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Biomedical subjects

B Teisner

Publications and source records attributed to B Teisner.

At least 127 records · Page 7Linked to original sources

Placental function studies in low birth weight infants with and without dysmaturity.

Maternal blood levels of human placental lactogen and schwangerschaftsprotein 1 were measured in 51 women who delivered a growth-retarded infant. The levels were substantially lower in the 27 women whose infants were clinically dysmature than in the 24 women whose infants were small but of normal appearance. About one-half (44%) the cases of true dysmaturity had abnormal concentrations of human placental lactogen (less than 4 mg/L), whereas none of the small but normal group had values in this zone. It is concluded that biochemical tests of this type reflect dynamic aspects of placental function and not simply the overall size of the fetus and placenta.

Female↗

Preparation of antibodies against the fourth complement component (C4) and development of a direct electroimmunoassay for quantification of C4d.

The specificity of several preparations of antihuman C4 antibodies were examined by crossed immunoelectrophoresis. Two antibody preparations with anti-C4c and anti-"total" C4 reactivity respectively were prepared by immunoadsorption procedures and defined by comparison with reference antibodies of known specificity. These two antibody preparations were used in the development of a rocket immunoelectrophoresis with an intermediate gel for specific and direct quantification of C4d. This method permits the selective quantification of activation of the classical complement pathway as opposed to the alternative pathway activation.

Antibodies↗

The third complement factor (C3) and its in vivo cleavage products: interaction with lectins and precipitation with polyethylene glycol.

Five molecular forms of C3 expressing D but not C epitopes were identified following in vivo activation of the complement system. Examination of concanavalin A (Con-A) reactivity in crossed immunoelectrophoresis revealed that native C3, C3c and the beta mobile form 4 of C3d were completely precipitated by 100 micrograms Con A/cm2. The alpha-1 mobile form 1 of C3d did not interact with Con A, whereas the alpha-2 mobile forms 2 and 3 were retarded in electrophoretic migration by Con A. Native C3, C3c, and forms 4 and 5 of C3d were precipitated by 12% (w/v) polyethylene glycol (PEG). Form 1 of C3d was soluble in these PEG concentrations, whereas forms 2 and 3 were partially precipitated.

Antigen-Antibody Reactions↗

Complement activation during cardiopulmonary bypass by heparin-protamine interaction.

Circulating concentrations of split products of the third complement factor (C3c and C3d) were measured in five patients before, during and after cardiopulmonary bypass. In all patients, C3d concentrations increased significantly in samples obtained after the administration of protamine sulphate. Similarly, circulating C3c was seen only in those samples obtained immediately after protamine administration. In vitro experiments demonstrated that activation of the complement system was attributable to the heparin-protamine complex, and was dose-dependent. The activation of complement was not associated with any clinically detectable adverse effects.

Adult↗

Factor I deficiency and C3 nephritic factor: immunochemical findings and association with Neisseria meningitidis infection in two patients.

The complement system was examined in two patients with systemic Neisseria meningitidis infections, both of whom had reduced or nondetectable CH50 as analysed by both pathways. C3 measured by conventional technique revealed 19% anti-C3c-reactive protein in the plasma of patient 1 and 3% in patient 2. Patient 1 had circulating C3b but no detectable C3c, C3d, or C4d, whereas patient 2 had normal levels of C3c and C4d and strongly elevated levels of C3d. Factor B analysis revealed no demonstrable native factor B and small amounts of Bb in patient 1 and normal concentration of native factor B plus trace amounts of Bb in patient 2. The depletion of C3 in both patients was due to uncontrolled activation caused by complete factor I deficiency (patient 1) and circulating C3 nephritic factor (patient 2). Both parents of patient 1 had factor I concentrations below (mean-2 SD) that seen in normal healthy individuals (n = 20). Circulating immune complexes (IC) were demonstrated in patient 1 only, whereas serum from both patients had strongly reduced capacity to solubilize preformed IC.

Adolescent↗

Placental protein measurements in complicated pregnancies. I. Intrauterine growth retardation.

