Cervicovaginal fluid proteomic analysis to identify potential biomarkers for preterm birth.

Background: Spontaneous preterm birth is a leading cause of neonatal morbidity and mortality. Early identification of at-risk women by reliable screening tests could reduce the spontaneous preterm birth rate, but conventional methods such as obstetrical history and maternal cervical length screening identify only a minority of spontaneous preterm birth cases. Cervicovaginal fluid might prove to be a useful, readily available biological fluid for identifying spontaneous preterm birth biomarkers.

The Placental Atlas Tool (PAT): A collaborative research and discovery platform for the placental research community.

Introduction: The placenta is one of the least understood, yet arguably one of the most important organs for human health and development. While there have been numerous research efforts dedicated to understanding the placenta's critical role, these studies and the data they produced remain separated and largely disparate. In order to facilitate placental research, the Eunice Kennedy Shriver National Institute of Child and Human Development (NICHD) released in October 2018 the Placental Atlas Tool (PAT) (https://pat.

DASH, the data and specimen hub of the National Institute of Child Health and Human Development.

The benefits of data sharing are well-established and an increasing number of policies require that data be shared upon publication of the main study findings. As data sharing becomes the new norm, there is a heightened need for additional resources to drive efficient data reuse. This article describes the development and implementation of the Data and Specimen Hub (DASH) by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) to promote data sharing from NICHD-funded studies and enable researchers to comply with NIH data sharing policies.

Onset of human preterm and term birth is related to unique inflammatory transcriptome profiles at the maternal fetal interface.

Background: Preterm birth is a main determinant of neonatal mortality and morbidity and a major contributor to the overall mortality and burden of disease. However, research of the preterm birth is hindered by the imprecise definition of the clinical phenotype and complexity of the molecular phenotype due to multiple pregnancy tissue types and molecular processes that may contribute to the preterm birth. Here we comprehensively evaluate the mRNA transcriptome that characterizes preterm and term labor in tissues comprising the pregnancy using precisely phenotyped samples.

Pharmacogenomics of 17-alpha hydroxyprogesterone caproate for recurrent preterm birth: a case-control study.

Objective: To compare maternal genotypes between women with and without significant prolongation of pregnancy in the setting of 17-alpha hydroxyprogesterone caproate (17-P) administration for the prevention of recurrent preterm birth (PTB).

Design: Case-control.

Setting: Three tertiary-care centres across the USA.

Placental origins of adverse pregnancy outcomes: potential molecular targets: an Executive Workshop Summary of the Eunice Kennedy Shriver National Institute of Child Health and Human Development.

Although much progress is being made in understanding the molecular pathways in the placenta that are involved in the pathophysiology of pregnancy-related disorders, a significant gap exists in the utilization of this information for the development of new drug therapies to improve pregnancy outcome. On March 5-6, 2015, the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health sponsored a 2-day workshop titled Placental Origins of Adverse Pregnancy Outcomes: Potential Molecular Targets to begin to address this gap. Particular emphasis was given to the identification of important molecular pathways that could serve as drug targets and the advantages and disadvantages of targeting these particular pathways.

Predictors of response to 17-alpha hydroxyprogesterone caproate for prevention of recurrent spontaneous preterm birth.

Background: Prematurity is the leading cause of neonatal morbidity and death among nonanomalous neonates in the United States. Intramuscular 17-alpha hydroxyprogesterone caproate injections reduce the risk of recurrent prematurity by approximately one third. Unfortunately, prophylactic 17-alpha hydroxyprogesterone caproate is not always effective, and one-third of high-risk women will have a recurrent preterm birth, despite 17-alpha hydroxyprogesterone caproate therapy.

Cluster analysis of spontaneous preterm birth phenotypes identifies potential associations among preterm birth mechanisms.

Objective: We sought to use an innovative tool that is based on common biologic pathways to identify specific phenotypes among women with spontaneous preterm birth (SPTB) to enhance investigators' ability to identify and to highlight common mechanisms and underlying genetic factors that are responsible for SPTB.

Study Design: We performed a secondary analysis of a prospective case-control multicenter study of SPTB. All cases delivered a preterm singleton at SPTB ≤34.

