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Biomedical subjects

P R Bennett

Publications and source records attributed to P R Bennett.

9 recordsLinked to original sources
PubMed1992

The mechanisms of preterm labor: common genital tract pathogens do not metabolize arachidonic acid to prostaglandins or to other eicosanoids.

OBJECTIVE: Our aim was to determine the ability of pathogens commonly associated with genital tract infection and preterm labor to incorporate arachidonic acid and to metabolize it to prostaglandins or to other eicosanoids. STUDY DESIGN: Four common genital tract pathogens, Escherichia coli, Streptococcus viridans, Bacteroides fragilis, and a group B beta-hemolytic streptococcus, were incubated with tritium-labeled arachidonic acid for 2 to 48 hours. Uptake of arachidonic acid was calculated from uptake of radioactivity into the organisms. Tritium-labeled arachidonic acid within the medium was separated from any metabolites by high-performance liquid chromatography to assess metabolism of arachidonic acid within the bacteria. RESULTS: Although all organisms were able to take up arachidonic acid, analysis of its metabolism with high-performance liquid chromatography demonstrated that none of these organisms will synthesize cyclooxygenase, lipoxygenase, or epoxygenase products. CONCLUSION: Bacterial infection cannot initiate preterm labor by intrinsic biosynthesis and release of prostaglandins or other eicosanoids by the bacteria themselves.

Arachidonic Acid↗
PubMed1992

The mechanisms of preterm labour; the interaction between amnion cells and leukocytes in the metabolism of arachidonic acid.

Chorioamnionitis is frequently associated with preterm labour. We have used a cell culture model system to examine the effects of leukocytes upon the metabolism of endogenous arachidonic acid from within amnion cells. We have demonstrated that activated leukocytes release substances which increase the overall release and metabolism of endogenous arachidonic acid within amnion cells causing an increase in prostaglandin E2 production as well as a smaller increase in non-cyclo-oxygenase metabolism. When amnion cells and leukocytes are cultured together, in addition to prostaglandin E2 production by amnion cells, arachidonic acid released by the amnion cells appears to be metabolised by leucocytes to prostaglandin F2 alpha, prostacyclin and thromboxane A2. Prostaglandins E2 and F2 alpha are the principal cyclo-oxygenase products of this interaction. We postulate that chorioamnionitis stimulates preterm labour not only by causing an increase in prostaglandin E2 synthesis by amnion cells but by metabolism of amnion derived arachidonic acid to the powerfully oxytocic prostaglandin F2 alpha by leukocytes.

Amnion↗
PubMed1992

Changes in expression of the cyclooxygenase gene in human fetal membranes and placenta with labor.

OBJECTIVE: Our objective was to examine the expression of the gene coding for cyclooxygenase, the central enzyme in prostaglandin synthesis, in human placenta and fetal membranes during pregnancy and before and after labor at term. STUDY DESIGN: Expression of the gene for cyclooxygenase was examined with Northern hybridization to ribonucleic acid from human placenta throughout pregnancy and human amnion and chorion decidua in the late third trimester. RESULTS: Expression was undetectable in trophoblast during the first and second trimesters. Expression in amnion and trophoblast increased 3.5- and 2.5-fold, respectively, in association with labor. CONCLUSIONS: Our results suggest that the increase in prostaglandin synthesis within the uterus that is seen with the onset of labor is associated with an increase in the expression of the gene cyclooxygenase.

Amnion↗
PubMed1992

Expression of human chorionic gonadotrophin alpha and beta subunits is depressed in trophoblast from pregnancies with early embryonic failure.

The expression of the placental proteins human chorionic gonadotrophin alpha (HCG alpha), beta (HCG beta) and human placental lactogen (HPL) was examined in trophoblast from human normal pregnancy and early embryonic failure (EEF) using Northern blot analysis. Trophoblast from EEF expressed significantly depressed levels of HCG alpha (P < 0.05) and HCG beta (P < 0.01) when compared to normal pregnancy. Levels of expression of HPL in EEF were not significantly different to those from normal pregnancy. The gestational ages of the two groups were not significantly different. Immunocytochemistry on paraffin-fixed tissue sections supported these data and showed that mRNA levels reflected protein production of HCG within the tissue. It appears from these data that the depressed level of HCG found in the serum of women with early pregnancy failure is not solely a consequence of diminished placentation in these pregnancies, or placental necrosis, but that the genes of the alpha and beta HCG subunits are down-regulated. This study further suggests that there are two subsets of women with early pregnancy failure; those with apparently normal levels of placental proteins, and those with severely depressed levels. It would seem likely that these two groups have different aetiologies.

Abortion, Spontaneous↗
PubMed1991

Trophoblast from anembryonic pregnancy has both a maternal and a paternal contribution to its genome.

In a series of 14 anembryonic pregnancies, deoxyribonucleic acid from trophoblast was examined with locus-specific minisatellite probes. It was found in each case that trophoblast from anembryonic pregnancy has both a maternal and a paternal contribution to its genome. This means that although anembryonic pregnancy shares characteristics with complete hydatidiform mole and androgenetic development in the mouse in that there is no embryo, it does not arise by the same genetic process. Of three anembryonic pregnancies that were successfully karyotyped, two had normal female 46,XX chromosome constitutions and one had an abnormal 47,XX + 16 complement. The sex of the trophoblast in each anembryonic pregnancy was determined with a deoxyribonucleic acid probe with Y-specific bands. A male-to-female ratio of 6:8 was found, which is not significantly different from normal.

Chromosome Mapping↗
PubMed1991

Genetic conservation of cyclo-oxygenase.

Homology between sheep and mouse cyclo-oxygenase cDNA and a range of other species was investigated using "zoo blots". Both the sheep and mouse cDNAs showed a high degree of homology to other species. Human cyclooxygenase appears to have greater homology to sheep and other ruminants than to mouse. Both sheep and mouse cDNAs detected identically sized transcripts in human placental total RNA.

Animals↗
PubMed1990

Mechanisms of parturition: the transfer of prostaglandin E2 and 5-hydroxyeicosatetraenoic acid across fetal membranes.

Prostaglandin E2 production by amnion is thought to be an important event in the onset of human labor. It has been suggested that 5-hydroxyeicosatetraenoic acid, also produced in the amnion, may mediate prelabor contractions. For either of these compounds to play a paracrine role they need to cross the chorion, which has a high capacity to metabolize prostaglandins. With the use of an in vitro system we have shown that both prostaglandin E2 and 5-hydroxyeicosatetraenoic acid cross either amnion or intact amnion-chorion-decidua at a rate similar to that of an extracellular marker sucrose. Analysis by high performance liquid chromatography revealed that at physiologic concentrations neither prostaglandin E2 nor 5-hydroxyeicosatetraenoic acid were metabolized by amnion alone. Moreover, 100% of the 5-hydroxyeicosatetraenoic acid and 72% of the prostaglandin E2 remained in the active form after passage across intact amnion-chorion-decidua. There did not appear to be any difference in the rate of transfer or permeability of the membranes before or after spontaneous labor. We conclude that both 5-hydroxyeicosatetraenoic acid and prostaglandin E2 synthesised in the amnion can cross the membranes by diffusion through the extracellular space, remaining largely unmetabolized, and may play a role in the onset of human labor.

Biological Transport↗