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Biomedical subjects

R F Feinberg

Publications and source records attributed to R F Feinberg.

30 records · Page 2Linked to original sources
PubMed1991

Preeclampsia, trisomy 13, and the placental bed.

Genetic predisposition and abnormal trophoblastic function are thought to contribute to the development of preeclampsia. A multipara developed severe preeclampsia and subsequently delivered a live growth-retarded infant with trisomy 13. Biopsy of the placental bed taken immediately after delivery demonstrated inadequate trophoblastic remodeling of the maternal uterine vasculature, with an absence of normal physiologic changes in the spiral arteries. This case suggests that fetal trisomy 13 can be associated with preeclampsia in multiparous women and that abnormal trophoblastic invasion may contribute to the pathophysiology.

Adult↗
PubMed1991

Is oncofetal fibronectin a trophoblast glue for human implantation?

Using an antibody probe specific for the class of fibronectins that contain the oncofetal domain, it was shown that oncofetal fibronectin (onfFN) is present wherever trophoblasts make contact with extraplacental extracellular matrix (ECM). In normal human implantation sites, onfFN was localized to a highly specific region-the ECM connecting extravilous trophoblasts and trophoblastic cell columns to the uterine decidua. This same zone of onfFN was present in an analogous location in extrauterine gestations. Like these in vivo extravillous trophoblasts, isolated cytotrophoblasts in primary culture synthesized and secreted onfFN as they underwent differentiation. Furthermore, when cocultured with an ECM gel, cytotrophoblast aggregates deposited onfFN at cell-ECM contact sites, resembling early implanting trophoblasts in vivo. In the presence of cyclic AMP agonists, onfFN synthesis was inhibited markedly. It is concluded from these results that onfFN is a trophoblast protein that, under cAMP regulation, could mediate implantation and placental-uterine attachment throughout gestation.

Cells, Cultured↗
PubMed1990

Human trophoblast-extracellular matrix (ECM) interactions in vitro: ECM thickness modulates morphology and proteolytic activity.

Trophoblast invasion of the uterine extracellular matrix, a critical process for human implantation and uteroplacental vascular development, is a striking example of controlled invasiveness. To examine cellular behavior relevant to this process, human trophoblasts were cultured on (i) Millicell filters prelayered with Matrigel and (ii) coverslips precoated with a gentle slope of Matrigel (Matribeach). Histologic sections of the Millicell system demonstrated significant invasion. However, on Matribeach the cells exhibited markedly different characteristics depending on the thickness of the Matrigel. On zone 1 (1-4 microns thick), flat aggregates and syncytia were seen. In contrast, cells on zone 2 (4-14 microns) formed rounded aggregates with intercellular processes. In this zone, prominent degradation of pericellular Matrigel proteins was assessed by both light microscopy and scanning electron microscopy. Treatment with 8-bromo-cAMP inhibited this proteolytic process. On zone 3 (14-60 microns), unicellular trophoblasts or small aggregates caused minimal matrix degradation. JEG-3 human choriocarcinoma cells exhibited similar morphologic and degradative properties on Matribeach, but zone 2 proteolysis was not affected by 8-bromo-cAMP. Our results suggest that extracellular matrix thickness has profound effects on cellular morphology and proteolytic activity. Furthermore, while both normal and malignant human trophoblasts can degrade extracellular matrix proteins, only normal trophoblast extracellular matrix degradation is inhibited by 8-bromo-cAMP.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1989

The prevalence and biologic significance of lupus anticoagulant and anticardiolipin antibodies in a general obstetric population.

Circulating antibodies to negatively-charged phospholipids have been implicated in the genesis of adverse pregnancy outcomes. However, it has yet to be established that these antibodies are causative or that they are invariably associated with untoward perinatal outcomes. To address this issue, the prevalence of lupus anticoagulant and anticardiolipin antibodies was recorded in a low-risk obstetric population, and the outcome of untreated pregnancies were evaluated. Two of 737 patients (0.27%) had lupus anticoagulant documented by a prolonged activated partial thromboplastin time that did not correct this mixing studies. In comparison, greatly elevated concentrations of immunoglobulin M-anticardiolipin antibodies or immunoglobulin G-anticardiolipin antibodies were identified in 16/737 (2.2%) patients by means of an enzyme-linked immunosorbent assay. Spontaneous abortions occurred in both lupus anticoagulant-positive patients, suggesting that the activated partial thromboplastin time used was a relatively insensitive but specific marker for antiphospholipid antibody-associated adverse pregnancy outcomes. In contrast, although 12 of 16 anticardiolipin antibodies-positive pregnancies were complicated by perinatal loss, preterm delivery, or fetal growth retardation, four patients had uncomplicated pregnancies. Moreover, the distribution of anticardiolipin antibodies concentrations in these four patients was not clustered among the lowest anticardiolipin antibodies values, and anticardiolipin antibodies concentrations correlated weakly with adverse outcomes. These findings suggest that antiphospholipid antibodies are related to adverse pregnancy outcomes in a complex fashion and that therapy is not always required for acceptable outcomes in patients without other risk factors.

Adult↗
PubMed1989

Plasminogen activator inhibitor types 1 and 2 in human trophoblasts. PAI-1 is an immunocytochemical marker of invading trophoblasts.

