Metastatic MHC class I-negative mouse cells derived by transformation with human papillomavirus type 16

In the endeavour to develop a model for studying gene therapy of cancers associated with human papillomaviruses (HPVs), mouse cells were transformed with the HPV type 16 (HPV16) and activated H-ras oncogenes. This was done by contransfection of plasmid p16HHMo, carrying the HPV16 E6/E7 oncogenes, and plasmid pEJ6.6, carrying the gene coding for human H-ras oncoprotein activated by G12V mutation, into secondary C57BL/6 mouse kidney cells. An oncogenic cell line, designated MK16/1/IIIABC, was derived. The epithelial origin of the cells was confirmed by their expression of cytokeratins. No MHC class I and class II molecules were detected on the surface of MK16/1/IIIABC cells. Spontaneous metastases were observed in lymphatic nodes and lungs after prolonged growth of MK16/1/IIIABC-induced subcutaneous tumours. Lethally irradiated MK16/1/IIIABC cells induced protection against challenge with 105homologous cells, but not against a higher cell dose (5 × 105). Plasmids p16HHMo and pEJ6.6 were also used for preventive immunization of mice. In comparison with a control group injected with pBR322, they exhibited moderate protection, in terms of prolonged survival, against MK16/1/IIIABC challenge (P< 0.03). These data suggest that MK16/1/IIIABC cells may serve as a model for studying immune reactions against HPV16-associated human tumours. © 2001 Cancer Research Campaign http://www.bjcancer.co

Rich table but short life: Diffuse idiopathic skeletal hyperostosis in Danish astronomer Tycho Brahe (1546-1601) and its possible consequences

The exhumation of Danish astronomer Tycho Brahe (1546–1601) was performed in 2010 to verify speculative views on the cause of his death. Previous analyses of skeletal and hair remains recovered from his grave refuted the presumption that he died from poisoning. These studies also outlined the possibility that he actually died from an acute illness, echoing the rather vague and inaccurate testimony of some historical records. We performed a detailed paleopathological analysis of Tycho Brahe’s skeletal remains, along with a reconstruction of his diet based on carbon and nitrogen stable isotopes analysis and an estimate of his physical status (relative body fat) based on medullar and cortical dimensions of the femoral shaft. The astronomer’s remains exhibit bone changes indicative of diffuse idiopathic skeletal hyperostosis (DISH). The study further allows us to classify him as obese (100% reliability according to our decision tree designed from Danish males), and points out his rich diet (high input of animal protein and/or marine resources) and high social status. Comorbidities of DISH and obesity are reviewed, and their influence on health status is discussed. We further consider some conditions associated with metabolic syndrome as possible causes of Tycho Brahe’s final symptoms (urinary retention, renal failure and coma), including diabetes, alcoholic ketoacidosis and benign prostatic hypertrophy. Although a definite and specific diagnosis cannot be established, our study points to today’s civilization diseases often associated with DISH and metabolic syndrome as the possible cause of death of Tycho Brahe