Search PubMed⌕ Search

Biomedical subjects

E Dabelsteen

Publications and source records attributed to E Dabelsteen.

At least 55 records · Page 3Linked to original sources

The distribution of type 1 chain ABH and related histo-blood group antigens in normal cycling human endometrium.

Cycling endometrial tissue was examined immunohistochemically for blood group antigens using a panel of monoclonal antibodies with specificity to type 1 chain carbohydrates. Staining was evaluated against the genetic background (ABO, Lewis, and saliva-secretor status) and the subphase of the menstrual cycle. Expression of type 1 chain antigens in most cases correlated with the genetic background; however, Le(a) and Le(b) antigens were in a few cases demonstrated in endometria with the erythrocyte Le(a-b-) phenotype and Le(b) antigen in erythrocyte Le(a + b-) endometria also. In addition, Le(b) antigen was preferentially expressed in endometria from blood group O individuals. Type 1 chain antigens were, in general, maximally demonstrated in the surface epithelium. Chain 1 A, H, ALe(b), Le(a), and disialosyl-Le(a) (dsLe(a)) determinants were demonstrated only sporadically in functionalis and basalis glands of cycling endometria. Staining for most type 1 chain antigens showed variations that were related to the histomorphology (layer and menstrual phase), and monosialosyl-Le(a) (msLe(a)) seemed to be a marker of secretory differentiation in the endometrium. Our results support the view that synthesis and expression of type 1 chain antigens in human endometrium is influenced by the genetic background and is modulated by the hormonal environment.

ABO Blood-Group System↗

Simple mucin-type carbohydrate antigens in pleomorphic adenomas.

Simple mucin-type carbohydrate structures, T, Tn and sialosyl-Tn, are regarded as general markers of carcinomas in several epithelial tissues as a result of incomplete synthesis with precursor accumulation. The structures have a very limited distribution in normal tissues and secretions, including saliva and salivary glands. The expression of simple mucin-type carbohydrate structures and ABH(O) variants was studied in paraffin-embedded and frozen tissue sections from 37 pleomorphic adenomas with associated normal parotid tissue, using immunohistology and a panel of MAbs with well-defined specificity for T, Tn, sialosyl-Tn, and blood group H and A variants hereof. The immature Tn and sialosyl-Tn antigen structures were expressed in the epithelial ductular structures of the tumors, whereas they were almost absent from normal parotid tissue, indicating aberrant glycosylation with accumulation of precursor structures. Furthermore, the tumors showed loss of A antigen. The prognostic significance of these results is discussed. The modified myoepithelial cells in periductular and solid areas expressed T and sialosyl-T antigens, similar to normal myoepithelial cells and basal cells. Thus these modified MEC seem to have retained their normal simple mucin-type glycosylation pattern, suggesting that T antigen may be used as a marker of MEC in salivary gland tumors.

Adenoma, Pleomorphic↗

Dipeptidyl peptidase IV is sorted to the secretory granules in pancreatic islet A-cells.

Dipeptidyl peptidase IV (DP IV:EC 3.4.14.5) was localized in endocrine cells of pig pancreas by immunohistochemical and enzyme histochemical methods. Immunolight microscopy with both monoclonal and polyclonal antibodies demonstrated DP IV immunoreactivity in cells located in the peripheral part of the islets of Langerhans. The antigen is enzymatically active, as shown by enzyme histochemical analysis with a synthetic DP IV substrate. By immunoelectron microscopy (immunogold labeling), the labeling of DP IV in the islets was associated with the secretory granules of the A-cells, as identified by double labeling using a monoclonal glucagon antibody as the second primary antibody. These results show that DP IV is sorted to secretory granules in the pig pancreatic islet A-cells. Furthermore, this secretory granule enzyme, as opposed to intestinal brush border DP IV, is suggested to be a soluble protein, since the gold particles appear all over the granules and are not specifically associated with the granule membrane.

Animals↗

Expression of the endothelial leukocyte adhesion molecule-1 (ELAM-1) on endothelial cells in experimental gingivitis in humans.

