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Pregnancy associated plasma protein-A (PAPP-A) as an early marker for the diagnosis of acute coronary syndrome.
Full text linkAims and objectives
Pregnancy associated plasma protein-A (PAPP-A), a metalloproteinase plays a pivotal role in the pathogenesis of atherosclerosis. Recent studies have reported that elevated levels of PAPP-A, signal the onset of acute coronary syndrome (ACS). We, therefore, proposed to study the analytical competence of PAPP-A in patients admitted to the emergency department with chest pain and finally diagnosed as ACS.
Methods and results
Pregnancy associated plasma protein-A was measured using enzyme-linked immunosorbent assay (ELISA) in 485 patients admitted to emergency care unit, of which 89 patients were diagnosed as Non-cardiac chest pain (NCCP). Elevated levels of PAPP-A were observed in patients diagnosed as ACS on comparison with the controls. Receiver operator characteristic (ROC) curve analysis showed PAPP-A to be a good discriminator between ischaemic and non-ischaemic patients. The area under the curve was found to be 0.904, 95% CI (0.874–0.929) with 90% sensitivity and 85% specificity (P< 0.0001). The cut-off value from the ROC curve was 0.55 μg/mL above which PAPP-A was considered to be positive.
Conclusion
Pregnancy associated plasma protein-A seems to be a promising biomarker for identification and risk stratification for patients with ACS
Evaluation of Maternal Serum PAPP-A and hCG Levels at 10-14 Weeks of Gestation in Hyperemesis Gravidarum
No full textAim:The aim of this study is to determine the relationship between hyperemesis gravidarum and maternal serum pregnancy-associated plasma protein A (PAPP-A) and human chorionic gonadotropin (hCG) levels. This study was designed as a case-control study.Methods:The study group consists of 54 pregnant women of 10-14 weeks who were diagnosed with hyperemesis gravidarum in the İstanbul Training and Research Hospital Hospital while the control group consists of 54 pregnant women of 10-14 weeks who did not have any complaints. Thyroid stimulating hormone, free T3, free T4, aspartate aminotransferase, alanine aminotransferase, PAPP-A, and hCG values and age were retrospectively scanned from files.Results:We have observed that the hyperemesis gravidarum group has higher hCG levels as compared with the control group. The mean hCG level in control group and hyperemesis group was 1.10±0.569 and 1.55±1.140, respectively (p<0.05) The mean PAPP-A level in control group and hyperemesis group was 1.00±0.611, 1.36±0.887, respectively (p<0.05).Conclusion:Elevated levels of PAPP-A and hCG are associated with hyperemesis gravidarum. More comprehensive studies are needed to explain the role of PAPP-A in the pathogenesis of hyperemesis gravidarum
Association between PAPP-A and placental thickness
No full textBackground: Measuring of maternal serum pregnancy-associated plasma protein-A (PAPP-A) in first trimester can be a way for early detection of adverse prenatal outcome due to faulty placenta.
Objective: The aim was to Determination of association between placental thickness in second trimester with low level of PAPP-A in first trimester.
Materials and Methods: In this cohort study, serum PAPP-A of 187 pregnant women was measured in the first trimester of pregnancy. Patients who had PAPP-A ≤0.8 MOM were in exposed and others who had PAPP-A >0.8 defined as unexposed group. The criteria of placental thickness in ultrasound study was thickness of 4 cm or more than 50% of placental length.
Results: Of 187 patients, 87 patients had PAPP-A >0.8 and 93 patients had PAPP-A ≤0.8. Women with low levels of PAPP-A in the first trimester, had an increased incidence placental thickness of 34.4%, whereas another group had about 15% (p=0.002). Also, PAPP-A levels had acceptable sensitivity and specificity for placental thickness detection (71.1% and 54.8%, respectively.
Conclusion: Our study showed that serum level of PAPP-A generally was low (≤0.8) in women with a thick placenta (>4 cm or >50% of placental length). The first trimester of pregnancy measurement of PAPP-A will be more predictable for healthy placenta
p53 regulates PAPP-A levels.
