Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.7.49 (reverse transcriptase)
31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pre-eclampsia is an endothelial disorder and TNF-alpha has fundamental effects on endothelial cells by several means, including altering the balance between oxidant and anti-oxidant, changing the pattern of prostaglandin production and affecting expression of several cell surface components. To determine whether TNF-alpha mRNA expression is increased in pre-eclamptic patients, leucocytes from pre-eclamptic patients, normal pregnant women and normal non-pregnant women were studied for TNF-alpha expression using a quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) method. Using a model of 373A ABI Sequencer, TNF-alpha gene polymorphism was also analysed by GENESCAN and Genotyper software in order to explain the mechanism of abnormal TNF-alpha expression. Our results show that TNF-alpha mRNA expression is significantly elevated in pre-eclamptic patients compared with the other two control groups. The high expression of TNF-alpha may be associated with the TNF1 allele, whose frequency is markedly increased in pre-eclamptic patients. These observations are consistent with a major role for TNF-alpha in mediating endothelial disturbances, and suggest a key role for TNF-alpha in the development of pre-eclampsia.
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PMID:Tumour necrosis factor-alpha (TNF-alpha) gene polymorphism and expression in pre-eclampsia. 860 20

In pre-eclampsia, the ratio of prostacyclin:thromboxane production rate is decreased favouring the vasoconstrictive thromboxane. One of the rate-limiting steps in prostaglandin synthesis is cyclooxygenase (COX) activity. Therefore, we investigated the expression of COX-1 and COX-2 in human placenta and placental bed. Tissue specimens from the 29th to 40th week of pregnancy were obtained from Caesarean sections after uncomplicated and pre-eclamptic pregnancies before the onset of labour. COX-1 and COX-2 were localized immunohistochemically with the identification of positive cells by double immunofluorescence staining. The protein and mRNA levels were analysed by immunoblotting and quantitative reverse transcriptase-polymerase chain reaction. Expression of both COX-1 and COX-2 could be observed in placenta and placental bed. COX-1-like immunoreactivity was observed in most cell types with strongest staining in macrophages. Only macrophages, endothelium, vascular leiomyocytes and fibroblasts stained positively for COX-2. In placenta, COX-1 and -2 expression was unchanged after pre-eclampsia. In placental bed, protein and mRNA levels of COX-1 were increased in the pre-eclamptic group (P < 0.05), whereas COX-2 expression did not differ significantly from normal pregnancies. An increased expression of COX-1 could be involved in the pathophysiology of pre-eclamptic changes within the placental bed. A therapy with drugs inhibiting COX-1 might be beneficial in this condition.
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PMID:Cyclooxygenase-1 and -2 in human placenta and placental bed after normal and pre-eclamptic pregnancies. 940 2

There is accumulating evidence that deficient trophoblast invasion of the placental bed spiral arteries is crucial to the pathogenesis of pre-eclampsia and intrauterine growth restriction. However, the factors which regulate the process of trophoblast invasion remain unclear. We have investigated whether extravillous trophoblast invasion and motility are mediated by the angiogenic growth factors, vascular endothelial growth factor (VEGF) and placental growth factor (PlGF). The SGHPL-4 extravillous trophoblast cell line was utilized. Expression of mRNA for the receptors of VEGF and PlGF (KDR and flt-1) was determined using the reverse transcriptase polymerase chain reaction. An in vitro model of invasion assessed the number and length of trophoblast processes invading into an extracellular matrix. The motility of cells under standard culture conditions was also quantified. The effect of the addition of VEGF and PlGF (+/-heparin) on trophoblast invasion and motility was determined. The effect of VEGF and PlGF (+/-heparin) on SGHPL-4 cell proliferation was assessed by cell counts at 24, 48 and 72 h post-addition of growth factor. The SGHPL-4 cells expressed mRNA for the flt-1 but not the KDR receptor. The addition of VEGF resulted in a significant decrease in the number of trophoblast processes formed (P< 0.02); this effect was not influenced by the addition of heparin. However, there was no effect on the length of processes formed in response to VEGF (+/-heparin). The addition of PlGF had no effect on either the number or the length of processes formed. The addition of VEGF increased the motility of the SGHPL-4 cells (P< 0.002); the addition of heparin prevented this VEGF-induced increase in motility. The addition of PlGF had no effect on SGHPL-4 motility (+/-heparin). Neither growth factor had any effect on the proliferative ability of SGHPL-4 cells. Contrary to our hypothesis, we did not find that the angiogenic growth factors, VEGF and PlGF, mediated the in vitro invasion of trophoblast cells into an extracellular matrix. However, VEGF did increase trophoblast motility. Our findings of an effect of VEGF on trophoblast motility (and possibly invasion) suggests the presence of functional receptors, which can mediate the actions of VEGF. Caution must be exercised before any extrapolation to the in vivo situation, however, it could be speculated that the increased motility in response to VEGF may be an initial response to attract trophoblast cells to the decidua, and that VEGF might then limit the degree to which trophoblast cells invade.
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PMID:The effects of angiogenic growth factors on extravillous trophoblast invasion and motility. 1094 Feb 13