In inflammatory conditions, mediators such as interleukin-1 (IL-1) are released by resident tissue cells as well as by infiltrating inflammatory cells. IL-1 activates endothelial cells causing them to express an adhesion molecule called endothelial leukocyte adhesion molecule-1 (ELAM-1). IL-1 is produced by macrophages, but can also be produced by activated keratinocytes. Here we present data from a study of experimentally induced gingivitis, showing the expression of ELAM-1 on endothelial cells even in tissue with little or only minor signs of clinical or histological inflammation. These results indicate that ELAM-1 is found on endothelial cells of the gingiva early in the course of experimental gingivitis, before overt clinical or histological evidence of inflammation is apparent.

Cell Adhesion↗

Three monoclonal antibodies differentiate human from murine epidermis.

In order to establish a set of epidermal species markers, normal human skin, murine skin and human skin transplanted to nude mice were stained with monoclonal antibodies directed to cell membrane-bound carbohydrates, a basement membrane component and a structure in the cell nucleus. Three epidermal species markers were identified. Two markers stained exclusively human epidermis: LH7.2 detects type VII collagen and stained the basement membrane of human epidermis in unfixed frozen sections, while LP4N stained cell nuclei in human epidermis in methanol-acetone-fixed frozen sections. The third marker, HH14, stained exclusively murine epidermis. HH14 defines the histo-blood group H carbohydrate antigen and stained spinous cell membranes of murine epidermis in both frozen and formalin-fixed sections.

Animals↗

[Cell surface carbohydrates are involved in various biological processes].

All human cells show carbohydrate structures on the surface. New knowledge about the genetic mechanisms for the synthesis of these carbohydrates and the generation of monoclonal antibodies with high specificity shows that carbohydrates are involved in various cell-cell and cell-matrix interactions. For instance, cell surface carbohydrates seem to be important in connection with fertilization, embryonic development, cell differentiation, cancer, adhesion of microorganisms and immunological processes. This new knowledge will increase our understanding of various biological phenomena, and will thus be of value for diagnosis and treatment of various diseases.

Bacterial Adhesion↗

Expression of histo-blood-group-A/B-gene-defined glycosyltransferases in normal and malignant epithelia: correlation with A/B-carbohydrate expression.

Malignant transformation of oral and bladder epithelia is often associated with loss of histo-blood-group-A- and -B-carbohydrate antigens, whereas these antigens, which are absent in normal adult distal colon (but present in fetal colon) reappear in malignant distal colon. In order to gain insight into the genetic basis of the biosynthetic regulation for these changes, we have correlated the expression of the A- and B-carbohydrate antigens with that of the A/B-gene-defined glycosyltransferases in colon, bladder and oral carcinomas by immunohistology. A newly developed anti-A/B-transferase monoclonal antibody (MAb) was used to demonstrate the in situ localization of transferase expression at the individual cell level with correlation to carbohydrate antigen expression, and gave the essential information that the transferase is derived from the ABO gene complex. The reappearance of A- and B-carbohydrate antigens in carcinomas of the distal colon was found to be unrelated to the expression of the A/B-transferase proteins, which were expressed throughout normal adult colon in accordance with previous enzymatic studies. In contrast, the loss of A- and B-carbohydrate antigens in malignant bladder and oral epithelia was accompanied by concordant loss of enzymes.

ABO Blood-Group System↗

The distribution of type-2 chain histo-blood group antigens in normal cycling human endometrium.

