Publications by authors named "C S Potten"

Well-characterized animal models that mimic the human response to potentially lethal doses of radiation are required to assess the efficacy of medical countermeasures under the criteria of the US Food and Drug Administration's Animal Rule. Development of a model for the gastrointestinal acute radiation syndrome requires knowledge of the radiation dose-response relationship and time course of mortality and morbidity across the acute and prolonged gastrointestinal radiation syndrome. The nonhuman primate, rhesus macaque, is a relevant animal model that has been used to determine the efficacy of medical countermeasures to mitigate major signs of morbidity and mortality relative to the hematopoietic acute radiation syndrome, gastrointestinal acute radiation syndrome, and lung injury.

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Objective: To analyse the structural and kinetic response of small intestinal crypt epithelial cells including stem cells to highly active antiretroviral therapy (HAART).

Design: Crypt size and proliferative activity of transit and stem cells in jejunal mucosa were quantified using morphometric techniques.

Methods: Crypt length was measured by counting the number of enterocytes along one side of a number of crypts in each biopsy specimen and the mean crypt length was calculated.

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Stem cells have been identified in two locations in small intestinal crypts; those intercalated between Paneth cells and another population (which retains DNA label) are located above the Paneth cell zone, at cell position 4. Because of disadvantages associated with the use of DNA label, doxycycline-induced transient transgenic expression of histone 2B (H2B)-green fluorescent protein (GFP) was investigated. H2B-GFP-retaining putative stem cells were consistently seen, with a peak at cell position 4, over chase periods of up to 112 days.

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Article Synopsis
  • The intestinal epithelium relies on stem cells at the base of crypts to maintain cell turnover, with the study focusing on their roles in cell proliferation and apoptosis in the terminal ileum and various colon regions.
  • Under normal conditions, the ascending colon exhibited the smallest crypt size and had a similar pattern of proliferating cells to that of the terminal ileum, while post-radiation, apoptotic cells were primarily found at the crypt's base in the mid and descending colon but spread more evenly in the ascending colon.
  • The findings indicate that stem cell locations in both the ascending colon and terminal ileum share similarities in their profiles of cell proliferation and apoptosis, particularly after radiation exposure.
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