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Biomedical subjects

A W Pike

Publications and source records attributed to A W Pike.

At least 37 records · Page 2Linked to original sources
PubMed1986

The role of steroid metabolic profiling as an aid in the diagnosis of familial precocious puberty, a subgroup of true precocious puberty.

We report the results of a study of a rare form of true precocious puberty in a family with a history of the condition. Only the male members manifest the trait, whereas it appears to be carried by both males and females. Routine urinary steroid analysis rapidly eliminated most of the classical enzyme defects associated with premature sexual maturation. Further investigation of urinary steroid extracts using gas chromatography and gas chromatography-mass spectrometry revealed essentially normal prepubertal androgen values for the proband A at 4 years of age, and for his affected and carrier relatives when compared with healthy age-matched individuals. While his plasma gonadotropin levels were in the prepubertal range, his plasma testosterone value was significantly elevated with values just below the normal range for an adult male. This is the fourteenth reported family with a vertical pattern of familial sexual precocity, but the first to have a steroid profile. Analysis suggests sex-limited autosomal dominance with a greater than 90% penetrance. The elevated plasma testosterone concentration, prepubertal plasma gonadotropin concentration, minimal histopathologic evidence of gametogenesis and only moderate increase in testicular volume over the five-year course of follow-up support a diagnosis of the recently described condition of familial gonadotropin independent sexual precocity. The gas chromatography-mass spectrometry urinary profiling shows elevated cortisol output but otherwise normal adrenal function.

17-Hydroxycorticosteroids↗
PubMed1986

Progesterone metabolism in T47Dco human breast cancer cells--I. 5 alpha-pregnan-3 beta,6 alpha-diol-20-one is the secreted product.

Progesterone is a major hormone controlling normal breast development and function. In breast cancer, progesterone may be involved in tumor growth regulation, and the concentration of the intracellular receptor proteins for progesterone are used to distinguish hormone dependent from autonomous tumors. We have been studying the cytoplasmic and nuclear distribution of progesterone receptors after progesterone treatment of cultured T47Dco human breast cancer cells. Anomalous behavior of the receptors, when progesterone was compared to synthetic progestins, suggested that progesterone was being rapidly metabolized by the cells. We have now studied this metabolism in detail. When progesterone is added to medium of proliferating cells, it disappears with a half life of 2-4 h. A single metabolite (P-metabolite) is quantitatively released into the medium, but its release is delayed 10-14 h. The quantitative conversion of progesterone to P-metabolite was confirmed using two independent methods: gas chromatography with internal standards, and 14C-radioisotope measurements. We have used gas chromatography, gas chromatography/mass spectrometry, thin layer chromatography and nuclear magnetic resonance to identify the final metabolic product released into the medium as 5 alpha-pregnan-3 beta,6 alpha-diol-20-one.

Breast Neoplasms↗
PubMed1986

Progesterone metabolism in T47Dco human breast cancer cells--II. Intracellular metabolic path of progesterone and synthetic progestins.

We show here that progesterone added to the medium of proliferating T47Dco human breast cancer cells is metabolized with a half life of 2-4h. The final metabolic product, 5 alpha-pregnan-3 beta,6 alpha-diol-20-one, (P-metabolite) is released into the medium. This structure suggested that the intracellular metabolism of progesterone involves the enzymes 5 alpha-reductase, 3 beta-hydroxysteroid dehydrogenase, and 6 alpha-hydroxylase. To investigate this pathway, the cells were incubated with a variety of potential substrates. In addition to progesterone, only precursors with the 5 alpha-configuration served as substrates for the enzymes leading to P-metabolite formation. Some precursors with a 5 beta-configuration were also metabolized by T47Dco cells. This metabolism reflected activity by either 3 beta-hydroxysteroid dehydrogenase and/or 6 alpha-hydroxylase but, in contrast to progesterone metabolism, the rates were different and the products were often mixtures. In T47Dco and MCF-7 human breast tumor cells, the reduction at C-3 followed by 6 alpha-hydroxylation, appear to be the major, and possibly only, route of progesterone metabolism. In contrast, preliminary data suggest that in normal human breast epithelial cells, this is not an exclusive route. Androgens are partially subject to the same metabolic enzymes, but synthetic progestins are not metabolized by T47Dco during an 18 h incubation.

