African Green Monkeys

Simian varicella virus (SVV) infection of primates shares clinical, pathological, immunological, and virological features with varicella-zoster virus infection of humans. Natural varicella infection was simulated by exposing four SVV-seronegative monkeys to monkeys inoculated intratracheally with SVV, in which viral DNA and RNA persist in multiple tissues for more than 1 year (T. M. White, R. Mahalingam, V. Traina-Dorge, and D. H. Gilden, J. Neurovirol. 8:191-205, 2002). The four naturally exposed monkeys developed mild varicella 10 to 14 days later, and skin scrapings taken at the time of the rash contained SVV DNA. Analysis of multiple ganglia, liver, and lung tissues from the four naturally exposed monkeys sacrificed 6 to 8 weeks after resolution of the rash revealed SVV DNA in ganglia at multiple levels of the neuraxis but not in the lung or liver tissue of any of the four monkeys. This animal model provides an experimental system to gain information about varicella latency with direct relevance to the human disease