532 research outputs found

    Novel ex vivo ovarian cancer tissue explant assay for prediction of chemosensitivity and response to novel therapeutics

    No full text
    Data source: Supplementary data, https://doi.org/10.1016/j.canlet.2018.02.006Abstract not availableCarmela Ricciardelli, Noor A. Lokman, Ilhamjan Sabit, Kavyadharshini Gunasegaran, Wendy M. Bonner, Carmen E. Pyragius, Anne M. Macpherson, Martin K. Oehle

    Regions: Dead and buried or hope for resurrection?

    No full text
    To commemorate the 50th anniversary of the National Health Service, Gordon Macpherson has brought together this collection of chapters by distinguished figures in medicine and politics. Each author describes an aspect of the history of the NHS from his or her own perspective, and colours it with personal anecdotes. This collection celebrates the past, examines the present and points the way to the future

    Prometheus Atlas de Anatom\ueda

    No full text
    El Atlas de Anatom\ueda, creado por anatomistas y docentes tan ampliamente reconocidos como Anne M. Gilroy, Brian R. MacPherson y Lawrence M. Ross, incorpora todos los elementos necesarios para superar satisfactoriamente los desaf\uedos que presenta el aprendizaje de la anatom\ueda. Magn\uedficamente ilustrado con figuras a todo color realizadas por los galardonados artistas Markus Voll y Karl Wesker, el atlas est\ue1 organizado de tal modo que lo guiar\ue1 paso a paso a trav\ue9s de cada regi\uf3n corporal. Todas las secciones se inician con la descripci\uf3n del esqueleto, al que sucesivamente se le ir\ue1n incorporando los m\ufasculos, los \uf3rganos, los vasos, los nervios y, por \ufaltimo, la anatom\ueda topogr\ue1fica a fin de proporcionar una visi\uf3n integral de la regi\uf3n. Al final de cada secci\uf3n se expone la anatom\ueda de superficie junto con preguntas enfocadas a aplicar los conocimientos adquiridos en el contexto de la exploraci\uf3n f\uedsica de los paciente

    The Highlander

    No full text
    This thesis explores James Macpherson’s The Highlander (1758) in relation to originality, Scottish identity and historiography. It also situates the Ossianic Collections in the context of Macpherson’s earlier poetical and later historical works. There are three parts to it: a biographical sketch of Macpherson’s early life, the annotated edition of The Highlander, and discursive commentary chapters. By examining The Highlander in detail this thesis questions the emphasis of other Macpherson criticism on the Ossianic Collections, and allows us to see him as a writer who is historically minded, very aware of sources, well versed in established forms of poetry and thoroughly, and positively, British. The Highlander stands out among the corpus of his works not because it can give us insights into the Ossianic Collections, which is its usual function in Macpherson criticism, but because it can help us understand what it is that connects Macpherson’s earlier and later works with the Ossianic Collections: history, Britishness, tradition. Macpherson’s poetical works are united by a desire to translate Scotland’s factual past into sentimental British poetry. In the Ossianic Collections he does so without particular faithfulness to his sources, but in The Highlander he converts historical sources directly into neo-classic verse. This is where Macpherson’s originality lies: his ability to adapt history. In different styles and genres, and based on different sources, Macpherson’s works are early examples of Scotland’s great literary achievement: historical fiction. Instead of accusing him of forgery or trying to trace his knowledge of Gaelic ballads, this thesis presents Macpherson as a genuine historian who happened to write in a variety of genres

    Seminal plasma differentially regulates inflammatory cytokine gene expression in human cervical and vaginal epithelial cells

    No full text
    Copyright © 2007 European Society of Human Reproduction and EmbryologyExposure to semen elicits an inflammatory response in the female reproductive tract of rodents and other animals. The nature and regulation of any similar response in humans is poorly understood. This study investigated seminal plasma induction of inflammatory cytokine and chemokine gene regulation in human cervical and vaginal epithelial cells in vitro. Affymetrix microarray gene profiling revealed that inflammatory cytokine genes were prevalent among 317 known genes differentially expressed in immortalized ectocervical epithelial (Ect1) cells after incubation with pooled human seminal plasma. A dose- and time-dependent induction by seminal plasma of IL8, IL6, CSF2 and CCL2 mRNA expression in Ect1 cells was verified by quantitative RT–PCR. This was accompanied by increases in Ect1 secretion of immunoactive gene products IL-8, IL-6, GM-CSF and MCP-1. Similar cytokine responses were elicited in primary ectocervical epithelial cells. Endocervical epithelial (End1) and vaginal epithelial (Vk2) cells were less responsive to seminal fluid, with induction of IL-8 and MCP-1, but not GM-CSF or IL-6. In a panel of 10 seminal plasma samples, considerable variation in inflammatory cytokine-inducing activity was evident. These experiments show that seminal plasma can elicit expression of a range of inflammatory cytokines and chemokines in reproductive tract epithelia, and implicate the ectocervix as the primary site of responsiveness, with gene-specific differences in the kinetics and site-restrictedness of the response. Seminal factor regulation of inflammatory cytokines in the cervical epithelium is implicated in controlling the immune response to seminal antigens, and defence against infectious agents introduced at intercourse.David J. Sharkey, Anne M. Macpherson, Kelton P. Tremellen, and Sarah A. Robertso

