Imperial College London

ProfessorMarkJohnson

Faculty of MedicineDepartment of Metabolism, Digestion and Reproduction

Clinical Chair in Obstetrics
 
 
 
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Contact

 

+44 (0)20 3315 7887mark.johnson

 
 
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Location

 

H3.35Chelsea and Westminster HospitalChelsea and Westminster Campus

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Summary

 

Publications

Publication Type
Year
to

465 results found

Roos-Hesselink JW, Ruys TPE, Stein JI, Thilen U, Webb GD, Niwa K, Kaemmerer H, Baumgartner H, Budts W, Maggioni AP, Tavazzi L, Taha N, Johnson MR, Hall Ret al., 2013, Outcome of pregnancy in patients with structural or ischaemic heart disease: results of a registry of the European Society of Cardiology, EUROPEAN HEART JOURNAL, Vol: 34, Pages: 657-665, ISSN: 0195-668X

Journal article

Rossi A, van der Linde D, Yap SC, Lapinskas T, Kirschbaum S, Springeling T, Witsenburg M, Cuypers J, Moelker A, Krestin GP, van Dijk A, Johnson M, van Geuns R-J, Roos-Hesselink JWet al., 2013, Ascending aorta dilatation in patients with bicuspid aortic valve stenosis: a prospective CMR study., Eur Radiol, Vol: 23, Pages: 642-649

BACKGROUND: The aim of this study was to evaluate the natural progression of aortic dilatation and its association with aortic valve stenosis (AoS) in patients with bicuspid aortic valve (BAV). METHODS: Prospective study of aorta dilatation in patients with BAV and AoS using cardiac magnetic resonance (CMR). Aortic root, ascending aorta, aortic peak velocity, left ventricular systolic and diastolic function and mass were assessed at baseline and at 3-year follow-up. RESULTS: Of the 33 enrolled patients, 5 needed surgery, while 28 patients (17 male; mean age: 31 ± 8 years) completed the study. Aortic diameters significantly increased at the aortic annulus, sinus of Valsalva and tubular ascending aorta levels (P < 0.050). The number of patients with dilated tubular ascending aortas increased from 32 % to 43 %. No significant increase in sino-tubular junction diameter was observed. Aortic peak velocity, ejection fraction and myocardial mass significantly increased while the early/late filling ratio significantly decreased at follow-up (P < 0.050). The progression rate of the ascending aorta diameter correlated weakly with the aortic peak velocity at baseline (R (2) = 0.16, P = 0.040). CONCLUSION: BAV patients with AoS showed a progressive increase of aortic diameters with maximal expression at the level of the tubular ascending aorta. The progression of aortic dilatation correlated weakly with the severity of AoS.

Journal article

Kim SH, Blanks A, Thornton S, Johnson M, Bennett PR, Terzidou Vet al., 2013, Activation of NF-κB in Human Amnion Is Mediated through G<sub>ai</sub> and Is Mimicked by the Oxytocin Receptor Antagonist - Atosiban., 60th Annual Scientific Meeting of the Society-for-Gynecologic-Investigation (SGI), Publisher: SAGE PUBLICATIONS INC, Pages: 122A-122A, ISSN: 1933-7191

Conference paper

Mitsuya K, Singh N, Sooranna SR, Johnson MR, Myatt Let al., 2013, Epigenetics of Human Myometrium: Relationship to the Length of Gestation and the Onset of Labor, 60th Annual Scientific Meeting of the Society-for-Gynecologic-Investigation (SGI), Publisher: SAGE PUBLICATIONS INC, Pages: 174A-174A, ISSN: 1933-7191

Conference paper

Zollner J, Sooranna SR, Johnson MR, 2013, Myocardial Expression Level of Hypertrophy Marker Genes in a Guinea Pig Model of Left Ventricular Pressure Overload, 60th Annual Scientific Meeting of the Society-for-Gynecologic-Investigation (SGI), Publisher: SAGE PUBLICATIONS INC, Pages: 163A-163A, ISSN: 1933-7191

