Chris Redman - Academia.edu (original) (raw)
Papers by Chris Redman
Hypertension, 2020
Preeclampsia, a hypertensive pregnancy disorder, links to increased long-term maternal cardiovasc... more Preeclampsia, a hypertensive pregnancy disorder, links to increased long-term maternal cardiovascular disease (CVD). The risk is further increased with early-onset preeclampsia (EPE) and delivery of a growth-restricted child. We hypothesized that circulating biomarkers associated with CVD risk differed between preeclampsia subtypes and controls. We compared EPE; n=37, delivery
Placenta, 2018
Author contribution: The study was conceived, designed, conducted and led by SM. DT and RD isolat... more Author contribution: The study was conceived, designed, conducted and led by SM. DT and RD isolated, purified and characterized the STB-EVs. DT, IS and MV supervised all the experimental work. Patients were enrolled at John Radcliffe hospital, Oxford by CR. HM provided essential reagents including PP13 specific antibodies and PP13 ELISA kits and was involved in the ELISA testing, data analysis and statistical modeling. ASN performed the statistical analysis and mathematical modeling. All authors were involved in writing the manuscript, data analysis and discussions.
Pregnancy Hypertension: An International Journal of Women's Cardiovascular Health, 2017
Objectives: To determine the effect of HELLP Syndrome among severe preeclamptic women on low birt... more Objectives: To determine the effect of HELLP Syndrome among severe preeclamptic women on low birth weight, neonatal asphyxia and neonatal death. Method: A cohort of 296 severe preeclamptic women was conducted at Dr.Sardjito Hospital, Yogyakarta, Indonesia during the period of January 2009 to December 2011. Results: HELLP syndrome is a pregnancy-specific multi-systemic disorder, with laboratory evidence of hemolysis, hepatic dysfunction and thrombocytopenia; which is associated with preeclampsia. The presence of complete features of HELLP Syndrome and one or two features of HELLP Syndrome were 5.41% and 21.96%, respectively; yielding the HELLP Syndrome's incidence of 26.4% in the study. The risk of low birth weight increased by 2.57 times in HELLP syndrome compared to non-HELLP syndrome women (95% CI: 1.06-6.26). Women with HELLP syndrome was at higher risk of having neonatal asphyxia (OR 2.11; 95% CI: 1.5-4.83). Other significant risk factors for neonatal asphyxia were prematurity and caesarean section. There was no significant difference in neonatal death between women with HELLP Syndrome or without HELLP Syndrome (OR 2.44, 95% CI: 0.97-6.13), but gestational age was remained as significant risk factor for neonatal death. Conclusions: HELLP Syndrome among severe preeclamptic women resulted in an increased risk of low birth weight and neonatal asphyxia.
![Research paper thumbnail of [94-OR]: Extending the scope of individual patient data meta-analyses: Merging algorithms for biomarker measurements from heterogeneous laboratory platforms. The CoLAB Preeclampsia angiogenic factor study](https://attachments.academia-assets.com/112101876/thumbnails/1.jpg)
](Pregnancy hypertension, 2015
Circulating placental growth factor (PlGF) is a potential biomarker for preeclampsia. Prior studi... more Circulating placental growth factor (PlGF) is a potential biomarker for preeclampsia. Prior studies show its limited precision in predicting or diagnosing preeclampsia, underscoring a common problem in biomarker data analyses in general - that large studies are needed to overcome clinical heterogeneity and to provide sufficient statistical power. Attaining such sample sizes often requires aggregation of cohorts. Different studies may use disparate platforms for laboratory analyses, complicating data merging. Here, we assessed whether PlGF concentrations could be merged across studies using inter-platform standardization. Of 16516 pregnancies from 23 cohorts, 12,804 had at least one PlGF concentration (gestational age >20weeks), analyzed using one of four platforms: R&D Systems, Alere-Triage, Roche-Elecsys or Abbott-Architect. Two merging algorithms, using Z-Score or Multiple of Median (MOM) transformations, were applied. A single Best Reference Curve (BRC), based on merged non-ca...
