PubMed Health⌕ Search

Biomedical subjects

B Pym

Publications and source records attributed to B Pym.

At least 19 recordsLinked to original sources
PubMed1990

Cost-effectiveness of cimetidine maintenance therapy in chronic gastric and duodenal ulcer.

The effects of cimetidine maintenance therapy on the socioeconomic life of patients with peptic ulcers in the 3 years after healing and the extent to which treatment was cost-effective were studied. Three hundred eleven patients with healed ulcers (184 gastric, 127 duodenal) were studied for periods of up to 3 years; 261 patients (152 gastric ulcer, 109 duodenal ulcer) completed the 3-year follow-up. Cimetidine (400 mg at night) was compared with placebo in a double-blind, randomized prospective study. Intention-to-treat analysis was used. In the placebo group, the major costs of ulcer disease in gastric ulcer patients were attributable to endoscopic procedures and absenteeism; in duodenal ulcer patients, the major costs were endoscopic procedures, absenteeism, and surgery. Cimetidine was cost-effective in both gastric ulcer and duodenal ulcer patients in the first 2 years after healing. Over the 3-year period it was also cost-effective, but no benefit was seen in the third year.

Absenteeism↗
PubMed1990

Comparison of human ZFY and ZFX transcripts.

ZFY is a candidate for the primary sex-determining gene (TDF, testis-determining factor) on the human Y chromosome. We have isolated cDNA clones of ZFY and its homologue on the X chromosome, ZFX. The transcripts of these genes are very similar to each other and encode predicted proteins of equal size. The conceptual amino acid sequence of both proteins contains an acidic domain, similar to the activation domain of transcription factors, and a potential nucleic acid-binding domain of 13 "zinc fingers." We have used the polymerase chain reaction to demonstrate the expression of ZFY and ZFX in a wide range of adult and fetal human tissues and to show that ZFX is expressed from the inactive X chromosome present in human-mouse hybrids.

Amino Acid Sequence↗
PubMed1989

The pseudoautosomal boundary in man is defined by an Alu repeat sequence inserted on the Y chromosome.

The Y chromosome, which in man determines the male sex, is composed of two functionally distinct regions. The pseudoautosomal region is shared between the X and Y chromosome and is probably required for the correct segregation of the sex chromosomes during male meiosis. The second region includes the sex-determining gene(s), the presence of which is necessary for the development of testes. The two regions have contrasting genetic properties: the pseudoautosomal region recombines between the X and Y chromosome; the Y-specific region must avoid recombination otherwise the chromosomal basis of sex-determination breaks down. The pseudoautosomal region is bounded at the distal end by the telomere and at the proximal end by X- and Y-specific DNA. We have found that the proximal boundary was formed by the insertion of an Alu sequence on the Y chromosome early in the primate lineage. Proximal to the Alu insertion there is a small region where similarity between the X and Y chromosomes is reduced and which is no longer subject to recombination.

Base Sequence↗
PubMed1989

The MIC2 gene product: epitope mapping and structural prediction analysis define an integral membrane protein.

The MIC2 locus is located in the pseudoautosomal (pairing) region of human X and Y chromosomes (Goodfellow et al., Science 234, 740-743, 1986). Despite extensive molecular analysis of MIC2 (see Darling et al., Cold Spring Harb. Symp. quant. Biol. 51, 205-211, 1986), study of the gene product has been limited (Banting et al., EMBO J. 41, 1967-1972, 1985). Here we report the combined use of monoclonal antibodies, plasmid expression vectors and structural prediction analysis to define the MIC2 gene product as an integral membrane protein. Random overlapping fragments of a cDNA, corresponding to the MIC2 locus, were cloned into the plasmid expression vector pEX1 (Stanley and Luzio, EMBO J. 3, 1429-1434, 1984) to produce "epitope libraries". Six different monoclonal antibodies, known to recognize the extracellular region of the MIC2 gene product, were used to screen these libraries. Clones recognized by these antibodies were sequenced and their sequences aligned with one another and with the complete MIC2 cDNA sequence. All antibodies tested recognized adjacent and/or overlapping epitopes in the same region of the molecule. These results complement data from a hydropathy plot of a conceptual translation of the MIC2 sequence, which demonstrated the presence of a single long hydrophobic region in the mature protein. Since the antibodies recognize the extracellular portion of the molecule, we were able to determine the orientation in the plasma membrane. This method of analysis is generally applicable where antibodies and cloned cDNAs are available.

