Search PubMed⌕ Search

Biomedical subjects

T B Shows

Publications and source records attributed to T B Shows.

At least 235 records · Page 13Linked to original sources
PubMed1986

Heterogeneity of N-acetylglucosamine 1-phosphotransferase within mucolipidosis III.

The primary defect responsible for mucolipidosis III is a deficiency of UDP-N-acetylglucosamine:lysosomal enzyme N-acetylglucosamine 1-phosphotransferase activity (GlcNAc phosphotransferase). Genetic complementation analysis of cultured fibroblasts derived from 12 patients with mucolipidosis III identified complementation groups A, B, and C (Honey, N. K., Mueller, O. T., Little, L. E., Miller, A. L., and Shows, T. B. (1982) Proc. Natl. Acad. Sci. U.S.A. 79, 7420-7424). The GlcNAc phosphotransferase activity present in the cell lines comprising the complementation groups was characterized with respect to endogenous substrates and two exogenous acceptors, alpha-methyl-D-mannoside and high mannose glycopeptides. All group C cell lines and one group A cell line were found to have normal GlcNAc phosphotransferase activity levels at 37 degrees C when screened with these exogenous acceptors. The enzyme activity in group A cell lines was within normal range when assayed at 23 degrees C. Inhibition of the phosphorylation of alpha-methyl-D-mannoside in the presence of increasing amounts of endogenous substrate N-acetyl-beta-D-hexosaminidase B was demonstrated in normal cell lines at 23 and 37 degrees C and in group A cells at 23 degrees C. However, group C cell lines did not show any inhibition at either temperature. This suggests that the alteration of the GlcNAc phosphotransferase from individuals in group C affects the recognition site for the protein portion of lysosomal enzymes, whereas group A individuals have mutations which result in a temperature-sensitive enzyme.

Cell Line↗
PubMed1986

Mapping of human autosomal phosphoglycerate kinase sequence to chromosome 19.

In order to map human PGK sequences, DNA was prepared from 55 human-mouse somatic cell lines. The DNA was digested to completion with HindIII and Southern filters prepared. These filters were hybridized at high stringency conditions to a human PGK cDNA. Mouse and human X-linked and autosomal bands were distinguished and, in addition to known X-linked sequences, two autosomal PGK sequences were mapped: a 1-kb band to chromosome 19 and a 5-kb band to chromosome 6. The PGK cDNA probe was also hybridized to flow-sorted chromosomes confirming the presence of PGK sequences on the X chromosome and chromosomes 6 and 19.

Animals↗
PubMed1986

Mapping thyrotropin beta subunit gene in man and mouse.

Thyrotropin (TSH) is composed of two subunits: alpha and beta. Previously, we have mapped the TSH alpha gene to human chromosome 6 and mouse chromosome 4. In this study we have located the human TSH beta gene on chromosome 1 and the mouse TSH beta gene to chromosome 3. These data suggest that the TSH beta gene lies in a conserved linkage group with the genes for amylase 1 and 2, nerve growth factor, and the protooncogene Nras.

Animals↗
PubMed1986

Pks, a raf-related sequence in humans.

A human fetal liver cDNA library was screened at reduced hybridization stringency for v-raf-related sequences. In addition to the expected c-raf-1 cDNA, a second sequence was isolated. Comparison of the second gene (pks) to the other raf-related sequences revealed nucleotide homologies of 71%. The predicted amino acid sequence of the kinase domain is sufficiently similar to that of v-raf to suggest that pks may encode a polypeptide that exhibits serine/threonine kinase activity. The expression of pks mRNA (2.7 kilobases long) is elevated in peripheral blood mononuclear cells isolated from two patients with angioimmunoblastic lymphadenopathy with dysproteinemia, a disease in which autoantibodies are produced following the lymphoproliferative activation of B cells. Analysis of somatic cell hybrids for segregation of the pks locus revealed the presence of an additional locus closely related to the pks sequence.

Amino Acid Sequence↗
PubMed1986

Hepatitis B virus integration site in hepatocellular carcinoma at chromosome 17;18 translocation.

Integrated hepatitis B virus (HBV) DNA is almost invariably found in hepatocellular carcinomas (HCC) which develop in HBV carriers. Integrated HBV DNAs from two single-integration HCCs (C3 and C4) have been cloned, and the cellular integration sites have been analyzed. Integrated HBV DNA of C3 is present in chromosome 6 and contains a nearly complete linear HBV genome. The HBV DNA integration in tumor C3 was not associated with major rearrangements of cellular DNA. In contrast, the integrated HBV DNA in C4 contains a large inverted repeat of HBV DNA, in which each repeat consists of a linear HBV DNA segment similar to that present in C3. The C4 integration was also accompanied by a cellular DNA translocation at the HBV integration site. The translocation occurred between chromosomes 17 and 18, along with a deletion of at least 1.3 kilobases of chromosome 18 DNA at the translocation site. Our data support a model in which postintegration rearrangement of integrated HBV and cellular DNA results in the generation of chromosomal aberrations. These chromosomal aberrations may function in a multistage mechanism leading to fully malignant HCC.