Placenta, 2013
Objective: Though activin A has been shown to enhance human trophoblast cell invasion, whether tw... more Objective: Though activin A has been shown to enhance human trophoblast cell invasion, whether two additional activin isoforms, activin B and AB, exert similar effects remains unknown. While the mechanisms underlying these effects are unclear, we have recently demonstrated that expression of the mesenchymal adhesion molecule N-cadherin is associated with invasive behaviour in trophoblasts. Thus, the purpose of our study was to examine the effects of all three activin isoforms on human trophoblast cell invasion, and to define the molecular mechanisms involved, in particular the role of N-cadherin. Methods: The HTR-8/SVneo immortalized human trophoblast cell line was used as an in vitro model. The TGF-b type I receptor inhibitor SB431542 was used to block signaling from activin receptor complexes. Small interfering RNA (siRNA)-mediated knockdown approaches were used to investigate the molecular determinants of activin-mediated functions. RTquantitative real-time PCR and Western blot analysis were used to examine mRNA and protein levels, respectively. Cell invasiveness was assessed by Matrigel-coated transwell assays. Results: Treatment of HTR-8/SVneo cells with activin A, B or AB produced comparable increases in cell invasion as well as N-cadherin mRNA and protein levels. Interestingly, basal and activin-induced cell invasion were attenuated by siRNA-mediated down-regulation of N-cadherin. All activin isoforms induced equivalent phosphorylation of SMAD2 and SMAD3. In addition, activin treatment up-regulated the mRNA levels of Snail and Slug, but not TWIST, RUNX2, ZEB1 or ZEB2. Co-treatment with SB431542 abolished activin-induced cell invasion, up-regulation of N-cadherin, activation of SMAD2/SMAD3 and up-regulation of Snail and Slug. Interestingly, treatment with siRNA for common SMAD4, but not for Snail or Slug, abolished the effects of all three activin isoforms on N-cadherin. Conclusion: Activin A, B and AB increase human trophoblast cell invasion by up-regulating N-cadherin expression in a Smad-dependent manner.
Seminars in Nephrology, 2004
Normal pregnancy is associated with a systemic inflammatory response. The response is exacerbated... more Normal pregnancy is associated with a systemic inflammatory response. The response is exacerbated in preeclampsia and can account for its clinical features. Many of the physiologic changes of normal pregnancy are part of an acute-phase reaction, which is generated by an inflammatory response. The placenta is the proximal cause of these problems. There are several possible placental factors that may evoke the inflammatory responses that currently are being investigated. The special susceptibility of obese women, or those with diabetes or chronic hypertension, to preeclampsia is explained by the chronic systemic inflammatory responses that these women have. The clinical implications of these concepts are discussed.
Reproductive BioMedicine Online, 2006
and was Scientifi c Director of the Oxford Fertility Unit for nearly 20 years. He is a reproducti... more and was Scientifi c Director of the Oxford Fertility Unit for nearly 20 years. He is a reproductive immunologist with interests ranging from the expression of immunoregulatory molecules by human pre-implantation embryos, through trophoblast biology to the immunology of pre-eclampsia. He is a member of 'EMBIC', a European Network of Excellence (www.embic.org) within the 6th Framework Programme of the European Union (LSHM-CT-2004-512040).
Journal of Reproductive Immunology, 2010
Invariant natural killer T (iNKT) cells are implicated in the pathogenesis of several diseases. T... more Invariant natural killer T (iNKT) cells are implicated in the pathogenesis of several diseases. They influence both innate and adaptive immune responses through their capacity to rapidly produce large quantities of cytokines upon activation. During pregnancy maternal immunity is biased towards type 2 cytokine production to regulate type 1 cytokines that could be harmful for the developing fetus. This shift to type 2 cytokines does not occur in preeclamptic women and there is an exaggerated maternal inflammatory response which is dangerous for both mother and baby. We have therefore investigated the numbers, phenotype and functional activity of iNKT cells throughout pregnancy and in women diagnosed with preeclampsia. We demonstrate that the numbers of iNKT cells in the peripheral blood do not change between the first, second and third trimesters of pregnancy, but the cells become activated and less able to produce the type 1 cytokine IFN␥. However, iNKT cells are unchanged in preeclamptic women, when compared to normal pregnancy, suggesting that these cells are not primary players in the pathogenesis of the disease.
