Lectin binding of pregnancy-associated plasma protein A purified from different sources.
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Concanavalin A↗
Biomedical subjects
N A Bersinger
Publications and source records attributed to N A Bersinger.
The role of pregnancy-specific beta-1 glycoprotein (SP1) in assessing the human blastocyst quality in vitro.
The advent of new culture techniques resulting in more than 60% of embryos developing in vitro to the blastocyst stage suggests that blastocyst transfer in humans with its potential to increase in-vitro fertilization success rates could be a feasible option. Blastocyst quality markers, however, are required to ensure that an increase in numbers is not achieved at the expense of lowering quality. We have previously reported a morphology based method for grading blastocysts. The current study sought to determine whether the secretion of pregnancy-specific beta-1-glycoprotein (SP1) (a trophoblast product known to be associated with fetal well-being) by blastocysts of differing quality was reflected in the morphological grading. SP1 concentrations were measured in the culture medium of grade 1 (n = 19), grade 2 (n = 4) and grade 3 (n = 4) blastocysts as well as vacuolated morulae (n = 6) daily from day 1 to day 14. Cumulative SP1 concentrations secreted by blastocysts were significantly higher than those secreted by vacuolated morulae. However, SP1 levels could not distinguish between blastocysts of differing morphological grades. The inconsistent pattern of secretion suggests that at this early stage of development, SP1 secretion is probably not sufficiently defined to allow any differences in levels to be reflected by the morphological grading.
Biomarkers↗
Maternal serum Schwangerschafts protein-1 (SP1) and fetal chromosomal abnormalities at 10-13 weeks' gestation.
Maternal serum SP1 concentration was measured at 10-13 weeks' gestation in samples from 87 pregnancies with fetal chromosomal abnormalities (trisomy 21 n = 45; trisomy 18 n = 19; trisomy 13 n = 8; Turner syndrome n = 7; 47,XXX or 47,XXY n = 4; triploidy n = 4), and in samples from 348 matched controls. In the control group, SP1 increased significantly with fetal crown-rump length (r = 0.20, P < 0.0001) and there was no significant association with fetal nuchal translucency thickness (r = 0.03). Similarly, in the group with fetal chromosomal abnormalities, SP1 increased significantly with crown-rump length (r = 0.31, P < 0.01) and there was no significant association with nuchal translucency thickness (r = -0.08). In the groups with fetal trisomy 18 and trisomy 13, the median SP1 (0.76 MoM and 0.57 MoM, respectively) was significantly lower than in the controls (z = 2.64 and z = 3.27, respectively); in 21% and 25% of the cases, values were below the 5th centile. In the group with trisomy 21 and other chromosomal abnormalities the median SP1 (0.96 MoM and 0.93 MoM, respectively) was not significantly different from controls (z = 1.17 and z = 0.67, respectively). Measurement of SP1 concentration at 10-13 weeks' gestation is not likely to be useful in the prediction of fetal chromosomal abnormalities.
Adult↗
A sensitive enzyme immunoassay for pregnancy-associated plasma protein A (PAPP-A): a possible first trimester method of screening for Down syndrome and other trisomies.
Pregnancy-associated plasma protein A (PAPP-A) is a large glycoprotein produced mainly by the trophoblast during pregnancy and released into the maternal circulation. Its biological function is unknown. In the second trimester i.e. when Down syndrome (DS) screening is routinely performed, the level of maternal serum PAPP-A was found to be within the normal range in pregnancies affected by fetal trisomy 21. However, PAPP-A was shown to be a potent marker for DS before 14 weeks of gestation. Only radioimmunoassays (RIAs) based on labelled antigen competition reached the required sensitivity for early pregnancy PAPP-A determinations; but they have a very short shelf life due to inherent tracer half-life and, in the case of PAPP-A, instability of the labelled antigen after three weeks. We describe a convenient and novel enzyme immunoassay (ELISA) with high sensitivity and a long shelf life.
Abnormalities, Multiple↗
Pregnancy-associated plasma protein A (PAPP-A): measurement by highly sensitive and specific enzyme immunoassay, importance of first-trimester serum determinations, and stability studies.