Trophoblast implantation, vascular remodeling, and maintenance of intervillous blood flow may depend on the regulated production of proteolytic enzymes such as plasminogen activator (PA). Since the functional activity of plasminogen activators is determined not only by the quantity of protease but also by levels of specific plasminogen activator inhibitors (PAI), we examined trophoblasts both in vitro and in vivo for the presence of two PAIs, PAI-1 and PAI-2. Cytotrophoblasts were isolated from first trimester or term placentae, cultured, and immunocytochemically stained using specific anti-PAI antibodies. The antiserum against PAI-1 demonstrated prominent cell-surface staining and some cytoplasmic staining. The antiserum generated against PAI-2 revealed a cytoplasmic localization, with some trophoblasts staining intensely, whereas others had no apparent reactivity. We also found that cultured cytotrophoblasts contain the mRNAs for PAI-1 and PAI-2. Immunohistochemical analysis of tissue sections from 8-, 16-, and 40-week implantation sites using antisera against PAI-1 demonstrated weak staining of villous syncytiotrophoblasts but prominent cytoplasmic staining of trophoblasts invading the decidua and myometrium. Antisera against PAI-2 stained the cytoplasm of villous syncytiotrophoblasts, but no staining was evident in villous cytotrophoblasts or in invading trophoblasts. We conclude that 1) human trophoblasts can express both PAI-1 and PAI-2 in vitro and in vivo and 2) prominent PAI-1 immunostaining defines invading trophoblasts, whereas PAI-2 is the predominant PAI accumulated in villous syncytiotrophoblasts. Thus, the various trophoblast forms have distinctive patterns of PAI expression.

Cells, Cultured↗
PubMed1988

Sonographic diagnosis of a pregnancy with a diffuse hydatidiform mole and coexistent 46,XX fetus: a case report.

Placental molar change with a coexistent live fetus is an unusual entity, particularly when diagnosed in the second trimester of pregnancy. In this case report, the sonographic findings of an abnormally enlarged, diffuse molar placenta with a normal living fetus in the second trimester prompted karyotype analysis. Although triploidy was anticipated, a normal 46,XX chromosomal complement was identified. Histopathology of the placenta after delivery confirmed the rare syndrome of diploid partial mole. Antenatal management of this unusual pregnancy complication is addressed.

Adult↗
PubMed1983

Identification of glucocorticoid-induced genes in rat hepatoma cells by isolation of cloned cDNA sequences.

The expression of specific cellular genes in M1.19 rat hepatoma cells involves glucocorticoid regulation by mechanisms that are not well understood. To approach this problem we cloned cDNA prepared from dexamethasone-induced poly(A)-RNA and used a comparative colony hybridization method to identify recombinant clones containing hormone-regulated sequences. Two such cDNA clones, p1394 and p255, hybridize to a homogeneous RNA species of 900 nucleotides that is present in high abundance in 24-hr-induced cells but is undetectable in uninduced cells. This RNA can be seen as early as 1 hr after dexamethasone stimulation. Inhibition of protein synthesis with cycloheximide significantly reduces the accumulation of the RNA but does not abolish the induction response. In normal adult rat liver the RNA is abundant, and this RNA is induced by dexamethasone in adrenalectomized rats. Plasmids p1394 and p255 contain sequences that are homologous to the mRNA coding for the acute-phase reactant protein alpha 1-acid glycoprotein. Two other cDNA clones, p655 and p333, hybridize to a more heterogeneous RNA species 200-400 nucleotides in size with a lower induction response to dexamethasone. Southern blot analysis of M1.19 genomic DNA indicates that p1394 and p255 are complementary to a single DNA fragment, whereas p655 and p333 are complementary to repetitive sequences in the M1.19 genome. It appears that the genetic domain of glucocorticoid control in M1.19 rat hepatoma cells involves low copy number genes such as alpha 1-acid glycoprotein as well as repetitive sequence elements.

Animals↗
PubMedDate not supplied

Human trophoblast-endometrial interactions in an in vitro suspension culture system.

We developed an in vitro suspension co-culture system to examine the interaction of 1st, 2nd and 3rd trimester purified cytotrophoblasts with human endometrium. Endometrium explants were added to cytotrophoblast cell suspensions and placed on an angled gyrating platform in a 37 degrees C incubator. When endometrium was cultured alone it was able to remain viable for up to 3 days. When trophoblasts were cultured alone, they formed small and large aggregates, and occasionally spherical shells with hollow centers. When trophoblasts and endometrium were cultured together, the trophoblasts adhered to the exposed stromal surfaces of the tissue fragments. The surface epithelium was not receptive to trophoblast attachment except in one experiment when day 19 endometrium was used for the co-incubation, suggesting that surface attachment is usually restricted. A common finding was the presence of an acellular zone in the endometrium only adjacent to the attached trophoblasts. We speculate that this zone may be caused by proteolysis and resynthesis of ECM proteins by the trophoblasts. Based on our results, this in vitro suspension should prove useful for examining those factors which: (1) induce endometrial permissiveness, (2) promote paracrine effects on the endometrium, and (3) facilitate human trophoblast invasion.

Cell Communication↗
PubMedDate not supplied

Oncofetal fibronectin: new insight into the physiology of implantation and labor.

Oncofetal fibronectin is a newly studied protein produced by the trophoblast and is present in plasma and cervicovaginal secretions of pregnant women as labor approaches or when they have certain complications of pregnancy. Alterations in levels of oncofetal fibronectin occur in preterm labor, postterm pregnancy, and pregnancy-induced hypertension. Determining the presence or absence of full-term and preterm labor often is difficult in the clinical setting, and decision-making sometimes is hindered by the lack of a specific biochemical marker for labor. Oncofetal fibronectin may become a clinical indicator or predictor of true labor, preterm labor, or some complications of pregnancy. Assay techniques that identify clinically meaningful levels of oncofetal fibronectin are being developed and investigated and soon may be available to screen and identify pregnant women at risk. Research findings suggest new paths for investigation that may lead to important interventions in health care directed at identifying and decreasing maternal and neonatal morbidity and mortality. This article reviews pertinent aspects of placentation and the rationale for using oncofetal fibronectin detection as a clinical marker for abnormal pregnancy states.

Adenosine Monophosphate↗