Amino Acid Sequence↗
PubMed1988

MIC2: a human pseudoautosomal gene.

MIC2 and XGR are the only known pseudoautosomal genes in man. MIC2 encodes the 12E7 antigen, a human cell-surface molecule of unknown function. XGR regulates, in cis, the expression of the XG and MIC2 genes. DNA probes derived from the MIC2 locus have been used in the construction of a meiotic map of the pseudoautosomal region and a long range restriction map into the X- and Y-specific chromosome domains. MIC2 is the most proximal marker in the pseudoautosomal region and recombination between the sex chromsomes only rarely includes the MIC2 locus. Our long-range restriction maps and chromosome walking experiments have localized the pseudoautosomal boundary within 40 kilobases adjacent to the 3' end of the MIC2 gene. The same maps have been used to predict the chromosomal location of TDF.

Amino Acid Sequence↗
PubMed1988

Biochemical and genetic analysis of the OKa blood group antigen.

The monoclonal antibody TRA-1-85 recognizes a cell surface antigen which is expressed by all human cell types tested, including red blood cells (RBCs), but not by mouse cells. All the human RBCs tested were TRA-1-85 positive except those with the rare phenotype Ok(a-). Oka is a blood group antigen of very high frequency and only three unrelated Ok(a-) people are known. The red cells of all three propositi were negative with the TRA-1-85 antibody. To confirm the relationship between the TRA-1-85 antibody and anti-Oka, the immune antibody found in the serum of Ok(a-) individuals, Western blot analysis was used: the TRA-1-85 antibody and anti-Oka gave identical but complex patterns of reactivity in Western blot analysis of human cell lysates or membranes. This suggests that the anti-Oka and TRA-1-85 antibodies recognize the same cell-surface determinant and implies that Oka is not restricted in its expression to the surface of RBCs but is expressed on white blood cells (WBCs) of Ok(a+) individuals and all human cell lines tested to date. WBCs from one of the Ok(a-) propositi were tested and found to be negative with the TRA-1-85 antibody. Finally, the species specificity of the TRA-1-85 antibody has been exploited by the use of somatic cell hybrids and DNA transfection techniques to examine the genetic control of the Oka antigen defined by the TRA-1-85 antibody. We report that the determinant is controlled by a single gene OK present on human chromosome 19.

Animals↗
PubMed1988

Absence of methylation of a CpG-rich region at the 5' end of the MIC2 gene on the active X, the inactive X, and the Y chromosome.

We have identified and characterized a Hpa II tiny fragment (HTF) island associated with the promoter region of the pseudoautosomal gene MIC2. The MIC2 HTF island is unmethylated on both the active and inactive X chromosome and is similarly unmethylated on the Y chromosome. Unlike the majority of genes borne on the X chromosome, MIC2 fails to undergo X chromosome inactivation. HTF islands associated with X chromosome-linked genes that are inactivated are highly methylated on the inactive or transcriptionally silent homologue. The failure of MIC2 to undergo X chromosome inactivation correlates with the lack of methylation of the HTF island at the 5' end of the gene. These results provide further evidence that DNA methylation plays an important role in the phenomenon of X chromosome inactivation.

Antigens, Surface↗
PubMed1987

Pseudoautosomal genes in man.

