PubMed Health⌕ Search

Biomedical subjects

J G Bodmer

Publications and source records attributed to J G Bodmer.

At least 19 recordsLinked to original sources
PubMed1992

Loss of HLA class-I alleles, heavy chains and beta 2-microglobulin in colorectal cancer.

Using immunohistochemical methods, we have analysed colorectal biopsies of normal mucosa, metaplastic polyps (5 cases), adenomas (15 cases) and adenocarcinomas (70 cases) with 13 monoclonal antibodies (MAbs) to allelic products of the HLA-A, B, C loci. Nine of the 70 carcinomas showed total loss of HLA Class-I molecules due to an underlying defect regarding not only the expression of beta 2-microglobulin (beta 2-m), but also the heavy chains of HLA A, B and C loci, or both. Much commoner was a loss of one or more Class-I alleles as follows: A1/Aw36 (completely lost in 4 of 29 cases and focally lost in another 2), A2 (in 1 of 37 cases), A3 (in 2 of 14 cases), A1 1/28/31/33 (in 3 of 11 cases), B7 (in 3 of 13 and focally in 1 other case), B17 (in 1 case), Bw4 (in 8 of 45 and focally in another 6), Bw6 (in 9 of 62 and focally in another 3). Focal selective loss (Bw6 and a combined A1-Bw6), was observed in 2 adenomas. Normal colonic mucosa, as well as stromal and lymphoid cells present between the neoplastic glands, were studied in each case as a control. A particular allele was only considered to be lost by the malignant cells if it was still expressed on these adjacent tissues.

Alleles↗
PubMed1992

A microELISA assay for detection of anti-HLA activity of mouse monoclonal antibodies using an Astroscan 2100 automated plate reader.

A microenzyme-linked immunosorbent assay (microELISA) method has been developed using an Astroscan 2100 system automated plate reader which was initially designed for tissue typing by a two colour fluorescent microcytotoxicity assay. A 96-well plate ELISA used for screening mouse monoclonal antibodies raised against surface HLA antigens has been modified for use with the Astroscan plate reader and 72-well typing trays. The existing substrate 4-methylumbelliferyl-beta-D-galactoside (4MUG) has been replaced with fluorescein-di-beta-D-galactopyranoside (FDG), to provide a wavelength (530 nm) detectable by the Astroscan or other automated plate readers designed for reading microcytotoxicity assay plates. The assay volumes have also been reduced tenfold for use with Terasaki microtest plates. The assay now has the major advantage of requiring only 5 microliters of test supernatant allowing hybridomas to be screened earlier during a fusion and on a wider cell panel. The use of the large panel which includes B lymphoblastoid cell lines (B-LCL) and mouse L cell transfectants expressing HLA genes, reduces the length of time the hybridomas need to be kept in tissue culture before selection. Other advantages include the reduction in the number of target cells required, smaller volumes of reagents throughout the assay and the ability to screen cytotoxic as well as non-cytotoxic monoclonal antibodies. The sensitivity of this microELISA proved to be comparable with the original assay and so provides an efficient screening method for monoclonal antibodies.

Animals↗
PubMed1992

Direct sequence analysis of the t(14;18) chromosomal translocation in Hodgkin's disease.

There have been conflicting reports about the occurrence of the t(14;18) chromosomal translocation in Hodgkin's disease. A polymerase chain reaction analysis of biopsy specimens from 21 patients with Hodgkin's disease (HD) has shown the presence of the t(14;18) translocation in four cases (20%). All four patients had nodular sclerosing HD. Direct sequencing of the amplified 14q+ junctions established that the BCL-2 (major breakpoint region) sequence was fused to an Ig joining region (JH) (J6 in all four cases). Different breakpoints were observed in each case but were similar in nature to the breakpoints described in follicular lymphoma. The exact nature and cell of origin in HD remains obscure, although the presence of the t(14;18) translocation may reflect either a B-cell origin in these cases or associated lymphoid hyperplasia.

Adolescent↗
PubMed1992

Peptide-induced nonresponsiveness of HLA-DP restricted human T cells reactive with Dermatophagoides spp. (house dust mite).

The activation of CD4+ T lymphocytes, which play a central role in allergic inflammation, depends on the recognition of allergen-derived peptides in association with major histocompatibility complex class II gene products. In this report we demonstrate, at a clonal level, that a component of the T-cell repertoire reactive with Dermatophagoides spp. (house dust mite) in atopic individuals, is restricted by HLA-DP class II molecules. This supports the recent results emerging from genetic epidemiologic studies that indicate positive associations between the HLA-DP phenotype and immune responsiveness to a variety of common allergens. Our findings also reveal that the T cells restricted by HLA-DP recognize a species-specific epitope located in the group I allergen of Dermatophagoides pteronyssinus (residues 101-119). Furthermore, we report that the pretreatment of the T cells restricted by HLA-DP with the Der p I peptide renders them nonresponsive to an immunogenic challenge with house dust mite allergen, and the loss of antigen-dependent proliferation is associated with downregulation of membrane expression of the T-cell antigen receptor. The ability to functionally inactivate T cells restricted by HLA-DP, as well as those that recognize allergen in association with HLA-DR class II molecules, suggests that desensitization with allergen-derived peptides may have therapeutic potential in the management of allergic diseases irrespective of their HLA class II association.