Conference paper

Lei K, Sooranna S, Bennett P, Johnson MRet al., 2013, Enhancement of Inflammation-Associated Genes by Progesterone in IL-1β-Stimulated Human Myometrial Cells, 60th Annual Scientific Meeting of the Society-for-Gynecologic-Investigation (SGI), Publisher: SAGE PUBLICATIONS INC, Pages: 161A-162A, ISSN: 1933-7191

Conference paper

Zheng X, Zhao H, Sooranna SR, Ma D, Johnson MRet al., 2013, Development of a Clinically Relevant Model of Perinatal Hypoxic Ischaemic Encephalopathy in Mice., 60th Annual Scientific Meeting of the Society-for-Gynecologic-Investigation (SGI), Publisher: SAGE PUBLICATIONS INC, Pages: 300A-300A, ISSN: 1933-7191

Conference paper

Karda R, Waddington SN, Johnson MR, 2013, Perinatal Intra-Cranial Gene Transfer for Permanent Astrocyte Specific Expression in Mice, 60th Annual Scientific Meeting of the Society-for-Gynecologic-Investigation (SGI), Publisher: SAGE PUBLICATIONS INC, Pages: 282A-283A, ISSN: 1933-7191

Conference paper

Edey LF, O'Dea KP, Herbert BR, Takata M, Johnson MRet al., 2013, The Ability of Progesterone To Regulate the Inflammatory Monocyte Subset during Pregnancy, 60th Annual Scientific Meeting of the Society-for-Gynecologic-Investigation (SGI), Publisher: SAGE PUBLICATIONS INC, Pages: 121A-122A, ISSN: 1933-7191

Conference paper

MacIntyre DA, Migale R, Lee YS, Herbert B, Sykes L, Terzidou V, Johnson MR, Bennett PRet al., 2013, TLR4-Mediated Activation of AP1 Via JNK Induces Preterm Labour in the Mouse., 60th Annual Scientific Meeting of the Society-for-Gynecologic-Investigation (SGI), Publisher: SAGE PUBLICATIONS INC, Pages: 296A-296A, ISSN: 1933-7191

Conference paper

Edey LF, O'Dea KP, Herbert BR, Takata M, Johnson MRet al., 2013, The LPS Preterm Labour Model in Mice: An Inverse Relationship between Leukocyte Recruitment to the Myometrium and Delivery Time., 60th Annual Scientific Meeting of the Society-for-Gynecologic-Investigation (SGI), Publisher: SAGE PUBLICATIONS INC, Pages: 93A-94A, ISSN: 1933-7191

Conference paper

Howe L, Wang Z, Edey LF, James L, Johnson MRet al., 2013, Haemodynamic Profiling throughout Pregnancy in Normal and Lipopolysaccharide-Treated Mice, 60th Annual Scientific Meeting of the Society-for-Gynecologic-Investigation (SGI), Publisher: SAGE PUBLICATIONS INC, Pages: 122A-122A, ISSN: 1933-7191

Conference paper

Lai PF, Tribe RM, Johnson MR, 2013, Prolonged Elevation of cAMP Enhances Spontaneous Contractility in Human Myometrium from Pregnant Women at Term, 60th Annual Scientific Meeting of the Society-for-Gynecologic-Investigation (SGI), Publisher: SAGE PUBLICATIONS INC, Pages: 173A-173A, ISSN: 1933-7191

Conference paper

Shah N, Westrop S, Low-Beer N, Hawkins D, Imami N, Johnson Met al., 2013, Premature Delivery in HIV plus Mothers on HAART Is Associated with an Expanded Peripheral Blood CD56+Subset, 60th Annual Scientific Meeting of the Society-for-Gynecologic-Investigation (SGI), Publisher: SAGE PUBLICATIONS INC, Pages: 197A-197A, ISSN: 1933-7191

Conference paper

Shah N, Imami N, Johnson M, 2013, Pregnancy Is Associated with Greater PIBF Expression on Peripheral Blood CD8+T-Cells In-Vitro, 60th Annual Scientific Meeting of the Society-for-Gynecologic-Investigation (SGI), Publisher: SAGE PUBLICATIONS INC, Pages: 323A-323A, ISSN: 1933-7191