Base Sequence↗
PubMed1986

Sialidosis and galactosialidosis: chromosomal assignment of two genes associated with neuraminidase-deficiency disorders.

The inherited human disorders sialidosis and galactosialidosis are the result of deficiencies of glycoprotein-specific alpha-neuraminidase (acylneuraminyl hydrolase, EC 3.2.1.18; sialidase) activity. Two genes were determined to be necessary for expression of neuraminidase by using human-mouse somatic cell hybrids segregating human chromosomes. A panel of mouse RAG-human hybrid cells demonstrated a single-gene requirement for human neuraminidase and allowed assignment of this gene to the (pter----q23) region of chromosome 10. A second panel of mouse thymidine kinase (TK)-deficient LM/TK- -human hybrid cells demonstrated that human neuraminidase activity required both chromosomes 10 and 20 to be present. Analysis of human neuraminidase expression in interspecific hybrid cells or polykaryocytes formed from fusion of mouse RAG (hypoxanthine/guanine phosphoribosyltransferase deficient) or LM/TK- cell lines with human sialidosis or galactosialidosis fibroblasts indicated that the RAG cell line complemented the galactosialidosis defect, but the LM/TK- cell line did not. This eliminates the requirement for this gene in RAG-human hybrid cells and explains the different chromosome requirements of these two hybrid panels. Fusion of LM/TK- cell hybrids lacking chromosome 10 or 20 (phenotype 10+,20- and 10-,20+) and neuraminidase-deficient fibroblasts confirmed by complementation analysis that the sialidosis disorder results from a mutation on chromosome 10, presumably encoding the neuraminidase structural gene. Galactosialidosis is caused by a mutation in a second gene required for neuraminidase expression located on chromosome 20.

Animals↗
PubMed1986

The chromosome 11 gene map: genes for growth and development, Wilms' tumor deletions, and cancer chromosome breakpoints.

Human chromosome 11 is clearly a model autosome encoding genes and characteristics associated with both normal and abnormal growth and development, and several significant disorders. A fine-structure molecular, genetic, and physical map of this chromosome would add considerably to our knowledge of the organization and control of human genes and to an understanding of normal and abnormal human biology.

Animals↗
PubMed1986

Assignment of the human fibronectin structural gene to chromosome 2.

A cloned human cDNA probe for fibronectin (FN) containing 1.3 kb of the human FN coding region has been used to determine the chromosome that encodes the structural gene in human-mouse somatic cell hybrids. The results show that human chromosome 2 encodes the FN structural gene.

Animals↗
PubMed1986

The gene for human transforming growth factor alpha is on the short arm of chromosome 2.

Transforming growth factor alpha is a polypeptide growth factor that participates in the reversible transformation of cells in vitro and is secreted by many transformed cell lines. It also shares sequence and functional homologies with epidermal growth factor. Working with a cloned cDNA probe (lambda hTGF1-10) and derivatives, we have mapped this gene (TGFA) to 2p13 with the use of somatic cell hybrids and in situ hybridization. This is the same region involved in the 2;8 translocations of Burkitt lymphoma. Such a rearrangement could orient c-myc (8q24) adjacent to TGFA, resulting in activation of one or both of these genes.

Animals↗
PubMed1986

Regional assignment of the erythropoietin gene to human chromosome region 7pter----q22.

The chromosomal location of the human gene for erythropoietin (EPO) was determined by Southern blot hybridization analysis of a panel of human-mouse somatic hybrid cell DNAs. DNAs from cell hybrids containing reduced numbers of human chromosomes were treated with the restriction enzyme PstI and screened with a cloned human EPO cDNA probe. EPO is assigned to human chromosome 7 based on the complete cosegregation of EPO with this chromosome in all 45 cell hybrids tested. A cell hybrid containing a translocated derivative of chromosome 7 localizes EPO to 7pter----q22. A HindIII restriction fragment length polymorphism is detected by hybridization of the EPO cDNA probe to human genomic DNA.

Animals↗
PubMed1986

Chromosome 1 localization of the human alpha-L-fucosidase structural gene with a homologous site on chromosome 2.

Two cDNA clones coding for human alpha-L-fucosidase, one from the coding region and the other primarily from the 3' untranslated region, were used to map the location of the alpha-L-fucosidase gene. Southern filter analysis of somatic cell hybrid lines mapped the structural gene to the short arm of human chromosome 1, and in situ hybridization to chromosomes of human leukocytes further localized the homologous area to the 1p36.1----p34.1 region, with the most likely location being the distal region of 1p34. Further Southern filter analysis detected a second site of homology on chromosome 2. This alpha-L-fucosidase-like site has been designated FUCA1L.

