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Biomedical subjects

J G Westergaard

Publications and source records attributed to J G Westergaard.

At least 37 records · Page 2Linked to original sources

Two fetal antigens (FA-1 and FA-2) and endometrial proteins (PP12 and PP14) isolated from amniotic fluid: localisation in the fetus and adult female genital tract.

Monospecific antisera against two fetal antigens (FA-1 and FA-2), alphafetoprotein (AFP) and two endometrial proteins (PP12 and PP14) were used to examine the distribution of these proteins and antigens in human trophoblast and gestational endometrium in first and third trimesters of pregnancy, normal human ovary and fetal tissues by indirect immunoperoxidase histochemical localisation techniques. Fetal liver stained exclusively for FA-1 and AFP which was used as a reference protein. Staining for FA-2 was seen in fetal connective tissue, in particular the basement membrane. FA-1 and FA-2 did not stain positively in decidua, trophoblast or ovarian tissue. Gestational endometrium stained positively for PP14 exclusively in the glandular epithelium, whilst staining for PP12 was seen only in the stromal cells. Trophoblast, both early and late, and ovarian tissue did not stain positively for any of the four substances tested.

Amniotic Fluid↗

Two fetal antigens (FA-1 and FA-2) and endometrial proteins (PP12 and PP14) isolated from amniotic fluid; preliminary observations in fetal and maternal tissues.

Rabbit antihuman antibodies were derived by the injection of fractions of second trimester amniotic fluid known to contain proteins of endometrial/decidual origin. Using standard separation and absorption procedures, two antibody preparations were generated which demonstrated specificities against two and three proteins, respectively, in line immunoelectrophoresis and crossed immunoelectrophoresis. Analysis against proteins of fetal, maternal, endometrial and placental origin revealed that the bispecific antiserum reacted only with placental protein 14 (PP14; also known as progestagen-dependent endometrial protein, PEP) and one other hitherto undescribed antigen referred to as Fetal Antigen 1 (FA-1) molecular mass 60 kDa; electrophoretic mobility: slow; alpha 1-alpha 2; fast, albumin. The trispecific antiserum demonstrated specifities against placental protein 12 (PP12), alpha-fetoprotein (AFP) and another previously undescribed antigen referred to as Fetal Antigen 2 (FA-2) molecular mass 35 and 140 kDa; electrophoretic mobility: albumin. Following purification, monospecific antisera against each of these proteins (with the exception of AFP) were derived in new rabbits. Maternal and fetal blood, amniotic fluid and aqueous extracts from endometrial/decidual and placental tissues were analysed in rocket immunoelectrophoresis using these antisera to examine the distribution in these tissues. The analyses demonstrated a pattern of distribution typical for proteins of endometrial/decidual origin in these compartments in the case of PP12 and PP14, but suggested that the primary source of origin of FA-1 and FA-2 may be the fetus.

Amniotic Fluid↗

Complement factors in fetal and maternal blood and amniotic fluid during the second trimester of normal pregnancy.

Complement factors (C3, C4, C5; Factors B, H and I) were measured in maternal and fetal serum and amniotic fluid obtained from 55 women with singleton pregnancy undergoing diagnostic fetoscopy at 15 to 28 weeks gestation. Maternal serum levels were consistently 10 times higher than fetal levels which in turn were 10 times higher than levels in amniotic fluid. Spearman rank correlation analysis at weeks 20 to 22 (n = 20) revealed a statistically significant correlation between maternal and fetal levels of C3 and Factors B and I, and between maternal and amniotic fluid levels of Factors B and I. A significant increase in fetal levels of C3, C4 and Factor H, and in amniotic fluid levels of C3 and Factor B was seen in relation to advancing gestational age. These differences were not seen in maternal serum during the short interval of pregnancy studied. These data confirm earlier assumptions of fetal synthesis of complement factors, and provide normal reference ranges of complement factors in fetal blood and amniotic fluid.

Amniotic Fluid↗

Measurements of hCG and PAPP-A in uncommon types of ectopic gestation.

Seven out of 54 women with ectopic gestation had uncommon features such as extra-tubal implantation or multiple intratubal pregnancy. Depressed levels (less than 10th centile) or apparent absence of circulating human chorionic gonadotrophin (hCG) and pregnancy-associated plasma protein A (PAPP-A) were seen respectively in 5 and 7 of 7 women studied. Normal levels of hCG were seen in two women, one with an abdominal and one with an angular pregnancy. These data suggest that the synthesis of placental proteins in ectopic pregnancies is independent of the site of implantation and the number of embryos. Measurements of maternal levels of the 2 placental proteins seem to be applicable as auxiliary diagnostic tests for ectopic pregnancy, regardless of the site of implantation.

Chorionic Gonadotropin↗

Placental proteins in peripheral blood and tissues of ectopic pregnancies.

