Publications
122 results found
Brown NL, Alvi SA, Elder MG, et al., 1998, Regulation of prostaglandin production in intact fetal membranes by interleukin-1 and its receptor antagonist, JOURNAL OF ENDOCRINOLOGY, Vol: 159, Pages: 519-526, ISSN: 0022-0795
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- Citations: 41
Brown NL, Alvi SA, Elder MG, et al., 1998, Interleukin-1β and bacterial endotoxin change the metabolism of prostaglandins E<sub>2</sub> and F<sub>2α</sub> in intact term fetal membranes, PLACENTA, Vol: 19, Pages: 625-630, ISSN: 0143-4004
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- Citations: 41
Rajakulasingam K, Till S, Ying S, et al., 1998, Increased expression of high affinity IgE (FcεRI) receptor-α chain mRNA and protein-bearing eosinophils in human allergen-induced atopic asthma, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 158, Pages: 233-240, ISSN: 1073-449X
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- Citations: 50
Rajasingam D, Bennett PR, Alvi SA, et al., 1998, Stimulation of prostaglandin production from intact human fetal membranes by bacteria and bacterial products, PLACENTA, Vol: 19, Pages: 301-306, ISSN: 0143-4004
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- Citations: 16
Brown NL, Alvi SA, Elder MG, et al., 1998, A spontaneous induction of fetal membrane prostaglandin production precedes clinical labour, JOURNAL OF ENDOCRINOLOGY, Vol: 157, Pages: R1-R6, ISSN: 0022-0795
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- Citations: 43
Sullivan MHF, Clark NAC, de Swiet M, et al., 1998, Titration of antiplatelet treatment in pregnant women at risk of preeclampsia, THROMBOSIS AND HAEMOSTASIS, Vol: 79, Pages: 743-746, ISSN: 0340-6245
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- Citations: 10
Bar J, Zosmer A, Hod M, et al., 1997, The regulation of platelet aggregation in vitro by interleukin-1 beta and tumor necrosis factor-alpha: Changes in pregnancy and in pre-eclampsia, THROMBOSIS AND HAEMOSTASIS, Vol: 78, Pages: 1255-1261, ISSN: 0340-6245
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- Citations: 28
Seki H, Zosmer A, Elder MG, et al., 1997, The regulation of progesterone and hCG production from placental cells by interleukin-1beta., Biochim Biophys Acta, Vol: 1336, Pages: 342-348, ISSN: 0006-3002
We have investigated the roles of interleukin-1beta as a regulator of progesterone and chorionic gonadotrophin production from human placental cells. In primary placental cells IL-1beta increased hCG synthesis through a cyclic AMP-independent pathway, and was without effect on progesterone or cyclic AMP production. Since dibutyryl cyclic AMP increased progesterone production, this suggests that there is no coupling between the IL-1beta receptor and the adenylate cyclase enzyme in these cells. Immortalised trophoblast cells responded to IL-1beta by increasing progesterone production through a cyclic AMP-dependent mechanism, but hCG production by these cells was unaffected by IL-1beta or dibutyryl cyclic AMP. Further studies are needed to identify the role of IL-1beta as a possible regulator of progesterone production in primary placental cells. While hCG production in first-trimester trophoblast was increased by dibutyryl cyclic AMP and IL-1beta, both these effects may involve other factors such as IL-6, and their second messenger systems.
Zosmer A, Elder MG, Sullivan MH, 1997, Second messengers and the control of progesterone production from first trimester trophoblast., J Steroid Biochem Mol Biol, Vol: 62, Pages: 201-205, ISSN: 0960-0760
Basal progesterone production from first trimester placental cells in culture was high during the first 24 h of culture and fell to less than 30% of the initial level after 96 h in vitro. 22(R)-Hydroxycholesterol had a similar effect on progesterone production at all incubation times, indicating that the decline in basal steroidogenesis was not due to a loss of mitochondrial or post-mitochondrial enzymes. Continuous stimulation with dibutyryl (db) cyclic AMP maintained progesterone synthesis at a relatively constant high level despite the fall in basal progesterone production, and the optimum concentration of db cyclic AMP was 1.0 mM. The calcium ionophore A23187 had no effect on progesterone incubation during short-term cultures (<4 h), and inhibited steroidogenesis after 24 h. Repeated addition of A23187 during 96 h of culture also inhibited progesterone production. These findings indicate that progesterone production in human trophoblast is supported by a local factor which maintains a high level of steroid production through a cyclic AMP-dependent mechanism. The inhibitory effects of calcium ionophore in trophoblast differ from the stimulatory effects of this compound in other steroidogenic cells, but the reasons for the difference are not known at present.
