Imperial College London

DrMarkSullivan

Faculty of MedicineDepartment of Metabolism, Digestion and Reproduction

Senior Lecturer
 
 
 
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Contact

 

+44 (0)20 7594 2133mark.sullivan Website

 
 
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Location

 

G-027Institute of Reproductive and Developmental BiologyHammersmith Campus

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Summary

 

Publications

Publication Type
Year
to

122 results found

Kent AS, Sun MY, Sullivan MH, Elder MGet al., 1993, The effects of interleukins 1 alpha and 1 beta on prostaglandin production by cultured human fetal membranes., Prostaglandins, Vol: 46, Pages: 51-59, ISSN: 0090-6980

The effects of IL-1 alpha and IL-1 beta on cultured human fetal membranes were studied. These cytokines are known to regulate prostaglandin synthesis by the separated components of the fetal membranes (amnion, chorion and decidua), but their effects on intact tissue are unknown. IL-1 alpha increased PGE2 levels on the fetal side of the membrane, indicating increased production of prostaglandin from the amnion, but had little effect on levels of PGE2 on the maternal side of the membrane. Low levels of IL-1 beta (0.1-1.0 ng/ml) increased PGE2 levels on the fetal side of the membrane, and also increased the production of PGE2 metabolites and PGF2 alpha, suggesting that this cytokine stimulated the decidua as well as the amnion. High concentrations of both cytokines appeared able to stimulate prostaglandin production by the side of the membrane opposing that to which they were added, but it is not clear whether this was mediated by factors released by the stimulated membrane, or by direct transfer of small quantities of cytokines through the membrane. Taken together, these results indicate that IL-1 beta was a potent stimulator of the synthesis of prostaglandins by decidua and by amnion, whereas IL-1 alpha only stimulated the amnion.

Journal article

RUTHERFORD RAD, WHARTON J, MCCARTHY A, GORDON L, SULLIVAN MHF, ELDER MG, POLAK JMet al., 1993, DIFFERENTIAL LOCALIZATION OF ENDOTHELIN ET(A)-BINDING AND ET(B)-BINDING SITES IN HUMAN PLACENTA, BRITISH JOURNAL OF PHARMACOLOGY, Vol: 109, Pages: 544-552, ISSN: 0007-1188

Journal article

SULLIVAN MHF, ELDER MG, 1993, CHANGES IN PLATELET REACTIVITY FOLLOWING ASPIRIN TREATMENT FOR PREECLAMPSIA, BRITISH JOURNAL OF OBSTETRICS AND GYNAECOLOGY, Vol: 100, Pages: 542-545, ISSN: 0306-5456

Journal article

LEWIS MP, MORLESE JF, SULLIVAN MHF, ELDER MGet al., 1993, EVIDENCE FOR DECIDUA - TROPHOBLAST INTERACTIONS IN EARLY HUMAN-PREGNANCY, HUMAN REPRODUCTION, Vol: 8, Pages: 965-968, ISSN: 0268-1161

Journal article

Khan H, Sullivan MH, Elder MG, 1993, Modulation of decidual stromal cell activity by interleukin-1 beta and interleukin-6., Br J Obstet Gynaecol, Vol: 100, Pages: 393-394, ISSN: 0306-5456

Journal article

AHMED Y, VANIDDEKINGE B, PAUL C, SULLIVAN MHF, ELDER MGet al., 1993, RETROSPECTIVE ANALYSIS OF PLATELET NUMBERS AND VOLUMES IN NORMAL-PREGNANCY AND IN PREECLAMPSIA, BRITISH JOURNAL OF OBSTETRICS AND GYNAECOLOGY, Vol: 100, Pages: 216-220, ISSN: 0306-5456

Journal article

WHARTON J, GORDON L, BYRNE J, HERZOG H, SELBIE LA, MOORE K, SULLIVAN MHF, ELDER MG, MOSCOSO G, TAYLOR KM, SHINE J, POLAK JMet al., 1993, EXPRESSION OF THE HUMAN NEUROPEPTIDE TYROSINE-Y1 RECEPTOR, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol: 90, Pages: 687-691, ISSN: 0027-8424

Journal article

Morris C, Sullivan MH, Elder MG, 1992, Transfer and metabolism of platelet-activating factor by fetal membranes, amnion and chorio-decidua., Br J Obstet Gynaecol, Vol: 99, Pages: 895-898, ISSN: 0306-5456

