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Biomedical subjects

D R Fraser

Publications and source records attributed to D R Fraser.

At least 19 recordsLinked to original sources
PubMed1991

Bone mineral content of British and rural Gambian women aged 18-80+ years.

The bone mineral content (BMC) of the mid-shaft radius was measured in 446 rural Gambian and 349 British women aged 18-80+ years using single-photon absorptiometry. The two groups of women differed substantially in habitual calcium intake, calcium requirements for reproduction, physical activity and incidence of minimal-trauma fractures. The relationships of BMC with bone width (BW) and with body weight and height were explored using stepwise multiple regression analysis. The pattern of BMC with age was similar in The Gambia and Britain; BMC increased slightly to a peak at the end of the fourth decade followed by a decrease of about 30% between 40 and 70+ years. Gambian women had significantly lower BMC than British women of the same age (-5.6%, P less than 0.001) but after adjusting for weight, height and BW, the BMC of Gambian women was shown to be slightly higher than that of British women (+2.1%, P less than 0.05).

Absorptiometry, Photon↗
PubMed1990

Bone mineral content of Gambian and British children aged 0-36 months.

The influence of age, sex and body size on the bone mineral content of the radius (BMC) measured by single-photon absorptiometry has been studied in 134 British and 243 rural Gambian children aged 0-36 months. Growth rates and childhood nutrition, including calcium intakes, were markedly different in the two communities. In both groups BMC increased with age and was higher in boys (8%, P less than 0.001). Adjustment for body size (height, weight, bone width), using multiple regression analysis, removed the age effect and reduced the sex difference to 4% (P less than 0.01). Gambian children had significantly lower BMCs than British children of the same age (P less than 0.001), averaging 11% close to birth and diverging to a calculated difference of 31% at 36 months. The differential was reduced after adjustment for body size but remained significant (P less than 0.01) with BMC values diverging from birth to a predicted difference of 12% at 15 kg body weight. The extent to which these results reflect the low calcium intakes of Gambian children requires further study.

Aging↗
PubMed1990

Breast-milk calcium concentrations during prolonged lactation in British and rural Gambian mothers.

Detailed investigation of breast-milk calcium concentrations during 2 years of lactation have been conducted in Cambridge, UK, and rural Gambia. Mature milk concentrations remained steady for 3 months but declined during months 4-12 by over 25% (p less than 0.001). The pattern was identical in both communities despite differences in breast-feeding practices. Calcium concentrations were not related to feed frequency or breast-milk sodium concentrations, suggesting that breast involution is not responsible for the decrease after 3 months. Breast-milk calcium concentrations were characteristic of the individual, varied twofold between mothers and were independent of maternal age, parity and milk output. Gambian breast-milk contained 19% less calcium than Cambridge milk, throughout lactation (p less than 0.001). The extent to which this reflected the lower calcium intakes of Gambian mothers is unknown. Further studies are required to determine factors regulating breast-milk calcium secretion.

Breast Feeding↗
PubMed1988

Vitamin D supply to the rat fetus and neonate.

The prevention of neonatal rickets by oral supplementation with vitamin D2 (ergocalciferol) has tended to obscure our ignorance of the natural mechanism by which young mammals receive an adequate supply of vitamin D. To investigate the possibility of specific intrauterine transfer and storage of vitamin D in fetal tissues, vitamin D-deficient female rats were given depot injections of 3H- or 14C-labeled vitamin D3 (cholecalciferol) before mating and the 3H-labeled animals were killed at stages during the last third of gestation. Analysis of lipid extracts from whole fetuses revealed a linear increase in the concentration of 25-hydroxyvitamin D3, 24,25-dihydroxyvitamin D3, and D3 itself between days 14 and 19 of gestation. During this period the elimination half-time of 3H-labeled molecules in maternal plasma fell from 27.1 to 4.4 d, suggesting that a specific mechanism was transferring vitamin D molecules into the fetuses. The vitamin was stored predominantly as 25-hydroxyvitamin D3 and 24,25-dihydroxyvitamin D3, with the highest concentrations in fetal muscle. Immediately after birth, pups from 3H- and 14C-labeled mothers were exchanged and later killed after 1-3 wk of suckling. Analysis of total lipid extracts for 3H and 14C content determined the relative contributions of vitamin D supplied before birth via the placenta and after birth in the maternal milk. The vitamin D content of the rat milk was relatively high, between 1.0 and 3.5 micrograms/liter. Nevertheless, the supply of vitamin D in utero, rather than from milk, was the main determinant of vitamin D status in early neonatal life. This is the first indication in a mammal of a specific transfer mechanism that allows the fetus to accumulate vitamin D from the mother during the last third of gestation.

24,25-Dihydroxyvitamin D 3↗
PubMed1987

Metabolic inactivation of vitamin D is enhanced in primary hyperparathyroidism.

