Biomedical subjects
Publications and source records attributed to C S Potten.
Examination of carefully oriented 1-mum and 5-mum sections of mouse dorsal tongue together with scanning electron microscope observations indicates a high degree of cellular organization in the papillae. It has been suggested that each filiform papilla consists of 2 dominant and 2 minor columns of cells. Labelling patterns of the basal cells have been investigated in relation to these columns.
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A dose of 900 rad gamma-rays to mice reduces the number of cryptogenic cells (those capable of crypt regeneration) per small intestinal crypt from about 80 to about 2 per surviving crypt. The surviving cells repopulate the crypt, the estimated cell-number doubling-time being about 24 hours, and on the fourth day after irradiation their numbers are still slightly below normal. The regeneration patterns for cryptogenic and proliferative cells differ significantly over the first 4 days after irradiation. The numbers of proliferative cells fall initially and remain low while the cryptogenic cells are increasing in number. The low levels persist for the first 1-5--2 days, after which there is a rapid rise in proliferative cells per crypt with a significant overshoot on the third day and a peak on the fourth day. The number of proliferative cells per crypt in control animals is about twice the number of cryptogenic cells. This ratio is on average 12 after irradiation (days 1--4). These data add support to the hypothesis that the small intestinal crypts contain a sub-population of stem cells that are distinct from the proliferative cells.
Labeling and mitotic index data and estimates for the length of the S and M phases of the cell cycle from the literature have been compared with new data obtained over a 24-hr period from various epidermal sites in mouse. It has been found that values obtained at a single time of the day may give misleading results. All data have been interpreted in terms of cell production rates per epidermal proliferative unit (EPU). The final conclusions after consideration of cell production rates, labeling and mitotic indices, epidermal transit times, and epidermal structure are that dorsal and ear skin have rather similar cell production rates while tail and foot rates are 4 to 7 times higher. A comparison has also been made between the mouse results and the available human data. Hairless mouse dorsum appears from structural and proliferative aspects to be the best model for some regions of human skin. A new model has been proposed for epidermal proliferation based on the EPU. The model suggests a role for the Langerhans cells and suggests that there is a program of sequential cellular maturity in the EPU originating at the level of a central basal stem cell through committed proliferative cells and ending with cell loss from the skin surface.
Radio-isotope disappearance curves and autoradiography (labelled DNA precursors and labelled amino acids) have been used to estimate the minimum transit times for four regions of epidermis in mice. The post-mitotic maturation time in the basal layer has been estimated and the results interpreted in relation to proliferation rates and epidermal organisation.
A variable amount of cornified tissue removed from mouse dorsal epidermis results in stimulation of the entire basal layer. Stimulation does not appear to be dependent on damage to an indiviaual epidermal proliferative unit (EPU). The immediate reaction to wounding is a rapid movement of cells from the basal layer to the differentiating compartment resulting in depopulation of the basal layer, which is followed by a burst in DNA-synthetic activity. The result of the increased transit of cells through the epidermis is that various aspects of keratinization can appear abnormal. The Langerhans cells show several changes, often appearing suprabasal and becoming smaller, rounded cells with a less-clear cytoplasm and fewer granules. The initial migratory reaction results in a largely normal epidermis on the third day. This reaction is followed by a transient hyperplasia which reaches its peak on the sixth to seventh day and gradually returns to normal by the fourteenth to fifteenth day. The hyperplasia is characterized by a loss of the ordered stacking of cornified cells which become shorter and thicker than normal. There is a return to the stacked state beginning on the tenth day. The Langerhans frequency is apparently at its lowest on days 6-7 when the proliferation levels are at their maximum. An inverse relationship appears to exist between relative Langerhans cell frequency and cell proliferation rate. The data suggest that the frequency of Langerhans granules also changes during the course of the hyperplasia, peak levels being observed just before the decline in proliferative activity.
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