OBJECTIVE: To determine the metabolism of 3H-Platelet-activating factor (3H-PAF) during transfer through human fetal membranes. DESIGN: 3H-PAF was added to the fetal side of cultured intact fetal membranes, amnion and chorio-decidua obtained from three pregnancies ending in elective caesarean section. MAIN OUTCOME MEASURES: Radioactivity was measured on both sides of the tissue, and in the tissue itself. In some experiments, the metabolism of 3H-PAF was assessed by thin-layer chromatography. RESULTS: Very little 3H-PAF crossed the intact fetal membrane (< 2%) during 24 h of culture. Most of the 3H-PAF which accumulated in the membrane was converted to a range of metabolites in the chorio-decidua. CONCLUSIONS: These results suggest that PAF in amniotic fluid may not reach the decidua, and therefore is unlikely to be involved in the control of prostaglandin production from this tissue.

Journal article

Ishihara O, Khan H, Sullivan MH, Elder MGet al., 1992, Interleukin-1 beta stimulates decidual stromal cell cyclo-oxygenase enzyme and prostaglandin production., Prostaglandins, Vol: 44, Pages: 43-52, ISSN: 0090-6980

The cytokine interleukin-1 (IL-1 beta) increased prostaglandin production by decidual stromal cells in culture in a time and dose dependent manner. Optimum conditions for stimulation were found to be for 24 hours at a concentration of 100 pg IL-1 beta/ml. An apparent increase in cyclo-oxygenase enzyme synthesis accompanied the increase in prostaglandin production, and both changes were inhibited by the protein synthesis inhibitor cycloheximide. This implicates protein synthesis in the stimulatory effects of IL-1 beta, which may be mediated through the increase in cyclo-oxygenase enzyme. A pre-incubation period of 72 hours was found to be necessary to observe the stimulatory effect of IL-1 beta on prostaglandin production, but this did not seem to be due to any change in the sensitivity of the cells to IL-1 beta; the increase in the number of cyclo-oxygenase positive cells was the same if IL-1 beta was added on day 1, day 2 or day 3 of culture, even though prostaglandin production was not stimulated on day 1 or day 2. Cycloheximide increased prostaglandin production on the first two days of culture and had no effect on the third day of culture. This was interpreted as indicating that a factor inhibiting cyclo-oxygenase activity was synthesised during the initial period of culture, which prevented any increase in prostaglandin production following the increase in enzyme synthesis.

Journal article

Morris C, Khan H, Sullivan MH, Elder MGet al., 1992, Effects of platelet-activating factor on prostaglandin E2 production by intact fetal membranes., Am J Obstet Gynecol, Vol: 166, Pages: 1228-1231, ISSN: 0002-9378

OBJECTIVE: The hypothesis tested in this study is that platelet-activating factor increases prostaglandin E2 synthesis from fetal membranes. STUDY DESIGN: Fetal membrane disks obtained before or after labor were incubated with or without platelet-activating factor for time periods of up to 24 hours. The production of prostaglandin E2 and its inactive metabolites was determined by specific radioimmunoassays. RESULTS: Platelet-activating factor (1 to 10 mumol/L) stimulated the production of prostaglandin E2 and its metabolites by intact fetal membranes and chorion-decidua threefold to fourfold after 24 hours of incubation. Platelet-activating factor had far greater effects on the production of prostaglandin E2 by intact fetal membranes obtained after the onset of labor, such that prostaglandin E2 production was increased by tenfold to 100-fold. CONCLUSION: These results suggest that platelet-activating factor mainly stimulates prostaglandin E2 production by the chorion-decidua before labor and that it may act in synergism with other stimulatory factors present in the fetal membranes during labor.

Journal article

SULLIVAN MHF, ROSEBLADE CK, RENDELL NB, TAYLOR GW, ELDER MGet al., 1992, METABOLISM OF PROSTAGLANDIN-E2 AND PROSTAGLANDIN-F2-ALPHA BY HUMAN FETAL MEMBRANES, BIOCHIMICA ET BIOPHYSICA ACTA, Vol: 1123, Pages: 342-346, ISSN: 0006-3002

Journal article

Khan H, Ishihara O, Sullivan MH, Elder MGet al., 1992, Changes in decidual stromal cell function associated with labour., Br J Obstet Gynaecol, Vol: 99, Pages: 10-12, ISSN: 0306-5456