Journal of Reproductive Immunology, 2014
The release of extracellular vesicles by the trophoblast is an important mechanism by which the p... more The release of extracellular vesicles by the trophoblast is an important mechanism by which the placenta signals to the mother. These vesicles comprised exosomes (50-150 nm in size) and microvesicles (100-1000 nm). They are released from the placenta into the maternal circulation throughout gestation in normal pregnancy where they appear to play an immunoregulatory role, inhibiting T cell and NK cell responses. In preeclampsia they are released in significantly increased numbers and have proinflammatory, anti-angiogenic and procoagulant activity, which could explain the maternal systemic inflammation, endothelial dysfunction and activation of the clotting system that characterise the disorder. We have sought to determine the repertoire of molecules carried by the microvesicles and exosomes and how they differ in normal pregnancy and preeclampsia. To obtain sufficient vesicles for analysis we carried out placental perfusion on normal and preeclampsia placentas. We characterised the vesicles by nanoparticle tracking analysis and flow cytometry and investigated the proteins they carry by mass spectrometry. More than 2000 proteins have been identified in the vesicles, with some unique to preeclampsia and others unique to normal pregnancy. These proteins are being investigated as potential biomarkers for preeclampsia and may provide targets for future treatments.
European Journal of Immunology, 1995
Successful placentation in the human is dependent on the trophoblast evading recognition and dest... more Successful placentation in the human is dependent on the trophoblast evading recognition and destruction by the maternal immune system. However, invasive cytotrophoblast express HLA-G which may be able to present peptide to T cells. Transporter proteins are essential for peptide presentation and major histocompatibility complex (MHC) class I assembly. We have determined their expression by trophoblast in relation to HLA-G, using immunohistochemistry. Anti-transporter protein antibody (TAP1) labeling closely paralleled that of MHC class I, but the intensity of its expression was much greater on the HLA-G+ extravillous cytotrophoblast than any other fetal or maternal tissue in the first trimester and at term. This suggests that the extravillous cytotrophoblast are very actively assembling MHC class I antigens with peptides. However, expression of MHC class I by the cytotrophoblast was not correspondingly elevated. This pattern could result from HLA-G being shed from the surface of the trophoblast, a process which may play a central role in protecting the fetus from maternal immune attack.
BMJ, 2009
prophylactic internal iliac arterial catheters, and angiographic evaluation of bleeding points. P... more prophylactic internal iliac arterial catheters, and angiographic evaluation of bleeding points. Providers should be aware of potential ischemic complications from embolization. Complications arising from embolization for PPH include fever, bladder or rectal ischemia, nerve injury, and delayed re-bleeding. Other more rare complications include uterine necrosis, ovarian failure, infection, and amenorrhea. Whether embolization impacts subsequent fertility is uncertain, but most reports suggest that it is not impaired. Interventional radiology imposes risks of radiation complications with possible complications from contrast injection, arterial puncture, and catheterization. Conservative management of PA may reduce morbidity and mortality and preserve the uterus for future fertility, but antepartum planning for this approach can only occur if PA is diagnosed by either US or MRI before delivery. A total of 143 cases of conservative management have been reported in the literature. Most women underwent abdominal delivery, while 34 women delivered vaginally. The hysterectomy rate among these patients was 29%, with no reported deaths, which supports a role for conservative PA management in select women. Criteria for using this approach include preoperative consultation, a stable patient who presents without significant vaginal bleeding, a wish to preserve fertility, and availability of resources and experience for the management of PPH, including late PPH. The risk of hemorrhage, coagulopathy, and infection with retained placenta, and of recurrent PA following conservative management are high. A 2002 review suggested that the most frequently observed sequelae in subsequent pregnancies were increased risk of CS, preterm delivery, and abnormal modes of fetal presentation at delivery. The authors conclude that PA rates will continue to increase due to increases in CSs and the increasing number of older mothers, and that it is essential to screen those at risk, define PA by US and MRI, and prepare local strategies for a multidisciplinary approach to delivery and postpartum management. No single management strategy is optimal; thus, it must be tailored to individual cases and available resources. Known or suspected cases of PA should be managed in tertiary referral centers and the establishment of centralized regional specialist centers should be considered.