Bar J, Padoa A, Hod M, et al., 1997, Decreased pathological placental findings in aspirin-treated pregnant women at risk of hypertensive complications, HYPERTENSION IN PREGNANCY, Vol: 16, Pages: 435-444, ISSN: 1064-1955
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- Citations: 3
Lonsdale LB, Elder MG, Sullivan MHF, 1996, A comparison of cytokine and hormone production by decidual cells and tissue explants, JOURNAL OF ENDOCRINOLOGY, Vol: 151, Pages: 309-313, ISSN: 0022-0795
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- Citations: 25
Lewis MP, Clements M, Takeda S, et al., 1996, Partial characterization of an immortalized human trophoblast cell-line, TCL-1, which possesses a CSF-1 autocrine loop, PLACENTA, Vol: 17, Pages: 137-146, ISSN: 0143-4004
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- Citations: 64
Babawale MO, VanNoorden S, Pignatelli M, et al., 1996, Morphological interactions of human first trimester placental villi co-cultured with decidual explants, HUMAN REPRODUCTION, Vol: 11, Pages: 444-450, ISSN: 0268-1161
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- Citations: 23
Adeleye TA, Elder MG, Sullivan MHF, 1996, Preparation of a population of macrophages from human third trimester decidua, HUMAN REPRODUCTION, Vol: 11, Pages: 451-456, ISSN: 0268-1161
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- Citations: 3
Rutherford RAD, McCarthy A, Sullivan MHF, et al., 1995, Nitric oxide synthase in human placenta and umbilical cord from normal, intrauterine growth-retarded and pre-eclamptic pregnancies, BRITISH JOURNAL OF PHARMACOLOGY, Vol: 116, Pages: 3099-3109, ISSN: 0007-1188
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- Citations: 66
Cole OF, Seki H, Elder MG, et al., 1995, Interleukin-1 beta independently stimulates production of prostaglandin E2 and cyclic AMP from human decidual cells., Biochim Biophys Acta, Vol: 1269, Pages: 139-144, ISSN: 0006-3002
Interleukin-1 beta (IL-1 beta) increased the production of cyclic AMP and prostaglandin E2 (PGE2) by cultured human decidual cells during 24 h of stimulation, but not over short incubation times (< 6 h). At concentrations of IL-1 beta ranging from 1 to 100 pg/ml, there were parallel changes in cyclic AMP and PGE2 levels, but 1000 pg of IL-1 beta/ml inhibited cyclic AMP production while still stimulating PGE2 synthesis. The possible link between cyclic AMP and PGE2 was therefore studied further. Inhibition of IL-1 beta-stimulated PGE2 synthesis by indomethacin and direct addition of PGE2 had no effect on cyclic AMP levels, indicating that PGE2 did not increase cyclic AMP production by human decidual cells and confirming the independent synthesis of cyclic AMP and PGE2. The increase in cyclic AMP production induced by IL-1 beta is dependent on protein synthesis, but it is not known which component of the adenylate cyclase is increased. A phosphodiesterase inhibitor potentiated the effects of IL-1 beta on cyclic AMP synthesis, indicating that the cytokine may increase cyclic AMP metabolism. We suggest that high concentrations of IL-1 beta activate phosphodiesterase activity more than adenylate cyclase, which gives rise to the low levels of cyclic AMP noted above. IL-1 beta also decreased forskolin-stimulated cyclic AMP production, which again indicates increased cyclic AMP metabolism. Since most concentrations of IL-1 beta alone increased cyclic AMP levels, this stimulation must out-weigh the increase in metabolism apparent in the presence of forskolin, phosphodiesterase inhibitor or high levels of interleukin. It is clear that IL-1 beta increased decidual PGE2 production independently of cyclic AMP, and that other second messenger must mediate the action of this cytokine.