Conference paper

Bishop G, Johnson M, Bennett P, Lee Yet al., 2013, Characterisation of Cultured Human Myocytes to Passage Four as a Model To Investigate the Role of Progesterone in Myometrial Function., 60th Annual Scientific Meeting of the Society-for-Gynecologic-Investigation (SGI), Publisher: SAGE PUBLICATIONS INC, Pages: 296A-296A, ISSN: 1933-7191

Conference paper

Hua R, Pease JE, Cheng W, Sooranna SR, Viney JM, Nelson SM, Myatt L, Bennett PR, Johnson MRet al., 2013, Human Labour is Associated with a Decline in Myometrial Chemokine Receptor Expression: The Role of Prostaglandins, Oxytocin and Cytokines, AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Vol: 69, Pages: 21-32, ISSN: 1046-7408

Journal article

Sykes L, Herbert BR, MacIntyre DA, Hunte E, Ponnampalam S, Johnson MR, Teoh TG, Bennett PBet al., 2013, The CRTH2 agonist Pyl A prevents LPS induced fetal death but induces preterm labour, Immunology

We have previously demonstrated that the anti-inflammatory prostaglandin 15-deoxy-Δ 12,14- Prostaglandin J2 delays inflammation induced preterm labour (PTL) in the mouse and improves pup survival through the inhibition of NF-κB by a mechanism yet to be elucidated. 15dPGJ2 is an agonist of the second Prostaglandin D2 receptor, CRTH2. In human T helper cells CRTH2 agonists induce the production of the anti-inflammatory interleukins IL-10 and IL-4. We hypothesised that CRTH2 is involved in the protective effect of 15dPGJ2 in inflammation induced PTL in the murine model. We therefore studied the effects of a specific small molecule CRTH2 agonist on preterm labour and pup survival. An intrauterine injection of LPS was administered to CD1 mice at E16, ± CRTH2 agonist/ vehicle controls. Mice were sacrificed at 4.5 h to assess fetal wellbeing and to harvest myometrium and pup brain for analysis of NF-κB, and Th1/Th2 interleukins. To examine the effects of the CRTH2 agonist on LPS induced PTL, mice were allowed to labour spontaneously. Direct effects of the CRTH2 agonist on uterine contractility were examined ex vivo on contracting myometrial strips. The CRTH2 agonist increased fetal survival from 20% to 100% in LPS treated mice, and inhibited circular muscle contractility ex vivo. However, it augmented LPS induced labour and significantly increased myometrial NF-κB, IL-1β, KC-GRO, IFN-γ and TNF-α. This suggests that the action of 15dPGJ2 is not via CRTH2 and therefore small molecule CRTH2 agonists are not likely to be beneficial for the prevention of inflammation induced PTL.

Journal article

Lei K, Chen L, Georgiou EX, Sooranna SR, Khanjani S, Brosens JJ, Bennett PR, Johnson MRet al., 2012, Progesterone acts via the nuclear glucocorticoid receptor to suppress IL-1 beta-Induced COX-2 expression in human term myometrial cells, PLoS ONE, Vol: 7, ISSN: 1932-6203

Progesterone is widely used to prolong gestation in women at risk of preterm labour (PTL), and acts at least in part via theinhibition of inflammatory cytokine-induced prostaglandin synthesis. This study investigates the mechanisms responsiblefor this inhibition in human myometrial cells. We used reporter constructs to demonstrate that interleukin 1beta (IL-1b)inhibits progesterone driven PRE activation via p65 activation and that IL-1b reduced progesterone driven gene expression(FKBP5). Conversely, we found that the activity of a p65-driven NFkB reporter construct was reduced by overexpression ofprogesterone receptor B (PRB) alone and that this was enhanced by the addition of MPA and that both MPA andprogesterone suppressed IL-1b-driven cyclo-oxygenase-2 (COX-2) expression. We found that over-expressed Halo-taggedPRB, but not PRA, bound to p65 and that in IL-1b-treated cells, with no overexpression of either PR or p65, activated p65bound to PR. However, we found that the ability of MPA to repress IL-1b-driven COX-2 expression was not enhanced byoverexpression of either PRB or PRA and that although the combined PR and GR antagonist Ru486 blocked the effects ofprogesterone and MPA, the specific PR antagonist, Org31710, did not, suggesting that progesterone and MPA act via GRand not PR. Knockdown using siRNA confirmed that both MPA and progesterone acted via GR and not PR or AR to repressIL-1b-driven COX-2 expression. We conclude that progesterone acts via GR to repress IL-1b-driven COX-2 activation and thatalthough the interaction between p65 and PRB may be involved in the repression of progesterone driven gene expression itdoes not seem to be responsible for progesterone repression of IL-1b-induced COX-2 expression.