Maternal serum levels of human placental lactogen (hPL), schwangerschaftsprotein 1 (SP1) and pregnancy-associated plasma protein A (PAPP-A) were measured serially throughout pregnancy in 753 women who had a normal pregnancy when recruited during the second trimester. Thirty-three women were delivered of an infant with low birth-weight and with phenotypic features of intrauterine growth retardation (IUGR). The predictive value of an abnormal (less than 10th centile) hPL result (PVpos) in the identification of IUGR was between 28 and 32%, the sensitivity (36-54%) being greatest at 35 weeks gestation. The predictive value of a normal result (PVneg) was 87-96% at various stages of pregnancy, also greatest at 35 weeks gestation. For SP1, the sensitivity and predictive values were also greatest at 35 weeks gestation (PVpos, 20%; sensitivity, 32%; PVneg, 95%), but for PAPP-A these values were considerably less at all gestations. The trends in levels of hPL, SP1 and PAPP-A observed in individual patients with IUGR were not apparently related to any clinically recognizable feature of the pregnancy or the degree of fetal compromise, irrespective of whether the levels were within or outside the 80% confidence limits of the normal range or whether the levels fell from within the normal range. These data suggest that maternal hPL measurements are superior in the identification of IUGR in samples obtained at 30-35 weeks gestation.

Female↗

Placental protein measurements in complicated pregnancies. II. Pregnancy-related hypertension.

Maternal serum levels of pregnancy-associated plasma protein A (PAPP-A), human placental lactogen (hPL) and schwangerschafts-protein 1 (SP1) were measured serially during the second and third trimesters in 753 women with a normal pregnancy when recruited during the second trimester. Thirty-seven pregnancies were complicated by pregnancy-related hypertension after 28 weeks gestation. Maternal levels of PAPP-A and SP1, and trends of levels in individual patients, could generally not be distinguished from those seen in patients with a normal pregnancy, and were unrelated to the time of onset of the disease, its severity or the occurrence of other complications with one exception, in which decreased levels of SP1 and hPL were seen. Mean levels of hPL were significantly lower (P less than 0.05) at 35 weeks gestation. These data suggest that the measurement of the placental proteins examined here is of no value in the prediction of occurrence of pregnancy-related hypertension.

Female↗

Placental protein measurements in complicated pregnancies. III. Premature labour.

Maternal serum levels of pregnancy-associated plasma protein. A (PAPP-A), human placental lactogen (hPL) and schwangerschafts-protein 1 (SP1) were measured serially during second and third trimester in 753 women with normal pregnancy when they were recruited to the study. In 24 women spontaneous premature labour occurred before 37 completed weeks and these women had significantly lower mean levels of serum SP1 at 29-31 weeks and at 33-34 weeks gestations but similar mean levels of serum PAPP-A and hPL at all gestations compared with corresponding values in normal pregnancy. The predictive value of an abnormal SP1 result was 5.2% at 29-31 weeks and 10.3% at 33-34 weeks. Furthermore, trends of levels of the three placental proteins in individual patients were similar to those seen in normal pregnancy, and the trends were unrelated to the occurrence of other complications and the time of onset of labour. This study suggests that measurements of the three placental proteins are unlikely to be of any value in the prediction of spontaneous premature labour.

Female↗

C3 nephritic factor in a patient with recurrent Neisseria meningitidis infections.

A 15-year-old female experienced two systemic infections with N.meningitidis (group C and B) within a two months period. Classical as well as alternative pathway CH50 determinations on the patients serum showed no lysis. All individual complement factor concentrations, except for C3, were found to be within the reference area. Crossed immunoelectrophoretic analysis of C3 revealed no demonstrable native C3. The patient had normal levels of C3c and a markedly elevated C3d concentration. Serum from the patient was found to convert all native C3 in normal sera within 10 minutes at 37 degrees C. The active converting principle, present in the IgG fraction activated C3 in C4-depleted serum, and had a dose dependent stabilizing effect on the EA-C3bBb complex. The isolated factor showing the characteristics of C3 nephritic factor (C3 NeF), was unchanged in the patients serum over a ten months observation period. Circulating immune complexes (IC) could not be demonstrated by a C1q-dependent assay but the patients capacity to solubilize preformed IC in vitro was virtually abolished. The patient had no signs of renal disease or lipodystrophy.

Adolescent↗

Charge and size heterogeneity of C3d following in vivo and in vitro activation of the complement system.

