PubMed Health⌕ Search

Biomedical subjects

Christopher W G Redman

Publications and source records attributed to Christopher W G Redman.

10 recordsLinked to original sources
PubMed2006

NK cells and human pregnancy--an inflammatory view.

For several years, reproductive immunology has been dominated by the 'Th1/Th2' hypothesis, in which the fetus avoids maternal T-cell rejection through a bias towards T-helper (Th)2 cytokine production. The discovery that normal pregnancy is a controlled state of inflammation, at an early stage at the implantation site and also later systemically, has challenged this concept, as has the finding that the predominant immune interactions in the decidua are between the placental trophoblast and maternal natural killer (NK) cells instead of T cells. Here, we extend this concept to the interaction between the trophoblast and NK cells in the maternal circulation. We suggest novel ways in which the trophoblast might stimulate the maternal systemic inflammatory response, and how dysfunctional NK-cell activation could result in the maternal syndrome of pre-eclampsia.

Female↗
PubMed2005

Changes in systemic type 1 and type 2 immunity in normal pregnancy and pre-eclampsia may be mediated by natural killer cells.

A bias of T cell immunity towards type 2 (Th2) is thought to be critical for normal pregnancy. Pathological pregnancies, such as pre-eclampsia, are characterised by cell-mediated (Th1) immune dominance. The Th1/Th2 paradigm, however, is too simplistic. Normal pregnancy is associated with a systemic inflammatory response which increases throughout gestation. This inflammatory response is exaggerated in pre-eclampsia, a syndrome of the third trimester. T helper (Th) cells are considered the primary mediators of these altered immune responses, and other T cells, i.e. T cytotoxic (Tc) cells, and lymphocytes of the innate immune system, i.e. natural killer (NK) and NKT cells, have been largely disregarded. In this study, we have used novel pan type 1 (IL-18 receptor) and pan type 2 (ST2L) lymphocyte function markers in four-colour flow cytometry to broadly characterise peripheral blood lymphocyte populations from non-pregnant, normal pregnant and pre-eclamptic women. There were no changes in the Th1/Th2 or Tc1/Tc2 cell ratios between the three groups; however, the NK1/NK2 and NKT1/NKT2 cell ratios were significantly decreased in normal pregnancy compared with non-pregnant (p <0.001 and p <0.01, respectively) and pre-eclamptic women (p <0.05). These results confirm that immunoregulation occurs in pregnancy, but suggest a dominant role of the innate rather than the adaptive immune system.

Adult↗
PubMed2004

Combinations of maternal KIR and fetal HLA-C genes influence the risk of preeclampsia and reproductive success.

Preeclampsia is a serious complication of pregnancy in which the fetus receives an inadequate supply of blood due to failure of trophoblast invasion. There is evidence that the condition has an immunological basis. The only known polymorphic histocompatibility antigens on the fetal trophoblast are HLA-C molecules. We tested the idea that recognition of these molecules by killer immunoglobulin receptors (KIRs) on maternal decidual NK cells is a key factor in the development of preeclampsia. Striking differences were observed when these polymorphic ligand: receptor pairs were considered in combination. Mothers lacking most or all activating KIR (AA genotype) when the fetus possessed HLA-C belonging to the HLA-C2 group were at a greatly increased risk of preeclampsia. This was true even if the mother herself also had HLA-C2, indicating that neither nonself nor missing-self discrimination was operative. Thus, this interaction between maternal KIR and trophoblast appears not to have an immune function, but instead plays a physiological role related to placental development. Different human populations have a reciprocal relationship between AA frequency and HLA-C2 frequency, suggesting selection against this combination. In light of our findings, reproductive success may have been a factor in the evolution and maintenance of human HLA-C and KIR polymorphisms.

Female↗
PubMed2004

Preeclampsia and the systemic inflammatory response.

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.

Female↗
PubMed2004

Preeclampsia with abnormal liver function tests is associated with cholestasis in a subgroup of cases.

OBJECTIVE: To investigate whether women with preeclampsia and abnormal liver function tests have raised serum bile acids. DESIGN: Measurement of serum bile acids in serum specimens collected at the John Radcliffe Hospital, Oxford. SETTING: Imperial College School of Medicine. SAMPLE: Stored sera from 37 women with preeclampsia and abnormal liver function tests and from 19 controls. METHODS: Enzymic total bile acid assay. MAIN OUTCOME MEASURES: Total bile acid levels. RESULTS: Women with preeclampsia and abnormal liver function tests had higher median bile acid levels than controls (5.7 vs. 3.2, p = 0.01). The reason for the raised median serum bile acid levels in the patient group is that three (8%) women with preeclampsia had markedly raised serum bile acids levels. There were no obvious clinical or biochemical features specific to these patients. CONCLUSIONS: The pathological mechanisms causing hepatic impairment in some women with preeclampsia may predispose to cholestasis. As some women with preeclampsia and abnormal liver function complain of pruritus, we recommend checking the serum bile acids in this group of women. If these acids are raised the fetal prognosis may be adversely affected.

