Biomedical subjects

E D Gallery

Publications and source records attributed to E D Gallery.

At least 19 recordsLinked to original sources

PubMed2001

A novel in vitro co-culture system for the study of maternal decidual endothelial cell-trophoblast interactions in human pregnancy.

Investigation of the pathophysiology of pre-eclampsia (characterised by insufficient invasion of the intrauterine vasculature by cytotrophoblasts) has been hampered by the absence of a suitable animal model, and ethical constraints in clinical studies. We have developed a novel in vitro human cell co-culture system allowing direct assessment of cytotrophoblast invasion of a decidual endothelial cell monolayer from the abluminal side, as occurs in vivo. This model will facilitate detection, at the cellular level, of abnormal endothelial cell-trophoblast functional interactions in pre-eclampsia and other pregnancy disorders with abnormal placentation.

Cell Communication↗

PubMed1999

Preeclamptic decidual microvascular endothelial cells express lower levels of matrix metalloproteinase-1 than normals.

In preeclampsia, invasion of intrauterine decidual blood vessels by placental cytotrophoblasts is significantly reduced. This study examined the secretion of matrix metalloproteinases (MMP) by cultured human decidual endothelial cells from normal (NDEC) and preeclamptic (PEDEC) pregnancies. MMPs secreted into the culture medium were measured using zymography, Western blotting, and ELISA. Results were confirmed by Northern analysis. Phorbol myristate acetate, known to induce protease activity in other endothelial cell populations, stimulated MMP1, MMP9, and TIMP1 secretion in both NDEC and PEDEC. Neither tumor necrosis factor-alpha nor transforming growth factor-beta, both thought to have significant roles in the control of placentation, affected MMP secretion. MMP9 and TIMP1 levels were similar between the two cell types; however, MMP1 secretion was markedly different between the cell types. NDEC expressed higher levels of MMP1 under both basal (160 +/- 32 ng/10(6) cells) and stimulated (275 +/- 50) conditions compared to PEDEC (32 +/- 24 and 70 +/- 53, respectively). The lower MMP1 expression of decidual endothelial cells from preeclamptic women may inhibit endovascular invasion by cytotrophoblasts. These findings may, at least partly, explain the relative failure of trophoblasts to invade maternal decidual blood vessels in preeclamptic pregnancy.

Capillaries↗

PubMed1999

Chronic essential and secondary hypertension in pregnancy.

Hypertension is a relatively common complication of pregnancy, increasing in frequency in older women. It is not a contraindication to pregnancy, but should be fully investigated, correctable causes addressed and those with specific relevance for pregnancy identified. With close supervision and appropriate management, the majority of hypertensive pregnant women have successful outcomes. Ideally all women with chronic hypertension should be seen prior to a planned pregnancy, for explanation and discussion of the significance, risks and treatment plan and for adjustment of antihypertensive medication as necessary. Those charged with the antenatal and perinatal care of the patient should be familiar with the expected physiological changes in pregnancy and of the risks and benefits of any treatment given. Close communication among the patient, her obstetrician and consultant physician will ensure the most appropriate treatment and facilitate decisions regarding admission to hospital, timing and mode of delivery, and management issues in the early postpartum period.

Antihypertensive Agents↗

PubMed1999

In vitro human decidual endothelial cell thromboxane secretion in preeclampsia is not abnormal.

