Biomedical subjects

B Teisner

Publications and source records attributed to B Teisner.

At least 37 records · Page 2Linked to original sources

PubMed1990

Zinc ions inhibit factor I-mediated release of CR1-bound immune complexes and degradation of cell-bound complement factors C3b and C4b.

ZnCl2 exerted a dose-dependent inhibition of citrate-phosphate-dextrose (CPD) plasma-induced release of 125I-labelled BSA-anti-BSA immune complexes (IC) bound to complement receptor type 1 (CR1, CD35) in human whole blood. Maximal inhibition was observed at 10 mM of ZnCl2. Furthermore, the release of IC bound to erythrocyte (E)-CR1 by purified factor I, factor I-deficient serum plus purified factor I, or normal human serum was reduced by approximately 90%, 64%, and 52%, respectively, in the presence of 10 mM ZnCl2. The effect of ZnCl2 on factor I-mediated degradation of cell-bound C3b/C4b was also investigated employing CPD blood or E from a factor I-deficient donor. These cells expressed covalently bound C3b and C4b as demonstrated by a simple agglutination technique. Upon incubation of CPD whole blood with purified factor I, or of E with purified factor I or normal CPD plasma, the C-fragments were cleaved and the cells were no longer agglutinated by antibodies to C3c and C4c. The presence of ZnCl2 prevented this factor I-mediated degradation of C3b and C4b, as evidenced by the unaffected agglutination of the cells by the antibodies. We conclude that ZnCl2 inhibited factor I activity since: (1) release of complement-preopsonized IC from E-CR1 by purified factor I was markedly inhibited (90%) in the presence of ZnCl2, (2) preincubation of the cells with ZnCl2 caused only a moderate inhibition (32-38%) of the IC release, and (3) degradation by purified factor I of covalently cell-bound C3b and C4b was abrogated in the presence of 10 mM ZnCl2.

Animals↗

PubMed1990

Infants and children with cow milk allergy/intolerance. Investigation of the uptake of cow milk protein and activation of the complement system.

Seventeen children with challenge-verified cow milk allergy/intolerance (CMAI), age 3-78 months, median 12 months, were re-challenged with cow milk in increasing doses. All subjects developed symptoms, such as bronchospasm, rhinitis, diarrhoea, erythema or eczema. Blood samples were taken before and up to 24 h after the start of the challenge. The cow milk protein beta-lactoglobulin (BLG) was determined in serum with ELISA (lower detection limit 0.3 micrograms/l). BLG was detectable in five children at low levels (below 2 micrograms/l). Analysis of the size distribution of the BLG by size exclusion chromatography indicated immunoreactive material as small aggregates. Plasma samples were analysed by electroimmunoassay for complement factor split product C3d, which was not demonstrable above background values in any of the cases. CMAI in infants and children may not be related to systemic activation of the complement system and may be elicited without considerable amounts of immunoreactive BLG in the circulation.

Animals↗

PubMed1990

Immune complex binding to erythrocyte-CR1 (CD 35), CR1 expression and levels of erythrocyte-fixed C3 fragments in SLE outpatients.

Erythrocytes (E) from a cross-sectional group of 22 outpatients with systemic lupus erythematosus (SLE) and/or mixed connective tissue disease (MCTD), the majority without active disease (n = 14), were analyzed for CR1 antigen expression and capacity to bind complement opsonized, radiolabelled immune complexes (IC). Furthermore, E-bound C3 fragments and the plasma C3d concentration were determined. E-bound C3b/iC3b fragments were not elevated in patients with SLE, whereas E from 11 out of 22 SLE patients had increased C3d levels which correlated with the plasma C3d concentration (Rs 0.73, p less than 0.001). E-fixed C3d fragments did not affect the binding of Mab or preopsonized IC to E-CR1 and were not correlated with disease activity or medical treatment. Antigen expression of E-CR1 measured by ELISA or agglutination showed positive correlation with the IC binding capacity of E-CR1 (Rs 0.92 and 0.72 respectively, p less than 001). The IC binding capacity of E-CR1 from SLE patients was significantly reduced (p less than 0.005), whereas the antigen expression of CR1 (ELISA) on E from the patients did not differ from that of E from healthy donors (p greater than 0.1). E-CR1 antigen was measured by Mab reacting with an epitope outside the IC-binding site of E-CR1. E-CR1 antigen expression or IC binding showed no correlation either with disease activity or prednisolone treatment. However, 4 og 5 patients with MCTD and 4 of 5 patients receiving Imurel were found to have low E-CR1 expression and capacity to bind IC. Thus, measurement of antigenic E-CR1 in a cross-sectional group of SLE outpatients by use of Mab reacting with an epitope outside the ligand-binding region of CR1 did not reveal a significantly reduced CR1 expression. However, an assay for CR1-mediated IC binding showed a clearly reduced E-CR1 function.

Antigen-Antibody Complex↗

PubMed1990

De novo synthesis of placental protein-14 (PP14) and not PP12 by monolayer cultures of glandular epithelium of gestational endometrium.