The blood group ABO(H) determinants are major allogenic antigens in both erythrocytes and tissue of man. These antigens and related carbohydrates are markers of cellular maturation and differentiation in many epithelial tissues and have recently attracted great interest as tumor-associated antigens. Previous studies of endometrial tissues have indicated that glycosylation in this tissue may be related to hormonal stimulation. We have investigated the immunohistochemical distribution of type-2 chain histo-blood group-related carbohydrates in specimens of normal, cycling endometria obtained from hysterectomies on women with known ABO/Lewis erythrocyte type and saliva secretor status. N-acetyllactosamine and Le(x) were demonstrated to be uninfluenced by the genetic background. A and Ale(y) antigens were exclusively demonstrated in endometria from blood group A individuals, while Le(y) was expressed in endometria from blood group 0 individuals mainly. The precursor N-acetyllactosamine as well as the terminal H, A, and ALe(y) antigens were shown in only a few cells. In contrast, N-acetyllactosamine substituted by sialic acid and/or fucose residues (Le(x), sialosyl-Le(x), Le(y)) were demonstrated in epithelial cells of normal, cycling endometrium, but with both quantitative and qualitative differences in staining relating to the menstrual cycle, indicating that type-2 chain antigens are expressed under both genetic and hormonal influence in human cycling endometrium.

Animals↗

Mucin-type carbohydrates (type 3 chain antigens) in normal cycling human endometrium.

Carbohydrates related to the ABO, Tn, and T blood group systems are markers of cellular differentiation in many epithelial tissues. Using a panel of specific monoclonal antibodies, we have immunohistochemically investigated the expression of mucin-type (type 3 chain ABO-related) antigens in 64 samples of normal cycling endometria of known ABO and Lewis blood type. Tn and T antigens had a highly restricted expression in normal cycling endometrial tissue. The expression of type 3 chain H and A antigens was always compatible with the ABO blood type of the individual and seems to be regulated by the secretor genes, as secretors [Lewis (a-b+)] expressed more A and H type 3 chains than nonsecretors [Lewis (a+b-)]. The expression of type 3 chain H and A, sialyl-Tn and sialyl-T antigens showed cyclic variations in the glandular epithelium of the functionalis, but not of the basalis layer of cycling endometrium. A hormonal regulation of the enzymes involved in blood group-related carbohydrate chain elongation in human endometrium is thus possible and may participate in the specialized secretory process of human cycling endometrium.

ABO Blood-Group System↗

The ELAM-1 ligand sialosyl-Le(X) is present on Langerhans cells isolated from stratified epithelium.

In this study we show the expression of the newly identified carbohydrate ligand, sialosyl-Le(X) on Langerhans cells. The receptor for sialosyl-Le(X) is the endothelial leukocyte adhesion molecule-1 (ELAM-1) present on activated endothelial cells. Using flow cytometry, Langerhans cells were selected due to positivity for an antibody against CD1a and low orthogonal light scatter. The CD1a antigen stained by the OKT6 antibody is considered a maturational marker of Langerhans cells in agreement with the specific labeling of dendritic cells in the epithelium only. Double immunostaining (OKT6/anti-sialosyl-Le(X)) using flow cytometry and immunohistochemistry demonstrated that almost all OKT6-positive cells in normal stratified epithelium expressed sialosyl-Le(X). Conversely, by immunohistochemistry of oral epithelium with acute inflammation, additional dendritic cells negative for OKT6 were found to express sialosyl-Le(X). In addition, sialosyl-Le(X)-positive but not OKT6-positive dendritic cells were found in the submucosa. These findings indicate that the carbohydrate antigen sialosyl-Le(X) is expressed earlier than the CD1a antigen in the maturation of the Langerhans cell lineage. Future studies should aim at investigating the importance of adhesion between sialosyl Le(X) and ELAM-1 in epithelial recruitment of Langerhans cells.

Antigens, CD↗

Molecular biology in oral research.

Molecular biology is a study of molecules that are associated with living organisms. In recent years major advances in molecular biology have had a strong impact on medical and dental science. The new knowledge has led to a change in strategies for controlling dental diseases. In the present review we give a short introduction to some major advances in dental research which are based on molecular biology methods. This includes studies of dental hard tissue formations, mucosal immunity, tissue degradation by proteolytic enzymes, and intercellular communication by surface carbohydrate structures.

Animals↗

Altered expression of ABO (H) carbohydrate antigens is seen in pleomorphic adenomas.

