Biomedical subjects

B Teisner

Publications and source records attributed to B Teisner.

At least 73 records · Page 4Linked to original sources

PubMed1992

Foetal antigen 2 (FA2) in the stromal reaction induced by breast carcinoma.

An indirect immunoperoxidase technique was used to examine the distribution of foetal antigen 2 (FA2), a recently described basement membrane (BM)-associated antigen, in invasive breast carcinoma (n = 34), fibroadenoma (n = 5) and normal breast tissue (n = 5), and to compare its distribution with that of laminin and collagen type IV. In normal breast tissue, FA2 was detected in the intralobular stroma as a broad band around acini and ducts, but was not present in the interlobular stroma. In areas of carcinoma in situ, FA2 was present diffusely around and in close contact with the glandular elements, the staining being more intense than that found around normal glandular structures. Two distinct patterns of FA2 distribution were found in adenocarcinomas of the breast. In the fibroblast reaction type, fibroblast staining dominated, whilst in the stromal reaction type, intense and extensive staining of the surrounding stroma dominated. Significant correlation was found between the degree of fibroblast activity and the degree of anaplasia (p = 0.005). FA2 extracted from breast carcinoma tissue was shown to be immunologically identical to FA2 fractions extracted from second trimester amniotic fluid (AF). The Mr of FA2 isolated from AF was estimated to be 26 kD, whereas the Mr of FA2 extracted from breast carcinoma tissue was slightly higher. The apparent Mr under reducing conditions were higher and three bands ranging from 26 to 29 kD were seen. FA2 was found to be immunologically distinct from collagen types I, III and IV, laminin, fibronectin and fibrinogen. The increased production and widespread distribution of FA2 in breast carcinomas suggest that FA2 is involved in the stromal changes which occur in response to tumour growth and/or invasion.

Adenocarcinoma↗

PubMed1992

Serum levels of fetal antigen 2 in hyperthyroidism and primary hyperparathyroidism.

Serum concentration of fetal antigen 2 (FA2) in patients with hyperthyroidism (n = 18) (median: 12.9 mAU/l; range: 3.2-22.4 mAU/l) was significantly (p < 0.002) higher than in age- and sex-matched healthy controls (median: 4.1 mAU FA2/l; range: 2.4-10.0 mAU FA2/l). Serum FA2 was positively correlated with thyroxine (T4) (Rs = 0.51; p < 0.05), triiodothyronine (T3) (Rs = 0.64; p < 0.01), bone-Gla protein (BGP) (Rs = 0.70; p < 0.01), total alkaline phosphatase (total-AP) (Rs = 0.62; p < 0.01), bone isoenzyme alkaline phosphatase (bone-AP) (Rs = 0.63; p < 0.01), N-terminal procollagen type III (PIIINP) (Rs = 0.65; p < 0.01) and urine OH-proline (OHP) (Rs = 0.79; p < 0.01). In patients with hyperparathyroidism the pretreatment levels of FA2 (n = 8) (median: 17.6 mAU/l; range: 5.2-35.0 mAU/l) were significantly (p < 0.001) higher than those of age- and sex-matched controls (median: 3.7 mAU FA2/l; range: 3.4-9.0 mAU/l). The pretreatment level of FA2 was positively correlated with the parathyroid hormone (PTH) (Rs = 0.80; p < 0.05). Following surgical treatment the serum concentrations of FA2, PTH, and BGP decreased compared to pretreatment levels and the fall in these three parameters revealed parallelism. These data indicate that serum FA2 can be used as a marker in the evaluation of metabolic bone diseases.

Adult↗

PubMed1992

Fetal antigen 2: an amniotic protein identified as the aminopropeptide of the alpha 1 chain of human procollagen type I.

Fetal antigen (FA2) was purified from second trimester human amniotic fluid by immunospecific chromatography, gel filtration and reversed-phase chromatography. Gel filtration revealed two molecular forms of FA2 eluting at volumes corresponding to an M(r) of approximately 100 kDa and 30 kDa. SDS-PAGE analysis gave an M(r) = 27 kDa under reducing and non-reducing conditions for both forms, whereas the exact M(r) determined by mass spectrometry was 14,343 +/- 3 Da. FA2 was N-terminally blocked and after tryptic digestion the amino acid composition and sequences of the peptides showed identity with the aminopropeptide of the alpha 1 chain of human procollagen type I as determined by nucleotide sequences. After oxidative procedures normally employed for radio-iodination (iodogen and chloramine-T), FA2 lost its immunoreactivity. An antigen which cross-reacted with polyclonal rabbit anti-human FA2 was demonstrated in fetal calf serum. Gel filtration with analysis of fractions by inhibition ELISA showed that the bovine homologue was present in the same molecular forms as those in human amniotic fluid, and immunohistochemical analysis with anti-human FA2 showed that its distribution in bovine skin was identical to that of FA2 in human skin. FA2 is a circulating form of the aminopropeptide of the alpha 1 chain of procollagen type I, and this is the first description of its isolation and structural characterization in humans.

