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H Clausen

Publications and source records attributed to H Clausen.

At least 145 records · Page 8Linked to original sources
PubMed1989

Establishment of an anti-A human monoclonal antibody from a blood group A lung cancer patient: evidence for the occurrence of autoimmune response to difucosylated type-2 chain A.

A human monoclonal antibody, NCC-HAL-27, has been established by a combination of transformation by Epstein-Barr virus (EBV) and a newly devised "micro cell fusion" technique. Lymphocytes used were derived from a blood group A lung cancer patient. Cancer cells, as well as normal epithelial cells of lung, stomach and colon (including autologous tissue) from blood group A individuals, fixed in formalin, were immunohistochemically stained by the antibody. A higher concentration (greater than 140 mg/ml) of the antibody agglutinated only type-A (not B or 0) erythrocytes. The structural specificity of NCC-HAL-27 was determined by particle-concentrated fluorescence immunoassay and thin-layer chromatography immunostaining using purified, well-defined glycolipids. The antibody was found to be directed against type-2 chain A and difucosylated type-2 chain A antigens with no cross-reactivity with known A-like antigens, such as Tn and Forssman antigen, generally expressed irrespective of ABO status. Interestingly, however, the antibody detected the expression of incompatible A antigen in colon cancers of B and 0 individuals with high incidence (30%-40%). The finding that a monoclonal antibody generated from a blood group A cancer-bearing host is directed against autologous A antigen is novel because the ABO blood group antigens are the major alloantigens in man, with strictly controlled immunotolerance. The induction of anti-A in this patient could, therefore, be directly associated with the lung cancer.

ABO Blood-Group System↗
PubMed1989

ABH and related histo-blood group antigens; immunochemical differences in carrier isotypes and their distribution.

This review summarizes present knowledge of the chemistry of histo-blood group ABH and related antigens. Recent advances in analytical carbohydrate chemistry (particularly mass spectrometry and NMR spectroscopy) and the introduction of monoclonal antibodies (MoAbs) have made it possible to distinguish structural variants of histo-blood group ABH antigens. Polymorphism of ABH antigens is induced by: (i) variations in peripheral core structure, of which four (type 1, 2, 3 and 4) are known in man; (ii) variation in inner core by branching process (blood group iI), leading to variation of unbranched vs. branched ABH determinants; (iii) biosynthetic interaction with other glycosyltransferases (Lewis, P. T/Tn blood systems) capable of acting on the same substrate as the ABH-defined transferases, and finally (iv) the nature of the glycoconjugate (glycolipid, glycoprotein of N- or O-linked type). ABH variants induced by item (i) above have been clearly distinguished qualitatively by MoAbs; e.g., at least six types of A determinants can be distinguished by qualitatively different classes of antibody. The variants induced by item (ii) create mono- vs. bivalent antigens which may be responsible for observed differences in antibody-binding affinity. Detailed studies of the chemistry of these antigens have increased our insight into blood groups, providing the basis for blood group iI and A subgrouping, as well as a relation between the ABH and Lewis, P, and T/Tn systems. A survey of the literature on distribution patterns of ABH variants is presented. It has been assumed that expression of histo-blood group antigens is developmentally regulated. Relationships between histo-blood group expression, development, differentiation and maturation, as well as malignant transformation, are discussed.

ABO Blood-Group System↗
PubMed1989

Coexpression of sialosyl-Tn (NeuAc alpha 2----6GalNAc alpha 1----O-Ser/Thr) and Tn (GalNAc alpha 1----O-Ser/Thr) blood group antigens on Tn erythrocytes.

Polyagglutinable erythrocytes expressing the rare human blood group phenotype Tn were tested for expression of both Tn (GalNAc alpha 1----O-Ser/Thr) and sialosyl-Tn (NeuAc alpha 2----6GalNAc alpha 1----O-Ser/Thr) antigens by agglutination with a panel of well-characterized monoclonal antibodies specifically directed to Tn and sialosyl-Tn antigens, respectively. Tn erythrocytes from 4 patients were strongly agglutinated by both sialosyl-Tn and Tn-specific monoclonal antibodies, indicating coexpression of sialosyl-Tn and Tn antigens on the cell membrane surface of Tn polyagglutinable erythrocytes. Human polyclonal anti-Tn antisera were found to express weak and variable anti-sialosyl-Tn antibodies in conjunction with the anti-Tn antibodies. The Tn phenotype thus involves not only the classically known Tn antigens but also sialosyl-Tn antigens. However, the human anti-Tn antibodies may be directed mainly toward the Tn antigen (GalNAc alpha 1----O-Ser/Thr).