Nine monolayer cell cultures of glandular epithelium from gestational endometrium were established from six apparently healthy women undergoing elective termination of pregnancy (7-11 weeks gestation). Radiolabel incorporation studies showed increasing incorporation of [35S]methionine into proteins present in supernatant and cytosol fractions over 48 h. The secreted proteins represented approximately 20% of the total incorporation of methionine into cytosolic proteins. De novo synthesis and secretion of placental protein-14 (PP14) and not PP12 was identified by a novel combination of line immunoelectrophoresis and autoradiography. All monolayer cultures demonstrated the presence of radiolabeled PP14, but not PP12, in the culture supernatants. These observations suggest that the glandular epithelial cells are the major site of synthesis and secretion of PP14 in human gestational endometrium.

Antibodies↗

PubMed1990

Characterization of pregnancy-associated plasma protein-A: comparison with alpha 2-macroglobulin.

Pregnancy-associated plasma protein-A (PAPP-A), like alpha 2-macroglobulin (alpha 2M), is a large protein with homotetrameric molecular conformation. Each monomer has Mr 205 kDa. Total carbohydrate content of PAPP-A (19.4%) exceeded that of alpha 2M (8.6%). In addition to glucose (9.4%), fucose (3.1%), mannose (2.3%) and galactose (0.8%), PAPP-A contained glucuronic acid (3.8%). The amino acid composition of PAPP-A differed most significantly from alpha 2M, in the content of glutamate, glycine and lysine. Although the peptide core of both proteins were of similar size, the difference in size, of native molecules was due to the carbohydrate moiety. Whereas alpha 2M monomer was autolytically cleaved into two smaller non-identical subunits (Mr 128 and 65 kDa), no such breakdown products were observed with PAPP-A. Unlike alpha 2M, PAPP-A is not a broad spectrum protease inhibitor. Both proteins inhibited human granulocyte elastase (HGE) in a dose dependent relationship, with PAPP-A (Ki 0.2 x 10(-6) M) being a more potent inhibitor than alpha 2M (Ki 1.02 x 10(-6) M). Since PAPP-A lacked internal thiolester groups, the mechanism of HGE inhibition was unlikely to be entrapment, as defined for alpha 2M. Inhibition kinetics of HGE for PAPP-A (noncompetitive inhibitor) and alpha 2M (uncompetitive inhibitor) were distinct. Thus, these findings do not support the tenet of a common ancestral protein for PAPP-A and alpha 2M.

Amino Acid Sequence↗

PubMed1990

Metabolism of C3 and factor B in patients with congenital factor I deficiency.

The metabolism of complement factor B and C3 was analyzed in three previously described patients with congenital deficiency of factor I (C3b/C4b inactivator). Samples taken at steady state contained elevated levels of Ba and Bb, whereas native factor B was not detectable. Following plasma infusion in two of the patients Ba was rapidly cleared (within 8-12 hr) from the circulation and native factor B increased transiently, reaching normal levels within 22-24 hr. In parallel with the increase in Ba, factor B decreased during the following days, reaching preinfusion level after seven days. This was in contrast to a continued increase in C3 concentration, which was still within the normal range 15 days after infusion, despite the presence of only trace amounts of native B. In vitro complement activation experiments, employing purified C3Nef IgG as alternative pathway activator and aggregated IgG as classical pathway activator, were performed on selected serum samples (base-line, 12 hr and 15 days postinfusion samples) from the plasma infusion series. It was demonstrated that (a) C3Nef could not induce alternative pathway C3-conversion in factor B depleted samples and (b) C3-degradation by CP-activation could still occur in B-depleted samples, although at a much slower rate compared to normal human serum. These results may partly explain the difference in kinetics of factor B and C3 metabolism seen after plasma infusion in patients with factor I deficiency.(ABSTRACT TRUNCATED AT 250 WORDS)

Autoantibodies↗

PubMed1989

Circulating levels of placental protein 12 in complications of first trimester pregnancy.

Serum placental protein 12 (PP12) levels were determined in 34 women with threatened miscarriage in whom a diagnosis of anembryonic pregnancy (n = 19), missed abortion (n = 4), complete or incomplete abortion (n = 5), hydatidiform mole (n = 1) and subsequent abortion of a live fetus (n = 5), was made ultrasonically and confirmed by histological examination. Twenty-four of the 34 patients had one or more levels between the 10th and 90th centiles of the reference range. In 7 of the 19 patients (37%) with anembryonic pregnancy and in 3 of the 4 patients (75%) with a missed abortion, PP12 levels were markedly elevated. However, in cases where serial measurements were available (n = 6), PP12 levels were seen to fall in all cases. It is concluded that pregnancies that have failed or will subsequently fail in the first or second trimester are not associated with depressed maternal PP12 levels, suggesting that the decidual synthesis of this protein is independent of the presence or viability of the fetus.

Abortion, Spontaneous↗

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↗