It has recently been established that maternal serum pregnancy-associated plasma protein A (PAPP-A) was reduced in pregnancies with fetal Down syndrome in the first but not in the second trimester of gestation. In comparison with two other placental proteins, human chorionic gonadotrophin and pregnancy-specific beta 1-glycoprotein, an explanation for this can be formulated based on the large molecular weight of PAPP-A. With the increasing clinical demand for fetal abnormalities to be diagnosed in the first rather than in the second trimester of pregnancy, maternal serum PAPP-A is a strong potential candidate for being used in routine trisomy screening. We have developed a sensitive enzyme immunoassay (ELISA) intended at smaller laboratories due to its long shelf life. Here we show that repeated freezing and thawing, or the addition of iodoacetate (5 mM) did not affect the results, at both high or low concentration of PAPP-A. It is also possible to introduce the serum into the test as a dry sample on blotting paper, easily posted in an envelope. A decrease of 21% was observed after such dry storage for three weeks at room temperature, which can be compensated for by the inclusion of a dried control serum, mailed with the sample(s).
Chorionic Gonadotropin↗
Endometrial and placental protein markers and ovarian steroids in serum during in-vitro fertilization cycles.
The objective of this study was to find the earliest time at which it was possible to detect clinical pregnancy in an in-vitro fertilization (IVF) treatment cycle supported with human chorionic gonadotrophin (HCG), and also retrospectively to diagnose abnormal ovarian- or endometrium-related situations in failure cycles. Serum samples were taken in 41 IVF cycles at frequent intervals from the beginning of ovarian stimulation until menstrual bleeding occurred or a pregnancy was established. Concentrations of oestradiol, progesterone, placental protein 14 (PP14), pregnancy-specific beta 1-glycoprotein (SP1), and pregnancy-associated plasma protein A (PAPP-A) were determined in the serum samples using commercially available (steroid) or purpose-developed (protein) immunoassays. The cycles were retrospectively distributed into four outcome groups: (i) fertilization failure (FF, n = 8); (ii) implantation failure (IF, n = 10); (iii) 'interaction' (embryo-endometrium) cycle (IC, n = 14), and (iv) clinical pregnancy (CP, n = 9). The embryo-endometrium interaction was detected by a rise in SP1 in 23 cycles (70% of embryo transfers) at a time when endogenous HCG was still masked by external support. Early ('false') positive SP1 concentrations were observed in two out of eight and five out of 14 cases in groups FF and IC respectively, but never amongst the ongoing pregnancies (CP). PAPP-A did not distinguish pregnancy from the other outcomes. The PP14/progesterone ratio was lower, later in the cycle, in CP than in the other groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
First trimester maternal serum alpha-fetoprotein in fetal trisomies.
OBJECTIVE: To evaluate the potential value of maternal serum alpha-fetoprotein concentration in the detection of fetal trisomy at 10 to 13 weeks gestation and to examine the possible association between maternal serum alpha-fetoprotein and fetal nuchal translucency thickness. DESIGN: Cross-sectional study. SETTING: Harris Birthright Research Centre for Fetal Medicine, King's College Hospital Medical School, London. SUBJECTS AND METHODS: Maternal serum alpha-fetoprotein concentration was measured at 10 to 13 weeks gestation in samples from 57 pregnancies with fetal trisomies (trisomy 21 (n = 35), trisomy 18 (n = 16), and trisomy 13 (n = 6)) in 228 matched controls in whom the fetal nuchal translucency was < 3 mm and in 114 chromosomally normal fetuses with translucency > or = 3 mm. RESULTS: In the control group maternal serum alpha-fetoprotein increased significantly with fetal crown-rump length (r = 0.451). In this group, the median maternal serum alpha-fetoprotein was not significantly different from that in the groups with trisomy 21 (median = 0.84 MoM), trisomy 18 (median = 0.86 MoM), or trisomy 13 (median = 0.94 MoM), respectively. Neither in the control group nor in the group with trisomic fetuses was maternal serum alpha-fetoprotein significantly associated with fetal nuchal translucency thickness (r = 0.01 and r = 0.03). CONCLUSION: Measurement of maternal serum alpha-fetoprotein concentration in the first trimester of pregnancy is not likely to be useful in the prediction of fetal trisomies.