Antibodies, Monoclonal↗
PubMed1989

Immunohistochemical analysis of stratum corneum components in oral squamous epithelia.

The generation of a stratum corneum in squamous epithelia involves marked changes in morphology and in the expression of cell products. We have examined the expression of some of the components involved in this process in oral squamous epithelia with different terminal differentiation patterns by use of immunofluorescent techniques. Involucrin and transglutaminase are involved in formation of cornified envelopes consistently seen in the stratum corneum. Both components were present in keratinized oral epithelia (palatal epithelium and hyperkeratinized buccal epithelium). The nonkeratinized normal buccal epithelium stained positive as well. Filaggrin, a protein derived from a precursor present in keratohyalin granules, is proposed to aggregate keratin filaments in the cornified layer. Although the staining differed markedly in quantity, this component was likewise detected in both keratinized and nonkeratinized epithelia. The staining patterns for different keratin polypeptides, however, showed qualitative differences between the different epithelia. Thus, it seems that the keratin composition shows differentiation-specific characteristics, whereas the presence of other important components needed to generate a stratum corneum is not as closely related to the terminal differentiation pattern of oral epithelia.

Antibodies, Monoclonal↗
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

1H-n.m.r. analysis of type-2 chain lacto-gangliosides. Confirmation of structure of a novel cancer-associated fucoganglioside, alpha-NeuAc-(2----6)- beta-D-Galp-(1----4)-beta-D-GlcpNAc-(1----3)-beta-D-Galp-(1----4)-[alp ha-L- Fucp-(1----3)]-beta-D-GlcpNAc-(1----3)-beta-D-Galp-(1----4)-beta -D-Glc p- (1----1)-Cer (VI6NeuAcIII3FucnLc6Cer).

Neolacto-glycosphingolipids, substituted with alpha-NeuAc-(2----3)- and -(2----6)-linked D-Galp residues were analyzed by one- and two-dimensional 1H-n.m.r. spectroscopy at 500 MHz in 49:1 (v/v) di(2H3)methyl sulfoxide-deuterium oxide solution. For the simplest structures analyzed, nLc4Cer, IV3NeuAcnLc4Cer, and IV6NeuAcnLc4Cer, sialosylation-induced changes in shifts of terminal and subterminal core residues were interpretable in terms of existing conformational models. Chemical shifts for H-3e and H-3a of NeuAc characteristic for the type of linkage, were also determined. In addition, regularly reproducible shifts were seen for H-1 and other resonances of terminal and subterminal core residues of all structures tested. Chemical-shift correlations proved to be useful in elucidating the structure of a unique ganglioside bearing an internal beta-D-Galp-(1----4)-[alpha-L-Fucp-(1----3)]-beta-D-GlcpNAc-(1---- 3) residue ("X-trisaccharide") with an alpha-NeuAc-(2----6)-substituted terminal group.

Carbohydrate Sequence↗
PubMed1988

Human sperm carbohydrate antigens defined by an antisperm human monoclonal antibody derived from an infertile woman bearing antisperm antibodies in her serum.

The epitope structure of the human sperm antigen reacting with antibodies present in sera of infertile women has been studied using mAb H6-3C4, which produces immobilization of human sperm in the presence of complement. Another antibody, NUH2, which also induces human sperm immobilization, was used to substantiate the presence of a receptor on sperm involved in susceptibility to immobilization. Both antibodies defined type 2 chain polylactosamine structure. H6-3C4 is directed to internally located repetitive N-acetyllactosamine, i.e., sialyl-i, i, or fucosyl-i. NUH2 defines binary alpha 2----3 sialyl type 2 chain, i.e., sialyl-I. Thus, the presence of antibodies in the sera of infertile women directed to sperm lactosaminoglycan or lactosaminolipid could be the basis for infertility in these cases.

Amino Sugars↗
PubMed1988

Preparation and characterization of monoclonal antibodies directed to the tumor-associated O-linked sialosyl-2----6 alpha-N-acetylgalactosaminyl (sialosyl-Tn) epitope.