No full text<p>A) HBL-100 cells express wild type p53, while HS578T cells express mutant p53. The levels of PAPP-A mRNA in these cell lines were determined by qRT-PCR. B) Western blot of the levels of p53 in HBL-100 and HS578T cells. C) the expression of p53 was inhibited in HBL-100 cells using siRNA and the PAPP-A mRNA levels were determined by qRT-PCR. D) the efficiency of siRNA against p53 was determined by western blot. E) the expression of p53 was inhibited in HS578T cells using siRNA and the PAPP-A mRNA levels were determined by qRT-PCR. F) the inhibition of p53 by siRNA in HS578T cells was monitored by western blot. G) Duplicate human breast carcinoma tissue microarray slides (Zymed) were stained by IHC using the DO1 antibody against p53 and the rabbit polyclonal antibody against PAPP-A (Dako). H) The percentage of tumors positive for p53, PAPP-A or both was determined.</p
Association between PAPP-A and placental thickness
No full textBackground: Measuring of maternal serum pregnancy-associated plasma protein-A (PAPP-A) in first trimester can be a way for early detection of adverse prenatal outcome due to faulty placenta. Objective: The aim was to Determination of association between placental thickness in second trimester with low level of PAPP-A in first trimester. Materials and Methods: In this cohort study, serum PAPP-A of 187 pregnant women was measured in the first trimester of pregnancy. Patients who had PAPP-A �0.8 MOM were in exposed and others who had PAPP-A >0.8 defined as unexposed group. The criteria of placental thickness in ultrasound study was thickness of 4 cm or more than 50 of placental length. Results: Of 187 patients, 87 patients had PAPP-A >0.8 and 93 patients had PAPP-A �0.8. Women with low levels of PAPP-A in the first trimester, had an increased incidence placental thickness of 34.4, whereas another group had about 15 (p=0.002). Also, PAPP-A levels had acceptable sensitivity and specificity for placental thickness detection (71.1 and 54.8, respectively. Conclusion: Our study showed that serum level of PAPP-A generally was low (�0.8) in women with a thick placenta (>4 cm or >50 of placental length). The first trimester of pregnancy measurement of PAPP-A will be more predictable for healthy placenta. © 2016, Research and Clinical Center for Infertitlity. All rights reserved
Low PAPP-A Levels and Pregnancy Outcomes
No full textIntroduction: Pregnancy-associated plasma protein A, or PAPP-A, is a high molecular weight glycoprotein used as an analyte for first trimester aneuploidy screening along with hCG. There is significant association between low PAPP-A and adverse pregnancy outcomes, such as: preterm birth, intrauterine growth restriction, stillbirth, and preeclampsia.1 A recent retrospective study further supports an association of low PAPP-A with aneuploidy and adverse pregnancy outcomes.2 A systematic review also suggested an association between low serum PAPP-A and adverse pregnancy outcome, but indicated that the predictive values of low PAPP-A remain poor and that further studies should focus on PAPP-A as a prediction model.3 Because PAPP-A affects placental function, it may affect labor. The objective of this study was to determine if low PAPP-A is associated with labor dysfunction. Methods: This is a retrospective study of pregnant women who gave birth at GW Hospital between July 2013 and July 2016. Women with PAPP-A in the 5th percentile (5%ile) were compared to women with PAPP-A less than or equal to the 1st percentile (≤1%ile). The primary outcome examined was cesarean delivery (CD) rate and the secondary outcomes were indication for CD and perinatal outcomes. Women with fetuses with known or suspected aneuploidy were excluded from the study. Results: 139 women were included in the study; 91 women with PAPP-A in 5%ile and 48 women with PAPP-A ≤1%ile. Demographics were similar except for gestational age at delivery (38.6 ± 3.6 weeks in the 5%ile group vs. 35.9 ± 7.4 weeks in the 1%ile group, p = 0.004). There was no difference in CD rate (27/91 (29.7%) vs. 12/48 (25%), p = 0.6), fetal indication for CD (8/27 (29.6%) vs. 4/12 (33.3%), p = 0.8). Birth weight was significantly higher in the 5%ile group vs. the 1%ile group (3264.6 ± 580.8 grams vs. 2935.4 ± 715.3 grams, p = 0.004). Neonatal morbidity composite score was different between groups; (18/91 (19.8 %) in the 5%ile group vs. 18/48 (37.5%) in the 1%ile group p = 0.02). Conclusion: PAPP-A levels less than or equal to the 1st percentile does not seem associated with delivery mode or indication for cesarean delivery in comparison to PAPP-A levels in the 5th percentile. However, PAPP-A levels less than or equal to the 1st percentile may be associated with increased neonatal morbidity during labor, as well as lower birth weight and preterm birth in comparison to PAPP-A in the 5th percentile
La PAPP-A et le système des IGFs
No full textKlotz Communications: Evolution of hormones during pregnancyNational audienceFirstly discovered as a placental protein present abundantly in the circulation of pregnant women, pregnancy-associated plasma protein-A (PAPP-A) is widely expressed in multiple tissues. PAPP-A is a metalloproteinase that is able to specifically cleave three insulin-like growth factor binding proteins (IGFBPs): IGFBP-2, -4 and -5. PAPP-A binds tightly to glycosaminoglycans present on the surface of cells, thus functioning within tissues as a growth-promoting enzyme, releasing bioactive IGF in close proximity to the IGF receptor. Pro-MBP and stanniocalcin-2 (STC2) appear to be the main inhibitors of PAPP-A activity, by forming a covalent complex with the protease. According to in vivo experiments, IGFBP-4 is believed to be the main PAPP-A substrate to regulate IGF bioavailability. The regulation of PAPP-A includes transcriptional control of its gene, competing reactions with other IGFBPs potentially sequestering IGF from IGFBP-4 and hence antagonizing PAPP-A-mediated IGF activation, and proteolytic inhibition of PAPP-A. Finally, PAPP-A may serve as a therapeutic target to indirectly inhibit IGF signalling in tissues where this is driven by increased PAPP-A activity. By taking advantage of the intricate interaction between PAPP-A and IGFBP-4, highly specific and selective inhibition of PAPP-A is possible.D’abord découvert comme une protéine placentaire abondamment présente dans la circulation de femmes enceintes, la protéine-A plasmatique associée à la grossesse (PAPP-A) est largement exprimée dans de multiples tissus. La PAPP-A est un métalloprotéase qui peut spécifiquement dégrader trois protéines de liaison des insulin-like growth factors (IGFBPs) : IGFBP-2,-4 et-5. La PAPP-A se fixe à des glycosaminoglycanes sur la surface de cellules, et fonctionne ainsi comme une enzyme favorisant la croissance dans les tissus, en rendant les IGFs biodiposnibles au niveau du récepteur de l’IGF-I. La pro-MBP et la stanniocalcin-2 (STC2) semblent être les inhibiteurs principaux de l’activité de la PAPP-A, en formant un complexe covalent avec la protéase. Selon des expériences in vivo, l’IGFBP-4 est supposé être le substrat principal de la PAPP-A pour moduler la biodisponibilité des IGFs. La régulation de la PAPP-A inclut le contrôle transcriptionnel de son gène, des réactions de compétition avec d’autres IGFBPs, isolant potentiellement les IGF et par conséquent l’activité de la PAPP-A (qui dépend de la présence d’IGFs), et l’inhibition de l’activité protéolytique de la PAPP-A. Finalement, la PAPP-A pourrait servir de cible thérapeutique pour indirectement inhiber l’activité des IGF dans les tissus où la protéase joue un rôle important. En profitant de l’interaction complexe entre PAPP-A et IGFBP-4, une inhibition spécifique et sélective de la PAPP-A est possible
p53 regulates PAPP-A levels by binding to the PAPP-A promoter.