BMJ, 2005
New proteinuria Presence of proteinuria as shown by ≥ + (300 mg/l) on dipstick testing, a protein... more New proteinuria Presence of proteinuria as shown by ≥ + (300 mg/l) on dipstick testing, a protein to creatinine ratio of ≥ 30 mg/mmol on a random sample, or a urine protein excretion of ≥ 300 mg in 24 hours Quantified proteinuria Urine protein excretion ≥ 300 mg in 24 hours Pre-eclampsia New hypertension and quantified proteinuria at or after 20 weeks of pregnancy, confirmed if it resolves after delivery Superimposed pre-eclampsia Development of features of pre-eclampsia in context of pre-existing hypertension or pre-existing proteinuria, or both Further details concerning the guideline are on bmj.com
Annals of the New York Academy of Sciences, 1994
Annals of the New York Academy of Sciences, 1994
The passage of fetal blood cells into the maternal circulation is presumed to result from fetal-m... more The passage of fetal blood cells into the maternal circulation is presumed to result from fetal-maternal hemorrhage, although the mechanism has yet to be defined. In particular, it is not known whether these bleeds take place as part of the normal development of the placenta or whether they are sporadic events resulting from trauma. There is now good evidence, however, that fetal nucleated erythrocytes can enter the maternal blood in early pregnancy,'~* and it must be assumed that fetal leukocytes will traffic at the same time. If fetal leukocytes do enter the maternal circulation, they have some potential advantages over fetal nucleated red cells or trophoblasts for noninvasive prenatal genetic diagnosis. They are uniquely identifiable as fetal by virtue of their HLA antigens (which are not expressed by either trophoblasts or fetal nucleated red cells), and they do not exhibit the genetic mosaicism shown by some trophoblast cells. EVIDENCE FOR TRAFFIC OF FETAL LEUKOCYTES INTO MATERNAL BLOOD There are three main bodies of evidence for the presence of fetal leukocytes in maternal blood. These are the development of anti-fetal HLA antibodies by pregnant women, the direct identification of XY metaphases or Y-chromatin, and the isolation of fetal leukocytes by flow cytometry.
American Journal of Reproductive Immunology, 2002
... I10 INTRACELLULAR MOVEMENT OF RTF REGU-LATES APOPTOSIS AND CELL GROWTH Ken-neth D. Beaman, Ri... more ... I10 INTRACELLULAR MOVEMENT OF RTF REGU-LATES APOPTOSIS AND CELL GROWTH Ken-neth D. Beaman, Richard Derks, Roxanne Sperry, Evan ... I19 NOT TH1 NOR TH2 BUT 'DANGER' FOR WHOM THE BELLE TOLLS David A. Clark1,2, Reginald M. Gorczynski2 ...
PloS one, 2015
Pre-eclampsia (PE) complicates around 3% of all pregnancies and is one of the most common causes ... more Pre-eclampsia (PE) complicates around 3% of all pregnancies and is one of the most common causes of maternal mortality worldwide. The pathophysiology of PE remains unclear however its underlying cause originates from the placenta and manifests as raised blood pressure, proteinuria, vascular or systemic inflammation and hypercoagulation in the mother. Women who develop PE are also at significantly higher risk of subsequently developing cardiovascular (CV) disease. In PE, the failing endoplasmic reticulum, oxidative and inflammatory stressed syncytiotrophoblast layer of the placenta sheds increased numbers of syncytiotrophoblast extracellular vesicles (STBEV) into the maternal circulation. Platelet reactivity, size and concentration are also known to be altered in some women who develop PE, although the underlying reasons for this have not been determined. In this study we show that STBEV from disease free placenta isolated ex vivo by dual placental perfusion associate rapidly with pl...