1. The elimination half-time of 25-hydroxyvitamin D in plasma was estimated after intravenous injection of the radioactively labelled metabolite in seven patients with primary hyperparathyroidism before and after excision of a parathyroid adenoma. 2. The elimination half-time of 25-hydroxyvitamin D was significantly shortened in primary hyperparathyroidism and reverted towards normal after parathyroidectomy. 3. The increased metabolic clearance of 25-hydroxyvitamin D in primary hyperparathyroidism was accounted for by an increased excretion of vitamin D-derived inactivation products in the faeces. 4. Enhanced hepatic inactivation of 25-hydroxyvitamin D may be important in the development of vitamin D deficiency in primary hyperparathyroidism.

Aged↗
PubMed1984

Enterohepatic circulation of vitamin D: a reappraisal of the hypothesis.

Vitamin-D metabolites in bile were investigated after oral and intravenous doses of radioactively labelled vitamin D had been given to six patients with T-tube biliary drainage after cholecystectomy. The vitamin was mainly excreted as highly polar inactivation products and less than 4% of the metabolites in bile were present as 25-hydroxyvitamin D or its glucuronide conjugate. There was insufficient vitamin D or 25-hydroxyvitamin D in bile for the reabsorption of these metabolites to make a significant contribution to normal vitamin-D status. Therefore interference with an enterohepatic circulation of vitamin-D metabolites cannot be a cause of vitamin-D deficiency.

Administration, Oral↗
PubMed1983

Mitochondrial Ca2+ transport in lean and genetically obese (ob/ob) mice.

Isolated mitochondria from liver or brown adipose tissue of obese ob/ob mice demonstrated increased rates of Ca2+ uptake and release compared with those of lean mice. This enhanced transport activity was not found in mitochondria from kidney or skeletal muscle. Respiration-induced membrane potential was the same in mitochondria from lean and ob/ob mice. It is therefore concluded that the increased Ca2+ uptake rates reflect an activation of the Ca2+ uniporter rather than a change in the electrophoretic driving force. As mitochondria from pre-obese ob/ob mice did not show elevated rates of Ca2+ transport, the activated transport in the obese animals was thus a consequence of the state of obesity rather than being a direct effect of the ob/ob genotype. It is suggested that the enhanced activity of the Ca2+-transport pathways in liver and brown adipose tissue may alter metabolic functions in these tissues by modifying cytoplasmic or intramitochondrial Ca2+ concentrations.

Adipose Tissue, Brown↗
PubMed1983

The influence of GDP on Ca2+ uptake by mitochondria of brown adipose tissue from lean and genetically obese (ob/ob) mice.

The specific binding capacity for purine nucleotides in brown-adipose-tissue mitochondria is thought to indicate the capacity of the proton-conductance pathway which leads to uncoupled respiration. This functional relationship was investigated in studies measuring initial Ca2+-uptake rates and membrane potential in the presence or absence of GDP in brown-adipose-tissue mitochondria with different GDP-binding capacities. The mitochondria from pre-obese and obese ob/ob mice were less able than those from lean control mice to dissipate membrane potential in the absence of GDP. Mitochondria from the obese animals also maintained a higher Ca2+-uptake rate without GDP in comparison with the rate found with mitochondria from the lean mice. The GDP-dependence of Ca2+ uptake was greater in brown-adipose-tissue mitochondria from cold-adapted animals than in those from animals kept at 22 degrees C or at thermoneutrality (33 degrees C). It is concluded that Ca2+-uptake rate and membrane-potential values are depressed in the absence of GDP and indicate indirectly the influence of purine nucleotides on maintaining the proton electrochemical gradient in brown-adipose-tissue mitochondria. It is also apparent that the lower GDP-binding capacity in mitochondria from ob/ob mice is related to a decreased ability to dissipate the proton electrochemical gradient.

Adipose Tissue, Brown↗
PubMed1983

Effect of dietary cereals on intestinal permeability in experimental enteropathy in rats.

A sensitivity to dietary cereal has been reported previously in niacin-deficient rats by measuring a change in the intestinal absorption of radioactively-labelled cellobiotol and mannitol. The possibility that other stimuli could produce this sensitivity, the range of cereals that could induce the permeability change and the nature of the toxic component in cereal have now all been investigated. Treatment with triparanol induces sensitivity in rats to wheat, rye, barley, oats, and maize but not to rice or soybean. These cereals caused a similar response in niacin-deficient rats. Mucosal damage produced by methotrexate or cetrimide, however, did not sensitise the intestinal mucosa to dietary cereals. Gluten, zein, and pepsin/trypsin digests of gluten all induced the permeability defect in triparanol-treated rats. It is concluded that although gross disruption of the mucosal structure may not sensitise rats to cereals, various causes of mucosal cell damage can produce a susceptibility to gluten toxicity that resembles gluten-sensitivity in man.

