The flag sign in the hair of an alcoholic.
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Biomedical subjects
Publications and source records attributed to R E Chapman.
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When N-[5-(4-aminophenoxy)pentyl]phthalimide was administered to sheep in sufficient quantities to permit manual removal of the fleece (400 mg/kg body weight orally, or 75 mg/kg body weight intravenously during a period of 48 h), cell division ceased in the wool follicle bulbs within 1 day. Dark-staining bodies (autophagic vacuoles) developed concomitantly in the cytoplasm of the bulb cells. The nuclei of cells in the keratogenous zones of the fibres became pycnotic 2 days after dosing and subsequent keratinization of these portions of the fibres was impaired. All the follicles retrogressed prior to day 7 after dosing, and the root ends which formed on the fibres moved towards the skin surface, reaching the level of the sebaceous glands by day 7. At this time mitotic activity recommenced around the dermal papillae in about 50% of the follicles. A small number of tips of new fibres emerged from the skin surface of some of the depilated sheep by day 14. The root ends on the fibres in the fleeces harvested at days 7-15 were fragmented with various degrees of taper. By 21 days, most follicles were growing emergent fibres. Thickening of the epidermis, increase in sebaceous gland size and decrease in skin thickness occurred in some of the depilated sheep. Smaller doses of the compound (200 mg/kg body weight orally or 40 mg/kg body weight intravenously during 24 h) produced weakness in the wool. Fewer autophagic vacuoles were present in follicle bulbs 1 day after dosing and not all follicles regressed. The weakened region of the fleece contained a mixture of shed fibre ends and continuously growing fibres with thin regions proximal to poorly keratinized lengths of fibre. No change was observed in other components of the skin of the sheep with weakened wool. The follicular changes produced by this compound are similar in some respects to those produced by other depilatory compounds or that occur during natural cyclic hair growth.
Migration of cells in wool follicles of an adult Merino sheep was studied autoradiographically in skin samples taken at intervals after an intravenous injection of [3H]thymidine. Fibre and inner root sheath cells incorporated [3H]thymidine in a cone-shape region of the follicle bulb. Labelled inner sheath cells migrated out of the bulb ahead of contemporaneous cells in the fibre and remained in advance, although to a progressively lesser extent, until the inner sheath cells sloughed into the follicle lumen. Outer root sheath cells incorporated [3H]thymidine along the length of the follicle. Cells in the proximal half of the outer sheath migrated inwards and distally and sloughed into the follicle lumen before contemporaneous inner sheath cells. Other cells in the distal half of the outer sheath migrated past the level where cells from the proximal population were shed and also sloughed into the lumen. In the most distal part of the outer sheath, which formed the epidermis-like lining of the follicle canal, little migration of cells was observed during 8 days of observation. The specific activity of tritium in fibres plucked from the same sheep at intervals after the intravenous injection of [3H]thymidine was determined by scintillation counting and assessed in terms of cell migration and hardening of the fibres. The time which the specific activity of solvent-degreased fibres reached a maximum was found to give an estimate of the time for cells in the fibre to migrate to the upper limit of the keratogenous zone. When the plucked fibres were extracted with 8 M urea the times of the maximum specific activities of the urea-dispersible and urea-insoluble material provided respectively estimates of the times at which hardening of the fibres began and ended. The effects of different planes of nutrition were examined in two other Merino sheep by radioassay of fibres plucked after intravenous injections of [3H]thymidine given after equilibration period of at least 2 months on each level of feeding. A high plane of nutrition the rate of cell migration and hastened the onset of hardening of the fibres, but prolonged the hardening process. The prolongation of the hardening process was confirmed by the specific activities of fibres plucked after intravenous injections of [35S]cystine.