OBJECTIVE: To determine whether decidual cells produce altered levels of prostaglandins after labour. DESIGN: Decidual stromal cells and macrophages were isolated before and after labour, and the production of prostaglandins E2 and F2 alpha measured. Changes in the numbers of cyclooxygenase enzyme positive cells were assessed by immunocytochemistry. RESULTS: Decidual stromal cells obtained after labour produced 30 times more prostaglandins E2 and F2 alpha in culture than cells obtained before labour. The increased production persisted for up to 72 h of culture, and was associated with an increase in the numbers of cyclooxygenase-positive cells from less than 5% to greater than 95%. No changes in macrophage function were observed. CONCLUSION: Increased levels of prostaglandins E2 and F2 alpha were released from decidual stromal cells after labour, suggesting that these cells may be an important source of prostaglandins in labour.

Journal article

SULLIVAN MHF, FUSI L, BROSENS J, ELDER MGet al., 1992, PROSPECTIVE MODULATION OF PLATELET-FUNCTION AND VOLUMES BY ASPIRIN AND DIPYRIDAMOLE IN AN AT-RISK PREGNANCY, BRITISH JOURNAL OF OBSTETRICS AND GYNAECOLOGY, Vol: 99, Pages: 75-76, ISSN: 0306-5456

Journal article

AHMED Y, SULLIVAN MHF, PEARCE JM, ELDER MGet al., 1991, CHANGES IN PLATELET-FUNCTION IN PREGNANCIES COMPLICATED BY FETAL GROWTH-RETARDATION, EUROPEAN JOURNAL OF OBSTETRICS & GYNECOLOGY AND REPRODUCTIVE BIOLOGY, Vol: 42, Pages: 171-175, ISSN: 0301-2115

Journal article

Khan H, Sullivan MH, Helmig R, Roseblade CK, Uldbjerg N, Elder MGet al., 1991, Quantitative production of prostaglandin E2 and its metabolites by human fetal membranes., Br J Obstet Gynaecol, Vol: 98, Pages: 712-715, ISSN: 0306-5456

Cultured amnion, choriodecidua and intact fetal membrane produced similar quantities of prostaglandin E2 (PGE2) (1-5 ng/ml). Choriodecidua and intact fetal membrane also produced very high levels of PGE2 metabolites (100-1000 ng/ml). The total production of PGE (PGE2 + PGE2 metabolites) was similar in intact fetal membrane and in choriodecidua, suggesting that the amnion, although a source of PGE2, contributes little to the overall PGE production by fetal membranes.

Journal article

AHMED Y, SULLIVAN MHF, ELDER MG, 1991, DETECTION OF PLATELET DESENSITIZATION IN PREGNANCY-INDUCED HYPERTENSION IS DEPENDENT ON THE AGONIST USED, THROMBOSIS AND HAEMOSTASIS, Vol: 65, Pages: 474-477, ISSN: 0340-6245

Journal article

AHMED Y, SULLIVAN MHF, ELDER MG, 1991, INCREASED PLATELET TURNOVER IN A PATIENT WITH PREVIOUS RECURRENT PREECLAMPSIA AND FAILURE OF ASPIRIN THERAPY - CASE-REPORT, BRITISH JOURNAL OF OBSTETRICS AND GYNAECOLOGY, Vol: 98, Pages: 218-220, ISSN: 0306-5456

Journal article

TANNIRANDORN Y, SULLIVAN MHF, ELDER MG, 1991, PRODUCTION OF URINARY 11-KETO-THROMBOXANE-B2 IN NORMAL AND HYPERTENSIVE PREGNANCIES, PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS, Vol: 42, Pages: 91-94, ISSN: 0952-3278

Journal article

SULLIVAN MHF, TRANTER PR, AHMED Y, ELDER MGet al., 1991, ALTERED PLATELET RESPONSES TO PAF IN PREGNANCY-INDUCED HYPERTENSION, ADVANCES IN PROSTAGLANDIN THROMBOXANE AND LEUKOTRIENE RESEARCH, Vol: 21, Pages: 807-810, ISSN: 0361-5952

Journal article

SULLIVAN MHF, TRANTER PR, AHMED Y, ELDER MGet al., 1991, ALTERED PLATELET RESPONSES TO PAF IN PREGNANCY-INDUCED HYPERTENSION, 7TH INTERNATIONAL CONF ON PROSTAGLANDINS AND RELATED COMPOUNDS, Publisher: RAVEN PRESS, Pages: 807-810

