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D J Dudley

Publications and source records attributed to D J Dudley.

At least 55 records · Page 3Linked to original sources
PubMed1992

Biosynthesis of interleukin-6 by cultured human chorion laeve cells: regulation by cytokines.

Intrauterine infection is an important cause of preterm labor and delivery and is characterized by increased production of inflammatory cytokines by gestational tissues. We evaluated the biosynthesis of the inflammatory cytokine interleukin-6 (IL-6) by human chorion laeve cells and its regulation by other cytokines essential to the inflammatory process. We found that cultured chorion cells secrete IL-6 in the presence of growth medium supplemented only with 10% fetal calf serum. IL-1 beta, tumor necrosis factor, and lipopolysaccharide all induced a significant concentration-dependent stimulation of IL-6 production by chorion cells. The concentration range of each cytokine tested (0.1-10 ng/mL) is within the range of values found in the amniotic fluid of women destined to deliver preterm due to infection of gestational tissues. Additionally, treatment of chorion cells with IL-1 beta in combination with actinomycin-D or cycloheximide attenuated the stimulatory action of IL-1 beta on IL-6 production. Northern blot analysis of total RNA from cultured chorion cells stimulated with IL-1 beta demonstrated that IL-6 mRNA increases over time. Our data suggest that IL-6 is produced by human fetal chorion in response to infection of maternal gestational tissues. In conjunction with other inflammatory mediators, fetally derived IL-6 may play a role in the pathophysiology of preterm labor due to infection.

Blotting, Northern↗
PubMed1991

Preliminary evidence for homoeostatic mechanism regulating endothelin production in pre-eclampsia.

To find out whether a serum factor in pre-eclamptic women is the cause of the raised serum endothelin concentrations associated with the disorder, the effect of serum from pre-eclamptic women on endothelin production by endothelial cells was compared with that of serum from pregnant and non-pregnant controls. The finding that pre-eclamptic serum suppresses endothelin production suggests that it contains a factor that might be part of a homoeostatic response to raised serum endothelin concentrations in pre-eclampsia.

6-Ketoprostaglandin F1 alpha↗
PubMed1991

Interleukin-6 stimulates prostaglandin production by human amnion and decidual cells.

The effects of interleukin-6 on prostaglandin production by cells from two key sources on intrauterine prostaglandin, i.e. amnion and decidua, have been evaluated. Interleukin-6 induced a concentration-related increase in prostaglandin production by amnion and decidual cells. The concentrations of interleukin-6 required for this stimulatory action are within the range measured in amniotic fluid of women with intrauterine infections and preterm labor. Hence, interleukin-6 may contribute to the mechanism of preterm labor under these conditions.

Amnion↗
PubMed1991

An endothelial cell model for the investigation of the molecular regulation of fetal vascular tone.

Human umbilical vessels are not innervated, and hence regulation of tone in these vessels must come from locally derived vasoactive substances such as prostacyclin. To evaluate the regulation of prostacyclin production by human umbilical vein endothelial cells, we incubated confluent cultures of these cells with various concentrations of inflammatory mediators (endotoxin, interleukin-1 beta, and tumor necrosis factor), protein kinase C agonists (phorbol 12-myristate 13-acetate, phorbol 12,13-dibutyrate), and calcium ionophores (A-23187 and ionomycin). Human umbilical vein endothelial cells were prepared from term pregnancies, and confluent cultures were incubated with test substances for 16 hours. Prostacyclin was measured as its metabolite 6-keto-prostaglandin F1 alpha by radioimmunoassay. Concentration-related increases in 6-keto-prostaglandin F1 alpha production were observed in response to endotoxin, cytokines, phorbol esters, and calcium ionophores. We conclude that human umbilical vein endothelial cell prostacyclin production is influenced by several intracellular messengers and that human umbilical vein endothelial cells may provide a useful in vitro model for investigating the physiology and pathophysiology of umbilical vessel vascular tone.

6-Ketoprostaglandin F1 alpha↗
PubMed1990

Regulation of murine lymphokine production in vivo. II. Dehydroepiandrosterone is a natural enhancer of interleukin 2 synthesis by helper T cells.

Dehydroepiandrosterone (DHEA) is an adrenal steroid hormone produced in abundance by humans and most other warm-blooded animals, is uniquely sulfated (DHEAS) prior to export into the plasma, and exhibits an age-related decline in production with progressive age. No major physiological functions have been ascribed to the activity of this steroid, although DHEA is known to serve as an intermediary in sex steroid synthesis. Studies on the effects of glucocorticoids (GCS) on the immune system led us to question whether DHEA had effects on the ability of activated lymphocytes to produce interleukin 2 (IL 2). We determined that (a) lymphocytes from DHEA- or DHEAS-treated mice consistently produced much greater levels of IL 2 than normals in response to stimulation, (b) direct lymphocyte exposure to DHEA at low doses (10(-10)-10(-7) M) caused an enhanced capacity to secrete IL 2 following activation, (c) IL 2 production by activated cloned T cell lines could be augmented by DHEA treatment, and (d) GCS-induced depressions in IL 2 synthesis by T cells or T cell clones could be overcome in vitro and in vivo by exposure to the effects of DHEA. These findings suggest that DHEA, presumably through receptor-mediated mechanisms similar to other types of steroid hormones, may represent a natural and important regulator of IL 2 production in both normal and pathologic conditions.

