Biomedical subjects
Publications and source records attributed to A Klopper.
Pregnancy-associated plasma protein A (PAPP-A) was measured in 26 women before and after hysterectomy. The PAPP-A concentration declined significantly in 24 of them. It is concluded that the uterus is a source of the protein.
The substances in the blood or urine of a pregnant woman which may give an indication of the state of fetal growth are examined. The drawback of measuring such substances is that the values are variable, making it difficult to distinguish between normal and abnormal. Variability arises from technical factors in measurements, from short-term changes of no significance and from the large spread of normal values from one individual to the next. Biochemical parameters of fetal growth can be applied in one of two ways: as screening tests or as control measures by serial assays to guide management. The criteria by which any test should be evaluated--sensitivity, specificity and relative risk--are examined. Particular substances whose measurement may be helpful are considered in terms of the steroids or proteins produced by the fetoplacental unit. The oestrogens, notably oestriol, hold pride of place among the steroids. Dynamic tests of steroid synthesis are also considered. The chief placental proteins of interest are chorionic gonadotrophin, placental lactogen and Schwangerschaftsprotein 1. It is concluded that the method to be recommended is to screen a whole obstetric population with assays of placental lactogen and to follow those with values below the normal limit with serial oestriol assays.
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1. Pregnant rats were fed either low (less than 1 p.p.m.) Zn or control (40 p.p.m. Zn) diets from day 10 of gestation. They were killed at intervals during the last 96 h preceding the normal time for onset of parturition, and differences in plasma progesterone, oestradiol-17 beta and ovarian 20 alpha-hydroxysteroid dehydrogenase were assessed. 2. Gestation was prolonged in Zn-deficient rats. 3. Although the preparturient decline in plasma progesterone began at the same time in all groups, at term, plasma progesterone concentration in Zn-deficient rats remained significantly higher than in normal females. 4. Induction of ovarian 20 alpha-hydroxysteroid dehydrogenase activity was delayed by about 8 h by Zn deficiency. This delay was not observed if prostaglandin F2 alpha was injected previously. 5. The results suggest a Zn-dependent step(s) in uterine synthesis and/or release of prostanoids.
The concentrations of the two components of Schwangerschaftsprotein 1 (SP1 beta and SP1 alpha), human chorionic gonadotrophin (hCG) and human placental lactogen (hPL), were measured in peripheral venous blood and in retroplacental blood at term delivery in 22 women. Like hCG and hPL, the values of SP1 alpha were higher in the retroplacental than in the peripheral blood, as might be expected with placental secretory products. On the other hand, the concentration of SP1 beta showed a reverse gradient, being higher in the peripheral than in retroplacental blood.
Schwangerschaftsprotein 1 (SP1) was measured in 10 women at intervals after delivery of the placenta. SP1 alpha decreased more sharply than SP1 beta and showed evidence of a two-compartmental distribution in the mother. Trace amounts of both proteins could still be detected 5 weeks after delivery. It is concluded that the findings support the view that the two proteins are separate biological entities and that there is a possibility that SP1 beta is generated from SP1 alpha in the maternal compartment.
The level of pregnancy-associated plasma protein-A (PAPP-A) in blood measured by rocket immunoelectrophoresis is affected by the addition of anticoagulants. When compared with levels in serum, those in heparin and sequestrene plasmas were higher, while those in sodium citrate, acid citrate dextrose and fluoride oxalate plasmas were lower. Similar results were obtained when the anticoagulants were added to serum and the effect on the measured level was dose-dependent within limits. Addition of anticoagulants to serum affected the mobility of PAPP-A in crossed immunoelectrophoresis, but this was not necessarily in keeping with the effect on rocket height. Addition of sodium chloride to serum did not influence the measured levels of PAPP-A.
