Genetic and environmental factors modify bovine spongiform encephalopathy incubation period in mice.

The incubation period (IP) and the neuropathology of transmissible spongiform encephalopathies (TSEs) have been extensively used to distinguish prion isolates (or strains) inoculated into panels of inbred mouse strains. Such studies have shown that the bovine spongiform encephalopathy (BSE) agent is indistinguishable from the agent causing variant Creutzfeldt-Jakob disease (vCJD), but differs from isolates of sporadic CJD, reinforcing the idea that the vCJD epidemic in Britain results from consumption of contaminated beef products. We present a mouse model for genetic and environmental factors that modify the incubation period of BSE cross-species transmission. We have used two mouse strains that carry the same prion protein (PrP) allele, but display a 100-day difference in their mean IP following intracerebral inoculation with primary BSE isolate. We report genetic effects on IP that map to four chromosomal regions, and in addition we find significant factors of host environment, namely the age of the host's mother, the age of the host at infection, and an X-cytoplasm interaction in the host.

Jejunal mucosal architecture and fat absorption in male homosexuals infected with human immunodeficiency virus.

Diarrhoea and weight loss are common features of human immunodeficiency virus (HIV) disease. The mechanism of diarrhoea occurring in the absence of known enteropathogens is currently unknown. We have measured fat absorption, using the 14C triolein breath test, and quantitatively assessed jejunal villous architecture in 20 male homosexuals at various clinical stages of HIV disease. Enteropathogens were not detected in any subject at the time of jejunal biopsy in stool or jejunal mucosa. Partial villous atrophy was the sole histological abnormality and was detected at any clinical stage of HIV disease. The 14C triolein breath test quantitatively correlated with the degree of jejunal villous atrophy. In addition subjective presence of diarrhoea was related to the detection of fat malabsorption. Thus diarrhoeal disease in HIV infected patients in the absence of enteropathogens may be due to jejunal enteropathy and may be present at early clinical stages of HIV disease.