Animals↗
PubMed1992

HLA class II nucleotide sequences, 1992.

The HLA class II sequences included in this compilation are taken from publications listed in these papers: Nomenclature for factors of the HLA system, 1991 [1], Nomenclature for factors of the HLA system, 1990 [2] and Nomenclature for factors of the HLA system, 1989 [3]. Where discrepancies have arisen between reported sequences, the original authors have been contacted where possible, and necessary amendments to published sequences have been incorporated into this alignment. Future sequencing may identify errors in this list and we would welcome any evidence that helps to maintain the accuracy of this compilation. In the sequence alignments, identity between residues is indicated by a hyphen (-). An unavailable sequence is indicated by an asterisk (*). Gaps in the sequence are inserted to maintain the alignment between different alleles showing variation in amino acid number.

Base Sequence↗
PubMed1992

p53 expression in Reed-Sternberg cells of Hodgkin's disease.

Mutation of the p53 protein may represent the commonest genetic event in human malignancy. Abnormal p53 expression has been reported in a variety of carcinomas, sarcomas and lymphoid neoplasms; however there is little information in relation to Hodgkin's disease. The expression of the nuclear phosphoprotein was investigated in paraffin-embedded biopsies from fifty patients with Hodgkin's disease using a polyclonal antibody, CM-1 and in snap-frozen material with monoclonal antibodies, PAb 1801 and PAb 240. Specifically, immunoreactivity was localised to the Reed-Sternberg cells or mononuclear variants in both nodular sclerosing (86% cases) and mixed cellularity (57% cases) subtypes of Hodgkin's disease. However, no positive staining was found in our cases of nodular lymphocyte predominant type Hodgkin's disease. Serial biopsies following recurrence of disease demonstrated consistent results. It is suggested that overexpression of p53, probably mutant, may have a role in the tumorigenesis of Hodgkin's disease.

Hodgkin Disease↗
PubMed1992

Familial testicular cancer: a report of the UK family register, estimation of risk and an HLA class 1 sib-pair analysis.

Forty-two families with two or more cases of testicular cancer have been reported to the UK Register for Familial Testicular Cancer, comprising two pairs of identical twins, 27 sets of other brothers (25 pairs, two triples), nine father-son pairs, two pairs of first cousins and two uncle-nephew pairs. In total 91 testicular tumours are described in 86 individuals (42 (46%) pure seminoma, 49 (54%) other germ cell tumours). The median age at diagnosis in these patients was significantly younger than that in a comparable series of non-familial patients (29 c.f. 32.5 years, P less than 0.01). In a case-control comparison of 794 testicular cancer patients, eight patients (1.0%) had a brother and four patients (0.5%) had a father with a previous diagnosis of testicular cancer at the time of their own diagnosis (and these families are all included in this report). Two out of 794 controls (0.3%) had a first degree relative with testicular cancer. The cumulative risk to a brother of a patient for developing testicular cancer by the age of 50 years was estimated to be 2.2% (95% C.I. 0.6-3.8%) which results in a relative risk of 9.8 (95% C.I. 2.8-16.7) in comparison with the general population. HLA Class I typing of 21 affected sib-pairs demonstrated four (19%) sharing two haplotypes, 13 pairs (62%) sharing one and four pairs (19%) sharing none. This did not differ significantly from the expected proportions of 25%/50%/25%. It is unlikely, therefore, that there is a major gene associated with testicular cancer predisposition within or closely linked to the major histocompatibility gene complex on chromosome 6.

Adolescent↗
PubMed1992

HLA class II nucleotide sequences, 1992.

The HLA Class II sequences included in this compilation are taken from publications listed in the papers: Nomenclature for factors of the HLA system, 1991 (1), Nomenclature for factors of the HLA system, 1990 (2), and Nomenclature for factors of the HLA system, 1989 (3). Where discrepancies have arisen between reported sequences, the original authors have been contacted, where possible, and necessary amendments to published sequences have been incorporated into this alignment. Future sequencing may identify errors in this list and we would welcome any evidence that helps to maintain the accuracy of this compilation. In the sequence alignments, identity between residues is indicated by a hyphen (-). An unavailable sequence is indicated by an asterisk (*), gaps in the sequence are inserted to maintain the alignment between different alleles showing variation in amino acid number.

Base Sequence↗