Conference paper

Ishihara O, Sullivan MH, Elder MG, 1991, Differences of metabolism of prostaglandin E2 and F2 alpha by decidual stromal cells and macrophages in culture., Eicosanoids, Vol: 4, Pages: 203-207, ISSN: 0934-9820

Intact decidual stromal cells and macrophages metabolized 3H-prostaglandins E2 and F2 alpha although the rate of metabolism of both prostaglandins was higher in the decidual macrophages than in decidual stromal cells. PGE2 was metabolised mainly to 13,14-dihydro-15-keto-PGE2 together with smaller quantities for PGB2 and 13,14-dihydro-15-keto-PGA2, whereas PGF2 alpha was metabolised to 13,14-dihydro-15-keto-PGF2 alpha, PGE2 and PGB2, and it seems that similar metabolic pathways were present in both cell types. The half-lives of both prostaglandins (8.8 +/- 3.4 h for PGE2 and 15.0 +/- 8.2 h for PGF2 alpha sigma in the presence of decidual stromal cells show that during incubations lasting more than a few hours significant metabolism of prostaglandins, especially PGE2, will occur, and that this must be allowed for in any assessment of total prostaglandin production by cultured decidual cells. One of the 6 tissue samples examined metabolised both prostaglandins very rapidly, such that the half-lives were less than 2 h. This may be the result of the presence of very high levels of metabolic enzymes, since the overall pattern of metabolites was similar to that from the other 5 samples.

Journal article

Sullivan MH, Roseblade CK, Elder MG, 1991, Metabolism of prostaglandin E2 on the fetal and maternal sides of intact fetal membranes., Acta Obstet Gynecol Scand, Vol: 70, Pages: 425-427, ISSN: 0001-6349

The metabolism of prostaglandin E2 (PGE2) added to the chorio-decidual side or the amnion side of the intact fetal membrane was compared. Similar rates of metabolism were found when the PGE2 was added to the fetal side or the maternal side of the membrane, even though the amnion (on the fetal side of the membrane) contains no metabolizing enzymes. The appearance of PGE2 metabolites on the opposing side of the membrane was also independent of whether the PGE2 was added to the fetal or maternal side, which suggests that the chorion, which lies between the amnion and the decidua, is the major determinant of the rate of metabolism of PGE2. Furthermore, it might be expected that less PGE2 metabolism subsequent to diffusion across the membrane may occur on the amnion side, since this tissue contains no metabolizing enzymes, but no evidence for this was found. PGE2 synthesized by the amnion would therefore have little effect on PGE2 levels on the maternal side of the fetal membrane, and may not be directly involved in labour.

Journal article

Ishihara O, Khan H, Sullivan MH, Elder MGet al., 1991, Differential metabolism of intracellular and extracellular arachidonic acid by decidual stromal cells and macrophages., Eicosanoids, Vol: 4, Pages: 143-147, ISSN: 0934-9820

Term decidual stromal cells metabolized extracellular arachidonic acid to cyclo-oxygenase, lipoxygenase and epoxygenase products. Prostaglandins were the major metabolites from extracellular arachidonic acid. In contrast, intracellular arachidonic acid was metabolized mainly to an epoxygenase product, together with some lipoxygenase products. Decidual macrophages showed similar results, though these cells had higher production rates per cell of most metabolites. The calcium ionophore A23187 increased the levels of arachidonic acid released from the intracellular stores of decidual stromal cells and had variable effects on the production of cyclo-oxygenase, lipoxygenase and epoxygenase metabolites. Less than 15% of the total metabolites released from A23187-stimulated cells were cyclo-oxygenase products, which suggested that the cyclo-oxygenase products released by decidual stromal cells or macrophages may be mainly derived from extracellular arachidonic acid. This implies that the regulation of decidual cyclo-oxygenase may have a major role in determining prostaglandin output from this tissue.

