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Biomedical subjects

C S Potten

Publications and source records attributed to C S Potten.

At least 253 records · Page 14Linked to original sources

Circadian rhythms in the epithelial cells and the pericryptal fibroblast sheath in three different sites in the murine intestinal tract.

Variations in percentage labelling (LI) and mitotic activity (mitoses per crypt) have been studied over a 24-hr period in the epithelial cells and pericryptal fibroblast sheath (PCFS) of the small intestine, caecum, and colon of the mouse. All three tissues displayed clear, synchronized circadian rhythms in DNA-synthetic activity in both the epithelial cells and PCFS. Peak values were coincident within a tissue, but staggered between tissues. In the epithelial cells, peak mitotic values were found between 3 and 6 hr after the peak LI values. The low level of mitotic activity in the PCFS appeared to be synchronized with the rhythms in the adjacent epithelia. The epithelial cells of the lowest crypt third displayed the clearest circadian rhythms. However, the PCFS cells at all levels produced similar curves. A craniocaudal wave of proliferative activity is proposed.

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Description and basic cell kinetics of the murine pericryptal fibroblast sheath.

The size of the pericryptal fibroblast sheath (PCFS) population was determined by scoring serial sections. There are 38 and 124 PCFS cells per murine small intestinal and colonic crypt, respectively. The cells of the PCFS are slightly weighted towards the lower two-thirds of the crypt in their distribution. The ratio of epithelial cells to PCFS cells is approximately 6.5:1. The in vivo cell kinetics were analysed under control and stressed (fasted-refed) conditions. The control labelling index increases from 8.9% in the small intestine and 7.0% in the colon to peaks 49% and 113% respectively above these values 24 hours after 3HTdR administration. Labelling is observed at all crypt levels equally, and no evidence of vertical migration of labelled PCFS cells was found. Colonic epithelial and PCFS cells show a similar pattern of response to feeding after a fast of 72 hours with respect to time, but a different distribution of response in terms of crypt position.

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Changes in proliferative activity as cells move along undulating basement membranes in stratified squamous epithelium.

The filiform papillae of mouse tongue provide evidence for a flow of interphase basal cells along the basement membrane. This implies that they are aligned on that structure according to age. In addition there is a decrease in proliferative potential as the basal cells age. This is probably due at least in part to a fall in growth fraction. Such a method of basal cell replacement may exist in other stratified squamous epithelia characterized by undulating basement membranes.

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A cell kinetic model to explain the time of appearance of skin reaction after X-rays or ultraviolet light irradiation.

Skin reactions to various doses of X-rays (300 and 10 kV) and ultraviolet light (u.v.) have been compared using hairless mice. Two regions of epidermis with widely differing cell kinetics and gross structure have been compared. Little evidence could be found to support the idea that the early phases of the reaction are dependent on cell cycle time. The data can be explained by a model based on the assumption that epidermis contains only a small fraction of clonogenic (stem) cells and this fraction may vary in different epidermal regions. X-rays appear to exert their greatest destructive action on these clonogenic cells while u.v. is more indiscriminate in its action, killing both clonogenic and non-clonogenic cells.

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Advances in epithelial kinetics--an oral view.

There is growing evidence that the basal layer of stratified squamous epithelia consists of cells of differing proliferative capacities and behaviour. These can be classified as stem cells, transient amplifying cells and post-mitotic maturing cells, the most important of which appear to be the stem cells which may be present throughout life and are responsible for all cell production under steady-state conditions. Recent stem cell concepts are reviewed for epidermis, intestinal crypt and oral mucosa and are compared with tissues such as bone marrow and testes which have for some time been thought to operate in a similar manner. These concepts are applied to several pathological conditions of oral epithelia in an attempt to explain some of the changes observed.

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Differential radiation response amongst proliferating epithelial cells.

Tissue irradiation results in both reproductive and histologically evident cell death. The correlation between these is poor. Irrespective of dose and fraction sterilized, many cells behave as if unirradiated (cell cycle and maturation activity). The fraction of histologically observable dead cells is usually less than 0.1, with most in the intestine being positioned in the presumptive stem cell region. The data strongly suggest different epithelial sub-populations with differing radioresponses. These may be the stem and differentiated proliferative cells.

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Circadian rhythms of presumptive stem cells in three different epithelia of the mouse.

Variation in the percentage of labelled cells (LI), mitoses (MI) and apoptosis (AI: i.e. shrinkage necrosis) have been studied throughout a 24 hr period (40 min after labelling with 3H-TdR) for tongue epithelium, epidermis and intestinal epithelium in the mouse. A room with reversed light cycle was used to obtain data for half of the 24 hr period. All three tissues showed marked variations in LI with peak values between 24.00 and 03.00 hours. In the intestine a maximum value for MI was observed 3-6 hr after that for LI and with a maximum value for AI slightly later. In all three epithelia the circadian rhythm was most striking in cells at positions which can be correlated with presumptive stem cell activity; e.g. in the crypts the labelling and mitotic peaks reflecting a circadian rhythm were most clearly distinguishable at the basal part of the crypts. These observations are discussed in relation to the validity of various proliferative models.

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Regeneration and dose-response characteristics of irradiated mouse dorsal epidermal cells.

A microcolony technique is described for measuring epidermal cell survival 3 days after whole-body X-irradiation. This assay provides a cell D0 value of 233 +/- 11 rad and a zero-dose extrapolate of 1-23 x 10(4) cells/cm2 for mice irradiated in oxygen 20 hours after hair plucking. The microcolony cellularity had an apparent doubling-time of 25 hours which may be an upper limit at least for some clones. The clones appeared to fragment continually and form new daughter clones, suggesting that few would form macroscopic nodules. Many of the clones were also apparently associated with hair follicles.

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Ultrastructural site variations in mouse epidermal organization.

Mouse dorsal, ear, tail and foot epidermis are compared according to their tissue architecture and cell kinetics. Cell proliferation is expected in terms of the daily volume of keratin replaced. The stratum corneum may be organized into vertical columns of squames, which may have minimal overlap as in dorsum and ear, or maximal overlap as in tail. Individual areas are adapted to their function both in squame fine structure and rate of cell replacement. The surface keratin loss/replacement rate is at its highest in foot and tail, and lowest in ear and dorsum. Observations on hairless mouse dorsum are also included.

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