Animals↗
PubMed1990

Lymphokine production during term human pregnancy: differences between peripheral leukocytes and decidual cells.

Although the fetus is considered to be an "allograft" there is little information concerning the role of lymphokines in human pregnancy. Lymphokines are polypeptides secreted by stimulated lymphocytes that direct the immune response by enabling immune effector cells to communicate with each other. To characterize lymphokine production during normal human pregnancy, we isolated peripheral leukocytes and decidual lymphocyte-like cells from women undergoing repeat cesarean section at term. After stimulation with mitogen and paternal antigen for 24 hours, culture supernatants were assayed for granulocyte-macrophage colony-stimulating factor and interleukin-2 by enzyme-linked immunosorbent assay. There was no difference in the amount of interleukin-2 produced by stimulated peripheral and decidual cells. However, granulocyte-macrophage colony-stimulating factor production by stimulated decidual lymphocyte-like cells was significantly greater than granulocyte-macrophage colony-stimulating factor produced by peripheral lymphocytes. Decidual lymphocyte-like cells produced granulocyte-macrophage colony-stimulating factor both spontaneously and after stimulation with mitogen or paternal antigen, whereas peripheral leukocytes did not. This suggests that the decidua constitutes a distinct immunologic microenvironment.

Cells, Cultured↗
PubMed1990

Pathophysiology of antiphospholipid antibodies: absence of prostaglandin-mediated effects on cultured endothelium.

Antiphospholipid antibodies are associated with recurrent pregnancy loss and thrombosis. Studies suggest that antiphospholipid antibodies may inhibit the production of prostacyclin by vascular tissues. We incubated sera from women with moderate to high levels of antiphospholipid antibodies with primary human umbilical vein endothelial cell cultures. Intact confluent, subconfluent, hydrogen peroxide-damaged, and mechanically damaged endothelial cell monolayers were evaluated for the production of the prostacyclin metabolite 6-keto-prostaglandin F1 alpha in the presence of sera that were positive and negative for antiphospholipid antibodies. All sera were assayed for baseline concentrations of 6-keto-prostaglandin F1 alpha before incubation with endothelial monolayers. Additionally, the extent of binding of antiphospholipid antibodies to intact and damaged endothelium was studied by immunofluorescent techniques and enzyme-linked immunosorbent assay. Our results indicate that prostacyclin production is not impaired by sera containing antiphospholipid antibodies, regardless of the condition of the endothelium. Further, we were unable to demonstrate binding of immunoglobulin from sera containing antiphospholipid antibodies to intact or damaged endothelium. However, the baseline concentration of 6-keto-prostaglandin F1 alpha was nearly fourfold higher in sera containing antiphospholipid antibodies. The finding of elevated baseline serum concentrations of prostacyclin metabolite in patients with antiphospholipid antibodies suggests a condition of long-term stimulation or altered metabolism of prostacyclin.

6-Ketoprostaglandin F1 alpha↗
PubMed1990

Immunoglobulin G fractions from patients with antiphospholipid antibodies cause fetal death in BALB/c mice: a model for autoimmune fetal loss.

We determined whether purified immunoglobulin G from patients with antiphospholipid antibodies causes fetal loss in pregnant mice. Sera were obtained from nonpregnant parous women (group 1) and nonpregnant women with antiphospholipid antibodies and a history of fetal loss (group 2). Pregnant BALB/c mice were given an intraperitoneal injection of 15 mg of IgG on day 8 of pregnancy. Typically, mice treated with IgG from antiphospholipid antibodies aborted within 48 hours. When animals were sacrificed on days 9 to 15, the uterus of each animal was inspected for the presence of live, dead, or resorbing fetuses. In contrast to mice injected with control IgG or saline solution, each mouse injected with IgG from antiphospholipid antibodies aborted and no live fetuses were found (p less than 0.05). Histologic examination of the uteroplacental interface showed decidual necrosis in the mice treated with IgG containing antiphospholipid antibodies, and immunofluorescent studies also showed prominent intravascular decidual IgG and fibrin deposition. We conclude that IgG from antiphospholipid antibodies of women with fetal loss causes fetal loss in BALB/c mice. It appears that the fetal loss is mediated by IgG binding in the maternal decidual vasculature.

Animals↗
PubMed1990

Pregnancy in the patient with rheumatic disease: the obstetrician's perspective.

