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E Dabelsteen

Publications and source records attributed to E Dabelsteen.

At least 19 recordsLinked to original sources
PubMed1992

[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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

Carbohydrates of the cell surface: molecular aspects of glycosyltransferases and their genes.

With the development of monospecific antibodies to transferase proteins as well as cDNA probes to cloned transferase genes, the study of glycosylation and its regulatory mechanisms holds great promise for the future. Here we provide a brief overview of the present knowledge of glycosyltransferases, their primary structure, cellular topography, regulation, and the basis of the genetic polymorphisms as revealed by blood groups.

Animals↗
PubMed1991

Prognostic value of Rhesus blood groups in oral squamous cell carcinomas.

In the current study of the prognosis of all patients (N equals 70) with squamous cell carcinomas (SCC) of floor of mouth in Norway during the period 1963 to 1972, the authors found that patients with Rhesus (Rh) (D)-negative blood group had significantly poorer prognosis (mean 5-year survival, 8%) than patients with Rh (D)-positive blood group (5-year survival, 30%) (P equals 0.04). This extends the authors' previous observations in another group of oral cancer patients. The authors do not know the explanation for this association. However, the Rh gene locus is located on the short arm of chromosome 1 which reportedly has shown rearrangements in some head and neck SCC and other human neoplasms. The authors therefore speculate that the Rh gene locus may be linked with chromosome 1 changes of importance for the progression of oral SCC.

Analysis of Variance↗
PubMed1991

A multivariate study of the prognosis of oral squamous cell carcinomas. Are blood group and hemoglobin new prognostic factors?

Because blood groups and hemoglobin concentration have been associated with the risk of the development of some cancers, this study evaluated the significance of ABO and Rhesus blood groups and hemoglobin concentration as prognostic factors in oral squamous cell carcinoma (SCC). The authors examined all registered primary SCC of buccal and maxillary alveolar mucosa in the Norwegian population between 1963 and 1972. The biopsy specimens from these patients were reevaluated and borderline cases excluded. The remaining 111 cases were included in the study, and features recorded on first admission were included in the survival analyses. ABO and Rhesus blood groups were found in 99 of these patients. Multivariate survival analysis showed that tumor size, hemoglobin concentration, stage, and Rhesus blood groups were significant prognostic factors, but sex, age, treatment, duration of symptoms, ABO blood groups, and clinical appearance of the tumors were not. The prognostic value of Rhesus blood groups and hemoglobin concentration has not been previously reported for oral SCC.

ABO Blood-Group System↗
PubMed1991

Loss of expression of blood group antigen H is associated with cellular invasion and spread of oral squamous cell carcinomas.

Membrane-bound carbohydrates may influence the metastatic behavior of cancer cells. Forty-two squamous cell carcinomas (SCC) of the buccal and maxillary alveolar mucosa were studied retrospectively using a monoclonal antibody (BE2) that reacts with blood group H (type 2 chain) structure. H-antigen staining within the entire tumor did not correlate with the stage of the tumor, i.e., spread of the tumors. However, loss of staining within the most invasive sites of the tumors correlated significantly with the stage of tumor development and histologic grade of malignancy. These findings support the view that features relating to the cells of deeper parts of the carcinomas are very important for the clinical behavior of the tumors, and that loss of H-antigen expression is related to the stage of tumor and invasion of carcinoma cells.

ABO Blood-Group System↗
PubMed1991

Simple mucin-type carbohydrates in oral stratified squamous and salivary gland epithelia.

Simple mucin-type carbohydrate antigens, T, Tn, and sialosyl-Tn, have been found to be good markers of malignant transformation in several epithelial tissues as a result of incomplete synthesis with precursor accumulation. The T, Tn, and sialosyl-Tn antigens represent the initial, most immature glycosylation of serine and threonine amino acids of proteins. In normal adult cells these structures are generally masked by addition of further saccharides to form more complex structures. We analyzed simple mucin-type carbohydrates in human labial stratified squamous and minor salivary gland epithelia in order to define the glycosylation pattern in normal cells in relation to epithelial differentiation and maturation. A panel of monoclonal antibodies with well-characterized specificity for T, Tn, sialosyl-Tn and the histo-blood group H and A variants hereof were used in immunohistology of sections from 30 individuals with known ABO, Lewis, and secretor status. In stratified epithelium the sialylated T structure was confined to cell membranes of immature basal cells, whereas the H and A variants were observed on cell membranes of more mature parabasal and spinous cell layers. Furthermore, superficial spinous cells produced a fine granular cytoplasmic staining for Tn and sialosyl-Tn antigens. In minor salivary glands mucous cells expressed Tn and sialosyl-Tn as well as the H and A variants in the area of the nucleus, whereas T and the H variant were found in duct cells and unsubstituted T antigen in myoepithelial cells. These results indicate that incomplete synthesis, i.e., deletion of sialyltransferases and/or histo-blood group ABH transferases, may result in accumulation of T, Tn, and sialosyl-Tn antigens in oral epithelia, thus offering a baseline for further studies of changes in premalignant and malignant oral epithelia.

Antibodies, Monoclonal↗