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E Dabelsteen

Publications and source records attributed to E Dabelsteen.

At least 91 records · Page 5Linked to original sources
PubMed1990

Expression of the histo-blood group ABO gene defined glycosyltransferases in epithelial tissues.

The histo-blood group ABO carbohydrate antigens are differentially expressed in epithelia in close correlation with cellular differentiation. In order to gain insight into the biosynthetic regulation of these carbohydrate antigens, we correlated the expression of A carbohydrate antigens with that of the A gene defined glycosyl-transferase by immunohistology of human oral epithelia using monoclonal antibodies. In glandular epithelium the A transferase was found in mucous cells similar to that of the A carbohydrate antigens. In stratified non-keratinized squamous epithelium the A transferase was expressed only in spinous cell layers, which is in accordance with the appearance of the A carbohydrate antigens in these more mature cell layers. This simultaneous acquisition of the primary and secondary gene product of a glycosyltransferase gene, provides evidence that the well-defined sequential expression of histo-blood group carbohydrate antigens in stratified squamous epithelium may be directly regulated at the transcriptional level of the glycosyltransferase. Future studies will address the mechanism behind loss of A antigens in premalignant lesions and carcinomas.

ABO Blood-Group System↗
PubMed1990

Cell surface glycosylation patterns in psoriasis.

Cell surface carbohydrates are excellent markers of cellular differentiation and maturation processes due to their great structural and antigenic diversity as well as their known biosynthetic precursor/product relationships. Using a panel of monoclonal antibodies with well-defined carbohydrate specificities we have studied the expression of biosynthetically related antigens in normal and psoriatic skin. Two "families" of carbohydrate structures were investigated. One series of structures based on N-acetyllactosamine chains (type 2 chain: N-acetyllactosamine and fucosylated derivates hereof of H, Lex, Ley and sialyl-Lex) and another based on the simple mucin type core structures (type 3 chain: Tn, T and sialylated derivates hereof as well as the fucosylated derivative, H). Previously we have found these carbohydrate structures define distinct cell layers in stratified squamous epithelia of mucosa of the cheek, esophagus and uterine cervix. In normal and uninvolved epidermis, N-acetyllactosamine and T carbohydrates were found in the spinous cell layer, whereas the fucosylated derivates, H structures, were found in the granular cell layers above. The fucosylated and sialylated derivate of N-acetyllactosamine, sialylated Lex, had the same distribution as N-acetyllactosamine and T structures. This sequential expression of carbohydrates is similar to our previous findings in mucosa. However, in contrast to mucosa, normal skin basal cells did not label. The glycosylation pattern in psoriatic epithelium was changed in two ways. 1) Some carbohydrates (types 2 and 3 chain H and T) were expressed at an earlier stage of cell maturation. 2) The biosynthetic precursors to T structures, Tn and sialyl-Tn, which are not expressed in normal skin, and are often considered cancer-associated antigens, appeared in psoriatic skin. The Tn-antigen was expressed on basal and lower spinous cells, whereas the sialyl-Tn was only found on basal cells above the dermal papillae. The findings in the present work support previous studies of changes in cell surface glycosylation in psoriatic epidermis and demonstrate the appearance of tumor-associated antigens in highly proliferative, but benign, stratified epithelium.

Adult↗
PubMed1990

Inhibition of human immunodeficiency virus (HIV) infection in vitro by anticarbohydrate monoclonal antibodies: peripheral glycosylation of HIV envelope glycoprotein gp120 may be a target for virus neutralization.

Carbohydrate structures are often involved in the initial adhesion of pathogens to target cells. In the present study, a panel of anticarbohydrate monoclonal antibodies (MAbs) was tested for their ability to inhibit in vitro human immunodeficiency virus infectivity. MAbs against three different N- and O-linked carbohydrate epitopes (LeY, A1, and sialyl-Tn) were able to block infection by cell-free virus as well as inhibit syncytium formation. Inhibition of virus infectivity was independent of virus strain (HTLVIIIB or patient isolate SSI-002), the cell line used for virus propagation (H9 or MT4), and the cell type used as the infection target (MT4, PMC, or selected T4 lymphocytes). Inhibition was observed when viruses were preincubated with MAbs but not when cells were preincubated with MAbs before inoculation, and the MAbs were shown to precipitate 125I-labeled gp120. The MAbs therefore define carbohydrate structures expressed by the viral envelope glycoprotein gp120, indicating that glycans of the viral envelope are possible targets for immunotherapy or vaccine development or both.

