Biomedical subjects

B Teisner

Publications and source records attributed to B Teisner.

At least 91 records · Page 5Linked to original sources

PubMed1989

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↗

PubMed1989

Circulating levels of placental protein 14 and progesterone following Mifepristone (RU38486) and Gemeprost for termination of first trimester pregnancy.

Ten patients underwent successful termination of first trimester pregnancies with RU38486 (Mifepristone, Roussel Laboratories Ltd., Broadwater Park, Uxbridge, Middlesex, United Kingdom) followed 2 days later by a prostaglandin (Gemeprost, May and Baker Ltd., Dagenham, Essex, United Kingdom) pessary. Four hours after administration of RU38486, the levels of progesterone (P) started to fall and continued to show a gradual decline until the abortion was completed, when a steep fall to follicular phase values was observed. Levels of placental protein 14 remained unaltered until 2 days after RU38486 administration, when levels were increased. The rise in placental protein 14 in association with falling P concentrations suggests that the decidual secretion of placental protein 14 might be independent of P. Fertil Steril 52:66, 1989.

Abortifacient Agents↗

PubMed1989

Localization of foetal antigen 2 (FA-2) in foetal and adult human skin.

Foetal antigen 2 (FA-2) is a connective-tissue-associated antigen isolated from second trimester human amniotic fluid. FA-2 has an alpha-electrophoretic mobility and is a single-chain molecule with a molecular weight of 26 kDa as determined by polyacrylamide gel electrophoresis (PAGE). Using indirect immunofluorescence and the immunoperoxidase technique, FA-2 was found to be in the lamina densa/sublamina densa region of the basement membrane zone (BMZ) in adult as well as in foetal skin. FA-2 was found throughout the dermis in foetal skin, whereas in adult skin it was found to be associated with the BMZ and around the blood vessels, hair follicles and eccrine glands. Intracellular FA-2 antigen was demonstrated in proliferating fibroblasts by the indirect immunoperoxidase technique and immunoelectron microscopy of the fibroblasts revealed staining of the antigen in the cisternae of the rough endoplasmatic reticulum at the trans-side of the Golgi complex as well as in vesicles close to the plasma membranes. FA-2, a hitherto undescribed antigen associated with human BMZ, is probably being synthesized by proliferating fibroblasts.

Adult↗

PubMed1989

Reduced erythrocyte CR1 (CD 35) receptor function and complement opsonization in factor I-deficient patients is restored by plasma infusion.

Erythrocytes (E) from three factor I-deficient patients were investigated for surface-bound complement factors and CR1 (CD 35) expression and function. The E were coated with C4b, C3b, and factor H. Following plasma infusion or in vitro incubation of the patients' E with normal human serum (NHS) or purified factor I, cell-bound C4b and C3b could no longer be detected. The E now expressed C3d, and factor H was unaffected, indicating that factor H was bound to the C3d part of the C3b molecules, providing the co-factor for effective cleavage of E-bound C3b when purified factor I was added. The binding of monoclonal anti-CR1 antibodies (M710) to the patients' E was markedly reduced compared with control E, and was not normalized by treatment with NHS, probably because covalently bound C3d/factor H interfered with the binding of M710. By contrast, the reduced ability of the patients' E-CR1 to bind complement-opsonized immune complexes (IC) was normalized after plasma infusion. This shows that the impaired CR1 function was acquired and emphasizes the importance of performing functional CR1 assays. Complement opsonization of IC for binding to normal E was severely compromised in the patients' sera due to consumption of factor B and C3. After plasma infusion the opsonization capacity of the patients' sera was restored. Thus, two mechanisms of importance for normal clearance of IC were compromised in factor I-deficient patients: (1) the opsonization of IC for binding to E-CR1, and (2) the capacity of E-CR1 to bind opsonized complexes. Both dysfunctions were temporarily corrected by plasma infusion.

Adult↗

PubMed1989

Quantification by ELISA of erythrocyte-bound C3 fragments expressing C3d and/or C3c epitopes in patients with factor I deficiency and with autoimmune diseases.

A sensitive ELISA assay for quantifying erythrocyte (E) bound C3 fragments was developed. The assay employs a double-antibody sandwich technique, using polyclonal anti-C3d or anti-C3c antibodies to quantify C3 fragments, expressing C3d and/or C3c epitopes in washed, detergent-solubilized E. The assay detected 50-120 molecules of C3d per E in healthy individuals. Antigens reacting with anti-C3c antibodies were also detected on E from normal individuals, but the density of C3c-epitopes was 0.9-2.4 times lower than that of C3d-epitopes. In 2 patients with congenital factor I deficiency significantly increased density of E-bound C3c- as well as C3d-antigen was observed. Plasma infusion in one of the patients induced a loss of E-bound C3c-antigens, indicating cleavage of E-bound C3b to iC3b and further to C3c and E-bound C3d. Loss of C3c-antigens also occurred following in vitro treatment with normal human serum of E from one of the patients. Two thirds of 22 patients with systemic lupus erythematosus (SLE) and of 18 patients with rheumatoid arthritis had significantly increased density of E-bound C3d, the highest density being 490 C3d molecules/E in an SLE patient. The density of E-bound C3d correlated with the plasma-C3d concentration, indicating that the coating of E with C3d reflects the degree of complement activation.