Seki H, Elder MG, Sullivan MH, 1995, Endothelin-1 regulates human decidual cells through both A- and B-type receptors., Mol Cell Endocrinol, Vol: 114, Pages: 111-116, ISSN: 0303-7207
The aims of this study were to investigate the effects of endothelin-1 (ET-1) on first trimester human decidual cells, identify the ET receptor sub-types through which these effects are mediated and assess the role of cyclic AMP in any effects of ET-1. ET-1 increased prostaglandin production by first trimester decidual cells, which was consistent with similar studies in third trimester decidual cells. The endothelin A-type receptor (ETA) was coupled to the increased prostaglandin production from first trimester cells, as shown by the inhibitory effects of BQ610, an ETA receptor antagonist. The time course of this effect was unusual, with a rapid increase peaking after 6 h of stimulation, followed by a longer effect over 12-24 h, which was paralleled by changes in cyclic AMP production. No evidence was obtained for any involvement of cyclic AMP in mediating the effects of ET-1 on prostaglandin production. ET-1 also increased decidual prolactin production with a maximum effect after 6 h of stimulation. This was mediated through the ETB receptor and may be linked to increased cyclic AMP production, indicating that the ETA and ETB receptors were coupled to different second messenger systems and affected decidual cell function in different ways.
ZOSMER A, RENDELL NB, TAYLOR GW, et al., 1995, FORMATION AND METABOLISM OF 14,15-EPOXYEICOSATRIENOIC ACID BY HUMAN REPRODUCTIVE TISSUES, BIOCHIMICA ET BIOPHYSICA ACTA-LIPIDS AND LIPID METABOLISM, Vol: 1258, Pages: 234-240, ISSN: 0005-2760
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- Citations: 8
Cole OF, Elder MG, Sullivan MH, 1995, Decidual adenylate cyclase and prostaglandin production in vitro., Prostaglandins, Vol: 49, Pages: 167-174, ISSN: 0090-6980
Human decidua contains an active adenylate cyclase, and a number of studies indicate that adenylate cyclase is functionally linked to increased in vitro prostaglandin synthesis. Increased decidual prostaglandin synthesis is associated with parturition, and therefore activation of adenylate cyclase may be involved in the control of human parturition. In this study, third trimester human decidual cells were preincubated for no more than 24 h prior to stimulation with a number of reagents which increase cellular cyclic AMP levels. Forskolin rapidly increased intracellular and extracellular cyclic AMP levels, but there was no increase in prostaglandin E2 biosynthesis during incubations ranging from 5 min up to 24 h. Dibutyryl cyclic AMP or 8-bromo-cyclic AMP were also without effect on PGE2 production, which suggests that the adenylate cyclase was not linked to the mechanisms regulating prostaglandin production. Cholera toxin increased basal cyclic AMP and PGE2 synthesis, and was without effect on IL-1 beta-stimulated PGE2 levels. PGE2 synthesis was increased by 24 h culture with IL-1 beta in all the cell preparations, indicating that the cells were biologically active, and that the lack of effect of changes in cyclic AMP synthesis on PGE2 levels could not be attributed to a defect in the prostaglandin synthetic pathway. Our findings did not agree with earlier work which showed that changes in cyclic AMP were correlated with changes in PGE2 production by human decidual cells. It is clear that in the previous studies the decidual cells were preincubated for 4-7 days prior to stimulation, in contrast with 24 h in our investigation.(ABSTRACT TRUNCATED AT 250 WORDS)
Cole OF, Seki H, Sullivan MH, et al., 1995, Interleukin-1 beta-stimulated prostaglandin synthesis by human decidual cells is independent of protein kinase C., Prostaglandins, Vol: 49, Pages: 69-77, ISSN: 0090-6980
Basal prostaglandin E2 (PGE2) synthesis by human decidual cells was stimulated by phorbol myristate acetate (PMA) which activates protein kinase C. Staurosporine, which is an inhibitor of protein kinase C in most systems, also increased basal PGE2 synthesis. Further work is needed to explain this finding, as another inhibitor of protein kinase C, H7, inhibited PGE2 production under similar culture conditions. Interleukin-1 beta (IL-1 beta)-stimulated PGE2 synthesis was potentiated by coincubation with PMA or staurosporine, indicating that IL-1 beta and protein kinase C increase decidual PGE2 synthesis through different mechanisms. Desensitization of the decidual cells for 24 h with PMA did not affect IL-1 beta-stimulated PGE2 synthesis. The complex roles of protein kinase C in regulating decidual prostaglandin synthesis require further investigation, but it is clear that the effects of IL-1 beta are not mediated by protein kinase C.