    Three new species of squat lobsters of the genus Munidopsis Whiteaves, 1874, from Guadeloupe Island, Caribbean Sea (Crustacea, Decapoda, Munidopsidae)

    No full text
    Este artículo contiene 12 páginas, 4 figuras, 1 tabla.The genus Munidopsis is one of the most diverse genera within squat lobsters. Here, three new species of Munidopsis, M. cornuata n. sp., M. senticosa n. sp., and M. turgida n. sp., from <500 m off Guadeloupe Island (Caribbean Sea), are fully described and illustrated. Among the Atlantic species of the genus, M. cornuata n. sp. belongs to the group of species having the dorsal surface of the carapace with spines and is most similar to M. robusta (A. Milne-Edwards, 1880), from the Gulf of Mexico and Caribbean Sea. Munidopsis senticosa n. sp. resembles M. barbarae (Boone, 1927) from the Bahamas and the Gulf of Mexico and M. penescabra, Pequegnat & Williams 1995, from off Georgia and Gulf of Mexico; the three species belong to the group having the carapace covered with sharp spines. Finally, M. turgida n. sp. is characterized by having the dorsal surface of the carapace, abdomen and pereiopods covered by granules; and resembles M. granulens Mayo, 1972, from NW Caribbean Sea. Apart from the morphological evidence, the analysis of mitochondrial genes (COI and 16S) supports establishing these new species, showing very high genetic divergences compared to their congeners (from 14.5 to 17% for COI, and 7.7 to 12.8% for 16S data).The study and the corresponding author were partially supported by the projects of the Ministry of Economy, Industry and Competitiveness (CTM2014-57949-R, CTM2013-48163- C2). The figures of the carapaces were illustrated by J. Macpherson. EM is part of the research group 2014SGR- 120 of the Generalitat de Catalunya.Peer reviewe

    Csf2 Null Mutation Alters Placental Gene Expression and Trophoblast Glycogen Cell and Giant Cell Abundance in Mice

    No full text
    Copyright © 2009 by the Biology of ReproductionGenetic deficiency in granulocyte-macrophage colony-stimulating factor (CSF2, GM-CSF) results in altered placental structure in mice. To investigate the mechanism of action of CSF2 in placental morphogenesis, the placental gene expression and cell composition were examined in Csf2 null mutant and wild-type mice. Microarray and quantitative RT-PCR analyses on Embryonic Day (E) 13 placentae revealed that the Csf2 null mutation caused altered expression of 17 genes not previously known to be associated with placental development, including Mid1, Cd24a, Tnfrsf11b, and Wdfy1. Genes controlling trophoblast differentiation (Ascl2, Tcfeb, Itgav, and Socs3) were also differentially expressed. The CSF2 ligand and the CSF2 receptor alpha subunit were predominantly synthesized in the placental junctional zone. Altered placental structure in Csf2 null mice at E15 was characterized by an expanded junctional zone and by increased Cx31+ glycogen cells and cyclin-dependent kinase inhibitor 1C (CDKN1C+, P57Kip2+) giant cells, accompanied by elevated junctional zone transcription of genes controlling spongiotrophoblast and giant cell differentiation and secretory function (Ascl2, Hand1, Prl3d1, and Prl2c2). Granzyme genes implicated in tissue remodeling and potentially in trophoblast invasion (Gzmc, Gzme, and Gzmf) were downregulated in the junctional zone of Csf2 null mutant placentae. These data demonstrate aberrant placental gene expression in Csf2 null mutant mice that is associated with altered differentiation and/or functional maturation of junctional zone trophoblast lineages, glycogen cells, and giant cells. We conclude that CSF2 is a regulator of trophoblast differentiation and placental development, which potentially influences the functional capacity of the placenta to support optimal fetal growth in pregnancy.Amanda N. Sferruzzi-Perri, Anne M. Macpherson, Claire T. Roberts and Sarah A. Robertso

    4-Methylumbelliferone inhibits cancer stem cell activation and overcomes chemoresistance in ovarian cancer

