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T Gedde-Dahl

Publications and source records attributed to T Gedde-Dahl.

At least 19 recordsLinked to original sources
PubMed1992

The gene encoding human transmembrane secretory component (locus PIGR) is linked to D1S58 on chromosome 1.

The human transmembrane secretory component (SC or poly-Ig receptor, PIGR) is expressed basolaterally on glandular epithelial cells and is responsible for the external translocation of polymeric IgA and IgM. SC is hence a key molecule in antibody protection of mucosal surfaces. The human SC gene (locus PIGR) is located on chromosome 1 (1q31-q41). Here we present the first genetic linkage study of PIGR versus syntenic markers, including D1S58 and F13B, which have been previously regionalized to 1q31-q32 and 1q31-q32.1, respectively. We found that PIGR is closely linked to D1S58 (lods + 5.06 at theta max = 0.06, without sex difference). PIGR versus F13B showed + 1.46 at theta max = 0.25 for both sexes combined. A recombination of 0.06 between F13B and D1S58 (lods + 2.24) was in contrast to a previously published study giving theta max = 0.22 (lods + 3.9), the combined lods being 5.6 at theta max = 0.20. The progeny of a triply heterozygotic female indicated that PIGR is the flanking locus, therefore suggesting a cen-F13B-D1S58-PIGR-qter gene sequence on human chromosome 1. Only negative lod scores to RH, C8@, and PGM1 on 1p, and FY on proximal 1q, were found. Current combined Norwegian allele frequencies were estimated for PIGR to be A1 = 0.63, A2 = 0.37 (370 chromosomes), and for D1S58 to be A1 = 0.44, A2 = 0.56 (218 chromosomes).

Chromosome Mapping↗
PubMed1992

Epidermolysis bullosa simplex: expression of gelatinase activity in cultured human skin fibroblasts.

We have measured the baseline level of gelatinase in fibroblast-conditioned medium from 41 Scandinavian individuals. They comprised 12 healthy persons, 11 individuals with the skin disorder dominant epidermolysis bullosa simplex (DEBS), 16 patients with other types of epidermolysis bullosa (EB) and 2 siblings with prolidase deficiency. These results divide the cell strains into those with low and those with high activity levels. Although this dual biochemical trait occurred in all the groups of individuals, the high-activity trait was more frequent among the DEBS patients. The localized DEBS forms showed an elevated activity level, in contrast to the previously reported generalized DEBS Köbner forms. Although a high level was found in some individuals with other EB forms, the high incidence in four families with localized DEBS Weber-Cockayne (eight of eight) and a single family with generalized DEBS--mottled pigmentation (two of two) may result from a close linkage between an EB gene and a gene responsible for the biochemical trait. In addition, in the single complete family tested, the level of gelatinase activity in cultured fibroblasts seemed to be regulated by codominant alleles or genes. A raised baseline level of gelatinase activity in cultured skin fibroblasts may be the result of either an altered expression of gelatinase or an allelic variant of this enzyme with increased specific activity. Further studies of gelatinase in cultured fibroblasts may provide insight into the regulatory mechanism and genetics behind this activity and allow formal linkage studies versus DEBS.

Analysis of Variance↗
PubMed1992

T-cell responses against products of oncogenes: generation and characterization of human T-cell clones specific for p21 ras-derived synthetic peptides.

Peptides derived from mutated human proto-oncogenes bound to HLA may represent a novel type of tumor-specific antigen. Mutated ras genes are the oncogenes most frequently identified in human cancer. The transforming genes carry a mutation in codons 12, 13, or 61. We have investigated whether the T-cell repertoire of healthy individuals contains T cells capable of recognizing and responding to oncogene-derived peptides. Synthetic peptides derived from mutated p21 ras proto-oncogenes, covering mutations at codons 12 or 13 were selected. It was feasible to elicit T-cell responses and isolate several new T-cell clones (TCC) with specificity for a number of different mutated ras peptides after repeated in vitro immunization. Four TCC were characterized with respect to fine specificity and HLA restriction. TCC B and I were restricted by HLA-DR molecules, and recognized the mutated p21 ras-derived peptide carrying Arg and Lys at residue 12, respectively. TCC E and F were restricted by HLA-DQ molecules, the former being specific for a mutated p21 ras-derived peptide with Val in position 13 and the latter more broadly reactive. Peptide competition experiments with a panel of ten peptides derived from p21 ras indicated that all could bind to HLA-DQ molecules of the T-cell donor, while several were also able to bind his HLA-DR molecules. These results show that several p21 ras mutations resulting in aa substitutions at residues 12 or 13 could be recognized by T cells derived from precursor T cells of relatively low frequency present in the normal repertoire of a single donor.