Afibrinogenemia↗

PubMed1989

Placental proteins 12 and 14 in pre-eclampsia.

The concentrations of circulating placental protein 12 (PP12) and placental protein 14 (PP14) were measured in 41 patients with pre-eclampsia and in 17 control subjects. The levels of PP12 were significantly elevated in patients with severe preeclampsia, whereas PP14 levels were unaffected. There was a negative correlation between the levels of both PP12 and PP14 and birthweight. PP12 and PP14 appear therefore to have different control mechanisms and, possibly, different cellular origins within the decidua.

Birth Weight↗

PubMed1988

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↗

PubMed1988

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↗

PubMed1988

Enhancing effect of autologous human erythrocytes on generation of C3 cleavage products beyond iC3b.

The in vitro formation of C3d and C3c in fresh normal human serum (NHS) after addition of five different activators of the complement (C) system was studied. Following C-activation in NHS (n = 53) by Sephadex G-200 beads, the conversion of C3 was found to proceed to iC3b with a variable but restricted generation of C3d. Similar results were obtained by use of heat-aggregated IgG, Escherichia coli, zymosan, and cobra venom factor. However, comparing the C3d concentration following activation in the presence and absence of autologous red blood cells (RBC) at 37 degrees C the generated C3d was found to be 2- to 3-fold higher in the presence of RBC after 30, 60, and 210 min. Preincubation of RBC with polyclonal anti-CR1 antibodies resulted in a dose-dependent reduction of the amount of C3d generated. C-activation induced by Sephadex G-200 beads, in the absence of RBC, generated iC3b without a significant production of C3d. After removal of the activator beads, addition of RBC resulted in a decrease of iC3b and a clear increase in the C3c and C3d concentration within 3 h. Western blotting analysis of the C3d produced in the presence of RBC showed that the molecular weight (36 kilodaltons) was similar to that of C3d formed in vivo.

Blotting, Western↗

PubMed1988

Screening for complement deficiencies in patients surviving from epidemic meningococcal disease.

Sera from 132 patients surviving from meningococcal disease during the high-endemic period 1 January 1980 to 31 December 1984 on the Faroe Islands were screened for deficiencies of the complement (C) system by measuring hemolytic complement function in serum. Samples from 12 patients with reduced C function were further investigated by immunochemical quantification of individual C proteins. One patients was identified with C3-deficiency (C3-concentration 6% of normal) due to the presence of C3 nephritic factor (C3NeF) in serum. In addition, eight patients had minor aberrations in one or several complement proteins. It is concluded, that C deficiency is not an important risk factor during epidemics of meningococcal disease. The C3NeF activity could not be absorbed with Neisseria meningitidis group B, type 15, indicating absence of crossreactivity between neisserial antigens and C3NeF.

Complement C3 Nephritic Factor↗

PubMed1988

Three cases of factor I deficiency: the effect of treatment with plasma.

Three patients with congenital factor I deficiency associated with different clinical manifestations are described. Case 1 had one single episode of meningococcal disease, case 2 experienced four episodes of meningococcal disease and several other severe infections, whereas case 3, without known predisposition for infections, died from a subacute immune-complex mediated syndrome, resembling polyarteritis nodosa. Family studies in cases 1 and 2 revealed healthy individuals with factor I concentrations below the lower reference limit, indicating heterozygous carriers. The pedigree analyses were consistent with autosomal codominant inheritance. The estimated minimal frequency of the deficient gene was 0.002. Pedigree analysis was not performed in case 3 but the father and sister was found to be probable heterozygous carriers. Cases 2 and 3 were treated with infusions of freshly frozen plasma (FFP) (40 and 27 ml/kg bodyweight) during acute illness and the immunochemical complement profile was monitored. Following plasma infusion factor I was cleared from the circulation with a half-life of 29-45 h. The plasma infusions induced generation of C3d and C4d, increase in native factor B and C3 concentrations and disappearance of Ba split products. Native C3 and C4 increased to normal concentrations and remained normal till 16 days after the plasma infusions, whereas native factor B decreased to preinfusion levels 8 days after plasma infusion. It is concluded, that congenital factor I deficiency can present with different clinical manifestations and may be more prevalent than hitherto anticipated. Furthermore, infusion of blood products containing small amounts of functional factor I can partly normalize the complement profile, with a more prolonged effect on C3 and C4 than on factor B metabolism.

ABO Blood-Group System↗

PubMed1988

Activation of classical pathway complement in chronic inflammation. Elevated levels of circulating C3d and C4d split products in rheumatoid arthritis and Crohn's disease.