Adult↗
Maternal serum hCG and fetal nuchal translucency thickness for the prediction of fetal trisomies in the first trimester of pregnancy.
OBJECTIVE: To compare the potential value of maternal serum total hCG and free beta-hCG in predicting the risk for fetal trisomies during the first trimester of pregnancy and to examine whether data on maternal hCG and fetal nuchal translucency thickness can be combined to derive risks. METHODS: Maternal serum total hCG and free beta-hCG were measured in samples from 83 singleton pregnancies with fetal chromosomal abnormalities (trisomy 21 (n = 41), trisomy 18 (n = 19), trisomy 13 (n = 8) sex chromosome aneuploidies (n = 11), triploidy (n = 4) and 394 chromosomally normal controls at 10 to 13 weeks gestation. In all cases, the fetal nuchal translucency thickness was measured at the time of fetal karyotyping. RESULTS: In the 249 chromosomally normal controls with fetal nuchal translucency less than 3 mm, total hCG and free beta-hCG decreased significantly with increased fetal crown-rump length. In 145 chromosomally normal fetuses with nuchal translucency 3 to 9 mm total hCG and free beta-hCG were not significantly different from the 249 with nuchal translucency less than 3 mm. In fetuses with trisomy 21, total hCG and free beta-hCG were significantly higher, whereas in trisomies 18 and 13 levels were lower than in chromosomally normal controls. When the cutoff levels for total hCG and free beta-hCG were selected to include 4% of chromosomally normal fetuses, the detection rates for trisomy 21 were 24% and 32%, respectively. There was no significant association between hCG and nuchal translucency thickness in either the chromosomally normal (r = -0.01) or abnormal group (r = -0.15). CONCLUSION: An improved estimate of risk for fetal trisomies at 10 to 13 weeks gestation can be derived by combining data on maternal age, maternal serum total or free beta-hCG and fetal nuchal translucency thickness.
Chorionic Gonadotropin↗
Production of endometrial placental protein 14 and prolactin by cultured endometrial explants after collagenase and freeze/thaw treatment, and in response to progesterone.
OBJECTIVE: Investigation of methods for maintaining functional endometrial explants in culture after cryopreservation with or without previous enzymatic dispersion of stromal cells and epithelial glands. Such a standardized culture system is a requirement for the development of a non-invasive bioassay for embryo quality in in vitro fertilization programs, a method that will eventually measure endometrial response to embryo conditioned media. METHOD: Culture of mid-luteal phase endometrial biopsies, in the presence of [35S]methionine, with or without prior collagenase treatment and/or storage in liquid nitrogen in the presence of dimethyl sulfoxide. Determination of released de novo synthesized total protein by trichloroacetic acid precipitation of culture media. Measurement, after culture in absence and presence of progesterone, of prolactin and placental protein 14 (PP14) production by sensitive non-isotopic immunoassays. RESULTS: Production of prolactin, but not PP14, was increased by 200 nmol/l progesterone, 2-8-fold after 4 days and 1.5-700-fold after 7 days in culture. After limited collagenase treatment (but without separation of stromal cells from glands), both marker protein productions were similar compared to untreated explants; however, there was no significant stimulation of prolactin by progesterone. After freezing and thawing, production was markedly reduced, particularly from explants frozen following collagenase treatment. CONCLUSIONS: Both stromal and glandular viability are maintained after collagenase treatment but the response to progesterone is lost. Cryopreservation reduced prolactin and PP14 production in subsequent culture. Therefore, novel freezing protocols should be developed which preserve both endometrial structure and function.
Collagenases↗
First trimester maternal serum pregnancy-associated plasma protein A and pregnancy-specific beta 1-glycoprotein in fetal trisomies.
