PubMed Health⌕ Search

Biomedical subjects

N F Taylor

Publications and source records attributed to N F Taylor.

At least 73 records · Page 4Linked to original sources

Changes in fetal rhesus monkey plasma dehydroepiandrosterone sulfate: relationship to gestational age, adrenal weight and preterm delivery.

These studies were performed to assess the concentrations of dehydroepiandrosterone sulfate (DHAS) in the rhesus monkey fetal circulation from midgestation through the neonatal period, to determine the relation between changes in fetal adrenal size and DHAS levels both during gestation and after surgical stress, and to explore possible relations between changes in the concentration of DHAS in the fetal circulation and the initiation of labor. When plasma DHAS was quantified in cord blood and in serial samples from chronically catheterized rhesus monkey fetuses, a significant increase in plasma DHAS concentration occurred after 150 days gestational age (404 +/- 37 vs. 1093 +/- 159 ng/ml), and an additional increase was found after 159 days (2246 +/- 712 ng/ml). A diurnal change in fetal plasma DHAS occurred in chronically catheterized fetuses, with evening samples having higher values than morning samples. Further, there was an increase in plasma DHAS concentrations in the 4-5 days after fetal surgery. A significant increase in fetal plasma DHAS concentration occurred in the newborn rhesus monkey. Although plasma DHAS concentrations remained significantly higher than in the late gestation fetus, they decreased by approximately half within the first 2 weeks of life. A close correlation existed between fetal plasma DHAS and fetal adrenal weight in control fetuses delivered by hysterotomy and fetuses that were delivered 5 days after fetal surgery. Adrenal weights in the latter were significantly higher than those in comparably aged fetuses delivered by hysterotomy that had not undergone the stress of fetal surgery. The possible relationship between the increase in plasma DHAS and the initiation of labor was studied by monitoring the changes in daily morning DHAS concentrations in long term catheterized fetuses and comparing these values to the mean cross-sectional DHAS values corresponding to that gestational age. In all but one case, the values of DHAS, although they increased preceding delivery, were still within the range found in fetuses of the same gestational age that were not in labor. These data indicate that increases in DHAS are intimately related to parallel increases in fetal adrenal weight, that there are striking increases in DHAS levels near the end of gestation, that an increase in DHAS is a component of the fetal response to surgical stress, and that there is no immediately apparent, direct relationship between fetal DHAS and preterm delivery.

Adrenal Glands↗

The definitive identification of the lignans trans-2,3-bis(3-hydroxybenzyl)-gamma-butyrolactone and 2,3-bis(3-hydroxybenzyl)butane-1,4-diol in human and animal urine.

The definitive identification of the first lignans to be found in humans and animals is described. Gas chromatography--mass spectrometry, n.m.r. spectroscopy, i.r. spectroscopy and chemical techniques were employed to establish the structures of two lignans as trans-2,3-bis(3-hydroxybenzyl)-gamma-butyrolactone and 2,3-bis(3-hydroxybenzyl)butane-1,4-diol. Both compounds are essetially racemic. Evidence was also found for several methoxy analogues of these lignans in the vervet monkey.

4-Butyrolactone↗

The in vivo effects of 3-deoxy-3-fluoro-D-glucose metabolism on respiration in Locusta migratoria.

The basis of the toxicity of 3-deoxy-fluoro-D-glucose (3FG) in adult Locusta migratoria is examined in vivo by a radiorespirometric analysis of 14CO2 from the locust after injections of 3FG prior to injections of D-[1-14C]glucose, D-[6-14C]glucose, or [1-14C]acetate. The results indicate that 3FG metabolism irreversibly inhibits glycolysis and not the hexose monophosphate pathway or the tricarboxylic acid cycle. It is also established that during metabolism of 3FG fluoride ion is released. Evidence for the metabolism of 3FG in the whole insect as far as triosephosphate isomerase is based on 3H2O release after injections of D-[3-3H]3FG. Further support for the metabolism of 3FG to fluorinated sugar phosphates is provided by chromatographic and 19F MNR analysis of 3FG poisoned locust tissue extracts. Based on these results a biochemical mode of toxicity of 3FG in locusts is discussed.

Animals↗

The uptake of 3-deoxy-3-fluoro-D-glucose by synaptosomes from rat brain cortex.

D-[3-3H]-3-deoxy-3-fluoroglucose was synthesized chemically and shown to be transported into rat brain synaptosomes by a saturable process with a Km 6.2 x 10(-4) M and a Vmax 2.8 nmole x mg protein-1. After an initial, rapid period of transport, further uptake of the fluorosugar is restricted by the rate of its phosphorylation. Both D-glucose and cytochalasin B are competitive inhibitors of 3-deoxy-3-fluoro-D-glucose transport with Ki values of 93 micron and 6.0 x 10(-7) M, respectively. Phloretin, N-ethylmaleimide and p-chloromercuribenzoate also inhibit the fluorosugar uptake, whereas ouabain and changes in K+, Na+, Mg2+ and Ca2+ ions have only a small effect. The recorded 3-deoxy-3-fluoro-D-glucose influx is slightly reduced by potassium cyanide, antimycin A, 2,4-dinitrophenol, and rotenone. The uptake reduction caused by these four reagents is relieved by the addition of exogenous ATP. The possible influence of hexokinse activity on the uptake process is discussed.