OBJECTIVES: The aims of this study were to describe levels of thromboxane secretion by decidual endothelial cells from normal pregnancies and to determine whether decidual endothelial cell secretion of thromboxane, implicated in the causation of the hypertension and vasoconstriction of preeclampsia, is increased in this disorder. METHODS: We measured thromboxane generation by cultured decidual endothelial cells from 13 normal pregnancies (NDEC) and 13 pregnancies complicated by preeclampsia (PEDEC), compared with a control population of 6 normal human umbilical vein endothelial cells (HUVEC). Responses to stimulation by bacterial lipopolysaccharide (LPS), tumor necrosis factor-alpha (TNF-alpha), and interleukin-1 beta (IL-1 beta) were examined. MAIN OUTCOME MEASURES: Thromboxane B2 levels in supernatants of cultured endothelial cells. RESULTS: The level of secretion over 24 h in culture by NDEC [14 (7-26) pg/10(6) cells] was approximately 25% that of HUVEC [63 (49-70) pg/10(6) cells]. Levels achieved in response to all stimuli examined were consistently lower in NDEC than in HUVEC (p < 0.01). Proportional stimulation by LPS and TNF-alpha was comparable in HUVEC and NDEC, whereas NDEC displayed a greater increase (25-fold) than HUVEC (10-fold) in response to IL-1 beta (p < 0.01). There were no significant differences between decidual endothelial cells from normotensive and preeclamptic women in basal secretion of thromboxane or in responses to the stimuli examined. CONCLUSIONS: In vitro thromboxane secretion by decidual endothelial cells is lower than that of HUVEC, and responsiveness to specific stimuli may be quantitatively different. These findings emphasize the importance of examining endothelial cells from the involved maternal vascular bed if intrauterine vascular pathophysiological events are to be clarified. No significant differences were noted in decidual endothelial cell thromboxane secretion between normal and preeclamptic subjects.

Cells, Cultured↗

PubMed1997

Serum from women with preeclampsia partially corrects the abnormal in vitro prostacyclin secretion of preeclamptic villous cytotrophoblasts but not that of prostaglandin E2 or endothelin-1.

OBJECTIVE: This study was conducted (1) to determine in vitro placental villous cytotrophoblast secretion of prostacyclin, prostaglandin E2, and endothelin-1, (2) to examine the effect of serum from normal and preeclamptic women on secretion of these vasoactive substances, and (3) to determine whether responses to these sera by cytotrophoblasts from preeclamptic pregnancies are different from those of normal pregnancies. STUDY DESIGN: Cytotrophoblasts isolated from human placentas collected at cesarean section from normal and preeclamptic women were incubated for 20 hours in 20% (vol/vol) sera from preeclamptic or gestational age-matched normal pregnant women. Levels of prostacyclin (measured as 6-keto-prostaglandin F1alpha), prostaglandin E2, and endothelin-1 were measured in cytotrophoblast supernatants. RESULTS: In normal pregnancy sera preeclamptic cytotrophoblasts secreted significantly lower amounts of prostacyclin and prostaglandin E2 but higher amounts of endothelin-1 than did normal cytotrophoblasts. In preeclamptic sera the abnormality of prostacyclin secretion by preeclamptic cytotrophoblasts was partially corrected, but there was no effect on prostaglandin E2 or endothelin-1 secretion. Preeclamptic sera had no effect on secretion by normal cytotrophoblasts. CONCLUSIONS: The differences between normal and preeclamptic cytotrophoblasts in prostacyclin, PGE2, and endothelin-1 secretion and in response to preeclamptic serum suggest altered arachidonic acid metabolism in preeclampsia.

Blood Physiological Phenomena↗

PubMed1997

Sublingual nifedipine in human pregnancy.

BACKGROUND: Nifedipine is widely used for acute lowering of blood pressure in obstetric hypertensive emergencies. It has not been approved for this indication or widely assessed. AIMS: To examine retrospectively the efficacy of nifedipine over a 12 month period in a high risk obstetric service. METHODS: Chart review of all patients admitted to hospital in the antenatal period with moderate to severe hypertension. Description of their management, usage of nifedipine, and pregnancy outcome. RESULTS: Sublingual nifedipine resulted in significant lowering of blood pressure without hypotension. Pregnancy outcome was satisfactory in all patients. CONCLUSIONS: Sublingual nifedipine was effective, easy to administer, and without serious complications in this retrospective study.

Administration, Sublingual↗

PubMed1996

In-vitro secretion of prostanoids by placental villous cytotrophoblasts in pre-eclampsia.

Villous trophoblasts isolated from term placentae of normal pregnancies, and pregnancies complicated by chronic hypertension or pre-eclampsia, were examined over 7 days in primary culture. Low levels of prostaglandin E2 and prostacyclin (measured as 6-keto prostaglandin Fl alpha) were secreted by trophoblast cells from all three clinical groups. Secretion was maximal at day 1 and decreased exponentially thereafter. Thromboxane secretion also fell sequentially from day 1. Thromboxane secretion by pre-eclamptic trophoblasts was three to four times that of cells from normal or chronically hypertensive subjects. Prostanoid secretion by isolated cultured cytotrophoblasts was not dependent on aggregation or morphological alteration, nor related to changes in progesterone or human chorionic gonadotrophin production. Because the local maternal circulation is exposed to substances secreted by this cell population, thromboxane could be the trigger for vasoconstriction and coagulation found within the maternal uteroplacental circulation in pre-eclampsia.