Journal article

Bansal AS, Bora SA, Saso S, Smith JR, Johnson MR, Thum M-Yet al., 2012, Mechanism of human chorionic gonadotrophin-mediated immunomodulation in pregnancy, EXPERT REVIEW OF CLINICAL IMMUNOLOGY, Vol: 8, Pages: 747-753, ISSN: 1744-666X

Journal article

Chatrchyan S, Khachatryan V, Sirunyan AM, Tumasyan A, Adam W, Aguilo E, Bergauer T, Dragicevic M, Eroe J, Fabjan C, Friedl M, Fruehwirth R, Ghete VM, Hammer J, Hoermann N, Hrubec J, Jeitler M, Kiesenhofer W, Knuenz V, Krammer M, Kraetschmer I, Liko D, Mikulec I, Pernicka M, Rahbaran B, Rohringer C, Rohringer H, Schoefbeck R, Strauss J, Taurok A, Waltenberger W, Walzel G, Widl E, Wulz C-E, Mossolov V, Shumeiko N, Gonzalez JS, Bansal S, Cornelis T, De Wolf EA, Janssen X, Luyckx S, Mucibello L, Ochesanu S, Roland B, Rougny R, Selvaggi M, Staykova Z, Van Haevermaet H, Van Mechelen P, Van Remortel N, Van Spilbeeck A, Blekman F, Blyweert S, D'Hondt J, Suarez RG, Kalogeropoulos A, Maes M, Olbrechts A, Van Doninck W, Van Mulders P, Van Onsem GP, Villella I, Clerbaux B, De Lentdecker G, Dero V, Gay APR, Hreus T, Leonard A, Marage PE, Reis T, Thomas L, Vander Velde C, Vanlaer P, Wang J, Adler V, Beernaert K, Cimmino A, Costantini S, Garcia G, Grunewald M, Klein B, Lellouch J, Marinov A, Mccartin J, Rios AAO, Ryckbosch D, Strobbe N, Thyssen F, Tytgat M, Verwilligen P, Walsh S, Yazgan E, Zaganidis N, Basegmez S, Bruno G, Castello R, Ceard L, Delaere C, du Pree T, Favart D, Forthomme L, Giammanco A, Hollar J, Lemaitre V, Liao J, Militaru O, Nuttens C, Pagano D, Pin A, Piotrzkowski K, Schul N, Garcia JMV, Beliy N, Caebergs T, Daubie E, Hammad GH, Alves GA, Correa Martins Junior M, Damiao DDJ, Martins T, Pol ME, Souza MHG, Alda Junior WL, Carvalho W, Custodio A, Da Costa EM, De Oliveira Martins C, Fonseca De Souza S, Matos Figueiredo D, Mundim L, Nogima H, Oguri V, Prado Da Silva WL, Santoro A, Soares Jorge L, Sznajder A, Anjos TS, Bernardes CA, Dias FA, Fernandez Perez Tomei TR, Gregores EM, Lagana C, Marinho F, Mercadante PG, Novaes SF, Padula SS, Genchev V, Iaydjiev P, Piperov S, Rodozov M, Stoykova S, Sultanov G, Tcholakov V, Trayanov R, Vutova M, Dimitrov A, Hadjiiska R, Kozhuharov V, Litov L, Pavlov B, Petkov P, Bian JG, Chen GM, Chen HS, Jiang CH, Liang D, Liang S, Meng Xet al., 2012, Measurement of the t(t)over-bar production cross section in the dilepton channel in pp collisions at √<i>s</i>=7 TeV, JOURNAL OF HIGH ENERGY PHYSICS, ISSN: 1029-8479

