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Biomedical subjects

H Clausen

Publications and source records attributed to H Clausen.

173 records · Page 10Linked to original sources
PubMed1985

Monoclonal antibodies defining blood group A variants with difucosyl type 1 chain (ALeb) and difucosyl type 2 chain (ALey).

Three hybridomas secreting monoclonal antibodies, HH1, HH2, and HH3, defining different difucosyl A structures (ALeb or ALey), have been established. Antibody HH1 (IgG2a) reacts specifically with the difucosyl A structure irrespective of a type 1 or type 2 chain, while antibody HH2 (IgG3) reacts exclusively with the difucosyl type 2 chain A (ALey) and does not react with the difucosyl type 1 chain or monofucosyl type 2 chain. Antibody HH3 (IgG2a) reacts exclusively with the difucosyl type 1 chain A (ALeb) and does not react with the monofucosyl type 1 chain A or mono- and difucosyl type 2 chain A. These hybridoma antibodies were obtained by immunization of mice with purified glycolipid antigens and were selected by their reactivity with the specific glycolipid structures. These antibodies, together with previously established monoclonal antibody AH-21, specific for monofucosyl type 1 chain A, and monoclonal antibody TH-1, specific for type 3 chain A, are extremely useful to define blood group A variants present in cells and tissues.

ABO Blood-Group System↗
PubMed1985

Blood group A determinants with mono- and difucosyl type 1 chain in human erythrocyte membranes.

Application of a monoclonal antibody defining monofucosyl type 1 chain A (AH21) revealed the presence of a glycolipid having the same thin-layer chromatography mobility as Aa but showing a clear reactivity with AH21. This glycolipid was detectable in Lea-b- erythrocytes but not in Lea+b- or Lea-b+ erythrocytes. Another monoclonal antibody defining difucosyl type 1 chain A (HH3) detected the presence of a glycolipid component reacting with this antibody in Lea-b+ erythrocytes but not in Lea+b- or Lea-b- erythrocytes. The component defined by monoclonal antibody AH21 and that defined by HH3 were isolated and characterized by 1H NMR spectrometry and methylation analysis as having the structures (Formula: see text) The 1H NMR spectra of these glycolipid antigens were characterized by resonances for anomeric protons that are identical with those of glycolipids with type 1 chain previously isolated but distinctively different from those of type 2 chain analogues. Resonances reflecting ceramide composition are characteristic for these antigens from human erythrocytes and are distinguishable from those of the same antigen from other sources.

ABO Blood-Group System↗
PubMed1985

Blood group A cross-reacting epitope defined by monoclonal antibodies NCC-LU-35 and -81 expressed in cancer of blood group O or B individuals: its identification as Tn antigen.

Two monoclonal antibodies, NCC-LU-35 and NCC-LU-81, have been established after immunization of mice with membrane preparations of human lung cancer Lu65 tumor xenograft cells grown in vivo and intact cells cultured in vitro, respectively. These two antibodies react specifically with a majority of human adenocarcinomas, irrespective of the host's blood group ABO status, as well as with normal tissues and erythrocytes of blood group A individuals. The antigenicity is associated with a high molecular weight mucin-like glycoprotein separated by gel filtration of Lu65 tumor extracts. The epitope of the mucin-like glycoprotein has been identified as alpha-N-acetylgalactosaminyl residue directly linked O-glycosidically to serine or threonine residues of polypeptides. This epitope was serologically detected several years ago and given the name Tn. Our identification of the epitope is based on the following results: The antigen is sensitive to alpha-N-acetylgalactosaminidase, but not to sialidase or alpha-fucosidase. Various mono- and difucosyl A determinants, either type 1 or type 2 chain, cross-react with both antibodies. The reactivity with both antibodies can be created by treatment of glycophorin A of normal erythrocytes with sialidase followed by beta-galactosidase. N-[3H]acetylgalactosamine can be released by galactose oxidase/NaB3H4 treatment from the Lu65 mucin-like glycoprotein but not from the mucin-like glycoprotein of normal colonic mucosa upon reductive beta-elimination (alkaline borohydride treatment). The antigen may be one of the tumor-associated A cross-reacting antigens occurring in a wide variety of human adenocarcinomas of hosts belonging to all ABO blood groups.

ABO Blood-Group System↗
PubMed1985

Repetitive A epitope (type 3 chain A) defined by blood group A1-specific monoclonal antibody TH-1: chemical basis of qualitative A1 and A2 distinction.

The IgG2a monoclonal antibody TH-1, which reacts specifically with blood group A1 but with neither A2 nor O erythrocytes, has been established. The antibody reacted only with A1 erythrocytes in hemagglutination and antibody absorption assays; it did not react with A2 erythrocytes, even after trypsin or sialidase treatment. This antibody detected, on TLC immunostaining, a series of glycolipids from A1 erythrocytes but virtually none or very weak bands from A2 erythrocytes. It did not react with type 1 or type 2 chain A, or with globo-A. The simplest reactive component was isolated from a previously assigned Ab fraction by HPTLC of acetylated compounds. The structure of the reactive component was characterized by 1H NMR spectroscopy, methylation analysis, and enzymatic degradation, as shown below: (Formula: see text). The structure is essentially a repetitive A epitope attached to type 2 chain and is hereby called type 3 chain A. The determinant can be carried on extended and/or branched structures, but it was not detectable in glycoproteins. The structure was characteristic of A1 erythrocytes and present in only trace amounts in A2 erythrocytes. The precursor H (Fuc alpha 1----2Gal beta 1----3GalNAc alpha 1----3[Fuc alpha 1----2]Gal beta 1----4GlcNAc beta 1----R; type 3 chain H) was present in greater quantity in A2 erythrocytes than in A1 erythrocytes, but it was absent in both O and B erythrocytes. The A1 transferase apparently can transfer alpha-GalNAc to type 3 chain H, while the A2 transferase may not have this ability.

ABO Blood-Group System↗
PubMed1985

Staining patterns of human pre-malignant oral epithelium and squamous cell carcinomas by monoclonal anti-keratin antibodies.

Formalin-fixed, paraffin-embedded biopsies of metaplastic keratinized oral mucosa (fibromas and leukoplakias), oral mucosa with epithelial dysplasia and oral squamous cell carcinomas were stained with two monoclonal anti-keratin antibodies (AE1 and AE2). Intense suprabasal staining was seen with AE1 in metaplastic keratinized epithelium, whereas staining of adjacent normal unkeratinized epithelium generally was restricted to basal cells. In dysplastic epithelium and squamous cell carcinomas, staining with AE1 revealed a highly disturbed anti-keratin staining pattern. AE2 stained metaplastic keratinized epithelium in a suprabasal pattern but adjacent unkeratinized epithelium did not stain. In dysplastic epithelium and squamous cell carcinomas, AE2 staining was variable and sometimes absent. Further studies are indicated to clarify whether changes in anti-keratin staining patterns can be used for diagnostic and prognostic purposes.

Antibodies, Monoclonal↗
PubMed1984

Blood group A glycolipid (Ax) with globo-series structure which is specific for blood group A1 erythrocytes: one of the chemical bases for A1 and A2 distinction.

A new blood group A-active glycolipid fraction, termed Ax, showing a chromatographic mobility between Aa and Ab was found in blood group A1 erythrocytes but not in A2 erythrocytes. Ax was identified by its conversion to "globo H" by alpha-N-acetylgalactosaminidase and by 1H-NMR spectroscopy as GalNAc alpha l----3[Fuc alpha l----2]Gal beta l----3GalNAc beta l----3Gal alpha l----4Gal beta l----4Glc beta l----lCer. Globo-H (Fuc alpha l----2Gal beta l----3GalNac beta l----3Gal alpha l----4Gal beta l----4Glc beta l----lCer) was found in blood group A, and O but not in A1 erythrocytes. Thus, one of the A1-specific determinants must be an A determinant carried by globo-series structure.

ABO Blood-Group System↗
PubMed1983

Keratin pattern in human and buccal and hard palate mucosa.

As a preliminary study the keratin proteins of human oral stratified epithelia from buccal mucosa and hard palate were investigated using SDS-PAGE technique. The keratinized hard palate consistently showed six polypeptides varying in molecular weight from 47 to 67 k daltons, whereas the nonkeratinized buccal epithelium lacked the larger polypeptides and showed three polypeptides with molecular weight from 50 to 56 k daltons. The individual variations in the SDS-gel pattern from eight clinically normal individuals were restricted to minor quantitative differences.

Cheek↗
PubMedDate not supplied

A heterozygous frameshift mutation in the Fanconi anemia C gene in familial T-ALL and secondary malignancy.

BACKGROUND: Patients with Fanconi Anemia (FANC) have a well documented increased risk to develop malignancies, especially Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS). The risk for heterozygous individuals is not clear, epidemiological data are inconsistent. If the risk for heterozygous individuals to develop malignancies was increased, they should be found in groups of patients with AML or MDS at higher proportion than in the normal population. We are currently screening a pediatric population with hematologic malignancies for mutations in the FANCA, FANCC and FANCG gene, and report here on siblings carrying a heterozygous frameshift mutation in the FANCC Gene. PATIENTS AND METHODS: Using PCR based single strand conformational analysis we screened the DNA from pediatric patients suffering from 1 degree or 2 degrees MDS, CMML/JMML or AML for mutations in the FANCA (43 exons), FANCC (14 exons) and FANCG (14 exons) gene, and included one patient with refractory T-ALL, being the brother of a patient with T-ALL and MDS transforming into AML. Aberrant PCR products were directly sequenced. Flowcytometric measurement of mitogen-sensitivity and G2-phase arrest is used to evaluate cultured stimulated lymphocytes from individuals carrying FANC-mutations. RESULTS: A novel heterozygous frame-shift mutation, 377-378delGA in the FANCC gene was found in 2 siblings, both suffering from T-ALL with subsequent MDS transforming to AML in one of them. No other mutation was found by direct sequencing of the complete FANCC gene. Both patients died under therapy. The parents (first degree cousins) and one healthy brother are also carriers. Their lymphocytes show a higher mutagen sensitivity than normal, but do not get blocked in G2 phase as being typical for Fanconi Anemia. CONCLUSION: As the mutation causes a premature Stopcodon within exon 4 of the FANCC gene it has to be regarded as a causal FANCC gene defect. The findings within this family support the hypothesis of an increased risk to develop malignancies in heterozygous carriers of FANC-mutations. A systematic screening of further patients is needed, and we are currently examining a larger cohort to get a better estimate of the true risk of heterozygosity.

DNA Mutational Analysis↗
PubMedDate not supplied

Simple mucins (T, sialosyl-T, Tn and sialosyl-Tn) are not diagnostic for malignant breast lesions.

Immunohistochemical study of the distribution of carbohydrate core-structures on O-linked glycoproteins (T, sialosyl-T, Tn and sialosyl-Tn) was performed using specific monoclonal antibodies on 148 primary breast lesions, including 10 normal breast tissues, 16 benign lesions and 122 invasive carcinomas (79 localized and 43 metastatic lesions). T antigen, not observed in normal breast tissue, was present in 31% of the benign lesions and in some cases of morphologically normal epithelium adjacent to tumor cells, compatible with altered glycosylation being an early event. Sialosyl-T (s-T) antigen was present in all cases of normal epithelium and in 81% of the benign lesions. Both Tn and sialosyl-Tn (s-Tn) antigen were present in normal breast lesions. Both Tn and sialosyl-Tn (s-Tn) antigen were present in normal breast tissue (30%) and benign lesions (31% and 19%). In the malignant lesions, 20% were positive for T antigen, 82% for s-T antigen, 66% for Tn antigen and 22% for s-Tn antigen. The staining pattern was nearly identical for carcinomas with and without lymph node metastases. In conclusion, immunostaining for simple mucins does not permit a clear distinction between benign and malignant breast lesions.

Antibodies, Monoclonal↗