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Biomedical subjects

M B Clark

Publications and source records attributed to M B Clark.

9 recordsLinked to original sources

Influence of contextual features on the activation of ambiguous word meanings.

Three studies examined whether initial meaning activation is sensitive to context. Experiment 1 demonstrated that contextually appropriate targets were activated more than inappropriate targets. Experiment 2 evaluated activation across intervals of 0, 300, and 600 ms. Constraining sentences activated contextually appropriate meanings over inappropriate meanings. This was maintained across the intervals for highly salient targets. Less-salient targets, although initially activated, were no longer activated 300 ms following the homograph. Experiment 3 converged on context-sensitive activation following a 50-ms exposure of the sentence-final homograph. Conclusions are (a) initial meaning activation can be sensitive to context, (b) when a homograph is instantiated, it is congruent with a broad scope of targets, and (c) less-salient targets receive less activation over the time course.

Adult

Loss of nerve cell bodies in caudal locus coeruleus following treatment of neonates with 6-hydroxydopa.

The locus coeruleus is a well defined nucleus in cresylechtviolet preparations and the perikarya are easily distinguished. The coeruleus neurons are thought to be noradrenergic and during development can be selectively affected by the neurotoxin, 6-hydroxydopa (6-OHDOPA). In 6-month-old rats that were treated on day of birth with 6-OHDOPA (60 mg/kg, i.p.) there was a 32% loss of nerve cell bodies in the locus coeruleus. While it was apparent that loss of cell bodies occurred throughout the entire nucleus, the greatest loss of perikarya was from the caudal extent of the nucleus. It is known that sprouting of noradrenergic terminals occurs in the cerebellum of rats following treatment of newborns with 6-OHDOPA. That there are fewer cell bodies to contribute additional terminals further dramatizes this sprouting phenomenon.

Animals

Fractured neck of femur in the elderly: an attempt to identify patients at risk.

1. During a 15-month period, 110 elderly patients admitted with fractured neck of femur were studied in comparison with 72 elderly control patients undergoing elective surgery admitted over the same period to the same orthopaedic wards. 2. A striking finding was the marked similarity of all variables measured in the fracture and control groups. The principal differences between the two populations were that the fracture patients had a lower mean forearm bone mineral content, and that their serum concentrations of albumin, globulin and phosphate were reduced. 3. Neither measurements of radioisotopic calcium absorption, nor those of the serum concentrations of calcium, 25-hydroxy-vitamin D3 nor alkaline phosphatase provided satisfactory discrimination between the groups. 4. Several indices were devised, based on linear combinations of the test results obtained, in an attempt to predict the liability to future fractures of patients being considered for prophylactic therapy with oestrogens or other drugs. However, further work is required to define an index of improved predictive power and to evaluate it prospectively.

Aged

The photobiogenesis and metabolism of vitamin D.

Provitamin D3 (7-dehydrocholesterol) is converted to previtamin D3 by the action of ultraviolet radiation on the skin. Previtamin D3 thermally isomerizes to vitamin D3 in the skin and the vitamin is then transported to the liver on the vitamin D-binding protein. Although there are extrahepatic vitamin D-25-hydroxylases, the liver is the major site for the 25-hydroxylation of vitamin D. In response to hypocalcemia and hypophosphatemia, 25-OH-D is metabolized by a renal-cytochrome. P450-dependent mixed function oxidase system is 1alpha,25(OH)2D. When calcium and phosphate homeostasis prevails the renal 25-OH-D-1alpha-hydroxylase activity is limited and instead a non-cytochrome P450 mixed function oxidase metabolizes 25-OH-D to 24R,25(OH)2D. Parathyroid hormone has clearly been shown to be a trophin for the renal synthesis of 1,25(OH)2D; however, the role and significance of the adrenal steroids, or gonadal and pituitary hormones, on the renal 25-OH-D-1alpha-hydroxylase is not well defined. The regulation of the photometabolism of provitamin D3 to vitamin D3, the role and significance of the side-chain metabolism of 1,25(OH)2D by the small intestine, and the metabolism of 25-OH-D to 24R,25(OH)2D by chondrocytes and its stimulation of protein synthesis in these cells are just a few issues that will require further investigation.

Animals

The metabolism of [6-3H]1alpha, hydroxycholecalciferol to [6-3H]1alpha,25-dihydroxycholecalciferol in a patient with renal insufficiency.

To evaluate whether 1alpha-hydroxycholecalciferol is metabolized to 1alpha,25-dihydroxycholecalciferol in man, [6-3H]1alpha-hydroxycholecalciferol was given intravenously to a patient with renal failure who was maintained daily on 100,000 IU vitamin D and calcium supplements. Using Sephadex LH-20 and high-pressure liquid chromatography, it was clearly demonstrated that 1alpha-hydroxycholecalciferol rapidly disappears from the blood and is metabolized to 1alpha,25-dihydroxycholecalciferol.

Dihydroxycholecalciferols

Treatment of hypoparathyroidism and pseudohypoparathyroidism with metabolites of vitamin D: evidence for impaired conversion of 25-hydroxyvitamin D to 1 alpha,25-dihydroxyvitamin D.

In hypoparathyroidism and pseudohypoparathyroidism, pharmacologic doses of vitamin D correct hypocalcemia, but the mechanism is unknown. In two children with hypoparathyroidism and one with pseudohypoparathyroidism we tested the hypothesis that in these conditions there is a defect in synthesis of 1 alpha,25-dihydroxyvitamin D3, the principal active metabolite of vitamin D. In both conditions, minute doses of the metabolite (0.04 to 0.08 mug per kilogram of body weight per day) quickly corrected hypocalcemia and increased intestinal calcium absorption. On the other hand, the effective dose of 25-hydroxyvitamin D3 to maintain normocalcemia was 3 to 4 mug per kilogram per day in the two conditions. Thus, the dosage ratio of 25-hydroxyvitamin D3 to 1 alpha,25-dihydroxyvitamin D3 approximated 100:1. By contrast this ratio was approximately 3:1 in two infants with vitamin D deficiency, a condition in which optimal metabolism of vitamin D would be expected. These findings suggest an impaired conversion of 25-hydroxyvitamin D to 1 alpha,25-dihydroxyvitamin D in both hypoparathyroidism and pseudohypoparathyroidism.

Administration, Oral