6-Ketoprostaglandin F1 alpha↗

PubMed1996

Alteration of in vitro human decidual endothelial cell growth, endothelin-1 and prostaglandin secretion, by growth factors and intracellular calcium.

Endothelial cells isolated from umbilical veins (HUVEC) and from decidual biopsies collected at caesarean section delivery (DEC) from both normal (N DEC) and pre-eclamptic (PE DEC) women, were maintained in culture until passage 2, when the effect on growth of removing heparin/ECGS (endothelial cell growth supplement) from the culture medium was assessed, and the effects of heparin-free incubation and of the Ca2+ ionophore A23187 on endothelin-1, prostacyclin and prostaglandin E2 secretion over a 24 h period were examined. Cell growth slowed significantly in all three cell types in the absence of heparin/ECGS, and cell death occurred in 1/3 samples of HUVEC, 4/6 of N DEC, but 0/2 of PE DEC over 4 days. During the 24 h incubation for prostaglandin in medium without these growth factors, there was further cell death in N DEC. The addition of A23187 to this stress led to a reduction in cell number in both N DEC and HUVEC, and to a lesser extent in PE DEC. Prostaglandin and endothelin-1 levels were higher in the absence of heparin/ECGS in all cell types There was significant suppression of endothelin-1 secretion at 24 h incubation, and stimulation of prostaglandin secretion by A23187. Incubation without heparin/ECGS magnified the effect of A23187 on prostaglandin secretion, although the proportional change was similar if compared to controls without heparin/ECGS. Withdrawal of heparin/ECGS from the medium altered the balance of PGE2/PGI2 secretion by HUVEC, but not DEC. Endothelial cells require the presence of heparin/ECGS for optimum growth and viability, and N DEC are particularly dependent on these growth factors. PE DEC appear relatively 'hardy' in this regard. The addition of a further potentially toxic stimulus may result in cell death, and experiments to be conducted in limited medium must take this into account. There are both qualitative and quantitative differences in the effects of these stimuli on secretion of vasoactive substances, between decidual and umbilical vein endothelial cells.

Calcimycin↗

PubMed1995

Effect of serum on secretion of prostacyclin and endothelin-1 by decidual endothelial cells from normal and preeclamptic pregnancies.

OBJECTIVE: Increasing circumstantial evidence suggests that the maternal endothelial cell is centrally involved in the syndrome of preeclampsia, and a number of reports have described the presence of a factor(s) that alters endothelial cell function in serum from women with preeclampsia. We have previously described differences between endothelial cells from the decidual vascular bed and those from the umbilical vein. The purposes of this study were (1) to examine the effect of serum from normal and preeclamptic women on secretion of vasoactive substances by maternal decidual endothelial cells, (2) to compare these results with those from umbilical vein endothelial cells, widely used as a surrogate for endothelial cells in general, (3) to compare responses to these sera by decidual endothelial cells from normal and preeclamptic pregnancies, and (4) to determine whether these responses are amplified by preincubation in test sera. STUDY DESIGN: Endothelial cells were isolated from umbilical veins and from decidual biopsy specimens collected at caesarean section delivery, from both normal and preeclamptic women. Cells were maintained in culture until passage 2, when secretion by the three endothelial cell populations of the vasodilator prostacyclin (measured as its stable metabolite, 6-keto-prostaglandin F1 alpha) and the vasoconstrictor endothelin-1 was compared in the presence of serum from preeclamptic or gestational age-matched normal pregnant women. RESULTS: Prostacyclin secretion by all endothelial cell populations was higher in the presence of serum from preeclamptic women than in medium containing serum from gestational age-matched normal pregnant women. Values for endothelin were not significantly different in cells incubated in serum from normal or preeclamptic women. Preincubation of decidual cells from preeclamptic women in test serum, particularly in preeclamptic serum, resulted in more marked stimulation of prostacyclin secretion. CONCLUSIONS: Preeclamptic serum contains a factor(s) that stimulates prostanoid secretion from endothelial cells. This effect was observed in both umbilical vein and decidual cells. Cells from preeclamptic women were more susceptible to perturbation of their secretion by this factor. Serum from preeclamptic women did not specifically affect endothelin-1 secretion.