MIC2, which encodes the 12E7 antigen, is the only well-defined pseudoautosomal gene in man. We have isolated cDNA and genomic sequences corresponding to MIC2 and have produced monoclonal antibodies reacting with the 12E7 antigen. These molecular tools have been used to investigate the genetics and biochemistry of the MIC2 system. Recent results suggest that MIC2 is the most proximal of the currently defined pseudoautosomal markers and that the escape of MIC2 from X-inactivation may be intrinsic to an associated HTF island found at the 5' end of the gene. Investigation of the inter-relationship between MIC2 and the XG locus has led us to postulate the existence of a second pseudoautosomal gene in man.

Antibodies, Monoclonal↗
PubMed1986

Cloning an expressed gene shared by the human sex chromosomes.

The existence of genes shared by mammalian sex chromosomes has been predicted on both evolutionary and functional grounds. However, the only experimental evidence for such genes in humans is the cell-surface antigen encoded by loci on the X and Y chromosomes (MIC2X and MIC2Y, respectively), which is recognized by the monoclonal antibody 12E7. Using the bacteriophage lambda gt11 expression system in Escherichia coli and immunoscreening techniques, we have isolated a cDNA clone whose primary product is recognized by 12E7. Southern blot analysis using somatic cell hybrids containing only the human X or Y chromosomes shows that the sequences reacting with the cDNA clone are localized to the sex chromosomes. In addition, the clone hybridizes to DNAs isolated from mouse cells that have been transfected with human DNA and selected for 12E7 expression on the fluorescence-activated cell sorter. We conclude that the cDNA clone encodes the 12E7 antigen, which is the primary product of the MIC2 loci. The clone was used to explore sequence homology between MIC2X and MIC2Y; these loci are closely related, if not identical.

Animals↗
PubMed1985

Biochemical analysis of an antigen produced by both human sex chromosomes.

It has been argued on both evolutionary and functional grounds that genes must be shared by the mammalian sex chromosomes. The only direct evidence for such genes is our previous finding that loci on the human X (MIC2X) and Y (MIC2Y) chromosomes encode a species-specific cell surface antigen recognised by the monoclonal antibody 12E7. These loci map to the regions of the sex chromosomes which pair at meiosis, and MIC2X has been shown to escape X-inactivation. We have used immunoprecipitation and Western blot analysis combined with one- and two-dimensional polyacrylamide gel electrophoresis to compare the products of MIC2X and MIC2Y. The human specific molecule recognised by the 12E7 antibody is a membrane-associated polypeptide of mol. wt. 32.5 kd and pI = 5.0. No difference in size or charge has been detected between X and Y encoded forms of this molecule confirming that MIC2Y is a functional homologue of MIC2X. An intracellular polypeptide of mol. wt. 29 kd and pI = 7.0 present in the cytoplasm of both human and mouse cells is also recognised by the 12E7 antibody.

Antigens↗
PubMed1985

The generation of monoclonal antibodies against human pancreatic exocrine cancer: a study of six different immunisation regimes.

Six different immunisation regimes have been used to generate spleen cells with reactivity against human pancreatic exocrine cancer. Immunised spleen cells were fused with an NSO/1 myeloma line and supernatants from these hybridomas selectively screened for monoclonal antibodies which bound predominantly to a pancreatic cancer cell line (GER). The spleen cells from hairy litter mates immunised with pancreatic cancer xenograft homogenates and viable GER cells generated 13% of hybridoma supernatants which showed some selectivity for GER pancreatic cancer cells in a fixed cell ELISA assay. The other methods produced only 4% of hybrids with selectivity for GER cells. The antigen distribution on gluteraldehyde fixed cells was similar to that found for viable cell monolayers but many antigens were unstable on formalin fixation. Immunohistochemical staining of GER cells grown on glass slides showed a heterogeneity of antigen distribution with up to 70% of the cells exhibiting a vesicular pattern of staining. Fifty percent of the antibodies which bound to GER cells were also reactive against antigens in formalin-fixed paraffin-embedded tissue sections of the original GER tumour. Monoclonal antibody DD9E7 identified an antigen expressed on 12/14 pancreatic adenocarcinomas. The antibody showed strong staining of malignant luminal membranes and cytoplasm. The antigen was also present in normal salivary and sweat glands, and colon and breast carcinomas, but its tissue distribution was unlike that of CEA or EMA. The expression of this antigen in 12/14 of pancreatic carcinomas suggests that DD9E7 may be a useful reagent for pancreatic tumour detection.