Cell surface carbohydrate antigens show changes in relation to differentiation, maturation and malignant transformation. The expression of type 2 chain ABH carbohydrate structures of the ABO histo-blood group system was investigated in 28 pleomorphic adenomas (PA) and normal parotid glands in order to study possible changes in the glycosylation pattern. The distribution of carbohydrate structures was investigated by immunohistological stainings of formalin-fixed paraffin-embedded material using monoclonal antibodies (MAbs) with well-defined specificity. A strong interindividual variation was found in the normal tissue as well as in the tumors. In normal tissue, acinus and duct cells all expressed elongated carbohydrate structures. The yoepithelial cells did not stain with any of the MAbs investigated. In the PAs, staining was seen in the ductular structures and myoepithelial cells. In contrast to normal tissue, the tumors expressed the short precursor molecule sialylated N-acetyllactosamine. Furthermore, the PAs showed loss of H and A antigens, and a reduced expression of Le(y) compared to normal tissue. The ductular structures as well as the modified myoepithelial cells expressed binary N-acetyllactosamine, which in the normal tissue could only be found in the striated and excretory ducts. Thus our study has shown that aberrant glycosylation is not only a feature of malignant neoplasms but also occurs in pleomorphic adenomas.

ABO Blood-Group System↗

Gliadin uptake in human enterocytes. Differences between coeliac patients in remission and control individuals.

The pepsin trypsin digest of the wheat prolamin gliadin (PT-gliadin) is deleterious to the small intestinal mucosa of coeliac patients. The handling of PT-gliadin by the intestinal epithelium in coeliac patients in remission and control individuals was investigated by in vivo instillation of PT-gliadin. The uptake of PT-gliadin was monitored by immunofluorescence microscopy of intestinal biopsy specimens, using affinity purified PT-gliadin antibodies. Control individuals show weak staining in the apical region of the enterocytes thereby showing an uptake of PT-gliadin. Coeliac patients have a conspicuous fluorescence in relation to the lateral membrane/intercellular space of enterocytes and intense staining intracellularly in the apical region. There is only weak staining in the enterocytes after the instillation was terminated, indicating an intracellular clearance. The study shows that normal enterocytes are able to take up PT-gliadin. The increased uptake in coeliac patients might be of importance for the pathogenesis either by direct toxicity or by presentation to immunocompetent cells. Furthermore, the results are in agreement with the suggestion of a functional alteration in the zonula occludens in the intestinal epithelium of coeliac patients.

Adult↗

The effect of insulin-like growth factor-I and human growth hormone on periodontal ligament fibroblast morphology, growth pattern, DNA synthesis, and receptor binding.

Repopulation of the detached root surface by cells from the periodontal ligament (PDL) is a prerequisite for new attachment formation. Stimulation of PDL-cell growth may therefore serve as an essential method to enhance formation of new attachment. Studies have demonstrated that insulin-like growth factor-I (IGF-I) has a mitogenic effect on fibroblasts originating from various connective tissues and cell-lines. Further, human growth hormone (hGH) is known to regulate the plasma concentration of IGF-I and to mediate cellular biological effects. In the present study we examined the effect of IGF-I and hGH on morphology, growth pattern, and DNA synthesis. The expression of IGF-I and hGH receptors on the surface of cultured PDL fibroblasts is also described. A primary fibroblastic cell line was established from rat PDL tissue, and blind, photographic recordings of morphology and growth pattern, as well as incorporation of [3H]thymidine in cellular DNA, was carried out in the presence and absence of IGF-I and hGH. The presence of specific membrane receptors was investigated by binding of [125I]IGF-I and [125I]hGH. The analysis of photographs showed that IGF-I and hGH had no effect on morphology and growth pattern. Incorporation of 3H-thymidine, however, was increased in a dose-dependent manner by IGF-I, whereas hGH alone or in combination with IGF-I produced no dose-dependent response. Maximum effect (% of control) on DNA synthesis was 176% for IGF-I and 91% for hGH.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Cancer-associated changes in glycosylation of fibronectin. Immunohistological localization of oncofetal fibronectin defined by monoclonal antibodies.