Activin A (beta A beta A) and inhibin A (alpha beta A) are dimeric glycoproteins secreted from early to term pregnancy in the maternal circulation. They circulate in higher amounts in women with gestational hypertension and/or pre-eclampsia, the most important gestational diseases also causing fetal growth restriction (FGR). Since no data are available in patients with pre-eclampsia and superimposed FGR, by using two-site immunoassays we evaluated serum activin A and inhibin A levels in serum samples collected from: healthy normotensive pregnant controls (n = 42); and women with pre-eclampsia with (n = 19) or without superimposed FGR (n = 21). In addition, by quantitative reverse transcriptase-polymerase chain reaction the changes of alpha- and beta A-subunit mRNA expression in placentas collected from healthy controls (n = 7) and pre-eclamptic pregnancies with (n = 6) or without (n = 6) superimposed FGR was also investigated. Activin A and inhibin A serum levels were significantly higher in pre-eclampsia, and the presence of FGR did not significantly modify these concentrations. Similarly, inhibin-subunit mRNA levels in placentas from pre-eclampsia were significantly higher than in controls, and FGR did not significantly affect this expression. The present data suggest that the increased placental expression of inhibin subunit mRNAs is part of the mechanism leading to increased serum activin A and inhibin A levels.
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PMID:Pre-eclampsia with fetal growth restriction: placental and serum activin A and inhibin A levels. 1258 30

The failure of placental trophoblasts to differentiate properly is thought to play an important role in the cause of pregnancy disorders such as preeclampsia. We looked at the effects of the bioactive lipid sphingosine-1-phosphate (S1P) on the differentiation of primary human cytotrophoblasts (CTs) into syncytiotrophoblasts (STs) in culture. We found that S1P inhibited CT differentiation measured by human chorionic gonadotropin (hCG) secretion and the expression of placental alkaline phosphatase but had no effect on their fusion into multinucleated syncytialized cells. G-protein-linked S1P receptors 1, 2, and 3 were found in CTs by reverse transcriptase-polymerase chain reaction, and receptor 1 was found by Western blot analysis. Disruption of G(i) signaling with pertussis toxin reversed the inhibitory effects of S1P. S1P reduced intracellular cAMP, and the addition of 8-bromo-cAMP reversed S1P inhibition of hCG secretion. Therefore, we suggest that S1P inhibits the differentiation of CTs into STs through G(i)-coupled S1P receptor interaction(s), leading to the inhibition of adenylate cyclase and reduced production of intracellular cAMP. This is the first reported effect of S1P on placental trophoblast function.
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PMID:Sphingosine-1-phosphate inhibition of placental trophoblast differentiation through a G(i)-coupled receptor response. 1599 75

