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R N Taylor

Publications and source records attributed to R N Taylor.

At least 91 records · Page 5Linked to original sources
PubMed1991

Trisomic pregnancies have normal human chorionic gonadotropin bioactivity.

Sera from women carrying either chromosomally normal or aneuploid fetuses in the first half of pregnancy were assayed for human chorionic gonadotropin (hCG) bioactivity in order to determine whether differences might provide the basis for a useful antenatal screen for aneuploidy. A mouse uterine weight assay was used to assess hCG bioactivity in sera from 35 patients undergoing chorionic villus sampling (12 normal pregnancies and 23 trisomic pregnancies) and in sera from 18 patients undergoing elective second-trimester abortion (12 presumed normal pregnancies, 3 trisomic pregnancies, and 3 pregnancies with neural tube defects). The hCG bioactivity to immunoactivity (B:I) ratio of normal pregnancies progressively decreased from 7.7 +/- 1.3 at 4-5 menstrual weeks, to 4.7 +/- 0.4 at 9-12 menstrual weeks, to 3.3 +/- 0.5 at 16-20 menstrual weeks. There were no significant differences in the B:I ratios between normal and aneuploid pregnancies in either the first-trimester (4.7 +/- 0.4 versus 5.2 +/- 0.3) or the second-trimester samples (3.3 +/- 0.5 versus 2.6 +/- 0.3), despite significantly greater hCG concentrations in the trisomic pregnancies. We conclude that while aneuploid pregnancies display dysfunctional regulation of hCG expression, the bioactivity of their hCG is normal and does not appear to form the basis for a useful screen for aneuploidy.

Aneuploidy↗
PubMed1991

First-trimester aneuploidy screening using serum human chorionic gonadotropin (hCG), free ahCG, and progesterone.

Immunochemical serum assays for human chorionic gonadotropin (hCG), the free ahCG subunit, and progesterone (P) were considered separately and in combination for their ability to screen for chromosomally abnormal pregnancies in the first trimester. Maternal serum was collected from 141 women undergoing chorionic villus sampling at 9-12 menstrual weeks. Trisomy 21 pregnancies had significantly higher hCG levels, while trisomy 18 and 13 pregnancies had markedly lower hCG and progesterone levels than those of chromosomally normal pregnancies. However, the discrimination of normal from aneuploid pregnancies was poor with either hCG alone, progesterone alone, or free ahCG alone. Much improved discrimination was obtained by combining hCG, free ahCG, and P into an aneuploidy index [(P/hCG)(free ahCG/hCG)]. This index distinguished 9 out of 17 (53 per cent) of the trisomy 21 pregnancies, while only misidentifying 5 out of 112 (4.5 per cent) of the normal pregnancies. The aneuploidy index thus appears promising as a first-trimester biochemical screen for aneuploid pregnancies.

Aneuploidy↗
PubMed1991

Selective effects of preeclamptic sera on human endothelial cell procoagulant protein expression.

Current concepts of preeclampsia suggest that dysfunction of maternal vascular endothelium in vivo is a central pathogenetic feature of this syndrome. This hypothesis is suggested by the activation of the coagulation cascade associated with preeclampsia and evidence for a role of endothelium in maintaining thromboresistance. Previous in vitro studies with monolayers of human umbilical vein endothelial cells demonstrated direct cytotoxic effects of sera from preeclamptic parturients. In the current studies, we have examined the in vitro expression of three procoagulant protein activities regulated by endothelial cells: cellular fibronectin, an important mediator of platelet aggregation known to be elevated in preeclamptic women in vivo; tissue factor, the most potent endogenous procoagulant activity; and von Willebrand factor, a major component of coagulation factor VIII. Monolayer cultures of human umbilical vein endothelial cells were incubated with pregnancy sera for 24 hours before these proteins and activities were quantified. Exposure of identical endothelial cell cultures to predelivery preeclamptic sera caused significantly greater release of cellular fibronectin than postdelivery preeclamptic or predelivery or postdelivery normal pregnancy sera (p less than 0.05). However, neither tissue factor activity nor von Willebrand factor expression appeared to be increased preferentially by preeclamptic sera. The data indicate that sera from women with preeclampsia induce a selective, but not a generalized, activation of endothelial cell procoagulant protein production.

