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H Y Elder

Publications and source records attributed to H Y Elder.

17 recordsLinked to original sources

Amiloride impairs the cholinergic regulation of potassium permeability in the human sweat gland but not in the rat submandibular gland.

Potassium permeability was monitored in human sweat glands and rat submandibular glands. Acetylcholine increased permeability in both tissues and the responses consisted of transient, calcium-independent and sustained, calcium-dependent components. Amiloride, a drug which inhibits Na(+)-H+ countertransport, impaired the regulation of potassium permeability in sweat glands but not in the submandibular gland. It is suggested that the stimulus-permeability coupling process in the sweat gland may be sensitive to the lowering of internal pH.

Acetylcholine

Histological and electron microprobe studies of mineralisation in aluminium-related osteomalacia.

AIMS: To determine a possible mechanism to explain the presence of aluminium lines within fully calcified bone in aluminium-related osteomalacia. METHODS: Fifty five bone cases shown by bone biopsy to be aluminium-related osteomalacia were studied. In 38 specimens aluminium lines were identified within calcified bone by means of the Aluminon stain and a characteristic form of patchy mineralisation was seen within thickened osteoid seams. Five representative examples were analysed quantitatively by histomorphometry and electronprobe X-ray microanalysis and compared with five cases of vitamin D deficiency-related osteomalacia which also had patchy mineralisation. RESULTS: The patchy calcification occupied 40 +/- 8% (mean +/- SEM) of the osteoid and consisted of small focal deposits (less than 40 microns diameter), often (52%) around osteoid osteocytes (probably an underestimate of the association), and larger areas that extended to the aluminium lines at the underlying mineralisation front. Small and large mineralisation nuclei were seen ultrastructurally in the patchy calcification. Quantitative electronprobe X-ray microanalysis showed that calcium concentrations and calcium:phosphorus ratios in the mineralisation nuclei and in the superficial layer of the fully calcified bone of the aluminium-related osteomalacia cases were significantly less than values measured at similar sites in the vitamin D deficiency-related osteomalacia cases. Furthermore, aluminium could not be detected by means of this technique at the mineralisation front or along cement lines in these specimens. CONCLUSIONS: Calcification can occur in thickened osteoid seams in osteomalacia. It can begin around osteoid osteocytes as small deposits that enlarge within the osteoid and extend to the underlying mineralisation front or cement line where aluminium lines may become trapped. Complete calcification of osteoid could account for the presence of aluminium lines within fully calcified bone. The Aluminon stain appears to be a more sensitive method for the detection of aluminium in bone than electronprobe X-ray microanalysis.

Adult

The role of potassium and other ions in the control of aldosterone synthesis.

Fast and slow K+ efflux components, independently regulated by angiotensin II (AII), have been identified in bovine adrenocortical cells. We have further investigated the role of potassium in the control of aldosterone synthesis in two ways. Firstly, isotopic tracers, in conjunction with channel modulators, have been used to study the interrelationship of K+ and Ca2+ in the control of AII-stimulated aldosterone synthesis. Secondly, electron probe X-ray microanalysis (EPXMA) was used to quantify potassium, sodium, chlorine and phosphorous in control and AII-stimulated cells. The effects of verapamil on 43K efflux were measured at two stages during AII stimulation. During the first ten minutes of treatment, when efflux via the fast component predominates, AII and verapamil both slowed efflux and their effects were additive. If verapamil was added later, at the time when efflux by the fast component appeared exhausted and the stimulatory effect of AII on the slow efflux component was apparent, it again slowed efflux. These data suggest that verapamil prevents calcium-gated K+ channels from opening by blocking Ca2+ channels. However, verapamil had no effect on AII-stimulated calcium efflux. In addition to blocking Ca2+ channels, verapamil may directly inhibit potassium efflux. EPXMA showed a bimodal distribution of potassium concentrations in control cells. However, in cells stimulated with AII for five minutes, the mean potassium content was less than in controls and was not bimodally distributed. Sodium content was increased by AII-treatment, chlorine was lowered and phosphorus remained unchanged. The data confirm previous observations that AII inhibits Na+/K+ ATPase activity.