Antibodies, Monoclonal↗
PubMed1989

Onset of transcription of the aminopeptidase N (leukemia antigen CD 13) gene at the crypt/villus transition zone during rabbit enterocyte differentiation.

The sequence of a cDNA clone (2.82 kbp) of rabbit intestinal aminopeptidase N (CD 13) is reported. Using the corresponding anti-sense RNA probe, the distribution of aminopeptidase N mRNA along the crypt/villus axis of the rabbit small intestine was studied by in situ hybridization. The aminopeptidase N gene is expressed along the whole length of the villus with a maximum at its base. Expression was not detected in the crypt cells. The distribution of aminopeptidase N mRNA correlates with the presence of active enzyme as monitored by histochemical staining. The results are compatible with onset of transcription of the aminopeptidase N gene at the crypt/villus transition zone during the enterocyte differentiation.

Amino Acid Sequence↗
PubMed1989

Blood group ABH-related antigens in normal and malignant bladder urothelium: possible structural basis for the deletion of type-2 chain ABH antigens in invasive carcinomas.

A complete panel of mouse monoclonal antibodies (MAbs) against Type-2 chain (GaI beta I-4GlcNAc-R) blood-group antigens (N-acetyl-lactosamine, Lex, H, Ley, A monofucosylated, Aley, repetitive A) was used in a detailed immunohistological study of the modulation of these carbohydrate antigens in transitional-cell carcinomas. The histological and cellular locations of these antigens were studied in 19 normal bladder biopsies and 53 transitional-cell carcinomas with as well as without neuraminidase treatment of tissue sections in order to uncover potential sialylated antigens. The antigen expression was correlated to individual A1A2BO, Lewis, and secretor status. Several alterations of blood group expression were found: (1) loss of A and H antigens with accumulation of Ley antigens; (2) loss of correlation between antigen expression and secretor status; (3) disruption of the orderly stratification of blood-group antigen expression in relation to cell layers; and (4) changes in subcellular location of antigen expression. The present data indicate that deletion of Type-2 chain ABH antigens in transitional-cell carcinomas is associated with alpha 1-3 fucosylation of the H antigen leading to accumulation of Ley antigens.

ABO Blood-Group System↗
PubMed1989

New malignancy grading is a better prognostic indicator than Broders' grading in oral squamous cell carcinomas.

The prognostic value of histopathologic grading of oral squamous cell carcinomas (SCC) has varied from not any to highly significant. We have retrospectively studied all (130) SCCs registered in Norway 1963-72 in the buccal and maxillary alveolar mucosa. From 68 of these cases biopsy specimens of acceptable quality were obtained. Broders' method of grading was compared with a modification of a recent malignancy grading system recommended by Anneroth et al. which was performed only within the histologically most invasive areas of the tumors. Cox's multivariate survival analyses showed that this grading in the invasive sites had highly significant prognostic value. Broders grade had no prognostic value. The stage of tumor had also prognostic value. These highly significant results indicate that the histologically invasive areas may be primarily responsible for the clinical behavior of the tumor, and this may be of importance for the choice of therapy for oral SCC.

Carcinoma, Squamous Cell↗
PubMed1989

Langerhans cells in oral epithelium of chronically inflamed human gingivae.

This study describes the histopathological features and the distribution of oral epithelial Langerhans cells in 19 gingival biopsies originating from an adult Tanzanian population characterized by very poor oral hygiene and severe gingival inflammation. Light-microscopically, all biopsies contained often large inflammatory connective tissue infiltrates, 6 of which predominantly contained plasma cells while the rest were dominated by lymphocytes. Seven specimens contained peculiar accumulations of round lymphoid and dendritic cells in the lower cell layers of the oral epithelium. These phenomena have not previously been demonstrated in human gingiva and deserve further attention in studies on the pathogenesis of periodontal diseases. Immuno-histochemical staining with OKT6, OKT4 and OKT8 antibodies showed markedly increased numbers of OKT6-positive cells in 7 specimens and clusters of OKT4- and OKT8-positive cells in the oral epithelium of 4 specimens. High numbers of OKT6-positive cells were not related to the presence of intra-epithelial, non-keratinocyte infiltrates or large connective tissue infiltrates. The variable numbers of oral epithelial Langerhans cells may therefore result from different bacterial antigens elucidating different responses or, alternatively, reflect different responses to similar plaque antigens penetrating the surface of the oral epithelium.