6-Ketoprostaglandin F1 alpha↗

PubMed1995

Secretion of prostaglandins and endothelin-1 by decidual endothelial cells from normal and preeclamptic pregnancies: comparison with human umbilical vein endothelial cells.

OBJECTIVE: An increasing amount of circumstantial evidence points to the maternal endothelial cell as centrally involved in the syndrome of preeclampsia. The purposes of this study were (1) to compare the secretion of vasoactive substances by maternal decidual endothelial cells with that of umbilical vein endothelial cells, widely used as a surrogate for endothelial cells in general, and (2) to compare secretion of the same vasoactive substances by decidual endothelial cells from normal and preeclamptic pregnancies. STUDY DESIGN: Endothelial cells were isolated from umbilical veins and from decidual biopsy specimens collected at cesarean section delivery from both normal and preeclamptic women. Cells were maintained in culture until passage 2, when secretion by the three endothelial cell populations of the vasodilators prostaglandin E2 and prostacyclin and the vasoconstrictor endothelin-1 was examined. In addition to control incubations, their responses to stimulation and suppression of secretion were compared. RESULTS: In control incubations normal decidual endothelial cells secreted lower amounts of prostacyclin, prostaglandin E2, and endothelin than did human umbilical vein endothelial cells. All cell types had qualitatively similar responses to the stimuli used, but quantitatively different responses were noted between human umbilical vein endothelial cells and normal decidual endothelial cells for all metabolites examined. Preeclamptic decidual endothelial cells secreted significantly more prostaglandin E2 than did normal decidual endothelial cells in response to stimulation. CONCLUSIONS: We have delineated levels of secretion of vasoactive substances by human late pregnancy decidual endothelial cells and their responses to manipulation of secretory pathways. There are differences between this endothelial cell population and human umbilical vein endothelial cells (which are widely used as a surrogate for maternal endothelial cells). The differences between normal and preeclamptic decidual endothelial cells in prostaglandin E2 secretion may point to altered regulation of arachidonic acid metabolic pathways in preeclampsia.

Cells, Cultured↗

PubMed1995

Neonatal outcome in a randomized, controlled trial of low-dose aspirin in high-risk pregnancies.

OBJECTIVE: To determine the value of low-dose aspirin in high-risk pregnancies, and assess its impact on fetal growth, as well as on perinatal mortality and morbidity. METHODOLOGY: One hundred and eight women with singleton pregnancies were enrolled in a randomized, double-blind, placebo-controlled trial of 100 mg/day aspirin from 17 to 19 week gestation. Enrolment criteria included pre-existing chronic essential hypertension or renal disease, or a history of previous early, severe pre-eclampsia. RESULTS: There were four stillbirths (all aspirin) and two neonatal deaths (both placebo), to yield respective perinatal mortality rates of 69/1000 and 40/1000 (P = 0.499). Liveborn infants in the aspirin group were significantly more mature (P = 0.017) and of heavier birthweight (P = 0.034) but had similar length (P = 0.091) and head circumference (P = 0.257). Fewer infants in the aspirin group were liveborn prematurely (5/54 vs 14/50; P = 0.016) or were of low birthweight (3/54 vs 9/50; P = 0.052). There were no significant between-group differences for standard deviation (Z) scores for weight, length or head circumference, or for skinfold thickness measurements. There was no significant difference in occurrence of low Apgar scores or in neonatal intensive care unit use between the groups. CONCLUSIONS: Low-dose aspirin does not appear to have a significant effect on perinatal morbidity. The increase in weight at birth associated with low-dose aspirin therapy is due to prolongation of pregnancy rather than prevention of intra-uterine growth retardation.

Aspirin↗

PubMed1995

Hypertension in pregnancy. Practical management recommendations.