Circulating human chorionic gonadotrophin (hCG), Schwangerschaftsprotein 1 (SP-1) and pregnancy-associated plasma protein A (PAPP-A) were examined in 10 women with ectopic gestation in relation to distribution and intensity of staining for these molecules using immunohistochemical techniques applied to matched trophoblastic and decidualized endometrial tissues. All 10 women revealed strong staining for hCG and SP-1 in the syncytiotrophoblast, which was apparently unrelated to maternal levels of hCG and SP-1, levels being less than the 10th centile of the normal range in 9/10 and 7/10 women, respectively. By contrast maternal PAPP-A levels seemed to correlate with the intensity and the distribution of staining for PAPP-A. Circulating PAPP-A was undetectable (less than 5 mIU/l) in 4 patients, and below the 10th centile in the remaining 6. Using immunohistochemical techniques hCG, SP-1 and PAPP-A could not be demonstrated in any of the decidualized endometrial tissues studied.

Chorionic Gonadotropin↗

Comparison of different antibody preparations against pregnancy-associated plasma protein-A (PAPP-A) for use in localization and immunoassay studies.

Four antibody preparations against pregnancy-associated plasma protein (PAPP-A) were compared in order to find an explanation for the contradictory results published on tissue localization, clinical usefulness and biological function of PAPP-A. One of the preparations studied was a rabbit anti-PAPP-A antiserum which has been offered for general scientific use (Bischof et al. 1979). Only the IgG fraction of anti-PAPP-A antisera which appeared to be monospecific and had been further absorbed with fetal connective tissue gave specific uniform staining of the cytoplasm of the syncytiotrophoblast exclusively. Circulating PAPP-A could not be detected by RIA employing this IgG preparation in the non-pregnant state, or before 18 days after conception. Circulating PAPP-A could be detected in all seven pregnant women studied within 4 weeks after conception. Identical results were obtained with a commercially available IgG fraction against PAPP-A.

Animals↗

Quantitative comparison of circulating immune complexes in normal pregnancy and pregnancy related hypertension.

Using two different Clq-dependent assays for quantification of circulating immune complexes (CIC), the levels were compared in sera from 32 women with pregnancy-related hypertension and in sera of 32 matched controls. No difference in the CIC levels was observed. The levels of CIC in the hypertensive patients were not correlated to placental weight, fetal weight, or diastolic blood pressure.

Antigen-Antibody Complex↗

Characterization of human pregnancy zone protein. Comparison with human alpha 2-macroglobulin.

Native human pregnancy zone protein (PZP), a close homolog of alpha 2-macroglobulin (alpha 2M), can be obtained in approximately 20% yield from pooled late pregnancy plasma or serum by a combination of polyethylene glycol precipitation, euglobulin precipitation, DEAE-Sephacel chromatography, zinc-chelate affinity chromatography, and negative affinity chromatography on insolubilized antibodies against human serum proteins. Both proteins are similarly organized as disulfide-bridged dimers of 360 kDa containing 180-kDa subunits. These dimers constitute the proteinase-binding units of PZP, and in contrast to alpha 2M, they appear to be only loosely associated, indicating a subtle difference in the quaternary structure of these alpha-macroglobulins. The preparations contain functionally intact beta-cysteinyl-gamma-glutamyl thiol esters, located in the same nonapeptide sequence as found in alpha 2M, and form complexes with a variety of proteinases in which a large fraction of the proteinase is bound covalently. Proteinases bound to PZP are still active and poorly accessible to reaction with large inhibitors like alpha 1-proteinase inhibitor. The structural and functional features of PZP indicate that PZP and alpha 2M, although extremely similar, may have different yet overlapping sets of proteinases as targets. It is possible that PZP mainly controls the activity of cellular proteinases released under conditions of increased cellular turnover and that PZP could be the human equivalent to the acute phase alpha-macroglobulins known in other species.

Chemical Precipitation↗

The selection of antibodies with defined desorption properties from precipitated immune complexes for use in immunoadsorption procedures.

A general method for preparing immunosorbents with preselected antibody avidity is described. The method, which is a modification of a method described previously, also includes immunospecific purification of the ligand prior to coupling on the gel matrix. Polyclonal anti-alpha-1-fetoprotein antibodies in precipitated immune complexes were separated according to their avidity (low, intermediate and high) by dissociation with agents of increasing efficiency. After solid-phase coupling the antigen binding activity of the separated antibody preparations was examined according to recovery, capacity and binding strength. Antibodies of intermediate avidity derived from the immune complexes demonstrated optimal properties for preparative affinity chromatography.

Antibody Affinity↗

Placental protein and hormone measurements in twin pregnancy.

Maternal serum levels of human placental lactogen (hPL), schwangerschaftsprotein 1 (SP1), pregnancy-associated plasma protein A (PAPP-A), placental protein 5 (PP5) and total oestriol (E3) were measured serially in 35 twin pregnancies during the third trimester. Eighteen pregnancies had major complications including dysmaturity of one or both fetuses in nine, premature labour in six, and placental abruption in three. Serum levels of all five variables were higher than in singletons, this distinction being greatest for hPL and lowest for SP1 and E3. The levels of hPL, PP5 and E3 just before delivery were significantly correlated with the total birthweight, a correlation with placental weight being evident only for hPL and PP5. A significant correlation between the five biochemical variables at 33-34 weeks was only seen between hPL and PAPP-A. Protein and hormone levels in the abnormal twin pregnancies were not apparently different from those in the normal twin pregnancies. These data suggest that only hPL levels biochemically reflect this extreme of fetal and placental growth, but that neither the levels of hPL nor any of the other biochemical indices examined are altered in abnormalities in twin pregnancy.