Adult↗
PubMed1989

Expression of blood group antigen-related carbohydrates by human gingival epithelia.

A panel of monoclonal antibodies was used to examine differentiation-related carbohydrate structures on the surfaces of gingival epithelial cells. The patterns of binding observed indicate distinct differences in the expression of the epitopes examined for three regions of the gingival epithelia corresponding approximately to the regions defined anatomically as the junctional, oral sulcular and oral epithelia. However, epithelium with the staining pattern of oral sulcular epithelium consistently extended beyond the sulcular region to cover the gingival crest and often the uppermost part of the oral aspect of the gingiva. Differential staining of basal and suprabasal cells indicated an unusual pattern of differentiation of the junctional epithelium. The phenotype of this epithelium appears to differ from patterns reported for any other oral epithelium and the possible functional significance of this difference is discussed.

Antibodies, Monoclonal↗
PubMed1989

Immunomicroscopic localization of the 10,000 molecular weight calcium-binding protein in the human enterocyte.

The cellular localization of the 10,000 molecular weight calcium-binding protein (CaBP or Calbindin-D) in the small intestinal epithelium of man was investigated by immunofluorescence and immunoelectron microscopy (immunogold staining). Indirect immunofluorescence on frozen sections showed intracellular staining in the enterocyte. The fluorescence was evenly distributed and no significant differences were observed between crypt and villus cells. No staining was found in goblet cells or in the submucosa. Correspondingly, immunogold labeled antibodies were scattered over the cytoplasm of the enterocyte. The terminal region appeared to be the most intensely decorated and the brush border region showed labeling above the background level. No labeling was associated with intracellular membranes or the basolateral membrane.

Calcium-Binding Proteins↗
PubMed1989

Loss of blood group ABO-related antigen expression in urothelium from patients with chronic cystitis.

A panel of mouse monoclonal antibodies was used to determine the expression of blood group ABH-related antigens carried by type 1 chain (H, Lea, Leb, ALed, ALeb) and type 2 chain (N-acetyllactosamine, H, Lex, Ley, A/ALey) core structures in biopsies of urothelium from patients with chronic cystitis. The biopsies originated from 17 individuals (9 A1, 7 H, 1 B) who had Le(a-b+) erythrocytes, and who were saliva secretors. Microscopic examination showed a variable extent of edema, hyperemia, bleeding, and infiltration. The expression of blood group antigens was determined in the 3 cell layers of urothelium by an indirect peroxidase method and compared with previous results from normal urothelium. Type 1 and type 2 chain A antigens and type 1 chain H antigens were deleted from urothelium in a significant (p less than 0.05) number of patients with chronic cystitis, and Lea (partly sialylated) expression was extended from the luminal cell layer to all cell layers. Antigen expression was independent of the presence or absence of polymorphonuclear cells in the infiltrate. In the basal cell layer of 44% of patients with chronic cystitis total deletion of type 1 and type 2 chain antigen expression was dominating. Both type 1 and type 2 chain antigens gradually appeared toward the luminal cell layer. The findings are parallel to some of those observed in transitional cell carcinomas, and should be taken into consideration when evaluating ABH deletion in carcinomas.

ABO Blood-Group System↗
PubMed1988

Structural variations of blood group A antigens in human normal colon and carcinomas.