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Swiss mouse 3T3 cells and rat liver-derived RLCW cells were grown in monolayers and perfused with culture medium. A flow-rate dependent increase in the growth rate was observed both by 3H-thymidine uptake and by a rise in cell numbers. The characteristics of the response were dependent on the recirculating volume and on whether serum was present in the culture medium. In RLC cultures perfused with serum-supplemented medium the growth promoting effect decreased with increasing density of the cells. In the absence of serum, recirculation of NCTC medium had no effect on RLCs but increased growth was observed in recirculated MEM. In 3T3 cultures, a linear response was observed over a limited density range in the presence of 10% serum-supplemented medium indicating that substances present in the serum substantially modify the behaviour of the monolayer to perfusion. In serum-free medium the effect of perfusion on 3T3 cultures was confined to a small density range and was consistent with the more rapid removal of a diffusible inhibitor from the pericellular environment by recirculating the medium. Treatment of the perfusing medium with immobilised proteinases (trypsin, chymotrypsin, protease) did not alter the response except in the presence of putrescine.
In wheat-fed sheep, supplemented abomasally with 1.5-6.0 g methionine per day, poor formation and improper keratinization of the wool fibres were evident 4 days after the start of the methionine supplementation. This led to kinking of the fibres. Subsequently severe distortion of the fibres, accompanied by gross thickening of the outer root sheaths, occurred in the distal (upper) halves of most follicles. Within this thickened region partial degradation of the distorted fibres occurred before emergence from the skin surface, causing a marked reduction in the tensile strength of the wool. It is postulated that kinking of the fibres stimulated the accumulation of outer root sheath cells, which led to hyperactivity of the process that normally degrades the inner root sheath, so that the poorly keratinized fibres were also partly degraded. Thickening of the epidermis and cellular infiltration of the upper dermis sometimes occurred during the infusions of methionine, whereas there were negligible effects on the sebaceous and sweat glands. Disappearance of the excess accumulation of outer root sheath cells after cessation of the methionine supplementation occurred gradually following improvement in keratinization and elimination of kinking of the fibres.
Twenty-two Merino sheep were dosed with various amounts of L-mimosine, given either as an intravenous or an intraperitoneal injection, or as a continuous intravenous infusion for periods of 1-4 days. Single injections of mimosine (1-16 g) had no effect on the strength of wool, and wool growth rates were not appreciably altered by injections of small amounts (4 g or less). Injections of larger amounts slightly reduced both length growth rate and diameter of tibres during the 4 days after dosing. The effects of intravenous infusions of mimosine depended on the rate and the duration of administration. Small amounts (0.5 or 1 g/day given for 4 days) has no effects on the strength of wool or on wool growth rates. Infusions of a total of 8 g, either at the rate of 2 or 8 g/day, weakened the wool but not sufficiently to allow the sheep to be defleeced. Both these treatments caused a temporary reduction in length growth rate and in diameter of fibres, and transient degenerative changes were observed in wool follicles. A region of the fibres representing 1-2 days' growth was constricted to about half the pre-infusion diameter when 8 g was given for 1 day. Infusions of at least 8 g mimosine over a period of 1 1/2-2 days were effective for defleecing all sheep dosed. This corresponded to a daily rate of infusion of about 80 mg/kg. No toxic effects were observed with infusions given for periods of 2 days. Defleecing was judged to be possible by 6-7 days after the start of infusion, and was readily carried out by about 14 days. Defleecing was associated with follicle retrogression and an abrupt cessation of wool growth within 2 days of the start of the infusions. It was estimated that fibre growth stopped for about 10 dyas; regrowth was first observed 17-18 days from the beginning of dosing. Low rates of infusion of mimosine (up to 2 g/day) resulted in plasma levels below 0.1 mmol/l. Infusion at the rate of 4 g/day or above, which produced defleecing, quickly resulted in levels of mimosine in plasma above 0.1 mmol/l; after 2 days the concentration was steady at aboug 0.2 mmol/l. Injections of 8 or 16 g mimosine resulted in very large, but transient, rises of the level in plasma.
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