Journal article

KHAN H, ISHIHARA O, ELDER MG, SULLIVAN MHFet al., 1991, A COMPARISON OF 2 POPULATIONS OF DECIDUAL CELLS BY IMMUNOCYTOCHEMISTRY AND PROSTAGLANDIN PRODUCTION, HISTOCHEMISTRY, Vol: 96, Pages: 149-152, ISSN: 0301-5564

Journal article

Zosmer A, Elder MG, Sullivan MH, 1990, Production of intracellular arachidonic acid metabolites by human granulosa cells., Prostaglandins Leukot Essent Fatty Acids, Vol: 41, Pages: 265-267, ISSN: 0952-3278

The major intracellular metabolites of arachidonic acid within human granulosa cells are an epoxy-eicosatrienoic acid (EET), and a dihydroxy-metabolite. The former which was present at higher levels, co-migrated with 5,6-EET on HPLC. Incubation of the cells with LH for 5 min stimulated the production of both 5,6-EET and the dihydroxy compound 2-4 fold. The production of other intracellular arachidonic acid metabolites was unaffected by stimulation with LH. These results suggest that one or both of these metabolites may have a role in steroidogenesis in human granulosa cells.

Journal article

Lumb MR, Roseblade CK, Helmig R, Uldbjerg N, Sullivan MH, Elder MGet al., 1990, Use of a new simplified assay for phospholipase A2 to measure bacterial enzyme levels., Clin Chim Acta, Vol: 189, Pages: 39-46, ISSN: 0009-8981

During investigation of possible phospholipase A2 (PLA2) production by pathogenic bacteria associated with preterm labour, a rapid and simple assay method was developed which involved few steps and which could be applied easily to large numbers of samples. The principle difference from previously described methods lies in separation of the reaction products by partitioning them between organic and aqueous solvents, rather than by using thin layer chromatography. This enabled us to determine that none of the bacteria studied released PLA2 into the culture medium spontaneously, and that only Escherichia coli contained high levels of PLA2.

Journal article

GLEESON RP, AYUB M, WRIGHT JT, WOOD CB, HABIB NA, SOUTTER WP, SULLIVAN MHF, WHITE JOet al., 1990, FATTY-ACID CONTROL OF GROWTH OF HUMAN CERVICAL AND ENDOMETRIAL CANCER-CELLS, BRITISH JOURNAL OF CANCER, Vol: 61, Pages: 500-503, ISSN: 0007-0920

Journal article

Sullivan MH, Zosmer A, Gleeson RP, Elder MGet al., 1990, Equivalent inhibition of in vivo platelet function by low dose and high dose aspirin treatment., Prostaglandins Leukot Essent Fatty Acids, Vol: 39, Pages: 319-321, ISSN: 0952-3278

In vitro platelet function was inhibited in healthy volunteers by two different doses of aspirin, as confirmed by measurement of maximum serum production of thromboxane B2 (TXB2) by platelets. 75 mg aspirin did not fully inhibit serum TXB2 production after 24 hours, whereas 300 mg aspirin did. Inhibition of platelet function in vitro was maintained by both 75 mg/day aspirin or 300 mg/alternate day aspirin. In contrast, in vivo production of TXB2, measured as urinary levels of the 11-keto-TXB2 metabolite, was inhibited similarly by both doses of aspirin throughout the study. These findings suggest that 75 mg/day aspirin may be sufficient adequately to inhibit platelet aggregation in vivo.

Journal article

SULLIVAN MHF, JOHNSON S, ELDER MG, 1990, PLATELET MALFUNCTION PRECEDING THE ONSET OF PREGNANCY INDUCED HYPERTENSION, JOURNAL OF OBSTETRICS AND GYNAECOLOGY, Vol: 10, Pages: 215-216, ISSN: 0144-3615

Journal article

Roseblade CK, Sullivan MH, Khan H, Lumb MR, Elder MGet al., 1990, Limited transfer of prostaglandin E2 across the fetal membrane before and after labor., Acta Obstet Gynecol Scand, Vol: 69, Pages: 399-403, ISSN: 0001-6349

The transfer of prostaglandin E2 (PGE2) across intact fetal membranes (amnion-chorion-decidua) obtained before and after the onset of labor was investigated using a novel system for in vitro fetal membrane culture. Studies using physiological concentrations of PGE2 showed that very little PGE2 will cross the membranes without being metabolised, before or after the onset of labor. It was only when pharmacological concentrations of PGE2 were used that the enzyme activity of the chorion was no longer able to prevent transfer of PGE2 without conversion to inactive metabolites. These results suggest that only small amounts of PGE2 from amnion are normally transferred across the chorio-decidua before or after the onset of labor, but the metabolism of PGE2 subsequent to transfer across the fetal membranes requires further assessment.

Journal article

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