Hypertension is a common and potentially serious complication of human pregnancy. It can be a marker of underlying maternal disease processes aggravated by pregnancy, or it can be directly related to the pregnancy (pre-eclampsia). It is associated with increased risks of fetal growth retardation and, if severe, can cause both maternal and fetal problems. The risks to both mother and neonate can be reduced by appropriate supervision and therapy. Close monitoring of maternal and fetal welfare will help to determine the optimum time for delivery. Maternal hypertension should be controlled with agents considered to be well tolerated in pregnancy. Following the index pregnancy, all patients with early and/or severe hypertension should be investigated for an underlying cause. Provided that there is clinical resolution of acute pregnancy-related hypertension, investigations are usually postponed until at least 3 months following delivery.

Antihypertensive Agents↗

PubMed1994

Volume homeostasis in normal pregnancy and pre-eclampsia: physiology and clinical implications.

The pieces of the jigsaw puzzle of volume homeostasis in human pregnancy are being put together gradually. This chapter has focused on recent advances in our understanding of factors controlling extracellular fluid volume in normal pregnancy and their disturbance in women who develop pre-eclampsia. We have explored the clinical implications of these guidelines for management of patients with pre-eclampsia. Clearly there is still much to be learned. Studies of the cellular and subcellular handling of sodium are still in their infancy and will add much to our understanding of the physiology of volume homeostasis in normal pregnancy and its disturbance in pre-eclampsia and other causes of hypertension in pregnancy.

Adult↗

PubMed1993

Secretion of prostanoids by platelets and monocytes in normal and hypertensive pregnancies.

OBJECTIVES: Secretory products of immune cells may induce or potentiate coagulation disturbances and vasoconstriction, both central features of pregnancy-induced hypertension. Women with chronic essential hypertension are at high risk of superimposed pregnancy-induced hypertension. The aim of our study was to compare secretory rates of prostanoids (active in coagulation and vascular reactivity) by peripheral blood monocytes and platelets from nonpregnant controls and from women in the third trimester of pregnancy, normals and those with either pregnancy-induced hypertension or uncomplicated chronic essential hypertension. STUDY DESIGN: From 100 ml blood, peripheral blood monocytes and platelets were isolated; their relative rates of in vitro production of prostacyclin, prostaglandin E2, and thromboxane were measured, and responses to stimulation by arachidonic acid or the calcium ionophore A23187 were compared among the four groups of subjects. RESULTS: Basal peripheral blood monocyte secretory levels of prostanoids were low in all groups, with responses to both stimuli. Cells from women with chronic essential hypertension had a relatively exaggerated rise in thromboxane secretion (and to a lesser extent, prostacyclin) in response to the stimuli used, with a similar but less marked trend for those with pregnancy-induced hypertension. Platelets from women with chronic essential hypertension had particularly high basal secretory levels of thromboxane, with little further response to stimulation by arachidonic acid or A23187. CONCLUSIONS: Our work demonstrates clearly for the first time that peripheral blood monocytes from pregnant women secrete low levels of vasoactive prostanoids and respond to the stimuli used in a manner similar to that of nonpregnant women, and that cells from pregnant women with hypertension have a tendency to increased reactivity that is most marked in those with chronic essential hypertension. Platelets from women with chronic essential hypertension secrete near-maximal amounts of thromboxane in the absence of exogenous stimuli, indicating a degree of prior activation.

Adult↗

PubMed1993

Urinary red blood cell and cast excretion in normal and hypertensive human pregnancy.

OBJECTIVE: Although the well-recognized pregnancy changes in renal blood flow, cellular function, tubular fluid composition, and flow rates may cause altered excretion rates of formed elements in the urine, relatively little attention has been paid to this in normal pregnancy. The urinary white cell excretion is known to be increased, with loss of the usual relationship between pyuria and urinary infection. Whether the same is true for other formed elements is unknown. Our purpose was to determine normal values for excretion of erythrocytes and casts and to establish whether they became abnormal in women in whom preeclampsia developed. STUDY DESIGN: Study subjects were 174 continuously normotensive pregnant volunteers, 22 women who had preeclampsia, and 8 women who had chronic essential hypertension. Early-morning midstream urine samples were collected at 17 to 20 and at 33 to 36 weeks' amenorrhea after insertion of a vaginal tampon. Urinary microscopy was performed by standard techniques (Kesson et al. Lancet 1978;2:809). RESULTS: The 95th percentile for concentration of erythrocytes was < or = 2500 red blood cells/ml; for casts the concentration was < or = 30 red blood cells/ml in normal pregnancy. Values for those who had preeclampsia and for the small group with chronic essential hypertension were within these limits. CONCLUSION: In an early-morning concentrated urine sample, values of < or = 2500 erythrocytes/ml and < or = 30 hyaline or granular casts per milliliter can be accepted as normal.