Adult↗
PubMed1991

High plasma cellular fibronectin levels correlate with biochemical and clinical features of preeclampsia but cannot be attributed to hypertension alone.

Current concepts of the pathogenesis of preeclampsia involve the generalized dysfunction of maternal vascular endothelial cells. We measured the endothelial isoform of fibronectin as a marker of endothelial cell injury throughout pregnancy in a prospective, case-control study. Nineteen women met strict criteria for the diagnosis of preeclampsia. Nineteen normal pregnant women, and 19 women with gestational hypertension but without other stigmata of preeclampsia (transient hypertension) were selected from the same cohort and matched according to race, age, nulliparity, and gestational age at delivery. Plasma levels of cellular fibronectin were significantly elevated in women meeting strict clinical and biochemical criteria for preeclampsia but not in women with normal pregnancies or transient hypertension. Moderate but significant elevations in mean levels were found in the second trimester in women destined to have preeclampsia, as compared with matched normal and transient hypertension groups (p less than 0.05). The results indicate that elevated plasma levels of cellular fibronectin are not simply the result of increased blood pressure but reflect a maternal insult specific to the syndrome of preeclampsia. Elevation of the mean concentration during the midtrimester is consistent with the hypothesis that endothelial cell injury is a specific lesion that occurs early in the course of preeclampsia, before clinical signs and symptoms.

Adult↗
PubMed1991

Forskolin and methotrexate induce an intermediate trophoblast phenotype in cultured human choriocarcinoma cells.

The human placenta and its associated membranes are vital to the maintenance, nutrition, and protection of the developing fetus. During placental development some cytotrophoblasts give rise to the chorionic membrane whereas others fuse to form a differentiated syncytium of cells that are responsible for placental protein and steroid hormone production. The mechanisms involved in the differentiation of the trophoblasts are unknown; however, an intermediate stage with a characteristic phenotype has been documented in vivo. We have observed that chemically dissimilar xenobiotic agents induced BeWo choriocarcinoma cells to change their usual cytotrophoblastic phenotype and acquire morphologic and functional characteristics typical of intermediate trophoblast. Incubation of BeWo cell cultures in the presence of 1 mumol/L methotrexate for 48 hours stimulated human chorionic gonadotropin secretion (2.3-fold) and aromatase activity (4.9-fold). Morphologic findings associated with these hormonal changes, including increased nuclear size and cytoplasmic expansion, were also observed. With the use of a computer-interfaced image analyzer, planimetric morphometry of the nuclear area of the cells revealed a 1.8-fold increase after incubation with methotrexate. The effect of forskolin, a direct activator of adenylyl cyclase, was also evaluated by means of this model of cytotrophoblast differentiation. The addition of 10 mumol/L forskolin to BeWo cultures also resulted in dramatic changes in trophoblast cell phenotype. Increases in human chorionic gonadotropin synthesis (7.3-fold), aromatase activity (13.5-fold), and nuclear area (3.0-fold) were induced over those of untreated cells. In addition, increases in [3H]thymidine incorporation (1.7-fold) were afforded by both treatments. These results suggest that biochemical and cytologic changes associated with human trophoblast differentiation can be induced in vitro via activation of the adenylyl cyclase pathway by forskolin and through unknown and apparently independent signals by methotrexate.

Cell Differentiation↗
PubMed1991

Clinical and biochemical evidence of endothelial cell dysfunction in the pregnancy syndrome preeclampsia.