The current study describes a statistically significant increase in macrophages (CD68-positive cells) in the decidua of preeclamptic patients. To elucidate the regulation of this monocyte infiltration, expression of monocyte chemoattractant protein-1 (MCP-1) was assessed in leukocyte-free first trimester decidual cells. Confluent decidual cells were primed for 7 days in either estradiol or estradiol plus medroxyprogesterone acetate to mimic the decidualizing steroidal milieu of the luteal phase and early pregnancy. The medium was exchanged for a serum-free defined medium containing corresponding steroids +/- tumor necrosis factor (TNF)-alpha or interleukin (IL)-1beta. After 24 hours, enzyme-linked immunosorbent assay measurements indicated that the addition of medroxyprogesterone acetate did not affect MCP-1 output, whereas 10 ng/ml of TNF-alpha or IL-1beta increased output by 83.5-fold +/- 20.6 and 103.1-fold +/- 14.7, respectively (mean +/- SEM, n = 8, P < 0.05). Concentration-response comparisons revealed that even 0.01 ng/ml of TNF-alpha or IL-1beta elevated MCP-1 output by more than 15-fold. Western blotting confirmed the enzyme-linked immunosorbent assay results, and quantitative reverse transcriptase-polymerase chain reaction confirmed corresponding effects on MCP-1 mRNA levels. The current study demonstrates that TNF-alpha and IL-1beta enhance MCP-1 in first trimester decidua. This finding suggests a mechanism by which recruitment of excess macrophages to the decidua impairs endovascular trophoblast invasion, the primary placental defect of preeclampsia.
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PMID:Regulation of monocyte chemoattractant protein-1 expression by tumor necrosis factor-alpha and interleukin-1beta in first trimester human decidual cells: implications for preeclampsia. 1643 59

The expanded use of multiple antiretroviral drugs during pregnancy has led to a reduction in the occurrence of perinatal transmission of HIV to <2%, but has led to concerns regarding both short-term toxicity and the long-term impact on the woman and her child. Enhanced toxicity of nevirapine has been noted among women with CD4+ lymphocyte counts >250 cells/microL at treatment initiation and among pregnant women on long-term didanosine and stavudine. These drugs should be avoided in such situations if alternatives are available. Efavirenz has been associated with birth defects in monkeys, and several cases of neural tube defects have been reported in humans after first trimester exposure, so treatment with this drug should be avoided during the first trimester. Protease inhibitors have been associated with an increased risk of maternal glucose intolerance, pre-eclampsia and preterm birth in some, but not all, studies. Pregnancies exposed to antiretroviral therapy should be registered with the Antiretroviral Pregnancy Registry as early in pregnancy as possible in order to provide data on the risk of birth defects after exposure. The pharmacokinetics of nucleoside and non-nucleoside reverse transcriptase inhibitors are not significantly changed in pregnancy, so standard dosing may be used. However, concentrations of several protease inhibitors are lower in pregnancy, so ritonavir-boosting or increased doses are required. Of great theoretical concern is the impact of resistance mutations that develop following single-dose nevirapine therapy on the response to later therapy among women and their infected infants. The use of dual nucleoside therapy for 3-7 days after single-dose nevirapine in the mother reduces but does not eliminate the risk of nevirapine resistance; alternative regimens for prevention of resistance are under study, as are the subsequent responses of the mother and her infant to therapy. Short courses of prophylactic zidovudine and nevirapine have been well tolerated in neonates. Concern has been raised, however, that these exposures may lead to persistent mitochondrial dysfunction or later cancers, underscoring the need for long-term surveillance of antiretroviral-exposed, HIV-uninfected infants.
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PMID:Treating HIV during pregnancy: an update on safety issues. 1675 31

Aspartyl-(asparaginyl) beta-hydroxylase (AAH) is a type 2 transmembrane protein with catalytic activity that hydroxylates epidermal growth factor-like domains of proteins that have a functional role in cell motility and invasion. Extravillous cytotrophoblasts (CTB) are motile and invasive unpolarized epithelial cells that mediate early implantation through interaction with the endometrium. This study characterizes the potential role of AAH in CTB implantation using human placentas from (1) terminated pregnancies (n = 11), (2) normal term deliveries (n = 21), (3) spontaneous abortuses (n = 21), and (4) small-for-gestational-age (SGA) term deliveries (n = 21). The SGA cases all had established clinical histories of intrauterine growth restriction or preeclampsia. Formalin-fixed, paraffin-embedded sections of placenta were immunostained using the 15C7 monoclonal antibody generated to recombinant AAH. In addition, snap-frozen or RNAlater-preserved specimens (Ambion, Austin, TX) were used for RNA analysis of AAH expression by real-time quantitative reverse transcriptase-polymerase chain reaction and protein analysis by Western blotting. The immunohistochemical staining studies demonstrated AAH expression in amniocytes, villous CTB, syncytiotrophoblast, extravillous CTB, decidua, and endometrial glands at all gestational ages and in all 4 groups. Higher levels of AAH immunoreactivity were observed in extravillous CTB compared with villous CTB. Immunohistochemical staining and RNA analysis demonstrated abundant AAH expression in placental trophoblastic cells as well as in decidua and endometrial glands, with reduced expression in spontaneous abortion and SGA, suggesting that AAH may serve as a biomarker of impaired implantation. The high levels of AAH in decidua and endometrial glands suggest a role for this molecule in "receptivity" of endometrium.
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PMID:Role of aspartyl-(asparaginyl) beta-hydroxylase in placental implantation: Relevance to early pregnancy loss. 1694 9