The phenotype of spontaneous preterm birth: application of a clinical phenotyping tool.

Objective: Spontaneous preterm birth (SPTB) is a complex condition that is likely a final common pathway with multiple possible causes. We hypothesized that a comprehensive classification system appropriately could group women with similar STPB causes and could provide an explanation, at least in part, for the disparities in SPTB that are associated with race and gestational age at delivery.

Study Design: This was a planned analysis of a multicenter, prospective study of singleton SPTBs.

A genome-wide association study of early spontaneous preterm delivery.

Preterm birth is the leading cause of infant morbidity and mortality. Despite extensive research, the genetic contributions to spontaneous preterm birth (SPTB) are not well understood. Term controls were matched with cases by race/ethnicity, maternal age, and parity prior to recruitment.

Maternal serum serpin B7 is associated with early spontaneous preterm birth.

Objective: We sought to identify serum biomarkers of early spontaneous preterm birth (SPTB) using semiquantitative proteomic analyses.

Study Design: This was a nested case-control study of pregnant women with previous SPTB. Maternal serum was collected at 19-24 and 28-32 weeks' gestation, and analyzed by liquid chromatography-multiple reaction monitoring/mass spectrometry.

Preeclampsia--a pressing problem: an executive summary of a National Institute of Child Health and Human Development workshop.

On September 21 and 22, 2006, the National Institute of Child Health and Human Development of the National Institutes of Health sponsored a 2-day workshop titled "Preeclampsia--A Pressing Problem." The purpose of the workshop was to bring together leaders in the field to present and discuss their diverse research areas, which ranged from basic science to clinical trials and management, and to identify scientific gaps. This article is a summary of the proceedings of that workshop.

Epidermal growth factor increases lung liquid clearance in rat lungs.

Epidermal growth factor (EGF) has been reported to stimulate the proliferation of epithelial cells and increase Na+ flux and Na+-K+-ATPase function in alveolar epithelial cell monolayers. Increases in Na+-K+-ATPase in alveolar type II cells (AT2) have been associated with increased active Na+ transport and lung edema clearance across the rat alveolar epithelium in a model of proliferative lung injury. Thus we tested whether administration of aerosolized EGF to rat lungs would increase active Na+ transport and lung liquid clearance.

Expression of the ErbB family of receptors in ovarian cancer.

Objective: To characterize the relative levels of the ErbB family of receptors and their relationship to one another in ovarian cancer.

Methods: A total of 17 serous cystadenocarcinomas were analyzed for epidermal growth factor receptor (EGF-R or ErbB-1) and ErbB-2, ErbB-3, and ErbB-4 receptor expression by Western blot analysis. Receptor levels were quantified by densitometry and expressed as relative densitometry units normalized to the level of alpha-tubulin.

Expression of epidermal growth factor and androgen receptors in ovarian cancer.

Ovarian cancer is the second most common malignancy of the female reproductive tract. Approximately 50% of ovarian cancers have elevated levels of epidermal growth factor receptor (EGFR). This overexpression is correlated with a poor prognosis for patient survival.

Expression of a truncated epidermal growth factor receptor-like protein (TEGFR) in ovarian cancer.

The epidermal growth factor receptor (EGFR) system has been implicated in the etiology of numerous cancers, including that of ovarian cancer. Elevated levels of EGFR are associated with poor patient prognosis. Moreover, a significant number of ovarian cancers express both the receptor and one of its ligands, suggesting an autocrine mechanism for autonomous tumor growth.

Possible role of variant RNA transcripts in the regulation of epidermal growth factor receptor expression in human placenta.

Epidermal growth factor receptor (EGFR) plays an important role in growth and differentiation. The human placenta expresses high levels of the receptor. In the placenta, as in many other human tissues, EGFR is encoded by two RNA transcripts of 5.

Effect of lipoxygenase products on choriogonadotropin secretion by cultured human choriocarcinoma JEG-3 cells pre- and post-stimulation with epidermal growth factor and a phorbol ester.

