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Biomedical subjects

N J Manning

Publications and source records attributed to N J Manning.

45 records · Page 3Linked to original sources
PubMed1987

Prenatal diagnosis of medium-chain acyl-coenzyme A dehydrogenase deficiency.

A fatal case of medium-chain acyl-coenzyme A dehydrogenase deficiency is described in a patient who presented with hypoglycaemia and a gross non-ketotic dicarboxylic aciduria. Cultured skin fibroblasts released 14CO2 from [1-14C] octanoic acid at half the normal rate. Prenatal diagnosis was undertaken in a subsequent pregnancy in which cultured amniotic fluid cells revealed a marked reduction in octanoate oxidation indicative of an affected fetus. The pregnancy was terminated and the diagnosis was confirmed by enzyme analysis of skin fibroblasts taken from the fetus. The high residual octanoate oxidation by affected fibroblasts together with the absence of any characteristic abnormality of amniotic fluid organic acids are a potential limitation to the reliability of this type of prenatal diagnosis.

Acyl-CoA Dehydrogenase↗
PubMed1987

Urinary organic acids in succinic semialdehyde dehydrogenase deficiency: evidence of alpha-oxidation of 4-hydroxybutyric acid, interaction of succinic semialdehyde with pyruvate dehydrogenase and possible secondary inhibition of mitochondrial beta-oxidation.

In addition to the previously reported abnormalities, urine extracts from three cases of succinic semialdehyde dehydrogenase deficiency have shown consistently increased amounts of 2,4-dihydroxybutyric acid, and its lactone, and 3-hydroxypropionic acid, metabolites related to the alpha-oxidation of 4-hydroxybutyric acid. Threo- and erythro-4,5-dihydroxyhexanoic acids have also been identified for the first time and probably arise from the reaction of succinic semialdehyde with an intermediate in the pyruvate dehydrogenase pathway. Adipic acid excretion is also consistently raised, suggesting secondary interference with mitochondrial beta-oxidation. The presence of these metabolites could be a source of diagnostic confusion.

Adipates↗
PubMed1985

Tracer studies of the interconversion of R- and S-methylmalonic semialdehydes in man.

Two human subjects were given separate oral doses of sodium [2H6]isobutyrate and [methyl-2H3]thymine and the labelling patterns of urinary metabolites were determined. Ingestion of deuterated isobutyrate resulted in the excretion of 2H5-labelled S-3-hydroxyisobutyric acid, formed on the direct catabolic pathway, and of S- and R-[2H4]-3-hydroxyisobutyric acids, formed by the reduction of S- and R-methylmalonic semialdehydes respectively. Only the R-enantiomer of urinary 3-hydroxyisobutyric acid was labelled by thymine. This labelling pattern indicates a flow from S- to R-methylmalonic semialdehyde, suggesting that the R-enantiomer is the substrate of methylmalonic semialdehyde dehydrogenase.

Butyrates↗
PubMed1985

The effect of temperature on testicular steroid production in the rainbow trout, Salmo gairdneri, in vivo and in vitro.

The effect of temperature on steroidogenesis in the male rainbow trout has been studied both in vitro using endogenous precursors under gonadotrophin stimulation and in vivo in fish held for 2 weeks at three different temperatures. In vitro, the optimum temperature for formation of testosterone and its 11-oxygenated derivatives was 10 degrees, whereas glucuronide formation showed an optimum at 18 degrees. In vivo, plasma levels of testosterone and 11-keto-testosterone were significantly higher at 6 than at 17 degrees, whereas glucuronide levels showed no significant difference. Milt was obtained only from fish held at 6 and 12 degrees. The optimum temperature for free steroid formation in response to gonadotrophin stimulus is shown to be dependent upon glucuronyl transferase content, and its progressive increase during the reproductive cycle may provide a mechanism for the inhibition of free steroid synthesis and hence spermiation at elevated temperatures where gamete survival is poor.

Animals↗
PubMed1984

Temperature regulation of ovarian steroid production in the common carp, Cyprinus carpio L., in vivo and in vitro.

The effect of temperature on ovarian steroid production in the common carp, Cyprinus carpio L., has been studied in vitro with exogenous and endogenous precursors, and in fish held at three different temperatures in vivo. With radioactive testosterone as substrate, the major metabolite was testosterone glucuronide, but androstenedione and 5 alpha-androstane-3 beta,17 beta-diol were also identified. 5 alpha-Androstane-3 beta,7 alpha,17 beta-triol was tentatively identified and two other polar metabolites were isolated, one of which was convertible to this triol. A significant increase in production of most metabolites occurred between 20 and 24 degrees. Production of estradiol and testosterone from endogenous substrate under gonadotrophin stimulation in vitro showed a marked temperature dependence, but the response was closely related to ovarian maturity. Stage 4-5 ovaries produced testosterone, while late Stage 3 tissue produced only estradiol. Neither steroid was produced in significant quantities by less mature ovaries. The results indicate that the "switch off" of ovarian aromatase activity at the end of vitellogenesis is actuated by an ovarian rather than by a pituitary factor. Secretion of testosterone and estradiol showed a very significant change with temperature with the optimum at 24-29 degrees. Profiles for individual fish show that this optimal range is extremely narrow, particularly for estradiol, where secretion may increase as much as twentyfold over 5 degrees. The results in general correlate well with 24 degrees as the most favourable temperature for reproduction in carp. Plasma concentrations of testosterone and estradiol closely paralleled the in vitro secretion rates of these hormones. Plasma testosterone levels were greatest in the most mature fish, whereas plasma estradiol was significantly higher in late Stage 3 fish than in those of greater or lesser ovarian maturity. More Stage 4 and 5 fish were found in the group held at 24 degrees than at 20 or 29 degrees for 4 weeks, but all groups contained a high proportion of early Stage 3 fish.

Androstane-3,17-diol↗