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Biomedical subjects

D R Fraser

Publications and source records attributed to D R Fraser.

At least 37 records · Page 2Linked to original sources
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

The metabolic origin of trigonelline in the rat.

A hypothesis of Mason & Kodicek [(1970) Biochem. J. 120, 515-521] that esterified nicotinic acid in niacytin from cereals is a precursor for trigonelline was investigated in rats. Single oral doses of niacytin resulted in the excretion of trigonelline in urine but only in rats that were niacin-deficient and were fed a cereal diet. These animals were found to have an abnormally permeable intestine, which allowed the uptake of molecules not usually absorbed. Orally administered synthetic [14C]nicotinoyl[3H]methylcellulose was shown to be absorbed by niacin-deficient rats on a cereal diet and [14C]trigonelline was excreted in urine. These data indicate that dietary cereal induces a permeability defect in the intestinal mucosa of niacin-deficient rats, which allows the uptake of macromolecular niacytin. The nicotinoyl pyridine nitrogen atom is then methylated and slow hydrolysis releases trigonelline from the macromolecule.

Alkaloids↗
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↗
PubMed1980

Isolation of Neisseria lactamica from the female genital tract. A case report.

Neisseria lactamica was isolated from the genital tract of a young patient with a persistent vaginal discharge. Although infection with N lactamica occurs very rarely, the importance of complete biochemical identification of neisseriae is emphasised in view of the serious social and medicolegal consequences which could result from a misdiagnosis of gonorrhoea.

Adolescent↗
PubMed1976

Vitamin D in the avian egg. Its molecular identity and mechanism of incorporation into yolk.

The chemical identity of vitamin D in the egg of the domestic fowl was studied by analysing radioactivity in eggs from hens injected with [3H]cholecalciferol. Labelled molecules were found throughout the egg, but the concentration of total radioactivity in albumin was only 5-7% of that in yolk. In lipid extracts of yolk, more than 90% of the radioactivity was as unchanged cholecalciferol and 5% as 25-hydroxycholecalciferol. Only about 3% of the radioactivity in albumin was chloroform-soluble, and of this 40% was 25-hydroxycholecalciferol and 15% was cholecalciferol. Evidence is presented to support the idea that the specific transport of cholecalciferol into yolk is mediated by a cholecalciferol-binding protein in blood. This protein forms a complex with yolk proteins in transit from liver to ovary via the blood. A cholecalciferol-binding protein, chromatographically similar to that from blood, was found in egg yolk. It is postulated that cholecalciferol forms part of a complex with its specific binding protein, Ca2+ and the yolk phosphoprotein, phosvitin. This complex is then incorporated into yolk by the thecal cells of the ovarian follicle.

Animals↗