Previous studies using arachidonic acid and preferential inhibitors of the arachidonic acid pathway have implicated the lipoxygenase system in choriogonadotropin (hCG) secretion by JEG-3 cells. Presently, JEG-3 cells are used in order to examine the effect of lipoxygenase products on hCG secretion. Results show that 30 microM 15-hydroxyeicosatetraenoic acid (15-HETE) induces an approximately 3-fold increase in basal hCG secretion, while 5-HETE, 12-HETE, and leukotriene LTA4 have no significant effect.

Epidermal growth factor receptor numbers in male and female mouse primary hepatocyte cultures.

Epidermal growth factor receptors (EGF-R) were measured in adult male and female mouse primary hepatocyte cultures. On culture day 1, female hepatocytes had significantly fewer EGF-R than male hepatocytes (1.3 x 10(4) versus 6.

Competitive studies with dehydroepiandrosterone sulfate and 16 alpha-hydroxydehydroepiandrosterone sulfate in cultured human choriocarcinoma JEG-3 cells: effect on estrone, 17 beta-estradiol, and estriol secretion.

The estradiol (E2) to estriol (E3) ratio during human pregnancy depends on fetal liver hydroxylation of fetal adrenal dehydroepiandrosterone sulfate (DHEAS) and conversion by the trophoblast of DHEAS and 16 alpha-hydroxy-DHEAS (16 OH-DHEAS) to estrone (E1), estradiol (E2), and estriol (E3), respectively. It is not known whether the conversion of DHEAS into E1 and E2 influence the conversion of 16OH-DHEAS into E3 and vice versa. To examine this question, we studied these interactions in human choriocarcinoma JEG-3 cells.

The effect of dehydroepiandrosterone sulfate on de novo and low-density lipoprotein-stimulated progesterone secretion by human choriocarcinoma JEG-3 cells.

It has been suggested that fetal adrenal steroids affect the secretion of progesterone by the human trophoblast and decrease the progesterone/estrogen secretory ratio at the time of parturition. In the present study, cultured human choriocarcinoma JEG-3 cells were used as an experimental model in order to examine the effect of dehydroepiandrosterone sulfate on both de novo and low-density lipoprotein-stimulated progesterone secretion. In serum-free and cholesterol-free Dulbecco's modified Eagle's medium, JEG-3 cell cultures demonstrated a significant secretion of both pregnenolone and progesterone.

Effects of epidermal growth factor, phorbol myristate acetate, and arachidonic acid on choriogonadotropin secretion by cultured human choriocarcinoma cells.

Epidermal growth factor (EGF) binds specifically (Ka = 4 X 10(9) M-1; 1.3 X 10(11) receptors/mg cellular protein) to JEG-3 cells, which respond in the succeeding 24 h by a 400% increase in hCG secretion without a significant change in cell number. Since JEG-3 cells store less than 2% of the 24-h hCG secretion, a significant increase in hCG in the culture medium reflects increased hCG biosynthesis.

Characterization of an immune suppressor from transformed human trophoblastic JEG-3 cells.

Cultured human choriocarcinoma JEG-3 cells secrete an immunosuppressor that inhibits lymphocyte proliferation stimulated by either an antigen or a mitogen. In this study, the immunosuppressive factor was characterized by three methods: ion-exchange and exclusion chromatography, partition in organic solvents, and thin-layer chromatography on silicic acid. This JEG-3 cell factor appeared to be a protein complex of about 150,000-200,000 Da that contained an immunologically active polar lipid.

Thin-layer chromatography for separation of phospholipids in amniotic fluid.

A method using a 1-dimensional, thin-layer chromatographic technique for the separation of phospholipids in amniotic fluid is described. The phospholipids of major importance in evaluating fetal lung maturity were separated: sphingomyelin, lecithin, and, notably, phosphatidylglycerol. Preliminary clinical results correlate the increasing appearance of phosphatidylglycerol with increasing lecithin : sphingomyelin ratios.

Endometrial prostaglandin F content in women wearing nonmedicated or progestin-releasing intrauterine devices.

Prostaglandin F (PGF) was measured in endometrial samples from eight women wearing Lippes Loops and 14 women wearing Progestaserts after 6 months' use of the intrauterine devices (IUDs). In addition, in 37 women wearing dydrogesterone-T IUDs, endometrial PGF was measured after 1 month, 3 to 7 months, and 8 to 12 months of use. Endometrial samples were also obtained from 51 women without IUDs.