Animals↗
PubMed1986

Assignment of the pepsinogen gene complex (PGA) to human chromosome region 11q13 by in situ hybridization.

The genes coding for human pepsinogen (PGA3, PGA4, and PGA5) were assigned to chromosome region 11q13 by in situ hybridization. Previously we localized the PGA gene complex to a centromeric region of chromosome 11 (p11----q13) by Southern blot analysis of mouse-human somatic cell hybrids. Our in situ hybridization results confirm this assignment and further localize the genes to a smaller region on the long arm.

Chromosome Banding↗
PubMed1986

Genes encoding pancreatic polypeptide and neuropeptide Y are on human chromosomes 17 and 7.

Pancreatic polypeptide and neuropeptide Y share 50% amino acid homology (18 out of 36 residues), suggesting that they may have common ancestral origins. cDNA clones complementary to human mRNAs encoding pancreatic polypeptide and neuropeptide Y were used to detect specific human genomic DNA sequences in human-mouse somatic cell hybrid lines. The pancreatic polypeptide gene (PPY) segregated with human chromosome 17, while the neuropeptide Y gene (NPY) segregated with human chromosome 7. Examination of cell hybrids with chromosomal rearrangements assigned PPY to the p11.1-qter region and NPY to the pter-q22 region of their respective chromosomes.

Amino Acid Sequence↗
PubMed1986

Interleukin-1 gene (IL1) assigned to long arm of human chromosome 2.

A complementary DNA (cDNA) probe for the predominant (pI 7) form of human monocyte-derived interleukin-1 (IL1) and a collection of 30 human-mouse somatic cell hybrids were used to assign the IL1 gene to human chromosome 2 by Southern blot analysis of hybrid cell DNA digested with the restriction endonuclease BglII. In situ hybridization to human metaphase chromosomes localized the IL1 gene to the long arm of chromosome 2 at position 2q13-2q21 between two fragile sites.

Animals↗
PubMed1986

Enhanced levels of insulin-like growth factor messenger RNA in human colon carcinomas and liposarcomas.

The insulin-like growth factors I and II (IGF-I and -II) are proteins which stimulate cell proliferation and are important in normal human growth and development. They are coded for by separate genes and bind to specific cell surface receptors, eliciting a mitogenic response. IGFs are secreted by several cell lines derived from adult tumors. We have examined a number of human adult tumors for IGF messenger RNA (mRNA) expression and found IGF-II mRNA levels were consistently elevated in two types, colon carcinoma and liposarcoma. Adult colonic mucosa contains low levels of IGF-I and -II mRNA while several colon tumors, particularly of rectal and rectosigmoid origin, contained significantly elevated levels of IGF-II message. Over 90% of liposarcomas examined contained greatly elevated levels of IGF-II mRNA while control tissue (adipose) contained very low or undetectable IGF mRNA levels. Many of these tumors also contained elevated IGF-I mRNA levels. Northern analysis of these RNAs revealed differences in the abundance and sizes of IGF transcripts compared to other normal and malignant tissues known to express IGF.

Carcinoma↗
PubMed1985

Chromosomal locations of human tissue plasminogen activator and urokinase genes.

A panel of human-mouse somatic cell hybrids and specific complementary DNA probes were used to map the human tissue plasminogen activator and urokinase genes to human chromosomes 8 and 10, respectively. This result is in contrast to a previous assignment of a plasminogen activator gene to chromosome 6. As neoplastic cells produce high levels of plasminogen activator, it is of interest that aberrations of chromosome 8 have been linked to various leukemias and lymphomas and that two human oncogenes, c-mos and c-myc, have also been mapped to chromosome 8.

Animals↗
PubMed1985

Deletion in chromosome 11p associated with a hepatitis B integration site in hepatocellular carcinoma.

Hepatitis B virus (HBV), a virus with known carcinogenic potential, integrates into cellular DNA during long-term persistent infection in man. Hepatocellular carcinomas isolated from viral carriers often contain clonally propagated viral DNA integrations. As small chromosomal deletions are associated with several types of carcinomas, the occurrence of chromosomal deletions in association with HBV integration in hepatocellular carcinoma was studied. HBV integration was accompanied by a deletion of at least 13.5 kilobases of cellular sequences in a human hepatocellular carcinoma. The viral DNA integration and deletion of cellular sequences occurred on the short arm of chromosome 11 at location 11p13-11p14. The cellular sequences that were deleted at the site of HBV integration were lost from the tumor cells, leaving only a single copy of the remaining cellular allele.

Animals↗