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Biomedical subjects

W L Ledger

Publications and source records attributed to W L Ledger.

46 records · Page 3Linked to original sources
PubMed1991

Localization of the sites of synthesis and action of prolactin by immunocytochemistry and in-situ hybridization within the human utero-placental unit.

While the fetal pituitary synthesizes and releases prolactin, it is also produced within the utero-placental unit during pregnancy in women and has been localized in the amnion, chorion and decidua. However, it is not clear whether prolactin is synthesized within all these non-fetal pituitary tissues. We have investigated prolactin production and its gene expression using tissue culture, immunocytochemistry and in-situ hybridization techniques. Prolactin was immunolocalized not only in the decidua but also in amnion and trophoblast cells. In contrast, the in-situ hybridization results showed that silver grains, formed by specific hybridization of a prolactin cDNA probe to prolactin mRNA, were confined to decidual cells of early and term pregnancy. The results from tissue cultures correlated well with those of in-situ hybridization, that is that only the decidua made detectable prolactin, while it was undetectable in the culture medium from trophoblast tissue, irrespective of the stage of pregnancy. This study, for the first time, establishes that only decidualized cells are involved in biosynthesis of prolactin; other prolactin-containing cells in the amnion and trophoblast appear to sequester prolactin, possibly via receptors, suggesting that prolactin may play an important paracrine role within the amnion and syncitio- and cytotrophoblast of the utero-placental unit.

Blotting, Northern↗
PubMed1989

Suppression of gonadotrophin secretion does not reverse premature ovarian failure.

The effect of prolonged inhibition of gonadotrophin secretion was studied in 12 women with premature ovarian failure. All the patients had plasma concentrations of follicle-stimulating hormone (FSH) greater than 20 i.u./l, and in six, primordial follicles had been seen on ovarian biopsy. Goserelin (Zoladex, ICI), a depot synthetic analogue of luteinizing hormone-releasing hormone (LHRH) was administered by three consecutive 4-weekly injections. Plasma concentrations of luteinizing hormone (LH) fell from 34 (SD 11) i.u./l to 2.4 (SD 1.9) i.u./l, and plasma concentrations of FSH fell from 106 (SD 29) i.u./l to 4.5 (SD 2.6) i.u./l 4 weeks after the first injection. Plasma concentrations of gonadotrophins returned to pretreatment values in every patient within 9 weeks of the final injection of goserelin. Regular ultrasonography during the period following the final injection failed to demonstrate the development of ovarian follicles in any patient, and plasma concentrations of oestradiol remained below 100 pmol/l. This study has failed to show that suppression of gonadotrophin secretion reverses premature ovarian failure.

Adult↗
PubMed1987

The influence of steroid hormones on the uterine cervix during pregnancy.

This paper reviews the evidence concerning the actions of steroid hormones on the connective tissues of the pelvis. Most available data concern the effects of steroids on the cervix. The time course of cervical softening in rats, sheep and humans suggests the possibility that the changes in connective tissue biochemistry that underlie the physiological phenomenon of cervical softening are under hormonal control. Both oestrogens and progestogens have been implicated in the control of cervical softening. However, recent experiments using inhibitors of 3 beta-hydroxysteroid dehydrogenase suggest that cervical softening can be produced in both sheep and humans by progesterone withdrawal in the absence of high circulating concentrations of oestradiol-17 beta.

3-Hydroxysteroid Dehydrogenases↗
PubMed1985

Increase in cervical extensibility during labor induced after isolation of the cervix from the uterus in pregnant ewes.

Surgical transection of the cervix was done on eight ewes in late pregnancy. This procedure resulted in most of the length of the cervix being mechanically disconnected from the uterus. Labor was induced by injection of dexamethasone phosphate into a fetal hind limb during operation in four of the eight ewes. The success of the induction of labor was confirmed by observation of increased uterine activity and by measurement of the concentrations of progesterone and 17 beta-estradiol in peripheral plasma. Ewes were put to death approximately 48 hours after injection of dexamethasone and the extensibility of the isolated portion of the cervix was determined. Cervices taken from ewes in which labor had been induced were found to have softened considerably compared to control cervices taken from ewes in which the cervix had been transected without induction of labor. The results suggest that cervical softening can still occur during labor in the absence of any direct mechanical or local vascular connection between the cervix and uterus.

Animals↗
PubMed1985

Effect of inhibition of prostaglandin synthesis on cervical softening and uterine activity during ovine parturition resulting from progesterone withdrawal induced by epostane.