Hypertension, 2020
Preeclampsia, a hypertensive pregnancy disorder, links to increased long-term maternal cardiovasc... more Preeclampsia, a hypertensive pregnancy disorder, links to increased long-term maternal cardiovascular disease (CVD). The risk is further increased with early-onset preeclampsia (EPE) and delivery of a growth-restricted child. We hypothesized that circulating biomarkers associated with CVD risk differed between preeclampsia subtypes and controls. We compared EPE; n=37, delivery
Placenta, 2018
Author contribution: The study was conceived, designed, conducted and led by SM. DT and RD isolat... more Author contribution: The study was conceived, designed, conducted and led by SM. DT and RD isolated, purified and characterized the STB-EVs. DT, IS and MV supervised all the experimental work. Patients were enrolled at John Radcliffe hospital, Oxford by CR. HM provided essential reagents including PP13 specific antibodies and PP13 ELISA kits and was involved in the ELISA testing, data analysis and statistical modeling. ASN performed the statistical analysis and mathematical modeling. All authors were involved in writing the manuscript, data analysis and discussions.
Pregnancy Hypertension: An International Journal of Women's Cardiovascular Health, 2017
Objectives: To determine the effect of HELLP Syndrome among severe preeclamptic women on low birt... more Objectives: To determine the effect of HELLP Syndrome among severe preeclamptic women on low birth weight, neonatal asphyxia and neonatal death. Method: A cohort of 296 severe preeclamptic women was conducted at Dr.Sardjito Hospital, Yogyakarta, Indonesia during the period of January 2009 to December 2011. Results: HELLP syndrome is a pregnancy-specific multi-systemic disorder, with laboratory evidence of hemolysis, hepatic dysfunction and thrombocytopenia; which is associated with preeclampsia. The presence of complete features of HELLP Syndrome and one or two features of HELLP Syndrome were 5.41% and 21.96%, respectively; yielding the HELLP Syndrome's incidence of 26.4% in the study. The risk of low birth weight increased by 2.57 times in HELLP syndrome compared to non-HELLP syndrome women (95% CI: 1.06-6.26). Women with HELLP syndrome was at higher risk of having neonatal asphyxia (OR 2.11; 95% CI: 1.5-4.83). Other significant risk factors for neonatal asphyxia were prematurity and caesarean section. There was no significant difference in neonatal death between women with HELLP Syndrome or without HELLP Syndrome (OR 2.44, 95% CI: 0.97-6.13), but gestational age was remained as significant risk factor for neonatal death. Conclusions: HELLP Syndrome among severe preeclamptic women resulted in an increased risk of low birth weight and neonatal asphyxia.
Pregnancy hypertension, 2015
Circulating placental growth factor (PlGF) is a potential biomarker for preeclampsia. Prior studi... more Circulating placental growth factor (PlGF) is a potential biomarker for preeclampsia. Prior studies show its limited precision in predicting or diagnosing preeclampsia, underscoring a common problem in biomarker data analyses in general - that large studies are needed to overcome clinical heterogeneity and to provide sufficient statistical power. Attaining such sample sizes often requires aggregation of cohorts. Different studies may use disparate platforms for laboratory analyses, complicating data merging. Here, we assessed whether PlGF concentrations could be merged across studies using inter-platform standardization. Of 16516 pregnancies from 23 cohorts, 12,804 had at least one PlGF concentration (gestational age >20weeks), analyzed using one of four platforms: R&D Systems, Alere-Triage, Roche-Elecsys or Abbott-Architect. Two merging algorithms, using Z-Score or Multiple of Median (MOM) transformations, were applied. A single Best Reference Curve (BRC), based on merged non-ca...
