Obstetrics and Gynaecology - Research Publications
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ItemAUTOIMMUNITY CAUSED BY IGNORANT CD8(+) T-CELLS IS TRANSIENT AND DEPENDS ON AVIDITY(AMER ASSOC IMMUNOLOGISTS, 1995-09-01)RIP-Kb mice, which express H-2Kb (Kb) molecules on their pancreatic beta cells, were used to examine the requirements for induction of autoimmune diabetes caused by CD8+ T cells. Previous studies showed that when these mice were crossed to mice expressing a Kb-specific TCR transgene, those CD8+ cells expressing the highest density of the transgenic TCR (presumably the highest avidity cells) were deleted intrathymically due to aberrant expression of Kb at this site. The remaining low avidity cells ignored Kb-bearing beta cells, even after priming, but were able to cause autoimmune diabetes when supplied with Il-2. To examine the properties of high avidity autoreactive CD8+ T cells, the thymic compartment of RIP-Kb mice was replaced with normal tissue to enable the maturation of CD8+ cells expressing the highest density of the transgenic TCR. These high avidity cells generally ignored Kb-expressing beta cells, but became autoaggressive after priming. Importantly, analysis of islet infiltration by CD8+ T cells revealed the presence of infiltrating cells in all mice examined within 3 wk of priming, but such infiltration was not usually apparent at later time points. In some cases, multiple primings were necessary for full development of autoimmunity. This implied that beta cells could act as transient targets for CD8+ T cell attack but could not sustain the stimulation of primed CD8+ cells. These studies indicate that the duration of priming stimulus and the avidity of the autoreactive CD8+ cells profoundly influence the severity of autoimmune disease.
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ItemFetal placental vascular responses to corticotropin-releasing hormone in vitro. Effects of variation in oxygen tension(W B SAUNDERS CO LTD, 2000-09)In this study, using the human placenta perfused in vitro with Krebs' bicarbonate solution, we have examined the effects of changes in oxygen tension on the vasoreactivity of fetal placental blood vessels to corticotropin releasing hormone (CRH). Vasodilatory responses to human synthetic CRH were measured during sub-maximal vasoconstriction of the fetal placental circulation with prostaglandin F(2alpha)(PGF(2alpha)) (1-100 micrometer). Decreases in fetal placental arterial perfusion pressure (FAP) were obtained with CRH under conditions of high oxygen or low oxygen tension, >/=450 mmHg and
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ItemEffects of nitrovasodilators on the human fetal-placental circulation in vitro(W B SAUNDERS CO LTD, 2001-04)This study examines the vasorelaxation of isolated human placental chorionic plate arteries and the perfused fetal-placental vasculature, in vitro, to a variety of nitrovasodilator compounds including glyceryl trinitrate (GTN) sodium nitroprusside (SNP), S-nitroso-N-acetylpenicillamine (SNAP), S-nitroso-N-glutathione (SNG) and NaNO(2). The effects of these compounds were also examined under conditions of high (>450 mmHg) and low oxygen (<50 mmHg) tension. In a separate series of experiments the effects of GTN and NaNO(2)were further investigated with addition of the antioxidants cysteine (100 microm), glutathione (100 microm) or superoxide dismutase (SOD) (30 I.U./ml). The order of nitrovasodilator potency, when added directly to isolated fetal vessels was GTN=SNP>SNAP=SNG>NaNO(2). The order under low oxygen tension was similar, GTN=SNP>SNG= SNAP>or=NaNO(2). SNG ( approximately fourfold) and NaNO(2)( approximately 50-fold) were significantly more potent under low oxygen conditions. Cysteine, glutathione and SOD were without effect on GTN induced vasodilatation. However, all three agents significantly enhanced (six- to ninefold) the effects of NaNO(2)under similar conditions. When infused directly into the fetal-placental circulation during in vitro perfusion experiments the order of potency was GTN>SNP>or=SNG>or=SNAP>or=NaNO(2). When the nitrovasodilators were infused indirectly via the maternal intervillous space the order of potency was GTN>or=SNP>or=NaNO(2)>or=SNAP=SNG. Our observations suggest that there are important differences in the action of different classes of nitrovasodilator compounds on the fetal-placental circulation. The changes observed with SNG and NaNO(2)may be influenced by levels of tissue oxygenation.