The blood group A determinant is carried by four basic carrier carbohydrate chains. This paper reports the expression of blood group A variants, as determined by immunohistology with highly specific monoclonal anti-A antibodies, in 18 adenocarcinomas of the distal colon, 4 specimens of normal proximal mucosa from group A persons, and 5 specimens of fetal colonic mucosa. Monoclonal antibodies directed to type 1 chain A, type 1 chain ALeb, type 2 chain A, type 2 chain ALey, and type 3 chain A (repetitive A) were used. In normal mucosa, type 1 chain A and ALeb were expressed in proximal regions. Type 1 chain A was expressed in columnar cells, whereas type 1 chain ALeb was found in goblet cells. Type 2 and type 3 chain A structures were not found in normal adult mucosa. All types of A antigens were detected in adenocarcinomas from the distal colon as well as in normal fetal mucosa. In fetal mucosa, type 1 chain A and ALeb antigens and type 3 chain A antigens were expressed in columnar cells, whereas type 2 chain A and Ley and type 1 chain ALeb antigens were found in goblet cells. The results indicate that blood group A antigens with type 1, 2, and 3 carriers are present in fetal mucosa and adenocarcinomas of distal colon, while epithelial mucosa of normal adult colon is characterized by the exclusive expression of type 1 chain A antigens.

ABO Blood-Group System↗
PubMed1988

Sequential expression of carbohydrate antigens with precursor-product relation characterizes cellular maturation in stratified squamous epithelium.

Cell surface carbohydrates are excellent markers for cellular differentiation and maturation due to great structural and antigenic diversity and to known precursor/product relations. Several blood group related carbohydrate antigens were analyzed in human labial stratified non-keratinized epithelium from 16 healthy individuals by immunohistology using monoclonal antibodies. The expression of these antigens was correlated with erythrocyte phenotype and saliva secretor status. Three distinct compartments of the epithelium were found and defined by the sequential expression of derivatives of Type 2 chain structures: lower, confined to basal cell layers (N-acetyllactosamine), middle, to parabasal cell layers (H) and upper, to spinous cell layers (Le(y)/Le(x)). Although the antigens are related to blood group antigens they are largely expressed independently of the ABO, Lewis and secretor types, and may therefore serve as "universal" markers in differentiation studies of normal and pathological epithelium.

ABO Blood-Group System↗
PubMed1988

Premalignant and malignant oral lesions are associated with changes in the glycosylation pattern of carbohydrates related to ABH blood group antigens.

The distribution of carbohydrate structures related to the ABO(H) blood group antigen system was studied in biopsies from eight squamous cell carcinomas, and eight erythroplakias with epithelial dysplasia. Twenty oral lesions without histological evidence of malignancy (13 lichen planus lesions and 7 homogeneous leukoplakias) were also examined. The distribution of Lex, Ley, H type 2 chain, and N-acetyllactosamine, all type 2 chain carbohydrate structures, was investigated by immunohistological staining using monoclonal antibodies with selected specificity. The histological pattern of expression of these antigens in the benign lesions was similar to that of normal oral mucosa, i.e. expression of: N-acetyllactosamine on basal cells, H antigen on parabasal cells, and Lex and Ley on spinous cells. However, lesions with epithelial dysplasia showed H antigen on all spinous cells, and often also on basal cells, with expression of Lex and Ley restricted to the most superficial part of the epithelium above the H-positive cell layers. In carcinomas most cells were negative for H antigen but were positive for Ley and Lex in 5 out of 8 cases.

ABO Blood-Group System↗
PubMed1988

Blood group related carbohydrate antigens in human fetal pancreas.

Many tumor-associated carbohydrate antigens are related to the blood group systems. Since several of these antigens are developmentally regulated, a systematic knowledge of the expression of blood group related carbohydrate antigens during organogenesis is important. By immunohistochemical methods we investigated the expression of carbohydrate structures related to the ABH, Lewis, T and Tn blood group systems in 28 fetal pancreas, from 13th-40th gestational week using a comprehensive set of well-defined monoclonal antibodies, reacting with type 1, 2, 3, and 4 chain carbohydrate structures. The following antigens were found in fetal pancreas: Type 1 chain: Lea, Leb, monosialylated Lea and disialylated Lea, type 2 chain: N-acetyllactosamine (the immediate precursor to blood group H antigen), branched N-acetyllactosamine, H-antigen, Lex and Ley; type 3 chain: H-antigen. The T-antigen was well expressed, whereas this was not the case with the Tn-antigen. As expected the A-antigen was found in 10 of 24 cases. The A-related antigens: ALeb, ALed and ALey were only found in a few of these ten specimens whereas type 3 chain A-repetitive was found in all of them. Since msLea, Lex, Ley and T-antigen have been described as tumor-associated antigens, we conclude that several carbohydrate tumorrelated antigens are expressed in fetal pancreas.