Adenocarcinoma↗
PubMed1985

A human cell-surface antigen defined by a monoclonal antibody and controlled by a gene on human chromosome 1.

An antigen expressed by most human cells, but not erythrocytes, has been defined by a murine monoclonal antibody, TRA-2-10. This antigen is expressed on the surface of human-mouse somatic cell hybrids, and segregation analysis indicates that it is controlled by a gene located on human chromosome 1. From lysates of most human cells, surface-labelled with 125I, TRA-2-10 immunoprecipitates two polypeptides with molecular weights in the range of about 55 000 to 73 000 depending upon the cell line. Since the TRA-2-10 polypeptides from a fibroblast cell strain and a hepatoma cell line from one individual differ, we conclude that the observed difference in molecular weight has an epigenetic origin.

Animals↗
PubMed1985

Cell surface differentiation antigen of human muscle encoded by a gene (MIC12) on chromosome 15.

Monoclonal antibody 30.2A8 was produced by a hybridoma made by fusing cells from rats that had been immunized with rat-human muscle cell hybrids. The 30.2A8 reacts with a differentiation antigen in human skeletal muscle that is synthesized by myoblasts but not myotubes. The gene controlling synthesis of the antigen recognized by 30.2A8 was found to be encoded by human chromosome 15.

Antibodies, Monoclonal↗
PubMed1984

Human muscle cell surface antigen 16.3A5 is encoded by a gene on chromosome 11.

A monoclonal antibody (McAb), 16.3A5, has been characterized that reacts with a cell surface antigen of human muscle cells and a variety of nonmuscle cells. The gene controlling synthesis of 16.3A5 antigen has been assigned to human chromosome 11 by assessing McAb reactivity on a panel of mouse-human cell hybrids. The 16.3A5 has a novel specificity distinct from other chromosome 11-encoded antigens such as W6/34, F10.44.2, TRA1.10, and 4D12 antigens.

Adult↗
PubMed1984

Relationships between genes on human chromosome 11 encoding cell-surface antigens.

Genes encoding seven monoclonal antibody-defined cell-surface antigens have been regionally mapped on human chromosome 11, and compared to those of the AL complex defined by polyclonal antibodies using mutational analysis. MIC1, encoding W6/34 antigen, is probably identical to S1, previously mapped to 11pter-p13. MDU1 and MIC8, encoding 4F2 and TRA-1.10 antigens, respectively, are probably identical to S2(a4) and map to 11q13-q22. MIC9, which governs expression of 4D12 and 2E2 antigens, and maps to 11q22-qter, is not related to any of the five AL genes. MIC4 and MIC11, both mapping to 11pter-p13, may have some relationship to S3 and S1, respectively, but identity has not been proven.

Antibodies, Monoclonal↗
PubMed1984

The cell surface antigen locus, MIC2X, escapes X-inactivation.

Recently, it was shown that the cell surface antigen defined by the monoclonal antibody 12E7 is expressed by both the human X and Y chromosomes; the gene loci on the X and Y chromosomes are referred to as MIC2X and MIC2Y, respectively. It was also shown that MIC2X is located in the region Xp22.3----Xpter and MIC2Y is in the region Ypter-Yq1.1. Here, we show that MIC2X escapes X-inactivation on structurally normal and abnormal inactive human X chromosomes.

Animals↗