The extracellular matrix adhesion molecule fibronectin exhibits different isoforms derived by alternative splicing as well as recently demonstrated variation in O-glycosylation. Although fibronectin is widely distributed in normal tissues, the individual isoforms have been found to show restricted tissue distribution and association with malignancies. The monoclonal antibody FDC-6 defines a cancer-associated de novo glycosylation of a specific threonine residue in the C-terminal region of the fibronectin molecule termed oncofetal fibronectin. Here we report an immunohistological study of oral squamous cell carcinomas (n = 33), premalignant lesions (n = 15), and normal oral mucosa (n = 10) using the FDC-6 antibody. A selective expression of the oncofetal fibronectin epitope was demonstrated in close relation to the invading carcinoma, whereas no staining was observed in premalignant lesions without epithelial dysplasia, or in normal epithelium. Furthermore, we attempted to identify additional carbohydrate-related epitopes distinguishing fibronectin of human hepatoma cell line HUH-7 from plasma fibronectin. No novel epitopes were identified, as all generated monoclonal antibodies lacking reactivity with plasma fibronectin showed the same specificity as FDC-6. Previous studies have indicated that the de novo glycosylation is induced by a novel transferase activity only found in fetal and carcinoma cell lines, placenta and hepatoma tissues. Here we provide further evidence that a purified UDP-GalNAc:peptide N-acetylgalactosaminyltransferase from normal bovine thymus and human placentae is incapable of utilizing the hexapeptide VTHPGY as a substrate. The results demonstrate that oncofetal fibronectin is highly associated with malignancy, and appears to be induced by expression of a unique glycosyltransferase or modification of the specificity of the normally expressed transferase.

Aged↗

Carbohydrate changes in squamous cell carcinomas.

Cell surface carbohydrates serve as differentiation and development markers characteristic of different cell and tissue types. The expression of these carbohydrate antigens is often significantly altered in tumours, particularly in those arising from epithelial tissues. Analyses of cell surface carbohydrates in stratified epithelium have shown a remarkable variation in glycosylation pattern in relation to terminal differentiation. The carbohydrate expression is altered in squamous cell carcinomas and in premalignant lesions. There is evidence that the expression of certain carbohydrate structures in the deep invasive part of the tumours is correlated with tumour prognosis. The change in carbohydrate expression can at present be explained by the lack of synthesis of specific glycosyltransferases. New evidence suggests that the expression of certain carbohydrate structures may be importance for the formation of metastasies.

Antigens, Tumor-Associated, Carbohydrate↗

Changes in the glycosylation pattern of histo-blood group antigens in benign, premalignant and malignant laryngeal epithelial lesions.

The glycosylation of epithelial cell surface antigens is an indicator of cellular differentiation, and changes in the pattern of expression are seen in different premalignant and malignant epithelial lesions. The purpose of this investigation was to study alterations in the sequential build-up of carbohydrate structures during development of malignancy in laryngeal epithelial lesions. Sixteen routinely processed biopsies showing grave dysplasia/carcinoma in situ were examined. All patients were observed without treatment until malignancy could be affirmed. Five of the patients normalized their laryngeal mucosa spontaneously during observation, whereas 11 progressed invasive carcinoma. Biopsies from normal, hyperplastic and carcinomatous laryngeal epithelium were used as controls. Six monoclonal antibodies (MAbs) related to the ABO- and the TTn blood group systems were used for demonstration of carbohydrate antigens by an indirect immunofluorescent staining method. Benign lesions had a normal sequence of glycosylation. Dysplasias showed accumulation of shorter chains in superficial layers, usually with a patchy dispersion. It is possible by carbohydrate distribution to objectively establish the diagnosis of grave dysplasias/carcinoma in situ, and on the basis of carbohydrate distribution we can divide the lesions into subgroups which are of prognostic relevance.

Antigens, Tumor-Associated, Carbohydrate↗