Two monoclonal antibodies, TKH1 and TKH2, directed toward the sialosyl-Tn structure (NeuAc alpha 2----6GalNAc alpha 1----O-Ser or Thr), which display a remarkable immunohistological tumor specificity, were generated by immunization with ovine submaxillary mucin. The reactivity of these antibodies was monitored by solid phase enzyme-linked immunosorbent assay with different native and glycosidase-treated mucins and glycoproteins. Binding of the antibody to ovine submaxillary mucin glycoprotein was strongly inhibited by the O-linked disaccharide NeuAc alpha 2----6GalNAc alpha 1----O-serine, less strongly by NeuAc alpha 2----6GalNAc beta 1----O-propyl, and weakly by the monosaccharide GalNac. The reactivity was compared with previously established anti-Tn antibodies B72.3, NCC-Lu-35, and NCC-Lu-81. The antibody B72.3 was prepared previously after immunization with metastatic breast adenocarcinoma and its epitope was claimed to be GalNAc alpha 1----O-Ser (or - Thr) by Springer and associates [Springer, G.F., et al. In: T. Dao, et al. (eds.), Tumor Markers and Their Significance in the Management of Breast Cancer, pp. 47-70. New York: A.R. Liss, 1986]. The antibody was found to show very similar reactivity as that of TKH1/TKH2, and its reactivity to ovine submaxillary mucin was inhibited specifically by NeuAc alpha 2----6GalNAc alpha 1----O-serine, indicating that the antibody is clearly directed to sialosyl-Tn antigen. Immunohistological study of the distribution of this antigen in various normal human tissues and carcinomas by TKH1/TKH2 antibodies, as well as B72.3 and monoclonal antibodies NCC-Lu-35/81, which are directed to GalNAc alpha 1----O-Ser or Thr (Tn), was performed. The sialosyl-Tn antigen was not found in normal tissue except for a weak expression in Leydig cells of the testis, goblet cells of the colon, and parietal cells of the stomach. In contrast, the sialosyl-Tn antigen was strongly expressed in a large number of adenocarcinomas. As expected from the specificity studies, B72.3 shows the same reactivity as TKH1 and TKH2. Thus, both sialosyl-Tn (NeuAc alpha 2----6GalNAc alpha 1----O-Ser/Thr) and Tn (GalNAc alpha 1----O-Ser/Thr) are good tumor markers, and combined use of antibodies directed to these structures might be useful in the screening and classification of cancer.

Animals↗
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

Monoclonal antibodies directed to the blood group A associated structure, galactosyl-A: specificity and relation to the Thomsen-Friedenreich antigen.

Two monoclonal antibodies, HH8 and HH9, have been established after immunization of mice with galactosyl-A glycolipid antigen having the terminal structure, Gal beta 1----3GalNAc alpha 1----3[Fuc alpha 1----2]Gal beta 1----R, which is the precursor for type 3 chain A (repetitive A) and type 3 chain H (A-associated H). Both antibodies react strongly and specifically with galactosyl-A, but HH8 (IgM) showed strong hemagglutination of blood group A1, A2, O and B erythrocytes after sialidase treatment, while HH9 (IgG1) did not react with human erythrocytes even after sialidase treatment. HH8 and anti-T antibody, but not HH9, reacted with glycophorin A after sialidase treatment. The reactivity of HH8 with glycophorin A was abolished by beta-galactosidase and was inhibited by liposomes containing galactosyl-A, but not other glycolipids. In addition, anti-T antibody and peanut lectin reacted specifically with galactosyl-A glycolipids. These findings indicate that HH8 recognizes the terminal disaccharide Gal beta 1----3GalNAc alpha 1----R, which is the same sequence as the classically known Thomsen-Friedenreich antigen (T-antigen), whereas HH9 does not cross-react with T-antigen but recognizes the entire galactosyl-A structure. The T-antigen was also demonstrated by immunohistology with HH8 after neuraminidase treatment in a subset of cells in stratified epithelium.

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

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↗
PubMed1987

Blood group ABO and Lewis antigen expression during neoplastic progression of human urothelium. Immunohistochemical study of type 1 chain structures.

The deletion of blood group ABO antigen expression in bladder carcinoma has attracted attention because of its potential as a prognostic parameter. Based on recently produced monoclonal antibodies against blood group antigens, it has become possible to elucidate the carcinoma-associated modulation of these antigens at a molecular level. In this study we have used a panel of monoclonal antibodies (H, Lea, Leb, A, ALeb) that are specific to type 1 chain structures. By the use of an immunohistochemical method, the histologic and cytologic location of these antigens in the urothelium was studied in 25 biopsies from transitional cell carcinomas and compared to 21 previously examined normal biopsies. Urothelial blood group reactivity was compared to Lewis and secretor status. The authors found a series of events associated with neoplastic progression of noninvasive urothelium: a disruption of the orderly stratification of blood group antigens in different cell layers; cytostructural relocation of cytoplasmic antigens to the cell surface; loss of correlation between urothelial blood group antigens and secretor status; and gradual deletion of antigens. In the invasive tissue these events were followed by a total deletion of A and H isoantigens and uniform expression of Lewis b and sialyted Lewis a antigen. These findings indicate that there is a complex modulation of blood group antigen biosynthesis associated with the neoplastic progression of the human urothelium.

ABO Blood-Group System↗