Amino Acid Sequence↗

PubMed1992

Tissue localization of conglutinin, a bovine C-type lectin.

The distribution of bovine conglutinin (BK) in sections of frozen bovine tissues was studied by the indirect immunoperoxidase technique using a monospecific rabbit anti-BK antibody. BK was found in the cytoplasma of all hepatocytes, indicating that the liver is a major site of synthesis of BK. In the germinal centres of the spleen, tonsils and lymph nodes the anti-BK staining was restricted to a population of cells with a distribution and morphology characteristic of follicular dendritic cells. Macrophages in lung and thymus, and glia cells in cerebrum, revealed a granular staining reaction within the cytoplasma. Endothelial cells of blood vessels reacted with anti-BK. The intensity of this reaction varied greatly between the organs, the most pronounced reaction being seen in the glomeruli of the kidney, and in the capillary sinusoides of the cortex of the adrenal gland. The high endothelial venules of lymph nodes and tonsils were also stained. These findings suggest that BK, which until now has been described only as a circulating molecule, may exhibit a biological function within the BK-positive tissues.

Adrenal Cortex↗

PubMed1991

Immunohistochemical studies on the localization of fetal antigen 2 (FA2), laminin, and collagen type 4 in basal cell carcinoma.

The localization of fetal antigen 2 (FA2), a recently described basement membrane (BM) associated antigen, was studied by immunohistochemical techniques in 21 basal cell carcinomas (BCC). In both superficial and infiltrating BCC, FA2 was located in a broad diffuse band around the tumor elements and in close contact with the BM. Compared to normal skin, a more extensive distribution of FA2 was seen in BCC. In the infiltrating BCC, FA2 staining was also present in the interstitial stroma between the tumor islands. FA2 was absent in areas with inflammatory cell infiltrates and elastoid degeneration. Epithelial and tumor cells were FA2 negative. The distribution of FA2 was clearly different from that of laminin and collagen type 4. Collagen type 4 and laminin were present as a continuous linear band corresponding to the BM surrounding the tumors. The close contact to the BM and the increased content of FA2 in the reactive stroma around BCC suggest that FA2 is involved in the matrix and/or BM changes taking place during tumor growth and invasion.

Antigens↗

PubMed1991

Fetal antigen 2 in primary and secondary brain tumors.

Immunohistochemical deposition and distribution of fetal antigen 2 (FA2) was examined in normal brain tissue and in primary and metastatic tumors of the brain. In normal brain tissue FA2 was exclusively found linearly around the vessels, along pia and in arachnoidea. A similar localization was seen in primary brain tumors except in gliosarcoma where FA2 was distributed diffusely in the sarcoma region and was absent in the glioma region. In metastatic carcinoma with tumor stroma a diffuse staining reaction was seen in the stroma and with a basement membrane (BM) like staining at the tumor cell/stroma interface. Intracytoplasmic FA2 staining of the tumor cells was seen in areas without tumor stroma. In metastatic melanoma a BM like FA2 staining was seen around and between individual tumor cells. The staining patterns seen in the metastatic tumors were in accordance with that of the corresponding primary tumors.

Biomarkers, Tumor↗

PubMed1990

Immunohistochemical analysis of the binding of human IgM to secretory component present in normal adult colon epithelia, but not in colon cancer and fetal colon epithelia.

We have analysed the binding of human IgM to fetal, normal adult and malignant colo-rectal tissues. Using an indirect immunoperoxidase technique on sections of frozen tissues human IgM binds to all normal adult colo-rectal epithelia (n = 15) tested. By contrast, 9 out of 25 colo-rectal adenocarcinomas were negative, and in the remaining 16 the staining reaction varied from staining of all the cancer areas to focal staining of a few areas. Human IgM did not bind to 14 samples of fetal intestinal epithelium (gestational age of 6-14 weeks). The binding of IgM was found to be mediated by secretory component (SC) as anti-SC antibody (anti-SC) showed a similar staining pattern as IgM and the IgM binding could be blocked by anti-SC. SC was also demonstrated in glandular epithelia of sections of all normal breast epithelia but only in 10 out of 15 breast adenocarcinomas. The loss of IgM binding and SC could not be correlated to the morphology of the adenocarcinomas. The observations on fetal, normal adult and malignant tissue suggest that IgM binding and SC may be gradually lost during dedifferentiation of normal cells, to malignant colo-rectal or breast epithelia.

Adenocarcinoma↗

PubMed1990

A baboon model for pregnancy-associated antigens (PAPP-A, PP5, PP14).