    No full text
    Data source: Supplementary materials, https://doi.org/10.3390/cancers11081187We have recently shown that the extracellular matrix molecule hyaluronan (HA) plays a role in the development of ovarian cancer chemoresistance. This present study determined if HA production is increased in chemotherapy-resistant ovarian cancers and if the HA inhibitor 4-methylubelliferone (4-MU) can overcome chemoresistance to the chemotherapeutic drug carboplatin (CBP) and inhibit spheroid formation and the expression of cancer stem cell (CSC) markers. We additionally assessed whether 4-MU could inhibit in vivo invasion of chemoresistant primary ovarian cancer cells in the chicken embryo chorioallantoic membrane (CAM) assay. The expression of the HA synthases HAS2 and HAS3 was significantly increased in chemoresistant compared to chemosensitive primary ovarian cancer cells isolated from patient ascites. 4-MU significantly inhibited HA production, cell survival, and spheroid formation of chemoresistant serous ovarian cancer cells. In combination with CBP, 4-MU treatment significantly decreased ovarian cancer cell survival and increased apoptosis of chemoresistant primary cells compared to CBP alone. 4-MU significantly reduced spheroid formation, expression of CSC markers ALDH1A1 and ABCG2 in primary cell spheroid cultures, and ALDH1 immunostaining in patient-derived tissue explant assays following treatment with CBP. Furthermore, 4-MU was very effective at inhibiting in vivo invasion of chemoresistant primary cells in CAM assays. Inhibition of HA is therefore a promising new strategy to overcome chemoresistance and to improve ovarian cancer survival.Noor A. Lokman, Zoe K. Price, Emily K. Hawkins, Anne M. Macpherson, Martin K. Oehler and Carmela Ricciardell

    Stress response genes are suppressed in mouse preimplantation embryos by granulocyte-macrophage colony-stimulating factor (GM-CSF)

    No full text
    BACKGROUND: Granulocyte-macrophage colony-stimulating factor (GM-CSF) is known to promote the development and survival of human and mouse preimplantation embryos; however, the mechanism of action of GM-CSF in embryos is not defined. METHODS: Mouse blastocysts were cultured from zygote stage in vitro with and without recombinant mouse GM-CSF (rmGM-CSF), and in vivo developed blastocysts were flushed from Csf2 null mutant and wild-type mice. The effect of GM-CSF on blastocyst expression of stress response and apoptosis genes was evaluated by microarray, qPCR and immunochemistry. RESULTS: Microarray analysis of the gene transcription profile showed suppression of stress response and apoptosis gene pathways in blastocysts exposed to rmGM-CSF in vitro. qPCR analysis confirmed that rmGM-CSF inhibited expression of heat shock protein (HSP) and apoptosis pathway genes Cbl, Hspa5, Hsp90aa1, Hsp90ab1 and Gas5 in in vitro blastocysts. Immunocytochemical analysis of HSP 1 (HSPA1A/1B; HSP70), BAX, BCL2 and TRP53 (p53) in in vitro blastocysts showed that HSPA1A/1B and BCL2 proteins were less abundant when embryos were cultured with rmGM-CSF. BAX and TRP53 were unchanged at the protein level, but Bax mRNA expression was reduced after GM-CSF treatment. In in vivo developed blastocysts, Csf2 null mutation caused elevated expression of Hsph1 but not other stress response genes. CONCLUSIONS: We conclude that GM-CSF inhibits the cellular stress response and apoptosis pathways to facilitate embryo growth and survival, and the protective effects of GM-CSF are particularly evident in in vitro culture media, whereas in vivo other cytokines can partly compensate for absence of GM-CSF.Peck Y. Chin, Anne M. Macpherson, Jeremy G. Thompson, Michelle Lane and Sarah A. Robertso

    Microarray analysis of mRNA from cumulus cells following in vivo or in vitro maturation of mouse cumulus-oocyte complexes

    No full text
    The IVM of mammalian cumulus–oocyte complexes (COCs) yields reduced oocyte developmental competence compared with oocytes matured in vivo. Altered cumulus cell function during IVM is implicated as one cause for this difference. We have conducted a microarray analysis of cumulus cell mRNA following IVM or in vivo maturation (IVV). Mouse COCs were sourced from ovaries of 21-day-old CBAB6F1 mice 46 h after equine chorionic gonadotrophin (5 IU, i.p.) or from oviducts following treatment with 5 IU eCG (61 h) and 5 IU human chorionic gonadotrophin (13 h). IVM was performed in α-Minimal Essential Medium with 50 mIU FSH for 17 h. Three independent RNA samples were assessed using the Affymetrix Gene Chip Mouse Genome 430 2.0 array (Affymetrix, Santa Clara, CA, USA). In total, 1593 genes were differentially expressed, with 811 genes upregulated and 782 genes downregulated in IVM compared with IVV cumulus cells; selected genes were validated by real-time reverse transcription–polymerase chain reaction (RT-PCR). Surprisingly, haemoglobin α (Hba-a1) was highly expressed in IVV relative to IVM cumulus cells, which was verified by both RT-PCR and western blot analysis. Because haemoglobin regulates O2 and/or nitric oxide availability, we postulate that it may contribute to regulation of these gases during the ovulatory period in vivo. These data will provide a useful resource to determine differences in cumulus cell function that are possibly linked to oocyte competence.Karen L. Kind, Kelly M. Banwell, Kathryn M. Gebhardt, Anne Macpherson, Ashley Gauld, Darryl L. Russell and Jeremy G. Thompso
    corecore