The pregnancy disorder preeclampsia continues as a major cause of maternal and infant mortality and morbidity. Despite intensive research since its recognition 100 years ago, our lack of understanding is evidenced by therapy which remains empiric, early delivery. Part of our failure to more completely understand the syndrome is due to excessive attention to the blood pressure elevation which accompanies the disorder, to the exclusion of a panoply of other physiologic aberrations. Although hypertension, if markedly elevated, can lead to maternal morbidity, it is not usually an important contributor to the pathophysiology of preeclampsia. It is primarily important as a marker for vasoconstriction, which in association with activation of coagulation reduces perfusion to many organs, including the fetal-placental unit. The earliest and likely most important pathophysiologic change is reduced placental perfusion secondary to abnormal implantation and/or a relative increase in placental mass. We propose that reduced placental perfusion results in the production of agent(s) by this organ, which injures or activates endothelial cells. The resulting endothelial cell dysfunction increases sensitivity to normal endogenous pressors, activates the coagulation cascade, and increases vascular permeability. These changes produce the characteristic pathophysiologic changes of the disorder. Evidence supporting this hypothesis includes abnormal endothelial morphology long recognized in glomerular capillaries, increased circulating fibronectin, and increased plasma mitogenic activity that long antedates the clinical disorder. In addition, an agent(s) is present in the blood of these women which activates endothelial cells in vitro as evidenced by increased release of [51Cr] chromium and increased production of PDGF. Preeclampsia is clearly more than "pregnancy induced hypertension."

Endothelium, Vascular↗
PubMed1991

Preeclamptic sera stimulate increased platelet-derived growth factor mRNA and protein expression by cultured human endothelial cells.

Monolayer cultures of human endothelial cells were incubated with pre- and postdelivery sera from five women with preeclampsia and four matched, normal pregnancies. Conditioned media collected from endothelial cells pretreated in vitro with prepartum sera from preeclamptic women contained greater mitogenic activity and elevated levels of platelet-derived growth factor (PDGF)-like peptides than cells exposed to normal pregnancy sera or postpartum preeclamptic sera. Under the same experimental conditions, predelivery preeclamptic sera stimulated greater expression of endothelial cell PDGF-B-chain mRNA than that accumulated in the presence of matched postdelivery sera. By contrast, no differences in endothelial cell PDGF-B mRNA levels were noted when pre- and postdelivery sera from normal parturients were tested. The results suggest that a factor(s) in the blood of preeclamptic women can stimulate the synthesis and release of a potent growth factor and vasoconstrictor from human endothelial cells.

Cells, Cultured↗
PubMed1991

Pathophysiology of preeclampsia.

Preeclampsia is a complex clinical syndrome, with hypertension representing but one manifestation. Pathogenetically important events in the development of preeclampsia include incomplete trophoblastic invasion of the maternal spiral arteries, poor trophoblastic perfusion, elaboration of a putative endothelial cell toxin, and endothelial cell injury with resulting activation of coagulation, impairment of vasodepressor function, and altered endothelial permeability. These changes lead to the clinical signs and symptoms, which occur relatively late in the course of preeclampsia. The primary immunologic, genetic, and biochemical basis of preeclampsia remains speculative.

Endothelium, Vascular↗
PubMed1990

Corpus luteum function in early pregnancies is primarily determined by the rate of change of human chorionic gonadotropin levels.

Regulation of human corpus luteum activity was studied with radioimmunoassays and bioassays of sera drawn serially from women suspected of having ectopic pregnancies. Progesterone values exhibited considerable overlap in pregnancies that were subsequently classified as normal intrauterine (n = 21), ectopic (n = 35), or spontaneous abortion (n = 14). The rate of change of human chorionic gonadotropin concentration was significantly correlated with progesterone levels in ectopic (r = 0.64) and all pregnancies (r = 0.70). There was no correlation (r = -0.18) between the rate of change of human chorionic gonadotropin and the bioactivity produced per volume of serum. Ectopic pregnancies and normal intrauterine pregnancies did not differ in their ratio of in vivo bioactivity to immunoactivity. From these data we conclude that corpus luteum activity is primarily regulated by the rate of change of human chorionic gonadotropin concentration, without the involvement of other serum factors. We also conclude that reduced corpus luteum function in ectopic pregnancies is not a result of biochemical modification of the human chorionic gonadotropin molecule. Finally, we discourage the use of single progesterone values in screening for ectopic pregnancies because of the considerable overlap in progesterone values among these and normal intrauterine pregnancies.

Abortion, Spontaneous↗
PubMed1990

Growth factor activity in the blood of women in whom preeclampsia develops is elevated from early pregnancy.