No full text<p>A) The mammary glands from wild type, pregnant (wild type) MMTV-Skp2B and tumors were analyzed for the mRNA levels of PAPP-A by quantitative RT-PCR. B) The level of IGFBP-4 in the mammary gland of wild type mice that are either virgin, pregnant, lactating or involuting was determined by western blot. C) The estrogen receptor null breast cancer cells MDA-MB-157 were transfected with 3 ug of estrogen receptor plasmid and D) after 24 hours cells were harvested for analyzing the expression of the estrogen receptor and mRNA levels of PAPP-A by quantitative RT-PCR. E) The p53 null MDA-MB157 cells were transfected with 2 µg of wild type p53 and PAPP-A mRNA levels determined. F) The level of expression of transfected wild type p53 was determined by western blot. G) MDA-MB 157 cells were transfected with 2 µg of different mutants of p53 (p53–143 and p53–248), 24 hours after, cells were harvested for analysis of PAPP-A mRNA. H) Western blot showing the expression of mutant p53. Tubulin was used as a loading control. I) p53 binding site on PAPP-A promoter. MDA-MB157 cells transfected with 2 µg of wild type and mutant p53 constructs. After 24 hours of transfection cells were fixed with formaldehyde and collected for chromatin immunoprecipitation (ChIP) using the p53 (DO-1) antibody. Normal mouse IgG served as a negative control.</p
Association of maternal serum PAPP-A levels, nuchal translucency and crown rump length in first trimester with adverse pregnancy outcomes: Retrospective cohort study.
Full text linkOBJECTIVE: Are first trimester serum pregnancy-associated plasma protein-A (PAPP-A), nuchal translucency (NT) and crown rump length (CRL) prognostic factors for adverse pregnancy outcomes? METHOD: Retrospective cohort women, singleton pregnancies (UK 2011-2015). Unadjusted and multivariable logistic regression, outcomes: small for gestational age (SGA), pre-eclampsia (PE), pre-term birth (PTB), miscarriage, stillbirth, perinatal mortality and neonatal death (NND). RESULTS: 12,592 pregnancies: 852 (6.8%) PTB, 352 (2.8%) PE, 1824 (14.5%) SGA, 73 (0.6%) miscarriages, 37(0.3%) stillbirths, 73 perinatal deaths (0.6%) and 38 (0.30%) NND. Multivariable analysis: lower odds of SGA [adjusted odds ratio (aOR) 0.88 (95% CI 0.85,0.91)], PTB [0.92 (95%CI 0.88,0.97)], PE [0.91 (95% CI 0.85,0.97)] and stillbirth [ 0.71 (95% CI 0.52,0.98)] as PAPP-A increases. Lower odds of SGA [aOR 0.79 (95% CI 0.70,0.89)] but higher odds of miscarriage [aOR 1.75 95% CI (1.12,2.72)] as NT increases, and lower odds of stillbirth as CRL increases [aOR 0.94 95% CI (0.89,0.99)]. Multivariable analysis of three factors together demonstrated strong associations: a) PAPP-A, NT, CRL and SGA, b) PAPP-A and PTB, c) PAPP-A, CRL and PE, d) NT and miscarriage. CONCLUSIONS: PAPP-A, NT and CRL independent prognostic factor for adverse pregnancy outcomes, especially PAPP-A and SGA with lower PAPP-A associated with increased risk
Associations between nausea and vomiting in pregnancy, disgust sensitivity, and first-trimester maternal serum free β-hCG and PAPP-A
Full text linkElevated levels of nausea and vomiting in pregnancy (NVP) and disgust sensitivity have been observed in the first trimester and both are thought to have a protective function for the mother and her fetus. Their aetiology is not clear, however, with previous studies attributing elevated NVP and disgust to various factors including endocrine changes, immunological changes, and psychological variables. To date, no study has directly assessed the relationship between disgust and NVP. Here, we prospectively collected two independent samples (S1 and S2; n1 = 201, n2 = 391) of women in the first trimester of pregnancy, who completed the Index of Nausea, Vomiting, and Retching and the Disgust Scale-Revised. We also measured free β-human chorionic gonadotropin (hCG) and pregnancy-associated plasma protein A (PAPP-A) in maternal serum. Our results did not confirm any association between NVP and disgust; in addition, they indicate that NVP and disgust may have different proximate causes. Disgust sensitivity was significantly negatively correlated with free β-hCG and (only in S1) with PAPP-A. In contrast, NVP was significantly positively associated with free β-hCG levels and (only in S1) with PAPP-A. While low hCG levels seem to be an important indicator for activation of the behavioral immune system in the first trimester, increased hCG levels play a role in stronger symptoms of NVP, a result consistent with previous studies. Levels of PAPP-A are likely part of a larger network of immunological and endocrine responses and do not appear to provide sufficient information for predicting women's NVP and disgust sensitivity
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