By radioimmunoassays established on human derived antigens, PAPP-A, PP5 and PP14 immunoreactivity was detected in placental extracts and blood of pregnant baboons. None of the serial dilution curves suggested parallelism between respective human and baboon samples. Based on slopes of regressed logit-log transformed binding data, PAPP-A demonstrated the greatest degree of interspecies immunological crossreactivity. PP14 showed the least conservation of antigenic determinants. Physicochemical characterization on heparin, zinc chelate and bovine thrombin affinity matrices could not distinguish human from baboon-derived antigens. As in the human, baboon PAPP-A and PP5 were not detected in blood of male or non-pregnant animals. PP14 was detected in baboon follicular fluid, and only PP5 immunoreactivity was measured in culture media of baboon embryos. Of the three antigens, PAPP-A was detected in pregnant baboons at about 61 days gestation, that is, 4 weeks before PP5 and PP14. With the exception of PP14 which attained peak concentration at 118 days of pregnancy, PAPP-A and PP5 concentrations were greatest at term. In conjunction with physicochemical and immunological criteria, these physiological kinetics clearly support a role for developing a baboon model to serve for further studies into feto-maternal signals, particularly antigens such as PAPP-A and PP5.

Animals↗

PubMed1990

Circulating levels of placental protein 12 in ectopic pregnancy.

Maternal serum placental protein 12 (PP12) was measured at the time of presentation in 33 women with a histologically confirmed diagnosis of ectopic pregnancy [tubal pregnancy (n = 29), tubal pregnancy with a live fetus (n = 2), cornual pregnancy (n = 1) and ovarian pregnancy (n = 1)]. All but four of the 33 patients had PP12 measurements within the reference range. Two women had circulating PP12 levels above the 90th centile of the normal range, at 7 and 8 weeks gestation, respectively. One of these had a live ectopic gestation and the other patient conceived after in vitro fertilization. Two remaining patients (one each with a cornual and tubal pregnancy) at 11 and 12 weeks, respectively had levels below the 10th centile of the normal range. It is concluded that regardless of the implantation site, ectopic pregnancy is not associated with depressed maternal PP12 levels, suggesting that the decidual synthesis of this protein is independent of the intimate relationship between decidua and trophoblast.

Decidua↗

PubMed1990

Identification of specific serum proteins synthesized de novo by monolayer cultures of glandular cells of gestational endometrium.

Monolayer cell cultures (n = 3) of glandular epithelium of gestational endometrium obtained from three apparently healthy women undergoing elective termination of pregnancy (7-9 weeks gestation) were established. De novo synthesis of eight serum proteins (albumin, alpha 1-antitrypsin, ceruloplasmin, beta-lipoprotein, alpha 2-macroglobulin, fibronectin and complement factors C3 and C4) was demonstrated by the incorporation of radiolabelled substrate ([35S]methionine) employing autoradiography (AR) in combination with crossed immunoelectrophoresis (XIE), referred to as ARXIE, and line immunoelectrophoresis (LIE), referred to as ARLIE. By contrast, there was no evidence for de novo synthesis of IgA, haptoglobin and orosomucoid. Our findings suggest that the gestational endometrium may contribute to the production of several proteins considered to be synthesized and secreted mainly by the liver and reticulo-endothelial system. The simple techniques used here to identify the de novo synthesis of human serum proteins could be applied to investigate protein synthesis by a wide range of tissues and cells.

Blood Proteins↗

PubMed1990

A biochemical test for the direct assessment of endometrial function: measurement of the major secretory endometrial protein PP14 in serum during menstruation in relation to ovulation and luteal function.

Circulating PP14 was measured by radioimmunoassay in ovulating (n = 12) and anovulatory (n = 3) women throughout the menstrual cycle, the highest levels of serum PP14 being seen during menstruation and in the late luteal phase in ovulating women. Mean serum PP14 levels on days 1-7 and 24-28 of the menstrual cycle were significantly higher than those observed from days 8 to 23 (P less than 0.0005 and P = 0.005 respectively). There was no difference in mean PP14 levels observed in the menstrual and luteal phase. By contrast, serum PP14 was rarely detected in anovulatory cycles. During the luteal phase, mean serum PP14 levels were apparently not related to serum progesterone levels. However, mean PP14 levels during the menstrual phase were significantly higher in the group of women with the highest progesterone production (Pmax greater than 39 nmol/l) (P less than 0.002) in comparison with levels seen in ovulating women with lower progesterone production (Pmax less than 32 nmol/l). These findings suggest that the synthesis and secretion of PP14 is influenced by ovulation and luteal function. Serum PP14 measurements may provide useful information about the endometrium in relation to fertility, and that these measurements during the menstrual cycle may distinguish between ovulatory and anovulatory cycles.

Adult↗

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↗