Patients with rheumatic diseases who become pregnant are justifiably categorized as having high-risk pregnancies. Utilizing a multidisciplinary approach, including perinatologists, rheumatologists and anaesthetists, successful pregnancies have become the rule rather than the exception. However, women with rheumatic disease are particularly prone to develop serious obstetric problems which often result in early hospitalization and delivery. Although vigilant obstetric care improves perinatal outcome, prematurity will continue to be a major problem complicating pregnancies in women with rheumatic disease.

Abortion, Spontaneous↗
PubMed1980

Enumeration of potentially pathogenic bacteria from sewage sludges.

To ascertain the health risks that may be posed by the land application of sewage sludges, a scheme was devised to determine the types and numbers of pathogenic and potentially pathogenic bacteria present in sludges. A processing treatment was adapted to sludge to give a homogenate which yielded the greatest numbers of viable bacteria. Conventional methods were successful in enumerating Klebsiella, Staphylococcus, gram-negative enteric bacteria, and commonly used indicator organisms. Modifications of conventional methods improved the enumeration of Salmonella, Mycobacterium sp., fluorescent Pseudomonas sp., and Clostridium perfringens. However, Shigella methodology yielded only one isolate. Utilizing the proposed scheme, the population densities of these organisms were estimated in three domestic wastewater sludges. In light of these results, the potential impact of land application of sewage sludges is discussed.

Bacteria↗
PubMedDate not supplied

Macrophage inflammatory protein-I alpha regulates prostaglandin E2 and interleukin-6 production by human gestational tissues in vitro.

OBJECTIVE: To determine if the inflammatory cytokine macrophage inflammatory protein-1 alpha (MLP-1 alpha) stimulates the production of prostaglandin E2 (PGE2) and interleukin-6 (IL-6) by human gestational tissues. METHODS: Human decidual cells, chorion cells, and amnion cells were isolated from term placentas of women with normal pregnancies, and primary cultures of each cell line were established. In various concentrations, MIP-1 alpha was then applied to each cell culture for 16 hours at 37C, and culture supernatants were assayed for PGE2 and IL-6. RESULTS: After incubation with MIP-1 alpha, decidual cells produced increased amounts of both IL-6 (P < .05) but not PGE2. When subjected to similar conditions, chorion cells produced increased amounts of both IL-6 and PGE2 (P < .05). Conversely, amnion cells produced increased amounts of only PGE2 in response to increasing concentrations of MIP-1 alpha (P < .05). CONCLUSION: Maternal and fetal gestational tissues differentially respond to MIP-1 alpha with regard to PGE2 and IL-6 production; MIP-1 alpha may play a role in both the initiation and propagation of the inflammatory response associated with intrauterine infection.

Amnion↗
PubMedDate not supplied

Amniotic fluid epidermal growth factor levels in normal and abnormal pregnancies.

OBJECTIVE: To determine the concentrations of epidermal growth factor (EGF) in amniotic fluid (AF) from women during late pregnancy, with and without pathophysiologic complications. METHODS: All AFs were collected by amniocentesis from the following groups: gestational age at least 38 weeks (n = 15); gestational age 36-37 weeks (n = 10); gestational age 35 weeks (n = 5); labor 34 weeks or less, delivered within 7 days (n = 10); labor 34 weeks or less, undelivered (n = 10); chorioamnionitis (n = 7); gestational age-matched controls (n = 7); term, in labor (n = 8); term, not in labor (n = 8); intrauterine growth restriction (IUGR) 38 weeks or more (n = 8); macrosomia at 38 weeks or more (n = 10). Epidermal growth factor was assayed using a specific radioimmunoassay. RESULTS: Amniotic fluid EGF levels increase rapidly in late pregnancy but are not altered by chorioamnionitis or by term or preterm labor. Intrauterine growth restriction is associated with lower EGF levels in AF, but macrosomia is without effect. CONCLUSIONS: Epidermal growth factor levels in AF are increased near term and decreased in pregnancies complicated by IUGR; they may be an indicator of specific maturational events.

Amniotic Fluid↗
PubMedDate not supplied

Antenatal steroid treatment and adverse fetal effects: what is the evidence?

This article reviews current animal and human data regarding possible adverse fetal effects from antenatal steroid treatment. Although it is now well accepted that such treatment is of benefit to fetal lung development, the potential for adverse fetal outcomes as a result of single or multiple glucocorticoid dosing has not been widely recognized. There are now growing concerns, based on animal and some human data, that repeated antenatal doses could lead to a decrease in birth weight, a decrease in fetal brain and other organ size, and abnormal neuronal development. Previous investigations have been hampered by nonstandardization in the type of glucocorticoid, route of delivery, timing of administration, and number of treatment courses. It is recommended that these concerns be addressed through large randomized, controlled clinical trials. In the meantime, it would be prudent to minimize antenatal steroid treatments to a single course with repeated dosing only if there is a persistent threat of preterm delivery. The practice of giving weekly injections of steroids starting at fetal viability and continuing into the third trimester is not supported.

Adrenal Cortex Hormones↗