OBJECTIVE: To examine the potential value of maternal serum levels of pregnancy-associated plasma protein A (PAPP-A) and pregnancy-specific beta 1-glycoprotein (SP1) in the detection of fetal trisomy. DESIGN: Cross-sectional study. SETTING: The Harris Birthright Research Centre For Fetal Medicine, King's College Hospital Medical School, London, UK and Division of Maternal-Fetal Medicine, Jefferson Medical College, Philadelphia, USA. SUBJECTS AND METHODS: Maternal serum PAPP-A and SP1 concentrations were measured at 10 to 13 weeks gestation in samples from 42 pregnancies with fetal trisomy (trisomy 21, n = 29; trisomy 18, n = 9; trisomy 13, n = 4) and in samples from 210 matched controls. RESULTS: In controls, both maternal serum PAPP-A and SP1 increased significantly with gestation and in trisomic fetuses levels of both hormones were reduced. However, discriminant analysis demonstrated that SP1 did not contribute significantly in the distinction between trisomic and control pregnancies. Although levels of PAPP-A were reduced throughout the gestational range examined (10 to 13 weeks), especially in cases with fetal trisomy 21, the deviation was more pronounced at 10 to 11 weeks than at 12 to 13 weeks gestation. In 45% of pregnancies with fetal trisomy 21 and 70% of pregnancies with trisomies 18 or 13 maternal serum PAPP-A levels at 10 to 11 weeks gestation were below the 5th centile of the normal range. CONCLUSION: Maternal serum PAPP-A concentration in the first trimester of pregnancy may prove to be useful in the prediction of risk for fetal trisomies.
Adult↗
Maternal serum pregnancy-associated plasma protein A and fetal nuchal translucency thickness for the prediction of fetal trisomies in early pregnancy.
OBJECTIVE: To determine if the risk for fetal trisomies during the first trimester of pregnancy can be derived by combining data from maternal serum pregnancy-associated plasma protein A (PAPP-A) and fetal nuchal translucency thickness. METHODS: Pregnancy-associated plasma protein A was measured in samples from 87 singleton pregnancies with fetal chromosomal abnormalities (45 trisomy 21, 19 trisomy 18, eight trisomy 13, 11 sex chromosome aneuploidies, four triploidies) and 348 chromosomally normal controls at 10-13 weeks' gestation. Likelihood ratios for trisomies 21, 18, and 13 in relation to PAPP-A, in multiples of the normal median (MoM) for crown-rump length, were derived from the overlapping gaussian frequency distribution curves for normal and abnormal pregnancies. RESULTS: In the chromosomally normal group, maternal serum PAPP-A correlated significantly with fetal crown-rump length (r = 0.421, P < .0001). In the chromosomally abnormal group, the median PAPP-A was significantly lower than in the normal controls. The respective median values expressed in MoM for trisomies 21, 18, and 13 and other aneuploidies were 0.5 MoM (90% confidence interval [CI] 0.09-1.67, z = 6.0, P < .001), 0.17 MoM (90% CI 0.06-1.45, z = 6.6, P < .001), 0.25 MoM (90% CI 0.10-0.62, z = 4.5, P < .001), and 0.72 MoM (90% CI 0.09-2.48, z = 2.2, P < .05), respectively. There was no significant linear association between PAPP-A and fetal nuchal translucency thickness in either the chromosomally normal (r = -0.01, P = .89) or abnormal groups (r = -0.19, P = .08). CONCLUSION: The risks for fetal trisomies at 10-13 weeks' gestation can be derived by combining data on maternal age, maternal serum PAPP-A, and fetal nuchal translucency thickness.
Crown-Rump Length↗
Pregnancy associated plasma protein A as a marker for Down syndrome in the second trimester of pregnancy.
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Down Syndrome↗
Pregnancy-associated plasma protein B (PAPP-B): isolation from human late pregnancy serum and biochemical characterization.
The pregnancy associated plasma protein B (PAPP-B) was first described by Lin et al. as a glycoprotein with a molecular weight of about 1,000 kD and a serum half life of less than 24 hours after delivery. We isolated PAPP-B from late pregnancy serum using liquid chromatography including HPLC. PAPP-B was found to be a glycoprotein with a molecular weight of 1,300 kD and to be an octadecamer of identical subunits (74 kD each). Cleavage of the carbohydrates with trifluoromethanesulfonic acid reduced the molecular mass to 65 kD (by SDS PAGE, 12.2%). Isoelectrofocusing and titration curves fixed the isoelectric point at 5.3. Spectroscopy measurements between 230 and 360 nm yielded a trp/tyr ratio of 1.1. Amino acid analysis showed that each subunit contained five methionines; this was confirmed by a CNBr cleavage experiment.