Preeclampsia is a pregnancy-specific disorder of uncertain cause and pathophysiology that appears to be associated with endothelial cell injury. Our current studies demonstrate that a pregnancy growth factor activity is elevated compared with postpartum values in the blood of women with preeclampsia months before the onset of clinical manifestations of toxemia. A cohort of primigravid women was followed throughout pregnancy and multiple serial plasma samples from six women with preeclampsia and six matched normal women were assayed for mitogenic activity. The data indicated that the ratio of predelivery/postdelivery plasma mitogenic activity was greater in women predestined to meet strict criteria for the diagnosis of preeclampsia compared with matched normal primigravid women. Growth factor activity could distinguish women in whom preeclampsia would develop from their normal peers throughout pregnancy, and as early as the first trimester of gestation (p less than 0.05). Similar studies performed with plasma obtained greater than 6 weeks post partum, when the two groups of patients were clinically indistinguishable, revealed no differences in this index of mitogenic activity. Our results indicate that elevated mitogenic activity ratios of prepartum versus postpartum plasma antedate the clinical recognition of preeclampsia, and return to normal with the resolution of the syndrome.

Adult↗
PubMed1990

Indirect immunofluorescence test performance and questionnaire results from the Centers for Disease Control Model Performance Evaluation Program for human immunodeficiency virus type 1 testing.

Results from laboratories performing indirect immunofluorescence (IIF) testing for human immunodeficiency virus type 1 antibody and participating in the Centers for Disease Control Model Performance Evaluation Program in 1988 are presented. Approximately 90% of all laboratories receiving specimen panels or questionnaires furnished results to the Centers for Disease Control. In September 1988, 111 reports were received from IIF laboratories from 34 states and nine countries; most of these laboratories did IIF testing in conjunction with other antibody tests. Hospital laboratories were the most common type of laboratory participating in the program. Laboratories that performed IIF employed fewer personnel and performed testing less frequently than did laboratories that performed enzyme immunoassays or Western blot (immunoblot) tests and were likely to use a commercial test kit. Most of the laboratories that referred specimens for IIF testing sent them to the state laboratory. The analytic specificity for the Model Performance Evaluation Program specimens was 98.5% when indeterminate results on a negative specimen were considered correct (negative) and 89.6% when indeterminate results on a negative specimen were considered incorrect; analytic sensitivity was 94.8% when indeterminate results on a positive specimen were correct (positive) and 91.4% when indeterminate results on a positive specimen were considered incorrect. When indeterminate results were considered correct, all types of laboratories (blood bank, state, hospital, independent, and other) had analytic specificities over 96%, and all manufacturers had analytic specificities above 95%. All types of laboratories had analytic sensitivities over 92%, and analytic sensitivities were above 94% for all manufacturers and reagent sources except Cellular Products. Comparison of percentages of correct responses between IIF and Western blot assays on those samples for which there was good agreement on the target interpretation revealed no significant differences. Both individual donor and diluted materials were included in the evaluations; the diluted donor material presented the greatest testing difficulty. Within-survey reproducibility was about 93% overall and by specimen type. Between-survey reproducibility was about 81% for negative and indeterminate specimens and 88.5% for positive specimens, for an overall between-survey reproducibility of 84.3%. Differences in performance were noted when results were compared by type of laboratory and test manufacturer.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Partial characterization of a novel growth factor from the blood of women with preeclampsia.

Sera obtained before delivery from women with preeclampsia contain greater mitogenic activity than sera drawn from the same women 24-48 h after parturition or sera from normal parturients. These studies describe the initial characterization of the blood-borne mitogenic factor(s) from preeclamptic women which we have named ELMER (Endogenous Ligand conferring MitogEnic Response). ELMER appears to be a unique mitogen with characteristics that are not identical to those of other known growth factors. ELMER is present in serum as an acid- and heat-labile protein, approximately 160,000 daltons in size, which is a potent mitogen for human fibroblasts but not for human endothelial cells. Its presence in plasma suggests that it is a circulating factor rather than a product of blood coagulation ex vivo. We believe that ELMER represents a potential serum marker of preeclampsia and that it may play roles in the vasospasm and proliferative vascular lesion, termed atherosis, frequently associated with the preeclamptic syndrome.