Placenta, 2013
Objective: Though activin A has been shown to enhance human trophoblast cell invasion, whether tw... more Objective: Though activin A has been shown to enhance human trophoblast cell invasion, whether two additional activin isoforms, activin B and AB, exert similar effects remains unknown. While the mechanisms underlying these effects are unclear, we have recently demonstrated that expression of the mesenchymal adhesion molecule N-cadherin is associated with invasive behaviour in trophoblasts. Thus, the purpose of our study was to examine the effects of all three activin isoforms on human trophoblast cell invasion, and to define the molecular mechanisms involved, in particular the role of N-cadherin. Methods: The HTR-8/SVneo immortalized human trophoblast cell line was used as an in vitro model. The TGF-b type I receptor inhibitor SB431542 was used to block signaling from activin receptor complexes. Small interfering RNA (siRNA)-mediated knockdown approaches were used to investigate the molecular determinants of activin-mediated functions. RTquantitative real-time PCR and Western blot analysis were used to examine mRNA and protein levels, respectively. Cell invasiveness was assessed by Matrigel-coated transwell assays. Results: Treatment of HTR-8/SVneo cells with activin A, B or AB produced comparable increases in cell invasion as well as N-cadherin mRNA and protein levels. Interestingly, basal and activin-induced cell invasion were attenuated by siRNA-mediated down-regulation of N-cadherin. All activin isoforms induced equivalent phosphorylation of SMAD2 and SMAD3. In addition, activin treatment up-regulated the mRNA levels of Snail and Slug, but not TWIST, RUNX2, ZEB1 or ZEB2. Co-treatment with SB431542 abolished activin-induced cell invasion, up-regulation of N-cadherin, activation of SMAD2/SMAD3 and up-regulation of Snail and Slug. Interestingly, treatment with siRNA for common SMAD4, but not for Snail or Slug, abolished the effects of all three activin isoforms on N-cadherin. Conclusion: Activin A, B and AB increase human trophoblast cell invasion by up-regulating N-cadherin expression in a Smad-dependent manner.
Seminars in Nephrology, 2004
Normal pregnancy is associated with a systemic inflammatory response. The response is exacerbated... more Normal pregnancy is associated with a systemic inflammatory response. The response is exacerbated in preeclampsia and can account for its clinical features. Many of the physiologic changes of normal pregnancy are part of an acute-phase reaction, which is generated by an inflammatory response. The placenta is the proximal cause of these problems. There are several possible placental factors that may evoke the inflammatory responses that currently are being investigated. The special susceptibility of obese women, or those with diabetes or chronic hypertension, to preeclampsia is explained by the chronic systemic inflammatory responses that these women have. The clinical implications of these concepts are discussed.
Reproductive BioMedicine Online, 2006
and was Scientifi c Director of the Oxford Fertility Unit for nearly 20 years. He is a reproducti... more and was Scientifi c Director of the Oxford Fertility Unit for nearly 20 years. He is a reproductive immunologist with interests ranging from the expression of immunoregulatory molecules by human pre-implantation embryos, through trophoblast biology to the immunology of pre-eclampsia. He is a member of 'EMBIC', a European Network of Excellence (www.embic.org) within the 6th Framework Programme of the European Union (LSHM-CT-2004-512040).
Journal of Reproductive Immunology, 2010
Invariant natural killer T (iNKT) cells are implicated in the pathogenesis of several diseases. T... more Invariant natural killer T (iNKT) cells are implicated in the pathogenesis of several diseases. They influence both innate and adaptive immune responses through their capacity to rapidly produce large quantities of cytokines upon activation. During pregnancy maternal immunity is biased towards type 2 cytokine production to regulate type 1 cytokines that could be harmful for the developing fetus. This shift to type 2 cytokines does not occur in preeclamptic women and there is an exaggerated maternal inflammatory response which is dangerous for both mother and baby. We have therefore investigated the numbers, phenotype and functional activity of iNKT cells throughout pregnancy and in women diagnosed with preeclampsia. We demonstrate that the numbers of iNKT cells in the peripheral blood do not change between the first, second and third trimesters of pregnancy, but the cells become activated and less able to produce the type 1 cytokine IFN␥. However, iNKT cells are unchanged in preeclamptic women, when compared to normal pregnancy, suggesting that these cells are not primary players in the pathogenesis of the disease.