Birth Weight↗

Does ultrasound examination render biochemical tests obsolete in the prediction of early pregnancy failure?

Serum levels of fetal, placental and maternal hormones and proteins [alpha-fetoprotein (AFP), human chorionic gonadotrophin, human placental lactogen, schwangerschaftsprotein 1, pregnancy associated plasma protein-A (PAPP-A), oestradiol-17 beta, progesterone, pregnancy zone protein] were measured in 108 women with bleeding during the first half of pregnancy. Ultrasound examination at the time of each blood sampling revealed a fetal heart action on at least one occasion in 77 women. Spontaneous abortion occurred in 42 pregnancies, 31 of these showed no ultrasound sign of fetal life, whilst the fetal heart action was observed repeatedly until abortion in the remaining 11 women. Abnormally low levels of PAPP-A were most likely to indicate pregnancy failure, in particular if the fetal heart action was seen at the time of blood sampling. The predictive value, sensitivity and relative risk of a single depressed PAPP-A level were respectively 49, 89 and 41%, the predictive value of a normal result being 99%. With the exception of AFP, all other biochemical indices examined were consistently in the normal range in this group of women. If ultrasound findings were not considered, the biochemical indices were of comparable value in the prediction of spontaneous abortion. PAPP-A levels were uniformly depressed in all patients who spontaneously aborted, frequently weeks before this event, in the presence of a live fetus.

Abortion, Threatened↗

15(S)-15-methyl-prostaglandin F2 alpha used for induction of delivery in the case of intra-uterine fetal death.

102 pregnant women with intra-uterine fetal death after the 12th week of gestation were treated with 15(S)-15-methyl-prostaglandin F2 alpha intramuscularly with doses of 125-250 micrograms at 2-3 hourly intervals. In all cases abortion or delivery was completed within 30 hours. The average time in primigravidae was 9 hours 43 minutes, and in multigravidae 9 hours and 59 minutes. In approximately two-thirds of the patients, mild or moderate gastrointestinal side effects were recorded in spite of prophylactic treatment with Retardin or Loperamide + Diphenoxylate. The therapy was found to be effective, easy to administer and the side effects acceptable. No serious side effects were recorded.

Abortion, Induced↗

Circulating and tissue concentrations of pregnancy-associated plasma protein-A (PAPP-A) in tubal ectopic gestation.

Concentrations of pregnancy-associated plasma protein-A (PAPP-A), human chorionic gonadotrophin (hCG) and pregnancy specific beta 1-glycoprotein (SP1) were measured by radioimmunoassay in 164 serum and 29 tissue samples obtained from 87 non-pregnant and 29 pregnant women with either tubal (n = 16) or intrauterine (n = 13) pregnancies. Of the 47 serum samples obtained from patients with a tubal pregnancy only two were positive for PAPP-A, whereas in excess of 94% of the samples were positive for both hCG and SP1. Serial measurements of hCG, and SP1, demonstrated an apparently normal growth rate for the tubally implanted trophoblast for the first 6 weeks of pregnancy. Thereafter, the tubal trophoblast is compromised since the tissue content of PAPP-A and hCG was significantly lower than that in intra-uterine derived trophoblastic tissue. By contrast, the content of both PAPP-A and hCG was significantly greater in the trophoblastic, both intra or extra-uterine derived, than in the endometrial/decidual, tissue. Furthermore, the absence of immunoreactive PAPP-A and the severely depressed circulating levels of PAPP-A in women with tubal pregnancies can be attributed to diminished secretion of PAPP-A into the maternal circulation. Therefore, in conjunction with a positive pregnancy test and the patient's clinical history, a severely depressed or absent serum PAPP-A level may aid in the diagnosis of extrauterine pregnancy.

Chorionic Gonadotropin↗

Single measurements of chorionic gonadotropin and schwangerschafts protein for assessing gestational age and predicting the day of delivery.

Human chorionic gonadotropin (hCG) and schwangerschafts protein 1 (SP1) were measured in blood samples from 26 women at 36-60 days of normal pregnancy. There was a highly significant linear correlation between the levels of these placental proteins and the stage of gestation as judged from the day of the last menstrual period and the day of spontaneous delivery at term. There was no relationship between hCG and SP1 levels in early pregnancy and the sex or birth weight of the child. These findings confirm the previous demonstration of the practical value of biochemical estimations in dating an early pregnancy. In addition, and for the first time, they demonstrate that such determinations may be used to ascertain the expected date of term delivery.

Chorionic Gonadotropin↗