Amino Acid Sequence↗
PubMed1992

Memory T cells of a patient with follicular thyroid carcinoma recognize peptides derived from mutated p21 ras (Gln-->Leu61).

Point mutations in ras genes resulting in substitutions of amino acid Gly in positions 12 and 13, and Gln in position 61 of the ras gene product p21, are commonly found in human tumors. Peptides derived from aberrant p21 may elicit a tumor specific T cell response, provided that these peptides can bind to HLA molecules of the tumor and the patient has T cells able to recognize the corresponding peptide-HLA complex. Here we report that CD4+ T cells of memory type (CD45RO+) from a patient with a follicular thyroid carcinoma respond against a synthetic peptide derived from aberrant p21 ras having a Gln-->Leu substitution at position 61. Such responses were not observed when T cells from healthy volunteers or cancer patients where this mutation does not usually occur were stimulated with this peptide. The responding T cells did not cross-react with the corresponding peptide derived from native p21 ras nor did they recognize peptides carrying other substitutions in position 61. T cells clones were generated which recognized this Leu61 peptide when presented by HLA-DQ8 molecules. These T cell clones also recognized the corresponding intact p21 ras protein. By using several different synthetic peptides, a peptide with optimal stimulatory capacity was defined. Performing polymerase chain reaction and oligonucleotide probing we were, however, not able to detect the p21 ras gene encoding the Gln-->Leu substitution in DNA from tumor biopsies from the patient. This may indicate that tumor cells harboring the mutation leading to the Gln-->Leu substitution had been eliminated and that tumor progression was due to cells that had deleted the mutated ras gene. The finding that ras derived peptides and recombinant mutated p21 ras are immunogenic in man may form the basis for the development of cancer immunotherapy based on synthetic oncogene derived peptides.

Adenocarcinoma↗
PubMed1992

Anchoring fibrils, collagen VII, and neutral metalloproteases in recessive dystrophic epidermolysis bullosa inversa.

Structure of the anchoring fibrils, expression of collagen VII, and gelatinolytic activity in skin fibroblasts were assessed in six patients with epidermolysis bullosa dystrophica (EBD) inversa and in control groups consisting of probands with other EBD subtypes and healthy individuals. All six patients with EBD inversa, as well as the patients with generalized non-mutilating and localized EBD, showed positive staining with antibodies to collagen VII, the major anchoring fibril protein. Four patients with severe generalized mutilating EBD exhibited negative staining. Ultrastructurally, normal anchoring fibrils were demonstrable in uninvolved skin of patients with localized, inversa, and generalized non-mutilating subtypes. At the same time, a high degree of variability was observed in the amount and quality of anchoring fibrils in the various stages of lesional skin, including co-existence of normal and partially degraded anchoring fibrils. Of all 12 patients only one localized and two inversa cases showed an increased gelatinolytic activity in vitro. However, the high activity was associated with neither the severity of the disease nor the inversa subtype. In addition, intact collagen VII could be extracted from the dermis of one inversa patient. The present data show no correlation between increased in vitro gelatinolytic activity and abnormalities of the anchoring fibrils or collagen VII in skin of patients with recessive EBD, and therefore suggest molecular heterogeneity of the causative pathogenetic mechanisms.

Adolescent↗
PubMed1992

Linkage and association studies with C8A and C8B RFLPs on chromosome 1.

Linkage relations for the C8A and C8B BamHI RFLPs have been investigated. A peak lod score of 4.52 at recombination fraction zero was obtained between the two C8 genes. Combined with our previously obtained linkage data (Rogde et al. 1986) the maximum lod score is 7.53 at recombination fraction zero. The compiled C8-PGM1 linkage data from this and the previous study gave a maximum lod score of 22.02 at recombination fraction 0.11 (0.07-0.16) with no sex difference. A chromosome 1p reference marker, D1S57, has been applied in this linkage study. A maximum lod score of 5.06 between the C8 cluster and D1S57 at theta = 0.18 (0.11-0.28) was recorded. The linkage analyses and triply informative families gave evidence that the C8 loci are situated about halfway between PGM1 and D1S57 on the short arm of chromosome 1. There was no evidence of allelic association between the C8A and C8B BamHI RFLPs in 62 unrelated haplotypes.

Chromosome Mapping↗
PubMed1990

High-resolution karyotypes of eighteen Norwegian polyposis patients.

