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Biomedical subjects

P Travers

Publications and source records attributed to P Travers.

26 records · Page 2Linked to original sources

Linkage map of two HLA-SB beta and two HLA-SB alpha-related genes: an intron in one of the SB beta genes contains a processed pseudogene.

Three overlapping cosmid clones contain coding sequences for four HLA Class II genes, provisionally identified as two HLA-SB alpha and two HLA-SB beta genes. The genes are in the order beta, alpha, beta, alpha, inverted with respect to each other. One of the SB beta genes contains a 513 bp sequence that appears to be a processed pseudogene, flanked by direct 17 bp repeat sequences, in the intron upstream of the beta 1 exon. The pseudogene is homologous to a family of sequences of approximately 25-40 members, most of which are not on chromosome 6. A cDNA clone, highly homologous to the pseudogene, except for its 5' end, contains a normal poly(A) addition site and a poly(A) tail. The cDNA clone is homologous to a single-copy gene in both man and mouse, encoded on human chromosome 15. A search of published DNA sequences identified a mouse sequence, with about 77% similarity to the pseudogene sequence, in the negative strand of an intron in a mouse dihydrofolate reductase gene. The second SB beta gene does not contain the pseudogene sequence.

Amino Acid Sequence↗

An immunohistological study of testicular germ cell tumours using two different monoclonal antibodies against placental alkaline phosphatase.

Using two monoclonal antibodies directed against placental alkaline phosphatase (H17E2 and D20L) the immunohistological staining of testicular germ cell tumours was compared with that of a wide range of normal and malignant tissues. All seminomas and malignant teratomas tested gave strong positive labelling with H17E2 but were either negative or only patchily positive with D20L. Neither antibody gave any positive reaction on the normal tissues tested. All other malignancies were negative with both antibodies apart from two cases of ovarian and one case of endometrical cancer (strongly stained by H17E2) and three cases of colonic carcinoma (weakly and patchily stained by both H17E2 and D20L). This indicates that germ cell neoplasms generally express a form of placental alkaline phosphatase recognised by antibody H17E2.

Alkaline Phosphatase↗

Isolation and sequencing of a cDNA clone for a human HLA-ABC antigen.

A cDNA clone, pHLA-A, containing sequences specific for a human class I HLA antigen heavy chain, was isolated from a bank of clones made from partially purified HLA-ABC heavy chain mRNA from the human lymphoblastoid cell line Bristol 8 (HLA-A1, A2, B8, B16). The clone corresponded to sequence for the -COOH-terminal 117 amino acids of an HLA-ABC alpha-chain. It differed in at least 15 positions from the published HLA-B7 amino acid sequence but in only two residues when compared to the partial HLA-A2 protein sequence, and was identical to the HLA-A3 protein sequence derived from the nucleotide sequence of the gene. It also differed from some published human HLA-ABC sequences by the addition of three extra -COOH-terminal amino acids: cysteine-lysine-valine. The clone may correspond to either the HLA-A1 allele, for which independent sequence information is not available, or to HLA-A2, in which case there are possible explanations for the discrepancies. Comparison of the pHLA-A sequence with genomic HLA sequences suggests variations in splicing at the end of the protein coding region in some HLA-ABC heavy chain genes, and the use of alternative poly(A) addition sites.

Amino Acid Sequence↗

Molecular analysis of the HLA-D region genes.

Analysis of the amino acid sequence of the HLA-DR alpha chain and the structure of the gene encoding it have shown strong homologies to membrane proximal domains of the DR beta chain and HLA-ABC, as well as to beta 2-microglobulin. Weaker, but nevertheless apparent homologies to C kappa and C lambda immunoglobulin domains support the interpretation that these genes diverged in evolution from a primordial immunoglobulin-like domain. Cosmid clones containing sequences related to the DR alpha chain have been isolated. These sequences probably represent the SB and DC alpha genes. In addition to the alpha "genes," some of the cosmids also contain sequences related to the DR beta chain suggesting that the human HLA-D region alpha and beta genes are interspersed.

Amino Acid Sequence↗

Expression of HLA-A, -B, and -C and beta 2-microglobulin antigens in human choriocarcinoma cell lines.

Immunoprecipitation of [35S]methionine-labeled cell extracts and analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed that cells from two human choriocarcinomas JaR and BeWo contained beta 2-microglobulin. The JaR cells, and one subline of BeWo, did not express surface HLA-A, -B, and -C (HLA-ABC) antigens, nor did JaR contain the antigens when cell-free extracts were measured in a sensitive radioimmunoassay. It may be concluded that the lack of expression of HLA-ABC antigens in choriocarcinoma (and in the trophoblast) is not a result of lack of beta 2-microglobulin, as is the case for the Burkitt's lymphoma cell line, Daudi.

Animals↗

The obstructed kidney: correlation between renal function and urodynamic assessment.

In 20 patients with pelvi-ureteric junction obstruction the results of quantification of the change in renal pelvis size during high-dose intravenous urography with a diuretic, pressure/flow studies, standard renography and deconvolution analysis of the gamma camera renogram have been compared. The results of high-dose intravenous urography and pressure/flow studies correlated well. Renography was unreliable in diagnosing obstruction unless deconvolution analysis of the gamma camera renogram was used to differentiate those showing an obstructive uropathy from those with an obstructing nephropathy.

Humans↗

Structural and evolutionary analysis of HLA-D-region products.

The major histocompatibility complex (MHC)--HLA in man and H-2 in mouse--encodes two classes of cell-surface antigens involved in the immune response. The amino acid sequences have been determined for a number of these molecules. Class I antigens, typified by the HLA-ABC antigens, are composed of a 43,000-molecular weight (MW) glycosylated transmembrane polypeptide with three external domains (alpha 1, alpha 2 and alpha 3), of which the one nearest the membrane (alpha 3) is associated with a 12,000-MW nonglycosylated polypeptide, beta 2-microglobulin. The HLA-D-region or class II antigens, DR, DC and SB, are composed of two glycosylated transmembrane polypeptides, of MWs 34,000 (alpha-chain) and 28,000 (beta-chain). Both chains have two external domains which presumably associate with each other, alpha 2, beta 2 being membrane proximal and alpha 1, beta 1 N-terminal and membrane distal. All four membrane-proximal domains (class I alpha 3, beta 2-microglobulin, class II alpha 2 and beta 2) have amino acid sequences that show significant similarities with immunoglobulin constant-region domains. This, together with the similarly placed internal disulphide bonds, suggests they might have an immunoglobulin-like structure (Fig. 1). We have now used computer graphics techniques to predict a detailed three-dimensional structure for the membrane-proximal domains of the class II antigens (alpha 2 and beta 2) based on the known coordinates of immunoglobulin constant domains (Fig. 2). The transmembrane regions of class II antigens have been modelled as two alpha-helices packed together. The proposed structure accounts for conservation of amino acids and leads to evolutionary predictions.

Amino Acid Sequence↗