Split products of the third complement factor (C3) expressing D but not C epitopes (C3d) were analyzed by crossed immunoelectrophoresis and size chromatography. Four molecular forms (termed 1, 2, 3, and 4 from the anodic side) were identified. The precipitation pattern of C3d in serum following acute in vivo activation was similar to the patterns observed using in vitro activation by MgCl2, zymosan, Escherichia coli, and delta IgG. These patterns were different from those observed in normal human serum and serum from a patient suffering from systemic lupus erythematosus. The molecular weights of forms 1 and 4 were approximately 170,000 daltons and those of forms 2 and 3 approximately 40,000 daltons.

Complement Activation↗

Induction of murine alpha-foetoprotein synthesis by oestradiol.

The synthesis of murine alpha-foetoprotein (m-AFP) was induced in 43 out of 47 adult mice of both sexes by sc administration of 100 micrograms oestradiol-17 beta every second day. The m-AFP serum levels of the oestrogen treated male and female mice were 7 and 17%, respectively, of the levels in mice during late pregnancy. Immunohistochemical examination of liver tissue revealed the intracellular presence of m-AFP in less than 0.5% of the hepatocytes scattered throughout the liver of the oestrogen treated mice.

Animals↗

Development and clinical application of electroimmunoassays for the direct quantification of the complement C3 split products C3c and C3d.

The present report describes the development of electroimmunoassays for the direct quantification of C3d and C3c, split products of the third complement factor (C3). Both methods were developed as rocket immunoelectrophoreses, using two antibody preparations with specificities against the C and D epitopes on C3. A stable calibrator preparation for C3c and C3d was produced by autolytic cleavage of C3. Investigations of patients with anaphylactic reactions or chronic immunological disorders showed that quantification of C3c and C3d in plasma by these methods reflected the degree and rate of complement activation. C3d determination was found to be the most sensitive and reliable indicator of C activation, both during acute and chronic activation since C3c is eliminated considerably faster from the circulation than C3d (estimated half lives of 2 h and 4 h, respectively). Treatment of rheumatoid arthritis patients with prednisolone caused a prompt decrease of plasma C3d values, indicating that the clinical effect may be due to inhibition of complement activation.

Antibody Specificity↗

Lack of effect of tranexamic acid on rheumatoid arthritis.

In a double-blind controlled study on 45 rheumatoid arthritis patients, no effect of tranexamic acid (Cyklocapron, 4.5 g per day for 6 weeks) was found in terms of subjective or objective parameters of disease activity. Tranexamic acid did not reduce complement activation, measured by plasma concentrations of the complement C3 split product C3d. Immune complex concentrations in serum were also unaffected. We conclude that plasmin inhibitors do not reduce immune complex mediated complement activation, and they should not be used for treatment of rheumatoid arthritis.

Adult↗

Pregnancy-associated plasma protein A in the prediction of early pregnancy failure.

Maternal circulating pregnancy-associated plasma protein A (PAPP-A) was measured in 51 patients with vaginal bleeding in the first half of pregnancy. Concentrations of PAPP-A were consistently lower in pregnancies which failed. In the prediction of early pregnancy failure, the predictive value of depressed maternal PAPP-A levels was 58%, the sensitivity was 91.9%, and specificity was 95.1%. These results compared favorably with other biochemical tests of placental function. However, if fetal life was demonstrated ultrasonically, depressed levels of PAPP-A substantially differentiated between those pregnancies which continued normally and those which did not, suggesting that PAPP-A estimations would be of clinical value in cases previously beyond the reach of any diagnostic measure.

Abortion, Threatened↗

Pregnancy-associated plasma protein A: a possible marker in the classification and prenatal diagnosis of Cornelia de Lange syndrome.

The concentration of human platelet lactogen (hPL), pregnancy specific beta-1 glycoprotein (SP-1) and pregnancy-associated plasma protein A (PAPP-A) were analysed in consecutive serum samples from a patient who gave birth to a child with Cornelia de Lange syndrome. HPL and SP-1 were present in normal concentrations from week 20 to week 35 of gestation whereas PAPP-A could not be detected in any of the samples examined. Immunohistochemical examination of two placentae from Cornelia de Lange syndrome revealed normal localization of hPL and SP-1 but the absence of PAPP-A from the syncytiotrophoblast. The significance of association between Cornelia de Lange syndrome and compromised synthesis of PAPP-A is discussed.

Adult↗