Journal article

Lee Y, Sooranna SR, Terzidou V, Christian M, Brosens J, Huhtinen K, Poutanen M, Barton G, Johnson MR, Bennett PRet al., 2012, Interactions between inflammatory signals and the progesterone receptor in regulating gene expression in pregnant human uterine myocytes, JOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Vol: 16, Pages: 2487-2503, ISSN: 1582-1838

The absence of a fall in circulating progesterone levels has led to the concept that human labour is associated with ‘functional progesterone withdrawal’ caused through changes in the expression or function of progesterone receptor (PR). At the time of labour, the human uterus is heavily infiltrated with inflammatory cells, which release cytokines to create a ‘myometrial inflammation’ via NF‐κB activation. The negative interaction between NF‐κB and PR, may represent a mechanism to account for ‘functional progesterone withdrawal’ at term. Conversely, PR may act to inhibit NF‐κB function and so play a role in inhibition of myometrial inflammation during pregnancy. To model this inter‐relationship, we have used small interfering (si) RNA‐mediated knock‐down of PR in human pregnant myocytes and whole genome microarray analysis to identify genes regulated through PR. We then activated myometrial inflammation using IL‐1β stimulation to determine the role of PR in myometrial inflammation regulation. Through PR‐knock‐down, we found that PR regulates gene networks involved in myometrial quiescence and extracellular matrix integrity. Activation of myometrial inflammation was found to antagonize PR‐induced gene expression, of genes normally upregulated via PR. We found that PR does not play a role in repression of pro‐inflammatory gene networks induced by IL‐1β and that only MMP10 was significantly regulated in opposite directions by IL‐1β and PR. We conclude that progesterone acting through PR does not generally inhibit myometrial inflammation. Activation of myometrial inflammation does cause ‘functional progesterone withdrawal’ but only in the context of genes normally upregulated via PR.

Journal article

Campbell JP, Mackenzie MJ, Yentis SM, Sooranna SR, Johnson MRet al., 2012, An evaluation of the ability of leucocyte depletion filters to remove components of amniotic fluid*, ANAESTHESIA, Vol: 67, Pages: 1152-1157, ISSN: 0003-2409

Journal article

Chen L, Sooranna SR, Lei K, Kandola M, Bennett PR, Liang Z, Grammatopoulos D, Johnson MRet al., 2012, Cyclic AMP increases COX-2 expression via mitogen-activated kinase in human myometrial cells, Journal of Cellular and Molecular Medicine, Vol: 16, Pages: 1447-1460, ISSN: 1582-4934

Cyclic AMP (cAMP) is the archetypal smooth muscle relaxant, mediating the effects of many hormones and drugs. However, recently PGI2, acting via cAMP/PKA, was found to increase contraction‐associated protein expression in myometrial cells and to promote oxytocin‐driven myometrial contractility. Cyclo‐oxygenase‐2 (COX‐2) is the rate‐limiting enzyme in prostaglandin synthesis, which is critical to the onset and progression of human labour. We have investigated the impact of cAMP on myometrial COX‐2 expression, synthesis and activity. Three cAMP agonists (8‐bromo‐cAMP, forskolin and rolipram) increased COX‐2 mRNA expression and further studies confirmed that this was associated with COX‐2 protein synthesis and activity (increased PGE2 and PGI2 in culture supernatant) in primary cultures of human myometrial cells. These effects were neither reproduced by specific agonists nor inhibited by specific inhibitors of known cAMP‐effectors (PKA, EPAC and AMPK). We then used shRNA to knockdown the same effectors and another recently described cAMP‐effector PDZ‐GEF1‐2, without changing the response to cAMP. We found that MAPK activation mediated the cAMP effects on COX‐2 expression and that PGE2 acts through EP‐2 to activate MAPK and increase COX‐2. These data provide further evidence in support of a dual role for cAMP in the regulation of myometrial function.

