Search PubMed⌕ Search

Biomedical subjects

M D Mitchell

Publications and source records attributed to M D Mitchell.

At least 271 records · Page 15Linked to original sources
PubMed1982

The prostaglandin synthase inhibiting ability of maternal plasma and the onset of human labor.

Using an enzyme incubation-radioimmunoassay technique we have cross-sectionally studied the prostaglandin synthase inhibiting ability of plasma in relation to human pregnancy. The inhibitory potency of human plasma did not change with the onset of pregnancy, at parturition or during the puerperium. A significant decrease in potency did occur however in the third trimester of pregnancy. This preparturient decrease raises the possibility of a role in the onset of human labor for the factor(s) causing the inhibition.

Adult↗
PubMed1982

Oxytocin in the fetal and maternal circulations during induced and spontaneous parturition in sheep.

Oxytocin has been measured in fetal and maternal plasma samples obtained serially from 6 sheep during late pregnancy, spontaneous labor and labor induced by intrafetal infusion of Synacthen (ACTH1-24). Fetal plasma contained significantly (P less than 0.001) greater concentrations of oxytocin than maternal plasma. Concentrations of oxytocin rose in maternal plasma during the later stages of spontaneous and induced labor, whereas concentrations in fetal plasma did not exhibit a consistent trend.

Animals↗
PubMed1982

Stimulants of prostaglandin biosynthesis in human fetal membranes, uterine decidua vera and placenta.

Modulation of prostaglandin (PG) biosynthesis by cytosolic fractions derived from homogenates of human amnion, chorion laeve, decidua vera and placenta was examined. PGF2 alpha and 6-oxo-PGF1 alpha synthesis by bovine seminal vesicle (BSV) PG synthase was stimulated by the cytosolic fractions of each tissue in a dose-dependent manner. The cytosols from decidua vera and placenta were the most effective in stimulating synthesis and also stimulated PGE2 biosynthesis. Reduced glutathione (GSH) acted to increase the biosynthesis of PGE2 at the expense of other PGs both in the presence and absence of various cytosols. These data are indicative that the mode of action of cytosolic fractions on the stimulation of PG biosynthesis is unlike that of GSH. Indomethacin and aspirin, inhibitors of fatty acid cyclo-oxygenase activity, strongly inhibited the cytosol-induced stimulation of BSV PG synthase. The cytosolic factors that stimulated PG biosynthesis exhibited differential behavior towards boiling and dialysis. The stimulatory effect of all cytosolic fractions was sensitive to boiling except in the the chorion laeve effects toward 6-oxo-PGF1 alpha production. In dialysis studies we found that the cytosolic components that stimulated the production of PGF2 alpha were not removed by dialysis except in the case of cytosol of placenta whereas the stimulatory effects of various cytosols toward the biosynthesis of PGE2 and 6-oxo-PGF1 alpha were removed by dialysis. These results are indicative of the presence of endogenous factors in human intrauterine tissues that preferentially stimulate the biosynthesis of PGF2 alpha and 6-oxo-PGF1 alpha and are further suggestive that PG biosynthesis in intrauterine tissues is, at least in part, regulated by cytosolic factors.

Animals↗
PubMed1982

Plasma 6-keto-prostaglandin F1 alpha in disorders involving hypokalemia.

We measured plasma levels of 6-keto-prostaglandin F1 alpha by radioimmunoassay in patients with hypokalemia due to various disorders. Plasma 6-keto-PGF1 alpha in patients with disorders involving hypokalemia was not different from that of normal controls. Treatment with inhibitors of prostaglandin synthesis for 5-7 days in three patients with Bartter's syndrome decreased 6-keto-PGF1 alpha plasma levels by about 25%. It is suggested that, plasma 6-keto-PGF1 alpha may, on occasions, be a poor index of circulating prostacyclin.

6-Ketoprostaglandin F1 alpha↗
PubMed1982

A sensitive radioimmunoassay for 11-deoxy-13, 14-dihydro-15-keto-11, 16-cyclo-prostaglandin E2: application as an index of prostaglandin E2 biosynthesis during human pregnancy and parturition.