Chromatography, High Pressure Liquid↗
Detection of human papillomavirus in vulvar carcinoma. A study by in situ hybridisation.
Fourty-four specimens of invasive cancers of the vulva, including 38 primary invasive squamous carcinomas, were analysed by in situ hybridisation with biotinylated HPV 6/11, 16 and 18 DNA probes. Four (9%) of the 44 carcinomas were positive for HPV DNA: three (7%) for HPV 16 DNA and one (2%) for HPV 6/11 DNA. HPV DNA was found only in squamous carcinomas. Of the 38 primary squamous carcinomas, 11% were positive (8% HPV 16, 3% HPV 6/11). The overall 5-year survival was 48.7%, 48.5% for the squamous carcinomas and 50.0% for the HPV DNA positive patients.
Adult↗
Effect of late pregnancy serum on the synthesis and release of pregnancy proteins by the perfused human term placenta.
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Female↗
Patterns of spontaneous pulsatile secretion of human chorionic gonadotropin and pregnancy specific beta 1 glycoprotein by superfused placental explants in first and last trimester. Lack of episodic human placental lactogen secretion.
We have recently reported that during superfusion of placental explants, human chorionic gonadotropin secretion is episodic. In the present work we have examined, using the superfusion model, the pattern of secretion of other glycoprotein hormones, pregnancy specific beta 1 glycoprotein and human placental lactogen, in the first trimester and term placenta. This was done by evaluating the pulsatile pattern by two different computerized programmes. By using different sampling intervals (6-0.5 min) of the effluent, two distinct patterns of hCG secretion were detected in the first trimester: a short one, occurring every 8-9 min and the other every 18-25 min. In contrast, at term the only episodic pattern detected was every 40-50 min, with a low amplitude, 20-30% above baseline, and a declining baseline. In two out of seven placentas, no pulsatility was detected. The secretion of pregnancy specific beta 1 glycoprotein was pulsatile, occurring every 14-15 min in the first trimester and every 6-7 min at term. Finally, the secretion of human placental lactogen at term was not pulsatile. The levels of this glycoprotein in the first trimester placenta were below detection limits. In conclusion, the patterns of the three glycoproteins during superfusion are different, suggesting different paracrine/autocrine control mechanisms. The dynamic superfusion model also enables identification of thus far not reported gestational age-dependent differences in the secretion pattern of hCG and pregnancy specific beta 1 glycoprotein.
Chorionic Gonadotropin↗
A comparison between pregnancy-associated alpha 2-glycoprotein (alpha 2-PAG), carcino-embryonic antigen (CEA), CA-125, and CA-15-3 as tumor markers in breast cancer.
Pregnancy-associated alpha 2-glycoprotein (alpha 2-PAG) has been advocated as a good marker for various malignant diseases, in particular carcinoma of the breast. Re-evaluation of previously published results was required and in this study the correlation between alpha 2PAG and CEA, CA-125, and CA-15-3 was investigated and the monitoring efficiency determined in comparison to these above mentioned markers. Overall monitoring efficiency of alpha 2-PAG was in the same range as the corresponding parameters of CEA and CA-125; specificity was very high at the expense of sensitivity, resulting in a high positive predictive value. Monitoring of such patients by alpha 2-PAG as sole marker is not recommended.
Adult↗
Antiserum to pregnancy-associated plasma protein A (PAPP-A) recognizes human haptoglobin.
The presence of pregnancy-associated plasma protein A (PAPP-A) in non-pregnancy serum has been questioned with reference to insufficient specificity of the antibodies raised against this glycoprotein in some departments and used in immunoassay. For convenience, but also because of this unclear situation, many laboratories now use the only commercially available anti-PAPP-A preparations in their assays. By analysing pregnancy and non-pregnancy serum with two-dimensional electrophoresis (2-DE) and Western blotting, we could demonstrate that this antiserum marketed by Dakopatts (Denmark) was capable of binding haptoglobin whereas our own (Dr P. Bischof) antibody preparation did not recognize haptoglobin.
Antibodies, Monoclonal↗