Split products of complement component 3 (C3) and complement component 4 (C4) derived from activation of the alternative and classical complement pathways were measured in untreated outpatients, 20 with Crohn's disease and 19 with rheumatoid arthritis. Elevated levels of the d split product of C4 (C4d) were observed in 12 of 19 patients with rheumatoid arthritis and in 9 of 20 patients with Crohn's disease. Levels of the d split product of C3 (C3d) were increased in 14 of 19 patients with rheumatoid arthritis and in 6 of 20 Crohn's disease patients. The median values of C4d and C3d were significantly increased in both groups of patients. C3d concentrations correlated positively with C4d levels (rs = 0.51-0.56, p less than 0.005). The complement activation was not reflected in reduced plasma levels of native C3 and C4. The data indicate activation of the classical complement pathway in both rheumatoid arthritis and Crohn's disease.

Adolescent↗

PubMed1987

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↗

PubMed1987

Bactericidal capacity against Neisseria meningitidis of normal human serum and sera with functional deficiencies of the third and eight complement factor.

The bactericidal capacity of serum with C3 deficiency secondary to circulating C3 nephritic factor, serum with C8 deficiency and normal human serum were assessed in vitro against Neisseria meningitidis groups A-C. Normal human serum and C8-deficient serum, originating from a 28-year-old male with two episodes of meningococcal meningitis, showed significant bactericidal capacity against meningococci groups A and B. Against group C meningococci the C8-deficient serum revealed significant bactericidal capacity, whereas normal human serum showed no bactericidal effect. Serum with C3 deficiency, obtained from a 16-year-old female with two episodes of meningococaemia, showed no bactericial effect against meningococci groups A-C. Incubation of normal human serum and C8-deficient serum with isolated nephritic factor resulted in C3 depletion and abolished the bactericidal effect.

Adolescent↗

PubMed1987

Heterogeneity of C4d and C3d and their complex formation with serum albumin.

High molecular weight (Mr around 175 KD) forms of C4d and C3d as well as free C4d and C3d (Mr about 40 KD) were demonstrable in normal human serum (NHS). Following in vitro C activation in NHS by delta IgG, the 40 KD C4d component increased markedly. By immunofixation it was shown that the high molecular forms of C4d and C3d reacted with biotinylated anti-human albumin IgG, whereas the 40 KD-free C4d and C3d fragments did not. Furthermore, the incorporation of anti-albumin IgG in the first dimensional gel in crossed immunoelectrophoresis caused retention of the 175 KD C4d component but not of free C4d. The 175 KD C4d had a distinctly higher electrophoretic migration velocity (post-albumin region) than the 40 KD C4d fragment. The C3d-, C4d-serum albumin complexes could not be dissociated by reducing agents (DTT, mercaptoethanol), a non-ionic detergent, or exposure to high and low ionic strength.

Complement Activation↗

PubMed1987

Production of pregnancy-associated plasma protein-A (PAPP-A) by cultured tumour granulosa cells.

Ten ovarian and 2 cervical tumour cell lines were analysed for the production of pregnancy-associated proteins. Pregnancy-associated plasma protein-A (PAPP-A) was detected by radioimmunoassay in culture media of 2 out of 4 (50%) tumour granulosa cell lines (mean = 104 microIU/10(5) cells/24 h) but not in any ovarian (n = 6) or cervical (n = 2) tumour cell lines. By contrast, human chorionic gonadotrophin (hCG), pregnancy specific beta 1-glycoprotein and alpha-fetoprotein (AFP) were not detected in any of the PAPP-A positive media. Only two cell lines produced hCG (58.5 and 25.5 mIU/10(5) cells/24 h). No AFP was produced by any of these 12 cell lines, whereas placental protein 5 was positive in 7. None of these proteins were detected in the culture media of 4 cell lines. In vitro derived PAPP-A was immunologically indistinguishable from either pregnancy or ovarian follicular PAPP-A. All PAPP-A species interacted reversibly with immobilised heparin and were determined by molecular sieve chromatography to have an apparent molecular weight of 820,000 daltons. Cultured tumour granulosa cells specifically synthesised and secreted a large protein which was immunologically and physicochemically indistinguishable from in vivo (pregnancy and ovarian follicular) derived PAPP-A.

Female↗

PubMed1987

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↗

PubMed1987

Immune complexes and complement activation following rupture of intracranial saccular aneurysms.

Circulating immune complexes (CIC) and complement activation (plasma C3d levels) were monitored during a 2-week period in patients with ruptured cerebral aneurysms and also in patients with cerebral hematoma unrelated to saccular aneurysms. Thirteen of 18 aneurysm patients were found to have CIC on admission as compared to three of 21 healthy blood donors (p less than 0.001). The presence of CIC in aneurysm patients was associated with a poor prognosis. Eight of nine patients who developed angiographic vasospasm had CIC on admission compared with one of four without vasospasm. Patients with vasospasm showed a twofold increase in plasma C3d levels at the time when the spasm occurred, whereas no significant changes in the C3d concentration could be demonstrated in aneurysm patients without spasm or in patients with hematoma unrelated to aneurysm rupture. These findings suggest that immunological processes involving complement-activating immune complexes are involved in the pathogenesis of cerebral vasospasm following rupture of saccular aneurysms.

Adult↗