Acids↗
PubMed1990

Women with preeclampsia have higher plasma endothelin levels than women with normal pregnancies.

Endothelin, a newly discovered endothelium-derived peptide, has potent vasoactive properties in vivo and in vitro. The actions of endothelin in clinical conditions of hypertension have not yet been defined. This study examined the possible role of endothelin in the vasospasm and hypertension associated with a well-defined syndrome of gestational hypertension, preeclampsia. Our results indicate that the concentration of immunoreactive endothelin is elevated significantly in plasma obtained from women with preeclampsia and rapidly returns to a normal pregnancy value within 48 hours of delivery, as predicted by the prompt clinical resolution of this disorder. The findings suggest that endothelin may contribute to the vasospasm associated with this syndrome and lend further support to the involvement of endothelial cells in the pathophysiology of preeclampsia.

Adult↗
PubMed1990

Centers for Disease Control perspective on quality assurance for human immunodeficiency virus type 1 antibody testing. Model Performance Evaluation Program.

Ensuring high quality in human immunodeficiency virus type 1 (HIV-1) antibody testing is an essential component of the organized public health response to epidemic HIV-1 infection. In 1986, the Centers for Disease Control designed the Model Performance Evaluation Program to assess and improve the analytic quality of HIV-1 antibody testing. In addition, the program was designed to gather information about HIV-1 antibody testing practices. The utility of this information is in identifying potential barriers to quality throughout the total testing process. Currently, 1405 laboratories participate in the program. Participating laboratories are located both within and outside the United States and consist primarily of hospitals, blood banks, health departments, and independent laboratories. The responses to a questionnaire completed by 1050 program-participant laboratories in September 1988 suggest that at several stages in the HIV-1 antibody total testing process, laboratory practices (including the interpretation of Western blot patterns) are variable and that standardization of these practices would improve quality.

Centers for Disease Control and Prevention, U.S.↗
PubMed1989

Preeclampsia: an endothelial cell disorder.

Despite intense study preeclampsia remains enigmatic and a major cause of maternal and fetal morbidity and mortality. Most investigative efforts have focused on the hypertensive component of this disorder with reduced attention given to other equally important characteristics. Increased sensitivity to pressor agents and activation of the coagulation cascade occur early in the course of preeclampsia, often antedating clinically recognizable disease. Inasmuch as endothelial cell injury reduces the synthesis of vasorelaxing agents, increases the production of vasoconstrictors, impairs synthesis of endogenous anticoagulants, and increases procoagulant production, these cells are likely to be implicated in the pathophysiology of preeclampsia. Indeed, evidence of endothelial cell injury is provided by the most characteristic morphologic lesion of preeclampsia, glomerular endotheliosis. Additional support for this hypothesis is derived from reports that indicate increased levels of circulating fibronectin (which can be released from injured endothelial cells) and increased factor VIII antigen present in the blood of preeclamptic women. More recently, direct evidence of activities that injure endothelial cells in vitro and increase the contractile sensitivity of isolated vessels has been presented. We propose that poorly perfused placental tissue releases a factor(s) into the systemic circulation that injuries endothelial cells. The changes initiated by endothelial cell injury set in motion a dysfunctional cascade of coagulation, vasoconstriction, and intravascular fluid redistribution that results in the clinical syndrome of preeclampsia.

Endothelium, Vascular↗
PubMed1989

Lipid peroxidation in pregnancy: new perspectives on preeclampsia.

Basic research during the past two decades has led to increased awareness of the role of lipid peroxidation in various physiologic and pathophysiologic processes. A number of reports indicate that preeclampsia is associated with elevated blood levels of lipid peroxidation products. In view of its potentially destructive character, uncontrolled lipid peroxidation has been suggested as an etiologic factor in preeclampsia. The present article summarizes current information regarding the occurrence of lipid peroxidation in normal and preeclamptic pregnancy. Recent progress concerning our understanding of the process of lipid peroxidation and its role in cardiovascular disease is also reviewed. This information is used to discuss potential mechanisms by which lipid peroxidation might contribute to the pathogenesis of preeclampsia.

Female↗