A radioimmunoassay for 11-deoxy-13, 14-dihydro-15-keto-11, 16-cycloprostaglandin E2 (PGEM-II) is described. At pH 10.5, in the presence of albumin, 13, 14-dihydro-15-keto-prostaglandin E2 (PGEM-I) is transformed quantitatively into PGEM-II. Hence, after plasma samples are subjected to this transformation procedure, PGEM-II can be measured in such samples and be a true reflection of PGEM-I production and thereby prostaglandin E2 (PGE2) biosynthesis. The antiserum raised against PGEM-II is minimally cross-reactive with all prostaglandins tested (less than 0.01%). The mean least detectable mass of PGEM-II is 0.8 pg and the mean mass of added PGEM-II required to displace zero-point binding by 50% is 16.6 pg. The assay meets all the standard criteria for accuracy, reproducibility and parallelism. Concentrations of PGEM-II measured by this assay in peripheral plasma from men and nonpregnant women are similar to those reported for PGEM-I after measurements by gas chromatography - mass spectrometry. Plasma concentrations of PGEM-II in men were greater than in nonpregnant women. PGEM-II in increased concentration was found in early pregnancy although concentrations declined in the third trimester until labor when a significant increase was found. Concentrations of PGEM-II in umbilical venous plasma were significantly greater than those in maternal plasma.

Adult↗
PubMed1982

Inhibition of prostaglandin biosynthesis by human low-density and high-density lipoproteins.

The ability of human low-density lipoprotein (LDL) and high-density lipoprotein (HDL) to inhibit the biosynthesis of prostaglandin (PG) E2, F2 alpha prostacyclin from arachidonic acid by bull seminal vesicle (BSV) PG synthase was studied. Both LDL an HDL inhibited the PG synthase activity in BSV microsomes. The greatest inhibitory effect was observed against th biosynthesis of PGE2. These results show an higher to unrecognised property of human lipoproteins that may mediate some of the biological actions of these substances.

Adult↗
PubMed1982

Prostaglandin biosynthesis in the human fetal adrenal gland: regulation by glucocorticosteroids.

Human fetal adrenal (HFA) tissue was maintained in organ culture to evaluate the biosynthesis of prostaglandins and hormonal regulation of prostaglandin formation by this tissue. The HFA tissue secreted substantial amounts of prostaglandin E(2), prostaglandin F(2alpha), 13,14-dihydro-15-ketoprostaglandin F(2alpha), 6-ketoprostaglandin F(1alpha), and thromboxane B(2); secretion of prostaglandin D(2) could not be demonstrated. Prostaglandin biosynthesis in HFA tissue was inhibited in a time-dependent manner by corticotropin (ACTH; 0.4 muM); by the fourth day of culture, the extent of inhibition of biosynthesis of each prostaglandin was 60-90%. Progesterone (1 muM), cortisol (1 muM), and dexamethasone (1 muM) inhibited prostaglandin biosynthesis whereas estradiol (1 muM) did not. Of the compounds tested for inhibitory activity, dexamethasone was the most potent. An inhibitor of 11beta-hydroxylase activity (metyrapone; 0.1 mM) effectively eliminated the inhibition of prostaglandin biosynthesis caused by corticotropin and progesterone. Metyrapone treatment alone caused a 3-fold increase in prostaglandin biosynthesis by fetal adrenal tissues. Similar stimulatory effects resulted from treatment with inhibitors of (i) 3beta-hydroxysteroid dehydrogenase (cyanoketone; 15 muM), (ii) steroid 17alpha-hydroxylase (SU 10603; 19 muM), and (iii) cholesterol side-chain cleavage (aminoglutethimide; 1 mM). Inhibition of prostaglandin biosynthesis by dexamethasone in the presence or absence of metyrapone was concentration dependent and 50% inhibition could be demonstrated at 1 nM. A competitive inhibitor of the binding of glucocorticosteroids to cytoplasmic receptors (cortisol 21-mesylate; 1 muM) significantly reduced the inhibition of prostaglandin biosynthesis effected by dexamethasone (10 nM). These findings suggest that prostaglandin biosynthesis in the HFA gland is regulated by endogenously synthesized glucocorticosteroids, the actions of which are mediated by a glucocorticosteroid receptor. Such glucocorticosteroids induce the synthesis of a substance that inhibits prostaglandin biosynthesis.

Adrenal Glands↗
PubMed1982

Pulsatile release of oxytocin during the estrous cycle, pregnancy and parturition in sheep.

Oxytocin has been measured in peripheral plasma from chronically catheterized sheep both during estrus and the early luteal phase of the estrous cycle and also during pregnancy at 122-124 days gestation, 141-145 days gestation and during spontaneous labor at term. In each experiment, blood samples were collected at 5-min intervals for 120 min and also at 1-min intervals for 10 min. In pregnant and nonpregnant sheep, pulsatile patterns of oxytocin concentrations were found in the experimental periods. Mean concentrations of oxytocin were significantly higher in plasma obtained during the luteal phase of the cycle when compared to samples taken during estrus. Moreover, concentrations of oxytocin were increased with length of gestation and labor. It is concluded that oxytocin secretion is episodic in sheep during both the estrous cycle and pregnancy.