3-Hydroxysteroid Dehydrogenases↗
PubMed1984

Semi-micro quantitative analysis of complex urinary steroid mixtures in healthy and diseased states.

A method for the determination of urinary steroid hormones in healthy and diseased states is described. The use of a Van den Berg all-glass injector coupled to a fused silica column has shown a dramatic increase in sensitivity and a significant reduction in gas chromatography analytical time. The increase in sensitivity also eliminates the need for processing large volumes of urine. The method has proven to be rapid, precise, reproducible and sensitive. Also, column life is increased due to the absence of solvent. This technique has shown to have broad applications in the analysis of such classes of compounds as sugars, steroids, prostaglandins and fatty acids.

Adrenal Hyperplasia, Congenital↗
PubMed1983

Progesterone receptor replenishment in T47D human breast cancer cells. Roles of protein synthesis and hormone metabolism.

T47D are unusual human breast cancer cells that do not require estrogen to synthesize high levels of progesterone receptors. These cells can, therefore, be used to study the mechanisms by which progesterone, freed of estrogen interference, controls the synthesis of its receptors. In a recent paper we described progesterone receptor translocation and a subsequent very rapid nuclear processing step that results in an apparent loss of 60 to 80% of cellular progesterone receptors, 30 to 60 min after progesterone treatment. This paper deals with the replenishment of cellular receptors following processing. If progesterone is removed from cells after 60 min of treatment, cytoplasmic progesterone receptors replenish in 16 to 20 h. However, replenishment occurs even during chronic progesterone treatment; this is an artifact created by the extremely rapid (t1/2 approximately 2 h) metabolism of progesterone in media exposed to cells. If progesterone metabolism is blocked, then replenishment is not seen, probably because the hormone continuously retranslocates the newly replenished sites. There is an early protein synthesis-dependent step; cycloheximide in the first 4 h inhibits replenishment 24 h later, but if cycloheximide is slightly delayed (beyond 4 h), replenishment proceeds normally. In contrast to progesterone, the synthetic progestin R5020 completely suppresses progesterone receptor replenishment even 96 h after its removal from the medium. This compound can bind covalently to receptors and may be very difficult to remove from cells. Clearly, progestin treatment, and by analogy, circulating progesterone, will have profound effects on cytoplasmic and nuclear progesterone receptor levels when these are measured in biopsied human tumors as an adjunct to endocrine therapy.

Breast Neoplasms↗
PubMed1981

Pregnanediols and breast milk jaundice.

Samples of breast milk collected from mothers of infants with breast milk jaundice were analysed for 5 beta-pregnane-3 alpha, 20 beta-diol, and other pregnanediols using gas chromatography-high resolution mass spectrometry. None was detected in any of the specimens and therefore it is unlikely to be the inhibitory factor in bilirubin conjugation. The plasma osmolalities of the infants, which were determined at the onset of jaundice, were within normal limits.

Breast Feeding↗
PubMed1981

Measurement of diethylstilbestrol in plasma from patients with cancer of the prostate.