Doppler analysis of the uterine arteries is currently used for pre-eclampsia (PE) screening. PLAC1 is a trophoblast-specific gene, and it is known that in normal pregnancies, trophoblastic cells are released into the maternal circulation, where specific trophoblastic mRNA can be detected. In PE, as in women who eventually develop PE, an abnormal passage of fetal and placental cells is also present. In this study, we aimed to verify whether, in normal pregnancies, Doppler waveform of the uterine arteries correlates with PLAC1 mRNA concentrations. Thirteen cases of normal pregnancies at 37 weeks' gestation (23-41) were enrolled in the study. PLAC1 mRNA was extracted from 2 mL of blood by ABI PRISM 6100 nucleic acid Prep Station (Applied Biosystems, Foster City, CA) and quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) analysis was performed by a PE 5700 Sequence detection system. Bulk RNA from normal placental tissue was used as the reference curve, and the amount of PLAC1 mRNA in the study samples was then expressed as the "relative amount" of weight of placental tissue (ng/mL). The uterine arterial mean resistance index (RI) and presence/absence of a dicrote waveform were calculated by using a 5 MHz transabdominal probe (Tecnos, ESAOTE) at the uterine cervico-corporal junction. Doppler measurement was performed on the same day as blood collection. The median of the means of uterine arterial RI was 0.52 (0.39-0.68). RI of uterine arteries and PLAC1 mRNA were significantly correlated in a log-linear regression (R(2) = 0.483, P = 0.024). Our data support that in normal pregnancy, the passage of trophoblast material into the maternal circulation is correlated with the quantitative measurement of uterine hemodynamics.
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PMID:PLAC1 mRNA in maternal blood correlates with Doppler waveform in uterine arteries in normal pregnancies at the second and third trimester. 1710 2

The primary placental defect in preeclampsia is shallow trophoblast invasion of the decidua leading to incomplete vascular transformation and inadequate uteroplacental perfusion. Soluble fms-like tyrosine kinase-1 (sFlt-1) seems to interfere with these events by inhibiting local angiogenesis and/or by impeding trophoblast invasion. Preeclampsia is also associated with maternal thrombophilias and decidual hemorrhage, which form thrombin from decidual cell-expressed tissue factor. Although sFlt-1 is highly expressed by trophoblasts, sFlt-1 expression has not been studied in decidual cells, which are the predominant cell type encountered by invading trophoblasts. Here, we demonstrate that isolated decidual cells express sFlt-1 mRNA, suggesting that they can synthesize sFlt-1. Moreover, in first trimester decidual cells, thrombin enhanced sFlt-1 mRNA levels, as measured by quantitative reverse transcriptase-polymerase chain reaction, and levels of secreted sFlt-1 protein, as measured by enzyme-linked immunosorbent assay. The thrombin antagonist hirudin blocked this effect, demonstrating that active thrombin is required. Emphasizing the specificity of the thrombin response, neither interleukin-1beta nor tumor necrosis factor-alpha affected sFlt-1 expression in the decidual cells. In contrast to first trimester decidual cells, thrombin did not affect sFlt-1 levels in cultured term decidual cells. In early pregnancy, thrombin may act as an autocrine/paracrine enhancer of sFlt-1 expression by decidual cells to promote pre-eclampsia by interfering with local vascular transformation.
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PMID:Thrombin regulates soluble fms-like tyrosine kinase-1 (sFlt-1) expression in first trimester decidua: implications for preeclampsia. 1739 78


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