KNOCK GA, SULLIVAN MHF, MCCARTHY A, et al., 1994, ANGIOTENSIN-II (AT(1)) VASCULAR BINDING-SITES IN HUMAN PLACENTAE FROM NORMAL-TERM, PREECLAMPTIC AND GROWTH-RETARDED PREGNANCIES, JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, Vol: 271, Pages: 1007-1015, ISSN: 0022-3565
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- Citations: 51
Sun MY, Sullivan MH, Elder MG, 1994, An endogenous inhibitor of prostaglandin synthesis in human decidua., Prostaglandins, Vol: 48, Pages: 69-79, ISSN: 0090-6980
Human first trimester decidual tissue has been reported to contain an inhibitor of cyclo-oxygenase enzyme, but a careful reading of the literature indicates that the inhibitor may be human albumin. Our own studies also showed that high levels of albumin were present in samples from homogenised decidual tissues. We therefore digested the tissue to obtain isolated cells and washed them extensively to minimise contamination with blood. Homogenates of such cells did not bind arachidonic acid, and inhibited cyclo-oxygenase enzyme-1 (COX-1) activity. The cellular factor inhibited COX-1 at concentrations of 60-100 micrograms protein/ml, and was therefore more potent than human albumin (0.5-2.0 mg/ml). The inhibitory activity was lost after heat treatment (100 degrees C for 10 mins) and after digestion with trypsin or papain, but was resistant to mercaptoethanol and urea. Preliminary data indicated that the protein had a molecular weight > 30 kD.
Lewis MP, Sullivan MH, Elder MG, 1994, Regulation by interleukin-1 beta of growth and collagenase production by choriocarcinoma cells., Placenta, Vol: 15, Pages: 13-20, ISSN: 0143-4004
Impaired trophoblastic invasion and proliferation have been implicated in the pathogenesis of eclampsia, pre-eclampsia, spontaneous abortions and intra-uterine growth retardation (IUGR). First trimester trophoblast cells (which do not grow in culture) and choriocarcinoma (BeWo) (which grow spontaneously, and are used as a model for proliferating trophoblast) were incubated with interleukin-1 beta (IL-1 beta). BeWo cell growth was decreased dose-dependently by exogenous IL-1 beta at concentrations of 100-1000 pg/ml. This effect was first detected after 24 h of incubation with IL-1 beta, and persisted for up to 96 h of culture. In contrast, trophoblast cells isolated from first trimester placental tissue showed no growth response when stimulated with IL-1 beta. The levels of active interstitial collagenase produced by BeWo cells were increased by IL-1 beta (100-1000 pg/ml), which paralleled the decrease in cell growth. First trimester trophoblast cells produced lower levels of collagenase and this was not affected by incubation of the cells by IL-1 beta. These results indicate that IL-1 beta may regulate placental development, but further development of culture systems for first trimester trophoblast will be needed before this result can be confirmed.
Kent AS, Sullivan MH, Elder MG, 1994, Transfer of cytokines through human fetal membranes., J Reprod Fertil, Vol: 100, Pages: 81-84, ISSN: 0022-4251
Intact human fetal membranes (amnion, chorion and decidua) were incubated with 125I-labelled cytokines added to the fetal or maternal sides of the membrane. The transfer of 125I-labelled interleukin-6 (IL-6), 125I-labelled tumour necrosis factor alpha (TNF-alpha), 125I-labelled interleukin-1 alpha (IL-1 alpha) and 125I-labelled interleukin-1 beta (IL-1 beta) was determined by measurement of radioactivity in a gamma counter and the integrity of the cytokines was assessed by acid precipitation and by radioimmunoassay. IL-1 alpha and IL-1 beta were transferred through human fetal membranes in both feto-maternal and materno-fetal directions at similar rates. Only 2-4% of the cytokine originally added appeared to be intact on the opposing side of the membrane after 24 h of culture. Transfer of intact TNF-alpha (5-7%) and IL-6 (8-17%) was greater than that of the IL-1 isomers. Low but variable amounts of the four cytokines tested may be transferred through the human fetal membrane. This finding suggested that concentrations of cytokines in amniotic fluid would not reflect those produced by decidua if the fetal membranes are intact.