Antibodies, Monoclonal↗
PubMed1988

Blood group antigen staining pattern during experimental carcinogenesis in rat palate.

During 4-nitroquinoline-1-oxide-induced carcinogenesis in the rat palate, animals were sacrificed at various intervals and stained for blood group antigens B and H (Type 2 chain) by an immunofluorescent method. In rats without signs of epithelial dysplasia, the staining pattern was identical with that in the normal control rats. In rats with definite or questionable (borderline cases) dysplasias, marked changes in blood group antigen staining pattern were seen. Thus, changes in cell-surface carbohydrates during malignant development in the rat palate seem to follow closely the histomorphological changes. As there is good evidence that carcinomas would eventually develop in all rats if they were not sacrificed, it seems that the blood group antigen staining pattern does not predict malignant development in the absence of histological suspicion.

4-Nitroquinoline-1-oxide↗
PubMed1988

Antikeratin antibodies in routine diagnostic pathology. A comparison of 10 different commercial antikeratins.

Ten commercially available antikeratin antisera were tested immunohistochemically on fresh frozen and formalin-fixed paraffin-embedded tissue. Eight of the antisera were in addition tested on protein-immunoblottings. For six of the antisera a good correspondence was found between our immunoblots and data given by the manufacturers. Two monoclonal antisera did not react with keratin proteins. On immunohistochemical testing two of the antibodies showed qualitatively identical staining on both frozen and paraffin sections without background staining. Three of the antibodies reacted weakly or not at all on paraffin sections but gave acceptable staining on frozen sections. Three of the antibodies showed acceptable staining on paraffin sections, but background staining on frozen sections and one antibody gave the reverse staining pattern. For one of the antibodies it was impossible to obtain an acceptable staining due to high non-specific binding of the secondary antibody. None of the antikeratins were true panepithelial tumour markers as all of them failed to detect keratin in at least one of the epithelial tumours. However, a combination of two or three antikeratins (Hybritech AE1 + AE3, Becton Dickinson No 7650, DAKO A622) covered most or all epithelial tumours examined. It is concluded that commercially available antisera show great variability with respect to quality and reactivity indicating that the majority need further purification, characterization and testing on tissues before they are introduced on the commercial market.

Antibodies↗
PubMed1988

Blood group ABO-related antigens in fetal and normal adult bladder urothelium. Immunohistochemical study of type 2 chain structures with a panel of mouse monoclonal antibodies.

Seven monoclonal antibodies with specificity for blood group antigens carried by type 2 chain core structures (N-acetyllactosamine, H, Le(x), LeY, A monofucosylated, A difucosylated (AleY), A type 3) were used to study the distribution of these antigens in normal human bladder urothelium. The urothelial samples were from 7 fetuses (aged 7 to 21 weeks), and 22 adults. By means of an immunohistochemical method applied to frozen and fixed tissues, localization of antigens in the 3 cell layers of urothelium was compared with individual ABO, Lewis, and Secretor type. During fetal development, N-acetyllactosamine, H, and LeY antigens were continuously expressed, whereas Le(x) varied with age. The A type 3 chain was present in fetal urothelium but A type 2 chain was not. In adults, we observed a unique blood group distribution: with complex antigens like LeY and ALeY in all cell layers, and a unique expression of most of the less complex antigens in the luminal cell layer. Pretreatment of tissue sections with neuraminidase proved that Le(x) and N-acetyllactosamine could be partly substituted by sialic acid A type 3 chain and most of N-acetyllactosamine antigens were present only in cytoplasm, whereas all other examined antigens could be present both in cytoplasm and on cell membranes. Blood group A antigen expression was related to erythrocyte A1 and A2 subtype, and a remarkable correlation was found between type 1 chain related secretor status and expression of Le(x), LeY, and A antigens.

ABO Blood-Group System↗