Adenosine Triphosphate↗

The causes of low oestrogen excretion in pregnancy: the development of diagnostic methods for the antenatal detection of familial congenital adrenocortical hypoplasia.

A pregnancy producing a boy with congeital adrenocortical hypoplasia is described. Consistently low oestrogen excretion, less than 10 umol/24 h, was not associated with any anatomical abnormality or diminished growth of the fetus as judged by ultrasound examination. Fetoplacental steroid sulphatase definciency was excluded by finding normal maternal excretion of oestrogen precursors, the 3Beta-hydroxy-5-ene steroid sulphates. Generalized adrenocortical hypoplasia was proven in the baby boy by analysis of steroid netabolites excreted in his urine. He suffered from salt loss and progressive jaundice. Both were responsive to gluco- and mineralo-corticoid replacement therapy. It is suggested that amniocentesis may be required for the antenatal diagnosis of congenital adrenocortical hypoplasia.

Adrenal Cortex Hormones↗

The causes of low oestrogen excretion in pregnancy: assessment of the fetal contribution by steroid measurements post partum.

Oestrogen levels in urine from 21 normotensive and 13 hypertensive pregnant women were moderately correlated (r = 0.48) with levels of 3 beta-hydroxy-5-ene steroids (oestrogen precursors) in urine from their infants. In five infants from otherwise normal pregnancies in which oestrogen excretion was very low, levels of 3 beta-hydroxy-5-ene steroids were significantly lower than normal while there was no difference between hypertensives and normals. Levels of urinary cortisol metabolites in the infants were moderately correlated with 3 beta-hydroxy-5-ene steroids (r = 0.55) and were especially low in 2 out of 5 infants in the series suffering from distress during delivery. We conclude that subnormal fetal steroidogenesis rather than reduced placental metabolism is the most common cause of low oestrogen excretion of unknown aetiology. A factor in the increased perinatal risk in this group may be an associated insufficient cortisol synthesis by the fetus.

Birth Weight↗

D-glucose and D-gluconate transport in vesicles from Pseudomonas putida.

Vesicles prepared from glucose-grown cells of Pseudomonas putida (ATCC, 12633) retain glucose oxidase (GOX) and gluconate dehydrogenase (GADH) activity and actively transport D-glucose, 2-deoxy-D-glucose (2DOG), 3-deoxy-3-fluoro-D-glucose (3FG), and D-gluconate by saturable processes. The transport of these substrates is stimulated by the addition of L-malate or reduced phenazine methosulphate (PMS). Vesicles prepared from succinate-grown cells of P. putida lose their capacity to transport D-glucose, 2DOG, and 3FG by a saturable process. The transport and accumulation of D-gluconate, however, is retained with a KX value of 65 microM and a Vmax of 1.0 nmol . mg protein-1 . min-1. The rate of D-gluconate transport is stimulated by the addition of reduced PMS of L-malate with a reduction in the KX value to 42.0 microM. Respirometric studies with these vesicles indicate the presence of an active GOX and L-malate dehydrogenase but a defective GADH. Thus a reductase activity is detected in the presence of D-gluconate and either 2,6-dichloroindophenol (DCIP) or ferricyanide, as measured by a decrease in absorbance at 500 and 420 nm, respectively. Measurements on these vesicles with the oxygen electrode, however, indicate that no electron transfer from GADH to oxygen occurs. This is in contrast to the results with glucose-grown vesicles or with L-malate or D-glucose as substrates in the succinate-grown vesicles. A comparison between glucose and gluconate oxidase activity in native and detergent-treated vesicles is made. The significance of these results in relation to the presence of a glucose carrier in P. putida and other pseudomonads is presented.

Ascorbic Acid↗

An alternative synthesis of 4-deoxy-4-fluoro-D-glucose and its transport in the human erythrocyte.

Treatment of methyl 4-O-mesy-alpha-D-galactopyranoside with benzyl bromide in N,N-dimethylformamide in the presence of silver oxide yielded methyl 2,3,6-tri-O-benzyl-4-O-mesyl-alpha-D-galactopyranoside which with tert-butylammonium fluoride at reflux underwent nucleophilic displacement to give methyl 2,3,6-tri-O-benzyl-4-deoxy-4-fluoro-alpha-D-glucopyranoside. This compound on hydrogenolysis provided crystalline methyl 4-deoxy-4-fluoro-alpha-D-glucopyranoside (9). The structure of 9 was established by its conversion to the 2,3,6-tri-O-acetyl derivative and by n.m.r. and m.s. analysis. Acid hydrolysis of 9 gave 4-deoxy-4-fluoro-D-glucose (1). A modification of an established synthesis of 4-deoxy-D-xylo-hexose (2) from methyl 2,3,6-tri-O-benzoyl-alpha-D-galactopyranoside is described. A systematic comparison was made of the transport parameters (Kx and Vmax) of D-glucose, 2, and 1 in human erythrocytes. The Kx values observed for the above sugars are: 4.0mM, 4.5mM, and 4.6mM, respectively. These results indicate that O-4 in beta-D-glucopyranose is not involved in hydrogen bonding to the carrier protein associated with the transport of D-glucose in the erythrocyte.