Adrenergic alpha-Agonists↗
PubMed2003

Decreased tryptophan catabolism by placental indoleamine 2,3-dioxygenase in preeclampsia.

OBJECTIVE: Tryptophan degradation and depletion resulting from activation of indoleamine 2,3-dioxygenase is characteristic of inflammatory reactions and may control their intensity. Normal third-trimester pregnancy is characterized by a maternal systemic inflammatory response, which is more intense in preeclampsia. Therefore, we studied tryptophan metabolism in pregnant women, with or without preeclampsia, as well as expression and function of placental indoleamine 2,3-dioxygenase. STUDY DESIGN: Plasma concentrations of tryptophan and kynurenine in women with preeclampsia, appropriately matched women with normal pregnancy, and healthy nonpregnant women were measured. Placental enzymatic activity and messenger RNA (mRNA) expression level of indoleamine 2,3-dioxygenase were determined from the same placental material. Peripheral blood mononuclear cell proliferation was determined in medium conditioned by prior culture with villous tissue. RESULTS: The plasma ratio of kynurenine to tryptophan, an in vivo index of enzyme activity, was significantly increased compared with nonpregnant controls in normal pregnancy but not in preeclampsia. The activity and mRNA expression level of indoleamine 2,3-dioxygenase in term placentas were significantly lower in preeclampsia. Medium conditioned by culture of villous tissue explants of preeclampsia was less effective in inhibiting peripheral blood mononuclear cell proliferation compared with that of normal pregnancy. CONCLUSION: These observations suggest that in preeclampsia, reduced placental indoleamine 2,3-dioxygenase activity (and relatively elevated plasma tryptophan) could cause dysregulation of the inflammatory response that is intrinsic to normal pregnancy. This may contribute to the pathogenesis of the maternal syndrome of preeclampsia.

Adult↗
PubMed2003

Low selenium status is associated with the occurrence of the pregnancy disease preeclampsia in women from the United Kingdom.

OBJECTIVE: Because the trace element selenium behaves as an antioxidant and peroxynitrite scavenger when incorporated into selenoproteins, our objective was to determine whether low selenium status was associated with a greater risk of occurrence of preeclampsia. STUDY DESIGN: Fifty-three preeclamptic patients and 53 matched pregnant controls at the John Radcliffe Hospital, Oxford, gave clippings of their toenails (laid down from 3-12 months previously) for selenium determination by neutron activation analysis. Clinical characteristics of the women and their infants were recorded. Statistical analysis was by Wilcoxon signed rank test and odds ratios were calculated by the ratio of discordant pairs. RESULTS: Median toenail selenium concentrations in the preeclamptic subjects were significantly lower than in their matched controls (P=.001). Being in the bottom tertile of toenail selenium was associated with a 4.4-fold (95% CI 1.6-14.9) greater incidence of the condition. Within the preeclamptic group, lower selenium status was significantly associated (P=.029) with more severe expression of disease, as measured by delivery before 32 weeks. CONCLUSION: In the light of the reduction in selenium status in a number of European countries in recent years, this study raises the question of whether a small increase in selenium intake might help prevent preeclampsia in susceptible women.

Adult↗
PubMed2002

A computer system for the numerical analysis of nonstress tests.

The development and clinical validation of a computer system for the numerical analysis of nonstress tests is reviewed, and recent improvements are reported. The analysis was developed by using a database of 73,802 nonstress test readings to provide a numerical definition of reactivity that is tailored to the gestational age of the fetus and independent of the presence of accelerations. When used at the bedside, the analysis minimizes monitoring time by alerting the operator when monitoring can be safely stopped because the fetal heart rate is normal. It also detects potentially sinister sinusoidal patterns and improves the quality of nonstress test readings by quantifying signal loss and, if significant, alerting the operator.

Cesarean Section↗
PubMed2002

Abnormal iron parameters in the pregnancy syndrome preeclampsia.

OBJECTIVE: Our purpose was to investigate iron status parameters in preeclampsia with a view to exploring their possible contribution to the etiology. STUDY DESIGN: In prepared serum samples from 40 preeclamptic women and matched pregnant control subjects at the John Radcliffe Hospital, Oxford, a number of iron status parameters were measured. Statistical analysis was by the Wilcoxon signed rank test and linear regression. RESULTS: Serum iron concentration, ferritin, and percent saturation of transferrin were significantly higher in the preeclamptic patients than in control subjects, whereas unsaturated iron-binding capacity and apotransferrin levels were significantly lower. No difference was found in hemopexin concentrations in the two groups. Gestational age at the time of sampling was correlated (positively) with only two parameters, total and unsaturated iron-binding capacity, but only in the preeclampsia group. Eighteen percent of preeclamptic subjects had percent transferrin saturation levels in the region associated with iron overload. CONCLUSION: Released iron species in preeclampsia may contribute to the etiology and will exacerbate lipid peroxidation and endothelial cell injury. Given the high prevalence of heterozygosity for hemochromatosis with the associated reduced ability to exclude ingested iron, it would seem inadvisable, in the absence of evidence of iron deficiency, to give iron supplements to pregnant women at high risk for preeclampsia.

Apoproteins↗