Journal article

Shah N, Imami N, Johnson M, 2012, T-cell phenotypic profile in pregnancy: link between immune activation and exhaustion, BJOG-AN INTERNATIONAL JOURNAL OF OBSTETRICS AND GYNAECOLOGY, Vol: 119, Pages: 62-62, ISSN: 1470-0328

Journal article

Zhuang L, Yang T, Zhao H, Fidalgo AR, Vizcaychipi MP, Sanders RD, Yu B, Takata M, Johnson MR, Ma Det al., 2012, The protective profile of argon, helium, and xenon in a model of neonatal asphyxia in rats, CRITICAL CARE MEDICINE, Vol: 40, Pages: 1724-1730, ISSN: 0090-3493

Journal article

Yang T, Zhuang L, Fidalgo AMR, Petrides E, Terrando N, Wu X, Sanders RD, Robertson NJ, Johnson MR, Maze M, Ma Det al., 2012, Xenon and sevoflurane provide analgesia during labor and fetal brain protection in a perinatal rat model of hypoxia-ischemia, PLoS ONE, Vol: 7, ISSN: 1932-6203

It is not possible to identify all pregnancies at risk of neonatal hypoxic-ischemic encephalopathy (HIE). Many women usesome form of analgesia during childbirth and some anesthetic agents have been shown to be neuroprotective when usedas analgesics at subanesthetic concentrations. In this study we sought to understand the effects of two anesthetic agentswith presumptive analgesic activity and known preconditioning-neuroprotective properties (sevoflurane or xenon), inreducing hypoxia-induced brain damage in a model of intrauterine perinatal asphyxia. The analgesic and neuroprotectiveeffects at subanesthetic levels of sevoflurane (0.35%) or xenon (35%) were tested in a rat model of intrauterine perinatalasphyxia. Analgesic effects were measured by assessing maternal behavior and spinal cord dorsal horn neuronal activationusing c-Fos. In separate experiments, intrauterine fetal asphyxia was induced four hours after gas exposure; on post-insultday 3 apoptotic cell death was measured by caspase-3 immunostaining in hippocampal neurons and correlated with thenumber of viable neurons on postnatal day (PND) 7. A separate cohort of pups was nurtured by a surrogate mother for 50days when cognitive testing with Morris water maze was performed. Both anesthetic agents provided analgesia as reflectedby a reduction in the number of stretching movements and decreased c-Fos expression in the dorsal horn of the spinal cord.Both agents also reduced the number of caspase-3 positive (apoptotic) neurons and increased cell viability in thehippocampus at PND7. These acute histological changes were mirrored by improved cognitive function measured remotelyafter birth on PND 50 compared to control group. Subanesthetic doses of sevoflurane or xenon provided both analgesiaand neuroprotection in this model of intrauterine perinatal asphyxia. These data suggest that anesthetic agents withneuroprotective properties may be effective in preventing HIE and should be tested in clinical trials in the fu

Journal article

Shah N, Benlarech A, Imami N, Johnson Met al., 2012, Phenotypic analysis of dendritic cell lineage and maturity, and T-Cell exhaustion indicate dampened immune activation in pregnancy, Joint International Congress of the American-Society-for-Reproductive-Immunology (ASRI) and the European-Society-for-Reproductive-Immunology (ESRI), Publisher: ELSEVIER IRELAND LTD, Pages: 50-50, ISSN: 0165-0378

Conference paper

Malawana J, Howe L, Herbert B, Hua R, Bennett PR, Johnson MRet al., 2012, Is immunomodulation the answer to in utero neurological insult caused by preterm labour?, BJOG-AN INTERNATIONAL JOURNAL OF OBSTETRICS AND GYNAECOLOGY, Vol: 119, Pages: e7-e8, ISSN: 1470-0328

Journal article

Curry RA, Fletcher C, Gelson E, Gatzoulis MA, Woolnough M, Richards N, Swan L, Steer PJ, Johnson MRet al., 2012, Pulmonary hypertension and pregnancy-a review of 12 pregnancies in nine women, BJOG-AN INTERNATIONAL JOURNAL OF OBSTETRICS AND GYNAECOLOGY, Vol: 119, Pages: 752-761, ISSN: 1470-0328

Journal article

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