The Schwangerschaftsprotein 1 (SP1)alpha values in blood measured by rocket immunoelectrophoresis are affected by the addition of anticoagulants. When compared with values in serum, those in heparin plasma were much higher, while those in sequestrene ethylenediamine-tetra-acetic acid), sodium citrate and fluoride oxalate were lower. On the other hand, SP1 and SP1 beta concentrations were not significantly affected in heparin or sequestrene and were only slightly depressed in sodium citrate and fluoride oxalate. The effect of heparin on SP1 alpha in serum was dose-dependent. We surmise that SP1 alpha forms a complex with heparin and that it may be involved in the coagulation system in pregnancy.
The plasma concentrations of Schwangerschaftsprotein 1 (SP1) and human chorionic gonadotrophin (hCG) were measured in 22 women before and after conception. In these pregnancies ovulation occurred spontaneously in seven subjects, or followed treatment with either clomiphene citrate (6 subjects), or human menopausal gonadotrophin (hMG) and hCG (6 subjects). The remaining three patients became pregnant after artificial insemination with donor semen. Seventeen of these pregnancies were normal and five were abnormal (3 abortions, 1 ectopic and 1 twin). SP1 could be detected 6-14 days after ovulation in all these patients. In contrast 40 non-pregnant women gave a negative test for SP1.
Maternal pregnancy-associated plasma protein A (PAPP-A) concentration was estimated in 272 pregnancies. Paired samples at 34 weeks of gestation and within 48 h before delivery were compared in relation to fetal and maternal blood group and fetal sex. The PAPP-A values were significantly higher both at 34 weeks and near delivery in rhesus-negative bearers. Mothers of male babies had higher PAPP-A values near delivery but not significantly higher at 34 weeks. This supports earlier findings that some placental hormones are higher in male bearers.
Mixtures containing a fixed amount of SP1 alpha, increasing amounts of SP1 beta and vice versa have been measured by rocket immunoelectrophoresis, by enzyme immunoassay and by radioimmunoassay. Both proteins have immunological determinants which react with standard antisera to SP1 and the value obtained for any particular mixture is dependent on the ratio of the proteins. The effect of the ratio on measurement by immunoelectrophoresis is different from that on measurement by enzyme immunoassay or radioimmunoassay. As these two proteins exist together in the blood of pregnant women, Results obtained by the two types of assay cannot be compared. Even with the same method the results will depend on the ratio which varies from subject to subject. It is concluded that until specific measurements for SP1 alpha and SP1 beta are designed, clinical application studies must be viewed with reserve.
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SP 1 alpha and SP 1 beta in pregnancy sera were separated by gel chromatography. When these proteins were subjected to crossed immunoelectrophoresis with an antiserum to non-pregnant human serum in the first dimension gel, SP 1 alpha was absorbed but SP 1 beta was unaffected. Similarly incubation with such an antiserum caused the precipitation of SP 1 alpha but not SP 1 beta. When SP 1 antiserum was absorbed with either SP 1 alpha or SP 1 beta it resulted in the removal of all antibodies to either SP 1 alpha or SP 1 beta.
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The alpha and beta forms of the pregnancy-associated protein, SP1, have been studied in late pregnancy serum and in similar serum after acidification. In both sera only two forms of the protein, SP1 alpha and SP1 beta, could be found; both reacting with antisera against SP1. On gel chromatography these two forms could be separated, with the intermediate effluent containing a varying mixture of both proteins. Immunoelectrophoresis of the effluent fractions from gel chromatography showed rocket shaped immunoprecipitates whose morphology depended on the mixture of SP1 alpha and SP1 beta. Crossed immunoelectrophoresis confirmed that only two proteins could be defined with SP1 antisera; the front running protein having an alpha 2 electrophoretic mobility and a molecular weight of 430,000, while the slower moving component had the electrophoretic mobility of a beta 1 globulin and a molecular weight of 90,000.
A blood protein, pregnancy-associated plasma protein A (PAPP-A), has been isolated from the plasma of pregnant women. An antiserum to this protein has been prepared and used to localize the protein within the placenta by immunofluorescence. It was found to be inconstantly present in the syncytiotrophoblast and intervillous fibrin. Neither antiserum nor antigen exerts a cytotoxic effect on peripheral blood lymphocytes, and neither affected blastogenic responses of lymphocytes to mitogens or in mixed lymphocyte culture reactions.