High-resolution karyotypes were analyzed from lymphocyte cultures of 18 Norwegian polyposis patients, of whom two had classic Gardner syndrome (GS). We focused on possible rearrangements of the long arm of chromosome 5. Previously the gene for familial adenomatous polyposis (FAP) was localized to the region 5q21-22 by linkage analysis. A patient with a constitutional deletion in this region would be of great value in the course of cloning the gene. At the level of high-resolution G-banding, however, none of these patients showed any interstitial deletion or other rearrangement on chromosome 5 or any other chromosome.

Adenomatous Polyposis Coli↗
PubMed1989

[A Norwegian polyposis family. From catastrophe to prevention].

A Norwegian polyposis family (PP29) including ten affected cases over five generations is reported with clinical case histories. In the first three generations one patient died in her thirties of "tuberculosis" and the other five affected patients died of gastrointestinal cancer. Of 12 at risk in the 4th generation, three had polyposis and underwent prophylactic colectomies, six were normal at regular follow-up rectoscopies till 35-40 years of age and three avoided examination. One of four at risk persons in the 5th generation had polyposis and underwent colectomi with ileoanal anastomosis. DNA-typing using D5S71 (p11c11) showed segregation which confirmed linkage and almost ruled out the possibility of any of the three non-controlled at risk persons being polyposis gene carriers. Another family (PP11) illustrates how typing, using the probe D5S71, may allow early and prenatal diagnosis.

Adenomatous Polyposis Coli↗
PubMed1989

The genes for apolipoprotein all (APOA2) and the Duffy blood group (FY) are linked on chromosome 1 in man.

We have cloned a cDNA probe for human apolipoprotein AII and used it to analyze linkage relationships on chromosome 1. We found no recombinations between APOA2 and the gene coding for the Duffy blood group antigens (FY) in the 19 meioses examined. Our maximal lod score is 4.2 at zero recombination rate. K. Berg (1987, Cytogenet. Cell Genet. 46:579) found a maximal score of 2.5 at recombination fraction 0.14 in 54 meioses. When results from both studies are combined, the most likely distance between FY and APOA2 is about 10% recombination with a combined lod score of 5.6 for both sexes.

Amino Acid Sequence↗
PubMed1989

Collagenase expression in skin fibroblasts from families with recessive dystrophic epidermolysis bullosa.

The collagenase production of cultured skin fibroblasts from Scandinavian families with dominant (D-EBD) and recessive (R-EBD) epidermolysis bullosa dystrophica has been investigated. Heterogeneity as a result of body location origin has been ruled out as fibroblasts obtained from predilection sites produce the same amount of immunoreactive collagenase as those obtained from non-predilection sites of the same subjects. Large variations in in vitro collagenase production were found between individuals and families. Within the R-EBD group, four out of eighteen patients showed an in vitro elevated level of immunoreactive collagenase compared to their healthy relatives, other EB types, and the control group. This shows that an in vitro elevated collagenase production is not a marker for the entire disease group and that the disease denoted as R-EBD probably is etiologically and pathogenetically heterogeneous.

Biopsy↗
PubMed1989

[The polyposis project].

A research project initiated in 1978 comprised establishment of a national polyposis registry, a genetic linkage study using classical and DNA markers, an in vitro study of fibroblasts for transformation parameters and chromosome instability, and a comparative study of DNA-RFLPs in cancer and constitutional tissue. The linkage study (to be reported elsewhere) confirmed the recently reported close linkage between the polyposis gene locus APC and D5S71. No in vitro test for the presence of the APC gene has been confirmed or revealed, but we detected increased chromosomal instability on a statistical basis and also recorded abnormal DNA-repair. As per 1. January 1988 the prevalence of adenomatosis of colon and rectum in Norway was 1/43,500. Among patients born in the period 1931-1950 the incidence at birth of developing the disease is 1/20,000 and the mutation rate is 1/72,000 per gamete per generation. In Norway new mutants in healthy families will comprise 1/3-1/2 of all new cases in the coming two decades, or one of 36,000 births.

Adenomatous Polyposis Coli↗
PubMed1988

Hepatoblastoma and familial adenomatous polyposis.

Eleven children have been identified as having hepatoblastoma and a family history of adenomatous polyposis, and 14 additional instances of this association have been collected from the literature. Among the 11 survivors of hepatoblastoma in the combined series, adenomatous lesions have been sought in seven and detected in six patients at ages 7 to 25 years. Five of these patients also have congenital hypertrophy of the retinal pigment epithelium, a marker for carriers of the polyposis gene. These findings strengthen the association between hepatoblastoma and familial adenomatous polyposis and have led to the establishment of the Hepatoblastoma-Adenomatous Polyposis Registry.

Adenomatous Polyposis Coli↗