Animals↗
PubMed1982

Inhibition of prostaglandin synthase by maternal plasma factor(s) in early human pregnancy.

Using an enzyme incubation-radioimmunoassay technique, we have tested the hypothesis that an increase in a maternal plasma factor(s) that inhibits prostaglandin synthase (EC 1.14.99.1) is responsible for the suppression of decidual prostaglandin production that occurs in early human pregnancy. Measurements made on serial maternal samples failed to reveal any significant increase in plasma inhibitory activity at this time, and it was concluded that the conceptus achieves the reduction in prostaglandin synthesis by a mechanism other than a systemically mediated direct inhibition of decidual prostaglandin synthase.

Cyclooxygenase Inhibitors↗
PubMed1982

Inhibiton of prostaglandin synthesis by human amniotic fluid: acute reduction in inhibitory activity of amniotic fluid obtained during labor.

Human amniotic fluid contains an inhibitor of prostaglandin synthesis. The activity of the inhibitor was measured in amniotic fluid obtained in early pregnancy, and at term both before and after the onset of labor. The inhibitory activity was greater in amniotic fluid taken in early pregnancy than in fluid taken at term before the onset of labor (P less than 0.05). There was a further significant reduction in inhibitory activity (P less than 0.01) in amniotic fluid collected during labor. These results are suggestive that the onset of labor is associated with a local withdrawal of inhibition of prostaglandin biosynthesis.

Albumins↗
PubMed1982

Effect of progesterone withdrawal in sheep during late pregnancy.

The concentration of progesterone in the peripheral plasma of seven sheep during late pregnancy was reduced by injection of an inhibitor of 3 beta-hydroxysteroid dehydrogenase activity. Concentrations of progesterone were 10.0 +/- 1.0 (S.E.M) ng/ml (n = 6) before injection of the inhibitor, fell to 1.39 +/- 0.40 ng/ml (n = 6) 30 min after injection, and remained within this lowered range for 6 h after injection. By 20-24h and 30-35h after injection progesterone concentrations had recovered to 4.63 +/- 0.94 and 14.07 +/-4.17 ng/ml respectively (n = 6). Six out of seven ewes delivered prematurely 32.5 +/- 2.9h after injection. Delivery appeared to be normal, and was associated with increasing concentrations of 13, 14-dihydro-15-oxo prostaglandin F2 alpha in peripheral plasma. Concentrations of oestradiol-17 beta in peripheral plasma were slightly raised immediately before delivery, at which time progesterone concentrations were within the preinjection range. These data suggest that progesterone withdrawal is one mechanism that initiates increased prostaglandin F2 alpha secretion in the pregnant sheep.

Abortifacient Agents↗
PubMed1982

Assay of plasma endogenous inhibitor(s) of prostaglandin synthase using an enzyme incubation - radioimmunoassay method.

A simple, reliable method with validations is described for the routine measurement of endogenous inhibitor(s) of prostaglandin synthase in blood plasma. Appropriate dilutions of plasma samples are incubated with bovine seminal vesicle prostaglandin synthase, sodium arachidonate and reduced glutathione. Prostaglandin E2 production is then quantitated by radioimmunoassay. The relative inhibitory potency of plasma samples is determined by comparison of prostaglandin E2 content in sample incubations with that of control incubations containing no plasma dilution. Possible applications and the suitability of this methodological approach are discussed.

Animals↗
PubMed1982

Formation of arachidonate lipoxygenase metabolites by human fetal membranes, uterine decidua vera and placenta.

Homogenates (1000 x g supernatant fraction) of human amnion, chorion laeve, decidua vera and placenta were incubated with [1(-14)C] arachidonic acid in the presence or absence of indomethacin, an inhibitor of cyclooxygenase activity and nordihydroguairetic acid (NDGA), an inhibitor of lipoxygenase activity. After incubation, the products were extracted with ethyl acetate and identified by thin layer chromatography and high performance liquid chromatography. The major lipoxygenase products formed by human amnion, decidua vera and placenta were 12-L-hydroxy-5,8,10,14-eicosatretetraenoic acid (12-HETE) and smaller amounts of 5-HETE. Chorion laeve produced only a trace amount of 12-HETE. The formation of these products was abolished by NDGA and slightly stimulated by indomethacin. These findings demonstrate the existence of lipoxygenase activity in human intra-uterine tissues and suggest that products of lipoxygenase activity in these tissues may regulate the recruitment of leukocytes and/or macrophages during pregnancy and parturition.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