Adrenal Glands

Automated image segmentation and serial section reconstruction in microscopy.

A technique for automatic 3-D reconstruction of specifically stained features in televised serial histological sections has been developed using an image analyser. Images which included these features were individually converted to binary images, compiled, displayed to show the 3-D morphology and used to quantify the structure. The criteria necessary for producing valid reconstructions and the problems associated with the manipulation of images of fine detail, particularly those containing several thousand features, are illustrated by examples from skin.

Animals

The effects of removing external sodium upon the control of potassium (86Rb+) permeability in the isolated human sweat gland.

The changes in cytoplasmic free calcium ([Ca2+]i) which occur in isolated human sweat glands during cholinergic stimulation have been studied indirectly by monitoring potassium permeability. The acetylcholine-evoked permeability increase normally consists of transient and sustained phases which are attributed to the mobilization of intracellular calcium stores and to calcium influx respectively. Such consistent responses to acetylcholine could not be obtained during superfusion with bicarbonate-free, HEPES-buffered solutions. The human sweat gland in vitro therefore appears to have a strict requirement for bicarbonate. The sustained component of the response was not affected by total removal of external sodium, suggesting that calcium influx does not occur via a sodium-dependent system. The transient component, however, was abolished when external sodium was replaced by N-methyl-D-glucammonium (NMDG+). It therefore appears that secretagogue-evoked mobilization of cytoplasmic calcium is dependent, in some way, upon external sodium. This dependence is not, however, absolute as the response was essentially normal when sodium was replaced by lithium.

Acetylcholine

Effects of season and lower ambient temperature on the structure of the sweat glands in anhidrotic horses.

Histological studies of the sweat glands of anhidrotic horses in the Hong Kong summer and under conditions of reduced thermal stress, both natural and controlled, were undertaken to determine if glandular regeneration occurs. Clinical data were collected for comparison with the histological results in each instance. Horses were assigned to one of three categories on the basis of the resulting change in the number of thin glandular profiles in a cooler environment. Group 1, which was classed as normal, had a low initial value, which was maintained. Group 2, typical of mild and moderately affected animals, had a high initial value, which fell markedly after as little as six weeks in the cool environment. Animals in Group 3, classed as severely affected, had a high initial value which remained high even after prolonged exposure to the cool environment. Light microscopical examination of the sweat glands in the heat, and after six weeks in a cool environment, provided a means of predicting the degree of anhidrotic severity and the potential for recovery in a cool climate. This was superior to clinical observation, although a diagnostic test based on glandular function is still required.

Animals

The control of potassium (86Rb+) efflux in the isolated human sweat gland.

Sweat glands, isolated from strips of human skin and pre-loaded with 86Rb+, a marker of potassium transport, were superfused with physiological saline and rate constants for 86Rb+ efflux calculated. The rate of efflux during superfusion with Ca2+-free saline was lower than that measured in the presence of calcium (2.56 mM). Acetylcholine increased the rate of 86Rb+ efflux and this response could be resolved into two components: an initial transient phase which was Ca2+-independent and a slowly declining Ca2+-dependent phase. Adrenaline only caused a Ca2+-dependent increase in efflux. It is suggested that the potassium permeability of the secretory cells increases during activity.

Acetylcholine

Potassium (86Rb+) efflux from the rat submandibular gland under sodium-free conditions in vitro.