Chronic Disease↗

PubMed1992

Proteinuria and its assessment in normal and hypertensive pregnancy.

OBJECTIVES: The purposes of this study were (1) to determine 24-hour urinary protein excretion rates in normal human pregnancy and (2) to assess the reliability of assessment of proteinuria by dipstick measurement. STUDY DESIGN: At 17 to 20 and 33 to 36 weeks of pregnancy, 174 normal volunteers collected a 24-hour urine sample; the volume and the protein and creatinine concentrations were measured. The result for protein was compared with dipstick analysis of an early morning midstream urine sample collected at the conclusion of the 24-hour period. Sixty-eight consecutive inpatients admitted to the antenatal ward with hypertension and positive urine dipstick tests for protein underwent the same procedure. The interobserver variability in dipstick analyses of urine samples of known protein content was assessed with the aid of 66 volunteers from the hospital staff. RESULTS: The upper 95% confidence limit of the normal population was less than 200 mg per 24 hours, at both stages of pregnancy investigated. In these women and in the hypertensive inpatients a high proportion of false-positive and false-negative results was found with dipstick analyses. Interobserver variation in assessment of proteinuria by dipstick was high, with an 18% false-positive rate and a false-negative rate approaching 40% for samples with 30 mg/dl. Even in the presence of 100 mg/dl the false-negative rate was 7%, whereas the concentration of protein was significantly underestimated in 20% of samples with 500 mg/dl. CONCLUSION: Dipstick urinalysis cannot be relied on either to detect or to exclude the presence of proteinuria in pregnant women.

Cross-Sectional Studies↗

PubMed1992

Renal function in unilateral nephrectomy subjects.

Renal function in 32 subjects who had undergone unilateral nephrectomy (17 transplant donors and 15 subjects with unilateral renal disease) was compared with that of 22 normal subjects. The age-adjusted glomerular filtration rate was lower in transplant donors (79 +/- 15% of normal) than in those whose nephrectomy was performed for unilateral renal disease (90 +/- 12% of normal). The donors were also significantly older at nephrectomy (48 +/- 10 years versus 24 +/- 13 years, p less than 0.001). This finding may represent less capacity for compensatory hypertrophy. Proximal tubular and medullary function as assessed by 15-minute phenolsulfonphthalein excretion, maximum urinary concentration in response to water deprivation plus exogenous vasopressin, and urinary acidification in response to an oral acid load were all within normal limits for glomerular filtration rate. Overall renal function was well preserved after nephrectomy. A small number of patients did have increased cast excretion, which may signify the presence of mild renal disease in these subjects.

Adult↗

PubMed1991

Isolation and purification of microvascular endothelium from human decidual tissue in the late phase of pregnancy.

Normal pregnancy demands significant structural and physiologic adaptations of the uterine microvasculature, to facilitate adequate placentation. In pregnancies complicated by pregnancy-associated hypertension (preeclampsia), this process is defective, resulting in a high incidence of intrauterine growth retardation. The microvascular endothelium, a focal point for both initiation and inhibition of coagulation and control of vascular tone, may well contribute to development and aggravation of these abnormalities. We describe a method for isolation, purification, and culture of human decidual endothelial cells from biopsies performed at the time of cesarean section. The separation procedure is technically simple, requires only a small piece of tissue, and takes approximately 2 hours to perform. Some of the unique features of these cells in culture are outlined. This technique will permit the close examination of various aspects of the function of these cells in normal pregnancy, and their comparison with cells from pregnancies complicated by hypertension.

Cell Division↗