The effects of an inhibitor of 3 beta-hydroxysteroid dehydrogenase (epostane) on uterine activity and cervical softening have been studied in eight sheep during late pregnancy. Treatment with epostane led to a rapid decline in the concentration of progesterone measured in utero-ovarian venous plasma, to less than 10% of the pretreatment value within 30 min of bolus injection. This was followed by a significant (P less than 0.02) increase in the concentrations of metabolites of prostaglandins E and F in utero-ovarian venous plasma and uterine activity similar to that seen in the final stages of normal labour. Measurements of cervical tissue extensibility made ex vivo showed the cervix to have softened considerably. These changes occurred without any significant change in the concentration of oestradiol-17 beta in utero-ovarian venous plasma. Infusion of mefenamic acid, an inhibitor of prostaglandin synthesis, prevented the changes in uterine activity and cervical softening that occurred after injection of epostane alone. Mefenamic acid also reduced the increase in concentrations of metabolites of prostaglandins E and F in plasma, although the concentration of progesterone in these animals showed the same abrupt fall which occurred in sheep after injection of epostane alone. These results suggest that progesterone withdrawal, in the absence of any subsequent rise in circulating oestrogen concentrations, is sufficient stimulus to induce cervical softening in the ewe. Cervical softening following progesterone withdrawal can be prevented by inhibition of prostaglandin synthesis.

3-Hydroxysteroid Dehydrogenases↗
PubMed1983

Cervical softening in late pregnant sheep by infusion of prostaglandin E-2 into a cervical artery.

Cervical softening was induced in late pregnant sheep by infusion of PGE-2 into a cervical artery. The effect of this treatment was assessed by measurement of the extensibility in vitro of a strip of cervical tissue. After infusion of a saline/ethanol mixture extensibility was 2.84 X 10(-3) +/- 0.3 X 10(-3) min-1 (mean +/- s.e.m., N = 5); after infusion of PGE-2 it increased significantly (P less than 0.02) to 8.6 X 10(-3) +/- 1.8 X 10(-3) min-1 (N = 6). Infusion of PGE-2 did not increase uterine activity, and there was no significant change in the concentration of progesterone in the maternal jugular venous plasma. These data suggest that PGE-2 might act as a mediator of cervical softening in vivo and show that the cervix can soften in the absence of uterine contractions.

Animals↗
PubMedDate not supplied

Inhibins and activins in human ovulation, conception and pregnancy.

The activins and inhibins are glycoproteins that belong to the transforming growth factor-beta superfamily and, as such, have diverse effects at many stages during growth and development. Originally identified by their effects on follicle stimulating hormone in males and females, the recent development of specific and sensitive assays for this group of polypeptides has permitted the elucidation of their role in 'fine-tuning' the hypothalamic-pituitary-gonadal axis. This review article focuses on the roles of inhibin and activin in female reproductive physiology with reference to possible future clinical applications in the investigation of infertility and abnormal pregnancy.

Activin Receptors↗
PubMedDate not supplied

Peritoneal healing and adhesion formation/reformation.

Intra-abdominal adhesion formation and reformation after surgery is a cause of significant morbidity, resulting in infertility and pain. The understanding of the pathogenesis of adhesion formation and reformation especially at the cellular and molecular level can help to further develop more effective treatments for the prevention of adhesion formation and reformation. Following an injury to the peritoneum, fibrinolytic activity over the peritoneal surface decreases, leading to changes in the expression and synthesis of various cellular mediators and in the remodelling of the connective tissue. The cellular response to peritoneal injury and adhesion formation and reformation are reviewed. Analysis of the available literature data on the cellular mediators in the peritoneal fluid showed variation in results from different investigators. The potential sources of variability and error are examined. It is still unclear if there is significant individual variation in the peritoneal response to injury.

Ascitic Fluid↗
PubMedDate not supplied

A computer-based flowcharting system for clinical protocols.

In medicine, scientific and technological developments for investigation and treatment are proceeding at an ever increasing rate. Protocols for patient management are becoming ever more complicated. Rational design and scientific evaluation of protocols requires precise documentation. We propose a notation based on a series of simple flowcharts which describe procedures in increasing detail. Each step in a flowchart is justified by a reasoned argument, possibly including reference to published articles. General correctness requirements of a protocol include, for example, conformity with known indications and contraindications for investigations and treatments. These correctness requirements can be specified declaratively in mathematical logic and justified by reasoned argument. This makes the correspondence between a protocol and its scientific foundation even more explicit. Flowcharts of this nature are more easily created and modified using a personal computer. Furthermore, use of the computer enables a protocol to be checked automatically against its specification for more rapid identification of errors during development and maintenance of the protocol. We present the structured design of our flowcharting system in the 'Z' specification language, and we examine the practicality of our approach by means of a case study; the management of infertility. Our flowcharting system may also have application outside medicine where it is necessary to describe formal protocols for complex procedures.

Algorithms↗