A specific radioimmunoassay has been developed for diethylstilbestrol (DES), using an antiserum raised against DES monocarboxymethyl ether and a tritium-labeled radioligand. Prior to radioimmunoassay, a fraction enriched in DES is obtained from a dichloroethane extract of plasma using Sephadex LH-20. The specificity of the assay is good, and the sensitivity (130 pg/ml) is adequate for accurate determination of DES in plasma from prostatic cancer patients treated with the drug. The precision is satisfactory, with an interassay coefficient of variation of approximately 10% at concentrations of approximately 1 ng/ml, and the blank values are negligible. Excellent agreement (r = 0.96) is observed between data obtained by radioimmunoassay and those obtained by a procedure using gas chromatography-high-resolution mass spectrometry. DES concentrations in the plasma of six treated (1 mg DES three times daily) patients were in the range 0.15 to 6.0 ng/ml. Increases in plasma concentration were observed within 2 hr of administration, with secondary rises occurring 5 to 6 hr later. Plasma testosterone concentrations were low in four of the patients; in a single subject, relatively high levels of testosterone were further elevated following administration of luteinizing hormone-releasing hormone.

Circadian Rhythm↗
PubMed1980

Analyses of steroids in saliva using highly selective mass spectrometric techniques.

Highly selective techniques of gas chromatography mass spectrometry have been used in the unequivocal identification of salivary steroids at concentrations ranging from 20 pg ml-1 to 20 ng ml-1. Oestradiol-17 beta, for example, has been identified in pregnancy saliva by gas chromatography high resolution mass spectrometry selected ion monitoring of the bis-TMS ether and by gas chromatography mass spectrometry metastable peak monitoring of the bis-tert-butyldimethylsilyl ether. Dehydroepiandrosterone sulphate has been identified in saliva, following enzymic hydrolysis, by gas chromatography high resolution mass spectrometry selected ion monitoring of the tert-butyldimethylsilyl ether and methyloxime tert-butyldimethylsilyl ether. These initial analyses have been designed to guide the development of routine immunoassay procedures which may subsequently be validated by comparison with reference gas chromatographic mass spectrometric methods.

Dehydroepiandrosterone↗
PubMed1980

Analysis of testosterone and dehydroepiandrosterone in saliva by gas chromatography-mass spectrometry.

Testosterone and 3 beta-hydroxyandrost-5-en-17-one (dehydroepiandrosterone) have been identified in human parotid fluid and saliva by gas chromatography-mass spectrometry/selected ion monitoring analyses of the t-butyldimethylsilyl ether and methyl oxime, t-butyldimethylsilyl ether derivatives. High specificity of analysis has been achieved by the use of high mass spectrometric resolution or by the monitoring of metastable peaks. Quantitative analyses indicate concentrations of both unconjugated testosterone and unconjugated dehydroepiandrosterone in the range 200-800 pmol/l in the saliva and parotid fluid of the normal males examined. These represent 1.5-7.5% of the concentrations of the steroids in blood plasma taken from the same subjects.

Dehydroepiandrosterone↗
PubMed1980

Mating activity of Nematospiroides dubius in laboratory mice.

Incidence of mating pairs in 40 worm infections in 5 week old female CBA mice increased up to day 30 post infection. By this time, and thereafter until the experiment ended on day 70, approximately 60% of the worm population occurred as mating pairs. Mating began during the ontogenetic migration of the worms. There was no difference between the percentage of worms mating in the more highly populated anterior sections of the small intestine as compared to the less densely populated more posterior sections. Significantly more female than male worms were recovered between days 8 and 20 post infection (P < 0.02 to 0.001) and there was a significant decline in overall recoveries during the experimental period (r = -0.77, P < 0.01). Low intensity infections, with 4 to 16 worms per mouse, demonstrated that a larger percentage of worms in the infection were mating at an earlier time post infection than in the 40 worm infections. Ontogenetic migration was reduced in low intensity infections because the initial distribution of worms was more restricted.

Animals↗
PubMed1980

Helminth parasites of wild cats in north-east Scotland.

Three cestode species, namely Taenia taeniaeformis Batsch, 1786, Taenia pisiformis (Bloch, 1780) and Mesocestoides litteratus (Batsch, 1786) and one nematode species, Toxocara cati Schrank, 1788, were found in wild cats collected in Grampian region, Scotland. Of the 41 cats examined, 25 were Felis silvestris, 12 were feral Felis catus and four were hybrids of F. silvestris and F. catus.

Animals↗