Animals↗
PubMed1983

Naturally developing antibodies to wheat gliadin fractions and to other cereal antigens in rabbits, rats and guinea pigs on normal laboratory diets.

Rabbits, rats and guinea pigs on normal laboratory diets were examined for gliadin and other cereal antibodies comparable to those found in the sera of human coeliac patients. Many of the rabbits had very high levels of gliadin antibodies. Rats showed much lower titres more comparable to the findings in normal human sera. In both these species the reactivity was directed principally against the alpha-gliadins. The spectrum of reactivity against the prolamines of other cereals was again comparable to that of human coeliac sera. A difference, however, was the high reactivity with maize prolamine; this was decidedly lower in sera of coeliac patients. Guinea pigs were distinctive in having relatively no serum antibodies to wheat gliadin and also minimal reactivity to the albumins, globulins and glutenins of wheat. Normal guinea pigs did, however, have antibodies to oat and maize prolamines. Following parenteral injection with total ethanol-soluble wheat gliadin, guinea pigs developed high-titred antibodies, not only to wheat gliadin fractions 1-8 (alpha-, beta-, gamma- and omega-gliadins), but also to all the cereal prolamines except those of rice. These investigations are steps in the evaluation of the role of circulating gliadin antibodies in gluten-sensitive enteropathy.

Animals↗
PubMed1982

Assessment of intestinal permeability in the experimental rat with [3H]cellobiotol and [14C]mannitol.

1. The intestinal absorption of a mixture of [3H]cellobiotol and [14C]mannitol was determined by measuring the 3H/14C ratio in urine after oral administration of the labelled sugars to rats. This index of intestinal permeability was used to identify cellular dysfunction in experimental enteropathy in rats. 2. Rats with mucosal damage induced with ethanol showed an increased uptake of [3H]cellobiotol and a decreased uptake of [14C]mannitol compared with normal controls. The increased 3H/14C ratio in urine reflected the abnormal cell function known to be caused by ethanol. 3. Methotrexate treatment reduced the absorption of the two sugars whereas cetrimide treatment enhanced their absorption. However, in both methotrexate-induced and cetrimide-induced enteropathy the 3H/14C ratio in urine was unaffected by the mucosal damage. Here the permeability change was not related to absorptive dysfunction of the mucosal cells. 4. It is concluded that this labelled sugar absorption test enables the rapid and accurate identification of malfunction of intestinal mucosal cells in the rat. Moreover, the test distinguishes between changes in permeability caused by abnormal cell function and changes caused by gross disturbance of the structure of the mucosal surface.

Animals↗
PubMed1981

Vitamin D plasma binding protein. Turnover and fate in the rabbit.

The metabolic disposition of the plasma binding protein (DBP) for vitamin D and its metabolites was studied in adult rabbits. Apo-DBP was purified from rabbit plasma and enzymatically labeled with radioiodine. The radioiodine-labeled protein retained its ability to bind vitamin D sterols and its physicochemical properties. When 125I-labeled DBP and 131I-labeled rabbit albumin were simultaneously injected intravenously, the 125I was cleared from plasma at a faster rate (t 1/2 = 1.7 d) than 131I (t 1/2 = 5 d) and 125I was present in excess of 131I in kidney, liver, skeletal muscle, heart, lung, intestine, testis, and bone 1 h after injection. In contrast to DBP, 25(OH)D3 was cleared more slowly (t 1/2 = 10.7 d). Compared to albumin, DBP radioactivity appeared earlier and in greater quantity in the urine of catheterized rabbits. Gel filtration analyses of plasma revealed most of the 125I to elute in the position of DBP, with only small amounts in the less than 1,000-dalton region. In contrast, almost all of the urine 125I eluted in this small molecular weight fraction. The molar ratio of DBP to 25(OH)D3 in normal rabbit plasma was 138/1. The extravascular pool of DBP was calculated to be 1.5-2.4 times larger than the intravascular DBP pool, and the molar replacement rate of DBP was 1,350-fold higher than that of 25(OH)D3. The plasma disappearance curves of holo-DBP, prepared either by saturating with 25(OH)D3 or by covalently linking 3 beta-bromoacetoxy-25(OH)D3, were very similar to that of apo-DBP. Neuraminidase treatment of DBP did not alter its plasma survival. These studies indicate that DBP or DBP-25(OH)D3 complex is removed from plasma by a variety of tissues, that the DBP moiety is degraded during this process, and that a significant recirculation of 25(OH)D3 probably occurs. The molar excess of DBP to 25(OH)D3 in plasma, and the relatively rapid turnover of DBP indicate that a high capacity, high affinity, and dynamic transport mechanism for vitamin D sterols exists in rabbit plasma.

Animals↗