HUTT R, OGUNNIYI SO, SULLIVAN MHF, et al., 1994, INCREASED PLATELET VOLUME AND AGGREGATION PRECEDE THE ONSET OF PREECLAMPSIA, OBSTETRICS AND GYNECOLOGY, Vol: 83, Pages: 146-149, ISSN: 0029-7844
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- Citations: 75
Cole OF, Sullivan MH, Elder MG, 1993, The "interleukin 1 receptor antagonist" is a partial agonist of prostaglandin synthesis by human decidual cells., Prostaglandins, Vol: 46, Pages: 493-498, ISSN: 0090-6980
In many systems the interleukin-1 receptor antagonist opposes the effects of interleukin-1 beta. We considered that it might block interleukin-1 beta-stimulated prostaglandin production from human decidual cells. Very high levels of interleukin-1 receptor antagonist (> 1000 pg/ml) had limited inhibitory effects on IL-1 beta-stimulated PGE2 synthesis, and lower levels of antagonist (< 1000 pg/ml) increased the effects of IL-1 beta. Low concentrations of the antagonist alone (1-100 pg/ml) increased basal PGE2 production, whereas higher levels (10-100 ng/ml) had less effect. It seems, therefore, that in human decidua the "antagonist" is more accurately described as a partial agonist. It has been suggested that the IL-1 receptor antagonist could be used to inhibit decidual prostaglandin synthesis and thereby prevent preterm labor, but this report shows that caution should be exercised before using the receptor antagonist.
BENNETT PR, SLATER D, SULLIVAN M, et al., 1993, CHANGES IN AMNIOTIC ARACHIDONIC-ACID METABOLISM ASSOCIATED WITH INCREASED CYCLOOXYGENASE GENE-EXPRESSION, BRITISH JOURNAL OF OBSTETRICS AND GYNAECOLOGY, Vol: 100, Pages: 1037-1042, ISSN: 0306-5456
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- Citations: 29
Kent AS, Sullivan MH, Sun MY, et al., 1993, Effects of interleukin-6 and tumor necrosis factor-alpha on prostaglandin production by cultured human fetal membranes., Prostaglandins, Vol: 46, Pages: 351-359, ISSN: 0090-6980
In this study we investigated the effects of the cytokines interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) on prostaglandin production by cultured human fetal membranes. These cytokines stimulate prostaglandin synthesis by isolated components of human fetal membranes, but their effects on the intact tissue comprising amnion, chorion and decidua were not known. TNF-alpha added to the maternal side of the membrane activated decidual production of PGF2 alpha but had no effects on synthesis of PGE2 or PGE2 metabolites. Addition of TNF-alpha to the fetal side of the membrane increased production of PGE2 by amnion and PGE2 metabolites from chorion. The addition of IL-6 to the fetal or the maternal side of the membrane increased production of PGE2 from amnion and PGE2m from chorion, suggesting that IL-6 might pass through the fetal membrane. IL-6 had no effect on decidual PGF2 alpha production. These results suggest that TNF-alpha may be involved in labor by increasing decidual prostaglandin synthesis, whereas IL-6 is less likely to have a role.
Sullivan MH, Kent AS, Lumb MR, et al., 1993, The amnion produces little of the prostaglandin E2 detected on the decidual side of human fetal membranes., Acta Obstet Gynecol Scand, Vol: 72, Pages: 520-525, ISSN: 0001-6349
Cultured intact fetal membrane disks initially produced high levels of prostaglandin E2 (PGE2) on the fetal and maternal sides which declined during four days of culture. The transfer of a bolus of PGE2 from the fetal side to the maternal side of the membrane ranged from 1% to 3% after 24 hours of culture, and was a minimum over the period of 48-72 hours from the start of the incubation. To assess the handling of PGE2 synthesized by the amnion, 3H-arachidonic acid was incorporated into cultured amnion and into the amnion side of cultured intact fetal membrane disks. Labelled amnion released 3H-PGE2 on both sides of the tissue, whereas similarly labelled cultured intact fetal membrane only had detectable levels of 3H-PGE2 on the fetal side. It was calculated that no more than 9.7 +/- 1.4% of the PGE2 synthesised by the amnion crossed to the maternal side of the membrane without being metabolised during the transfer through the membrane. These results are consistent with similar indirect methods which suggested that PGE2 from the amnion may have only a limited role in human labor, and indicates the importance of using appropriate culture systems to investigate intra-uterine prostaglandin production.
SULLIVAN MHF, AHMED Y, ELDER MG, 1993, EFFECTS OF A THROMBOXANE SYNTHETASE INHIBITOR ON PLATELET-FUNCTION - POSSIBLE RISKS OF USE IN PREGNANCY, PROSTAGLANDINS, Vol: 46, Pages: 21-26, ISSN: 0090-6980
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- Citations: 3
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