Journal of Reproductive Immunology, 2014
The release of extracellular vesicles by the trophoblast is an important mechanism by which the p... more The release of extracellular vesicles by the trophoblast is an important mechanism by which the placenta signals to the mother. These vesicles comprised exosomes (50-150 nm in size) and microvesicles (100-1000 nm). They are released from the placenta into the maternal circulation throughout gestation in normal pregnancy where they appear to play an immunoregulatory role, inhibiting T cell and NK cell responses. In preeclampsia they are released in significantly increased numbers and have proinflammatory, anti-angiogenic and procoagulant activity, which could explain the maternal systemic inflammation, endothelial dysfunction and activation of the clotting system that characterise the disorder. We have sought to determine the repertoire of molecules carried by the microvesicles and exosomes and how they differ in normal pregnancy and preeclampsia. To obtain sufficient vesicles for analysis we carried out placental perfusion on normal and preeclampsia placentas. We characterised the vesicles by nanoparticle tracking analysis and flow cytometry and investigated the proteins they carry by mass spectrometry. More than 2000 proteins have been identified in the vesicles, with some unique to preeclampsia and others unique to normal pregnancy. These proteins are being investigated as potential biomarkers for preeclampsia and may provide targets for future treatments.
European Journal of Immunology, 1995
Successful placentation in the human is dependent on the trophoblast evading recognition and dest... more Successful placentation in the human is dependent on the trophoblast evading recognition and destruction by the maternal immune system. However, invasive cytotrophoblast express HLA-G which may be able to present peptide to T cells. Transporter proteins are essential for peptide presentation and major histocompatibility complex (MHC) class I assembly. We have determined their expression by trophoblast in relation to HLA-G, using immunohistochemistry. Anti-transporter protein antibody (TAP1) labeling closely paralleled that of MHC class I, but the intensity of its expression was much greater on the HLA-G+ extravillous cytotrophoblast than any other fetal or maternal tissue in the first trimester and at term. This suggests that the extravillous cytotrophoblast are very actively assembling MHC class I antigens with peptides. However, expression of MHC class I by the cytotrophoblast was not correspondingly elevated. This pattern could result from HLA-G being shed from the surface of the trophoblast, a process which may play a central role in protecting the fetus from maternal immune attack.
BMJ, 2009
prophylactic internal iliac arterial catheters, and angiographic evaluation of bleeding points. P... more prophylactic internal iliac arterial catheters, and angiographic evaluation of bleeding points. Providers should be aware of potential ischemic complications from embolization. Complications arising from embolization for PPH include fever, bladder or rectal ischemia, nerve injury, and delayed re-bleeding. Other more rare complications include uterine necrosis, ovarian failure, infection, and amenorrhea. Whether embolization impacts subsequent fertility is uncertain, but most reports suggest that it is not impaired. Interventional radiology imposes risks of radiation complications with possible complications from contrast injection, arterial puncture, and catheterization. Conservative management of PA may reduce morbidity and mortality and preserve the uterus for future fertility, but antepartum planning for this approach can only occur if PA is diagnosed by either US or MRI before delivery. A total of 143 cases of conservative management have been reported in the literature. Most women underwent abdominal delivery, while 34 women delivered vaginally. The hysterectomy rate among these patients was 29%, with no reported deaths, which supports a role for conservative PA management in select women. Criteria for using this approach include preoperative consultation, a stable patient who presents without significant vaginal bleeding, a wish to preserve fertility, and availability of resources and experience for the management of PPH, including late PPH. The risk of hemorrhage, coagulopathy, and infection with retained placenta, and of recurrent PA following conservative management are high. A 2002 review suggested that the most frequently observed sequelae in subsequent pregnancies were increased risk of CS, preterm delivery, and abnormal modes of fetal presentation at delivery. The authors conclude that PA rates will continue to increase due to increases in CSs and the increasing number of older mothers, and that it is essential to screen those at risk, define PA by US and MRI, and prepare local strategies for a multidisciplinary approach to delivery and postpartum management. No single management strategy is optimal; thus, it must be tailored to individual cases and available resources. Known or suspected cases of PA should be managed in tertiary referral centers and the establishment of centralized regional specialist centers should be considered.