1. Fragments of rat submandibular gland were pre-loaded with 86Rb+, an isotopic marker of potassium transport, and rate constants for 86Rb+ efflux were determined during superfusion with a physiological salt solution. 2. In sodium-containing solutions acetylcholine evoked a rapid and immediate increase in efflux rate. After reaching a peak value, the efflux rate initially declined rapidly, but a second, slowly declining phase to the response was also evident. The response could be resolved into Ca2(+)-independent and Ca2(+)-dependent phases. 3. The basal efflux rate was elevated during superfusion with solutions in which sodium had been replaced with either lithium or N-methyl-D-glucammonium (NMDG+). Although lithium had a greater effect, which was absent under calcium-free conditions, addition of calcium to initially calcium-free, lithium-containing solutions did not affect the rate of efflux. 4. In the presence of calcium the response to acetylcholine was augmented during exposure to lithium-containing, sodium-free solutions but, in contrast, slightly inhibited when NMDG+ was used as a sodium substituent. 5. The transient, calcium-independent component of the response to acetylcholine was unaffected by exposure to lithium, whereas the calcium-dependent phase of the response was inhibited. 6. Responsiveness to acetylcholine was reduced during superfusion with a calcium-free, NMDG+-containing solution. The response normally observed when extracellular Ca2+ was subsequently elevated, in the continued presence of acetylcholine, was also inhibited. Sensitivity to acetylcholine was retained, however, when the tissue was initially exposed to a solution containing approximately 20 mumol l-1 Ca2+. The response was smaller than that evoked in sodium-containing solutions. 7. The use of lithium as a sodium substituent presents special problems, possibly related to the effects of this ion on the metabolic cycling of phosphatidylinositol-4,5-bisphosphate metabolites.

Acetylcholine

The ultrastructure of the sweat glands of the ox, sheep and goat during sweating and recovery.

The ultrastructure of the sweat glands of cattle, sheep and goats was studied before, during, and after, exposure of the animals to controlled warm environments. In cattle, sweating induced little ultrastructural change in the gland, although fluid-filled spaces appeared between the myo- and secretory epithelial layers. The mechanism appears to be one of fluid transport and exocytosis of secretory vesicles, which in this species seem to be derived from the Golgi apparatus and/or mitochondria. The glands of the sheep and goat also displayed signs of vesicle exocytosis and of fluid transport during sweating. The sweating 'fatigue' in these species was apparently due to failure of the secretory cells, some of which ruptured and were extruded into the lumen. The evidence during subsequent recovery indicates that neighbouring cells spread to make contact, encase remnants of atretic cells between them and the underlying myoepithelium, and engulf them. Sweat in these species appears to be formed (a) by secretion and (b) from cells which can no longer meet the demands of stimulation. The role in sweating of cell replacement, and of undifferentiated cells found between the myo- and secretory epithelia, is discussed.

Animals

Studies on the nature of the peripheral sudomotor control mechanism.

Electron microscopical studies of the sweat glands of the body surface of the cow, sheep, goat and cat demonstrated that there were few nerves or blood vessels near the glands. No varicosities were found within 10 micron of the glands, and the small number of unmyelinated nerve bundles traced were over 1.5 micron from the glandular myoepithelium, and situated outside a fibrocyte sheath surrounding the glands. It was concluded that the sweat glands of these species are not innervated. Unmyelinated nerve fibres were more abundant around, and were closer to, the sweat glands of man, the horse and cat footpads, and varicosities were observed within the fibrocyte sheath close enough to have a direct influence on the glands. It is postulated from the comparative evidence that the basic sudomotor mechanism is the same in all species, involving the action of adrenergic and cholinergic nerves on the cutaneous blood vessels and local catecholamine transfer to the gland; and that in species such as man where the blood supply and sympathetic nerves are in close proximity to the glands, transmitters released at the sympathetic nerve endings, in particular acetylcholine, will, in addition, have a direct action on the glands.

Adult

Biochemical investigations of separated epithelium and stroma from benign hyperplastic prostatic tissue.

Using arginase and hydroxyproline as biochemical markers, the yields and homogeneity of separated epithelial and stromal tissues from surgically removed benign hyperplastic prostate glands have been assessed. On the basis of these markers, about 30% of epithelial and 95% of stromal tissues were recovered. Dehydroepiandrosterone sulphate sulphatase activity was found predominantly in the epithelium, whereas testosterone 5alpha-reductase activity was predominantly in the stroma.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase