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M Christensen

Publications and source records attributed to M Christensen.

At least 91 records · Page 5Linked to original sources
PubMed1993

Simple mucin-type Tn and sialosyl-Tn carbohydrate antigens in salivary gland carcinomas.

BACKGROUND: Neoplastic transformation is associated frequently with changes in the glycosylation process. Simple mucin-type glycosylation in cancer cells has been found to be characterized by incomplete synthesis with precursor accumulation, leading to the exposure of the structures Tn and sialosyl-Tn, which are normally cryptic in human cells and secretions, including saliva and salivary glands. METHODS: Paraffin sections from 50 salivary gland carcinomas of different histologic types were investigated with immunohistologic studies and a panel of monoclonal antibodies with well-defined specificity for Tn and sialosyl-Tn. RESULTS: Tn and sialosyl-Tn antigens were expressed in the cytoplasm of glandular differentiated cells; in the luminal membranes and mucinous content of the glandular differentiated areas in almost all mucoepidermoid carcinomas and adenocarcinomas; and in carcinoma in pleomorphic adenoma, when the malignant component was an adenocarcinoma. In contrast, acinic cell carcinomas and adenoid cystic carcinomas expressed only minimal amounts of Tn and sialosyl-Tn, and the staining was seen only in relation to the luminal membrane and mucin of a few glandular structures. CONCLUSIONS: Mucin-type Tn and sialosyl-Tn may be regarded as markers of a glandular differentiation pattern in salivary gland carcinomas. The cellular location of the antigen-antibody complex indicates that they are synthesized and secreted from the tumor cells into saliva or serum.

Adenocarcinoma↗
PubMed1993

Purification and characterization of the trefoil peptide human spasmolytic polypeptide (hSP) produced in yeast.

Recombinant human spasmolytic polypeptide (r-hSP) has been produced in relatively large amounts in Saccharomyces cerevisiae. The two intronless trefoil domains of the hSP-DNA were cloned separately by PCR from human genomic DNA, and the remaining parts of the gene synthesized. Recombinant plasmids were constructed to encode a fusion protein consisting of a hybrid leader sequence and the hSP sequence. The leader sequence serves to direct the fusion protein into the secretory pathway of the cell and to expose it to the Kex 2 processing enzyme system. The secreted r-hSP was found in a glycosylated and an non-glycosylated form. The two forms of r-hSP were purified from the yeast fermentation broth by a combination of ion-exchange chromatography and preparative HPLC. The overall yield from 8 litres of fermentation broth was 160 mg r-hSP and 219 mg glycosylated r-hSP corresponding to 50% and 34%, respectively. The structure of the r-hSP and the glycosylated r-hSP was determined by amino acid analysis and carbohydrate composition analysis as well as by peptide mapping, amino acid sequencing and mass spectrometric analysis.

Amino Acid Sequence↗
PubMed1993

Fluorescence in situ hybridization mapping of human chromosome 19: cytogenetic band location of 540 cosmids and 70 genes or DNA markers.

We report here the band location of 540 cosmids mapped to chromosome 19. The cosmids were mapped by fluorescence in situ hybridization (FISH) relative to chromosomal bands produced by DAPI/actinomycin staining. The cosmids are distributed throughout the chromosome, with a sampling bias for the q-arm. A detailed analysis of the distribution of three different subtelomeric and 22 pericentromeric chromosome 19 cosmids on other chromosomes is also reported. Colony hybridization identified 142 cosmids that contain sequences representing genes or DNA markers that map to chromosome 19. FISH mapping of these cosmids sublocalizes a total of 70 genes and DNA markers on chromosome 19, revises the previously published map assignments of 2 genes, and narrows the location of over 20 markers.

Animals↗
PubMed1993

Magnetic resonance imaging of the nose with surface coils: a new technique to evaluate functional and aesthetic problems.

Determining the preoperative functional and aesthetic anatomy has been of critical importance to surgeons planning nasal procedures. Beyond skilled clinical examination, few objective studies exist to aid the surgeon. Magnetic resonance imaging (MRI) represents a potentially excellent method for precise anatomic imaging of the nose. Unlike computed tomography (CT) and conventional x-rays, MRI involves no radiation. Similar to CT, however, MRI can provide computer-enhanced three-dimensional and quantitative airway data. Full-head MRI has proven sensitivity in evaluation of tumors of the brain and sinuses and is the imaging modality of choice for many soft-tissue tumors. Due to the relatively high cost of conventional full-head MRI scanning ($600 to $1200 per scan), MRI of the nose utilizing full head scanning technique has been limited. The recent development of small field of view surface coils has enabled higher-resolution nasal scans at a fraction of the scanner time and cost ($200 to $500) of conventional MRI scans. We have developed a protocol utilizing a small field of view coil which results in reproducible high-resolution nasal scans requiring less than 6 minutes of scanner time. This protocol has been used in both the diagnosis and follow-up of patients with traumatic and congenital nasal and septal deformities. Image resolution obtained using the protocol is significantly better than with conventional coils. This technique is excellent for both diagnosing and documenting nasal anatomy and pathology.

Humans↗
PubMed1993

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↗
PubMed1993

Treatment for clients with cumulative trauma disorders: using an educational model to communicate choices.

1. Cumulative trauma disorders comprise more than half of all occupational injuries reported in the U.S. 2. Lack of clear definition about cumulative trauma disorders causes confusion for clients in the workers' compensation system. 3. A teaching poster about cumulative trauma disorders was developed (describing prevention, acute care, and rehabilitation) to assist clients in understanding this disorder. Emphasis was placed on clients' choice in decision making about treatment. 4. Evaluation was carried out using a survey questionnaire. The majority of clients thought the poster was "helpful" or "very helpful." Actual behavioral change was most noticeable in the categories of "took steps to reduce risk factors" and "asked more questions about care."

Audiovisual Aids↗
PubMed1992

Generation of Gla-domainless FVIIa by cathepsin G-mediated cleavage.

Coagulation factor VII contains ten gamma-carboxyglutamic acid residues in the N-terminal region (Gla-domain) which are essential for the hemostatic function of FVII. The present study shows that granulocyte cathepsin G degrades the Gla-domain of FVIIa in vitro. Characterization of the truncated FVIIa by SDS-PAGE and N-terminal amino acid sequence analysis revealed that cleavage had occurred between Tyr-44 and Ser-45 and that further cleavage was only obtained on extensive cathepsin G exposure. Cleavage of vitamin K-dependent coagulation factors by cathepsin G may play a role in vivo, and it offers a convenient way of obtaining proteins deprived of their Gla-domain for functional and structural studies.

1-Carboxyglutamic Acid↗
PubMed1992

Assignment of the gene encoding DNA ligase I to human chromosome 19q13.2-13.3.

The gene encoding DNA ligase I has been mapped on human chromosome 19 by analysis of rodent-human somatic cell hybrids informative for this chromosome and by two-color fluorescence in situ hybridization. The DNA ligase I gene (LIG1) is localized to 19q13.2-13.3 and is distal to ERCC1, the most telomeric of three DNA repair genes on this chromosome.

Blotting, Southern↗
PubMed1992

Fluorescence in situ hybridization mapping of human chromosome 19: mapping and verification of cosmid contigs formed by random restriction enzyme fingerprinting.

Automated restriction enzyme fingerprinting of 7900 cosmids from chromosome 19 and calculation of the likelihood of their overlap based on shared fragments have resulted in the assembly of 743 sets of overlapping cosmids (contigs). We have mapped 22% of the formed contigs (n = 165) and all of the contigs with minimal tiling paths exceeding 6 members (n = 50) to chromosomal bands by fluorescence in situ hybridization using DNA from at least one member cosmid. The estimated average size of the formed contigs is 60-70 kb. Thus, members of a correctly formed contig are expected to lie close to each other in metaphase and interphase chromatin. Therefore, we tested the contig assembly process by comparing the band assignment of two or more members selected from each of 97 contigs. Forty-two of these contigs were further characterized for valid assembly by determining the proximity of members in interphase chromatin. Using these tests, we surveyed a total of 431 joins counted along the minimal tiling path (280 in interphase as well as metaphase) and found 6 erroneous joins, one in each of 6 contigs (6% of tested).

Chromosomes, Human, Pair 19↗
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

Variability in teniposide plasma protein binding is correlated with serum albumin concentrations.

Teniposide is a widely used anticancer drug that is extensively bound to plasma proteins (greater than 95%). We evaluated the drug's plasma protein binding in nine patients with acute lymphocytic leukemia who were in their first complete remission, and in a second group of nine patients at the time of relapse and subsequently after achieving another complete remission. Plasma protein binding was assessed by equilibrium dialysis, with direct high-performance liquid chromatographic measurement of total and free teniposide. The mean unbound fraction was 0.44% (0.21-0.88%) in the plasma of patients in first remission. It was significantly higher in patients at the time of relapse (mean = 0.86%; range 0.68-1.08%) and after achieving another complete remission (mean = 1.25%; range 0.51-2.11%). Serum albumin values were significantly lower at the time of relapse (mean = 4.6 vs 4.0 mg/dl; p less than 0.014), and decreased further during intensive postremission therapy containing L-asparaginase (mean = 3.2; p less than 0.05). For all 18 patients, a significant negative correlation (r2 = 0.667; p less than 0.001) was found between serum albumin and unbound teniposide, with low albumin being associated with higher unbound fraction. Such patients have higher systemic exposure to unbound (presumably active) teniposide at any given total plasma concentration of the agent.

Adolescent↗
PubMed1992

Halothane 2% for caesarean section.

During the induction-delivery interval for Caesarean section delivery, 2% halothane in pure oxygen was administered. The technique was compared to a 0.5% halothane in 50% oxygen/50% nitrous oxide anaesthesia. When a continuous infusion of oxytocin was administered, no excessive haemorrhage was seen. No maternal reminiscence was seen using 2% halothane, but awareness was recorded using 0.5% halothane in 50% nitrous oxide in 15% of the mothers. When there were no signs of preoperative fetal distress, the neonates were unaffected by the halothane concentration provided the induction-delivery interval was short. In cases of fetal distress, the administration of 2% halothane further aggravated the condition of the neonates, as indicated by lowered 1-min Apgar scores, umbilical oxygen tensions, pH and base excess values.

Adult↗
PubMed1991

Human plasma and recombinant factor VII. Characterization of O-glycosylations at serine residues 52 and 60 and effects of site-directed mutagenesis of serine 52 to alanine.

Factor VII is a multidomain, vitamin K-dependent plasma glycoprotein that participates in the extrinsic pathway of blood coagulation. Earlier studies demonstrated a novel disaccharide (Xyl-Glc) or trisaccharide (Xyl2-Glc) O-glycosidically linked to serine 52 in human plasma factor VII (Nishimura, H., Kawabata, S., Kisiel, W., Hase, S., Ikenaka, T., Shimonishi, Y., and Iwanaga, S. (1989) J. Biol. Chem. 264, 20320-20325). In the present study, human plasma and recombinant factor VII were isolated and subjected to enzymatic fragmentation. Peptides comprising residues 48-62 of the first epidermal growth factor-like domain of each factor VII preparation were isolated for comparative analysis. Using a combined strategy of amino acid sequencing, carbohydrate and amino acid composition analysis, and mass spectrometry, three different glycan structures consisting of either glucose, glucose-xylose, or glucose-(xylose)2 were detected O-glycosidically linked to serine 52 in plasma and recombinant factor VII. Approximately equal amounts of the three glycan structures were observed in plasma factor VII, whereas in recombinant factor VII the glucose and the glucose-(xylose)2 structures predominated. In addition to the O-linked glycan structures observed at serine 52, a single fucose was found to be covalently linked at serine 60 in both human plasma and recombinant factor VII. Carbohydrate and mass spectrometry analyses indicated that the fucosylation of serine 60 was virtually quantitative. Metabolic labeling studies using [14C]fucose confirmed the presence of O-linked fucose at serine 60. In order to assess whether the carbohydrate moiety at serine 52 contributes to the biological activity of factor VII, we have constructed a site-specific mutant of recombinant factor VII in which serine 52 has been replaced with an alanine residue. Mutant factor VIIa exhibited approximately 60% of the coagulant activity of wild-type factor VIIa in a clotting assay. The amidolytic activity of mutant factor VIIa was indistinguishable from that observed for recombinant wild-type factor VIIa. In addition, the ability of mutant factor VIIa in complex with either purified relipidated tissue factor apoprotein or tissue factor on the surface of a human bladder carcinoma cell line (J82) to activate either factor X or factor IX was virtually identical to that observed for wild-type factor VIIa. These results indicate that the carbohydrate moiety O-glycosidically linked to serine 52 does not appear to be involved either in the interaction of factor VIIa with tissue factor, or the expression of its proteolytic activity toward factor X or factor IX following complex formation with tissue factor.(ABSTRACT TRUNCATED AT 400 WORDS)

Alanine↗
PubMed1991

Characterization of somatic cell hybrids by bivariate flow karyotyping and fluorescence in situ hybridization.

We report on the use of flow karyotyping and fluorescence in situ hybridization (FISH) to characterize the human chromosomes in somatic cell hybrids. The identity, DNA content, and relative frequency of human chromosomes are derived from flow karyotypes, i.e., measurements of Hoechst and chromomycin fluorescence intensities of chromosomes by dual beam flow cytometry. Chromosome integrity is assessed by comparing the peak position of a human chromosome in the flow karyotypes of a hybrid cell line and its human donor. When human donor cells are unavailable, the peak position of a human chromosome in a hybrid line is compared to the range of peak positions among normal individuals. The relative frequency of human chromosomes in subclones or hybrids grown in culture is monitored using the volumes of peaks in flow karyotypes. FISH with biotinylated human genomic DNA or chromosome-specific repeat sequence as probe is used in conjunction with flow karyotyping to confirm the number of human chromosomes in hybrids. Some small rearrangements are detected by flow karyotyping and not by FISH. On the other hand, translocations between human and rodent chromosomes are detected by FISH and not always by flow karyotyping. Flow karyotyping and FISH were used to characterize over 100 hybrid lines donated by other laboratories. A hybrid set useful for the construction of chromosome-enriched gene libraries is presented. In this set, each of the 24 human chromosome types is present and intact, as judged by these techniques, in a line containing little or no other human material.

Animals↗