Biological Transport↗

Analysis of glucocorticoid metabolites in the neonatal period: catabolism of cortisone acetate by an infant with 21-hydroxylase deficiency.

The urinary excretion of 27 individual 17-hydroxycorticosteroids by a female infant with 21-hydroxylase deficiency was studied using gas chromatography on an open-tubular column and combined gas chromatography-mass spectrometry. Samples were analysed from days 1, 3 and 4 of life, before cortisone acetate treatment commenced on day 6, and on days 9 and 192, during treatment. The pattern of metabolites before and after treatment showed similarities with extensive reductions at positions 3 and 20 of the steroid nucleus and hydroxylations at positions 1 and 6. The following new glucocorticoid metabolites were identified: 1beta,3alpha,17alpha,21-tetrahydroxy-5alpha(andbeta)-pregnane-11,20-dione; 3alpha,6xi,17alpha,21-tetrahydroxy-5xi-pregnane-11,20-dione (2 epimers); 1beta,3alpha,17alpha,20alpha(andbeta),21-pentahydroxy-5beta-pregnan-11-one, and 3alpha,6xi,17alpha,20alpha (andbeta),21-pentahydroxy-5beta-pregnan-11-one. These steroids comprised 50% of the total metabolites on day 9, but only 20% on day 192. They have also been detected in the urine of normal neonates.

17-Hydroxycorticosteroids↗

15alpha-Hydroxyoestriol and other polar oestrogens in pregnancy monitoring.

Although oestriol measurements are well established for the assessment of 'at risk' pregnancies, there are a number of other oestrogens, excreted during pregnancy, which contain additional hydroxyl groups and might be more sensitive indicators of the condition of mother or fetus. Some of these result from the action of hydroxylases possibly present only in the fetus and others from maternal hydroxylations. We review the evidence for the biosynthesis of these polar oestrogens, summarise methods of measurement, and compare values obtained in normal and pathological pregnancies. There is as yet insufficient evidence to enable their potential value to be confirmed.

Catechols↗

The metabolism of 3-deoxy-3-fluoro-D-glucose by Locusta migratoria and Schistocerca gregaria.

3-Deoxy-3-fluoro-D-glucose (3FG) administered by injection is toxic to adult Locusta migratoria or Schistocerca gregaria (LD50, 4.8 mg/g). temperature-programmed and isothermal gas chromatographic analysis of poisoned locust haemolymph reveals the presence of a fluorinated metabolite identified as 3-deoxy-3-fluoro-D-glucitol (3FGL). The enzymes responsible for the accumulation of this metabolite are located in the fat body of the insect and partially purified as aldose reductase (alditol: NADP+ 1-oxidoreductase, EC 1.1.1.21) and sorbitol dehydrogenase (L-iditol: NAD+ 5-oxidoreductase EC 1.1.1.14) 3FGL is shown to be both a competitive inhibitor of the NAD-linked sorbitol dehydrogenase with Ki 8¿x 10(-2) M as well as a substrate with Km 0.5 M. A kinetic rate equation is derived and verified to account for the kinetic duality of 3FGL. These results partially explain the toxic effects of 3FG and are consistent with the presence of a hitherto undetected sorbitol metabolism in locusts.

Alcohol Oxidoreductases↗

Some biochemical effects of 4-deoxy-4-fluoro-D-glucose on Escherichia coli.

The uptake of 4-deoxy-4-fluoro-D-glucose (4FG), without subsequent catabolism, by resting cells of Escherichia coli (ATCC 11775) is 0.06 mg/mg dry weight. In frozen-thawed cells of this organism, 4FG is a substrate for the phosphoenolpyruvate phosphotransferase system with a rate of phosphorylation twice that found for the isomeric 3-deoxy-3-fluoro-D-glucose. 4FG is not a carbon source for growth of this organism and it inhibits the extent of growth of cells in the presence of glucose. The inhibition of growth of E. coli K12 on lactose by 4FG is also observed and this is considered to be consistent with the fact that 4FG is an uncompetitive inhibitor of beta-galactosidase (EC 3.2.1.23) activity and that 4FG or 4-deoxy-4-fluoro-D-glucose-6 phosphate repress beta-galactosidase synthesis. These results support the view that catabolite repression may be produced by compounds which are not necessarily metabolised further than hexose-6-phosphates.

Cell Division↗