BMJ, 2005
New proteinuria Presence of proteinuria as shown by ≥ + (300 mg/l) on dipstick testing, a protein... more New proteinuria Presence of proteinuria as shown by ≥ + (300 mg/l) on dipstick testing, a protein to creatinine ratio of ≥ 30 mg/mmol on a random sample, or a urine protein excretion of ≥ 300 mg in 24 hours Quantified proteinuria Urine protein excretion ≥ 300 mg in 24 hours Pre-eclampsia New hypertension and quantified proteinuria at or after 20 weeks of pregnancy, confirmed if it resolves after delivery Superimposed pre-eclampsia Development of features of pre-eclampsia in context of pre-existing hypertension or pre-existing proteinuria, or both Further details concerning the guideline are on bmj.com
Annals of the New York Academy of Sciences, 1994
Annals of the New York Academy of Sciences, 1994
The passage of fetal blood cells into the maternal circulation is presumed to result from fetal-m... more The passage of fetal blood cells into the maternal circulation is presumed to result from fetal-maternal hemorrhage, although the mechanism has yet to be defined. In particular, it is not known whether these bleeds take place as part of the normal development of the placenta or whether they are sporadic events resulting from trauma. There is now good evidence, however, that fetal nucleated erythrocytes can enter the maternal blood in early pregnancy,'~* and it must be assumed that fetal leukocytes will traffic at the same time. If fetal leukocytes do enter the maternal circulation, they have some potential advantages over fetal nucleated red cells or trophoblasts for noninvasive prenatal genetic diagnosis. They are uniquely identifiable as fetal by virtue of their HLA antigens (which are not expressed by either trophoblasts or fetal nucleated red cells), and they do not exhibit the genetic mosaicism shown by some trophoblast cells. EVIDENCE FOR TRAFFIC OF FETAL LEUKOCYTES INTO MATERNAL BLOOD There are three main bodies of evidence for the presence of fetal leukocytes in maternal blood. These are the development of anti-fetal HLA antibodies by pregnant women, the direct identification of XY metaphases or Y-chromatin, and the isolation of fetal leukocytes by flow cytometry.
American Journal of Reproductive Immunology, 2002
... I10 INTRACELLULAR MOVEMENT OF RTF REGU-LATES APOPTOSIS AND CELL GROWTH Ken-neth D. Beaman, Ri... more ... I10 INTRACELLULAR MOVEMENT OF RTF REGU-LATES APOPTOSIS AND CELL GROWTH Ken-neth D. Beaman, Richard Derks, Roxanne Sperry, Evan ... I19 NOT TH1 NOR TH2 BUT 'DANGER' FOR WHOM THE BELLE TOLLS David A. Clark1,2, Reginald M. Gorczynski2 ...
PloS one, 2015
Pre-eclampsia (PE) complicates around 3% of all pregnancies and is one of the most common causes ... more Pre-eclampsia (PE) complicates around 3% of all pregnancies and is one of the most common causes of maternal mortality worldwide. The pathophysiology of PE remains unclear however its underlying cause originates from the placenta and manifests as raised blood pressure, proteinuria, vascular or systemic inflammation and hypercoagulation in the mother. Women who develop PE are also at significantly higher risk of subsequently developing cardiovascular (CV) disease. In PE, the failing endoplasmic reticulum, oxidative and inflammatory stressed syncytiotrophoblast layer of the placenta sheds increased numbers of syncytiotrophoblast extracellular vesicles (STBEV) into the maternal circulation. Platelet reactivity, size and concentration are also known to be altered in some women who develop PE, although the underlying reasons for this have not been determined. In this study we show that STBEV from disease free placenta isolated ex vivo by dual placental perfusion associate rapidly with pl...