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B A Taylor

Publications and source records attributed to B A Taylor.

At least 19 recordsLinked to original sources
PubMed1992

Mapping of ornithine aminotransferase gene sequences to mouse chromosomes 7, X, and 3.

Ornithine aminotransferase (OAT), a mitochondrial matrix enzyme, is deficient in patients with gyrate atrophy of the choroid and retina. In human, the OAT structural gene maps to Chromosome (Chr) 10q26 and several OAT-related sequences, some of which are known to be processed pseudogenes, which map to Xp11.3-11.21. Here, we report chromosomal localization in the mouse of the OAT gene and related sequences. Genomic DNA blot analysis of a well-characterized panel of Chinese hamster x mouse somatic cell hybrids using a human OAT probe revealed two murine loci, one on mouse Chr 7 and the other on Chr X. In addition, segregation of restriction fragment length polymorphisms (RFLPs) detected by the OAT probe in recombinant inbred (RI) strains detected a third locus on Chr 3 and positioned the X locus near Cf-8 and Rsvp. Progeny of an intersubspecific backcross were used to map the Chr 7 locus between Tyr and Int-2, near Cyp2e-1.

Alleles↗
PubMed1992

Dysplasia in chronic ulcerative colitis: implications for colonoscopic surveillance.

Mucosal dysplasia has been used as a marker for patients with chronic ulcerative colitis considered to be most at risk of developing cancer, and its identification is the basis for colonoscopic surveillance programs. To evaluate the reliability of this premise, colectomy specimens from two groups of patients who had undergone surgery for chronic ulcerative colitis (50 with cancer and 50 without) were retrieved. The groups were matched by age, sex, duration of disease, disease extent, and symptoms at the time of surgery. Using a standard technique of multiple random biopsies, we utilized the standard colonoscopic biopsy forceps to obtain four biopsies from mucosa that was not macroscopically suspicious for dysplasia or cancer in eight defined regions in each of the 100 colon specimens. This technique mimicked exactly the methods used in our clinical surveillance program. All 3,200 biopsies were evaluated blindly by one pathologist for presence and grade of dysplasia. Twenty-six percent of colons with an established cancer harbored no dysplasia in any biopsy from any region in the colon. While an overall association between the presence of cancer and high-grade dysplasia was detected (relative risk = 9.00; 95 percent CI of 2.73-29.67), the sensitivity and specificity of random colonic biopsies to detect concomitant carcinoma were 0.74 and 0.74, respectively. These findings prompt concern that reliance on random biopsies, obtained during colonoscopic surveillance, may be misplaced.

Adult↗
PubMed1992

Management of massive upper gastrointestinal haemorrhage from multiple sites of peptic ulceration with somatostatin and octreotide--a report of five cases.

Surgical management of massive upper gastrointestinal bleeding after failed medical treatment may be hazardous because of diffuse bleeding from several sites, further complicated in some patients by intercurrent disease, age, or previous surgery. Experience with combined somatostatin and octreotide therapy in five such patients is described. All were treated initially with either intravenous somatostatin (250 micrograms/hour) or octreotide (Sandostatin) (50 micrograms/hour) for periods ranging from three to five days, after which they were given subcutaneous octreotide (50 or 100 micrograms three times daily). Bleeding was controlled by this regimen in all cases. The patients were all discharged from hospital on either ranitidine (n = 4) or omeprazole (n = 1). Repeat endoscopy at the end of the treatment period with somatostatin and octreotide (n = 1) or four weeks after discharge (n = 3) showed complete healing of the bleeding sites. Somatostatin and octreotide may be of value in controlling severe upper gastrointestinal bleeding in patients in whom surgery is hazardous because of bleeding from several peptic lesions further complicated in some by intercurrent disease or age.

Adult↗
PubMed1992

Genetic and dietary interactions in the regulation of HMG-CoA reductase gene expression.

Inbred strains of mice exhibit large genetic variations in hepatic 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase activity. A tissue-specific genetic variation between the strains BALB/c and C57BL/6, resulting in about 5-fold higher levels in hepatic reductase activity in strain C57BL/6, was examined in detail. The activity difference between these two strains could be explained entirely by differences in hepatic reductase mRNA levels. In genetic crosses, the variation segregated as a single major Mendelian element. Surprisingly, the mode of inheritance was recessive since F1 mice exhibited the BALB/c levels of enzyme activity. Despite the fact that the rates of hepatic sterol synthesis also differed between the strains by a factor of about five, the altered hepatic reductase expression did not significantly influence plasma lipoprotein levels. The response to a high cholesterol, high fat diet between the strains was remarkably different. Thus, in BALB/c mice, both hepatic reductase activity and mRNA levels were affected only slightly, if at all, by cholesterol feeding, while in strain C57BL/6 mice both were reduced more than 10-fold by cholesterol feeding. Several lines of evidence, including analysis of cis-acting regulatory elements, the nonadditive mode of inheritance, and genetic studies of the HMG-CoA reductase gene locus on mouse chromosome 13, support the possibility that the variation in reductase expression is not due to a mutation of the structural gene but, rather, is determined by a trans-acting factor controlling reductase mRNA levels. The variation provides a striking example, at the molecular level, of the importance of dietary-genetic interactions in the control of cholesterol metabolism.

Animals↗
PubMed1991

Mouse minor satellite DNA genetically maps to the centromere and is physically linked to the proximal telomere.

As an adjunct to attempts to define functionally important sequences at human centromeres, we have undertaken a long-range physical analysis of these regions in the mouse. Mouse centromeres are usually situated very close to the chromosome ends and are closely associated with minor satellite sequences on the basis of cytological observations. Using pulsed-field gel electrophoresis we find that this satellite DNA is arranged as tandem arrays, predominantly uninterrupted by nonsatellite sequences. These arrays can be released largely intact by digestion with a range of enzymes that generally cleave frequently in non-satellite DNA. The restriction fragments carrying these arrays are polymorphic in size between inbred strains and provide direct markers for mouse centromeres. To illustrate the possible use of these polymorphic markers we have mapped a 1.3-Mb PvuII variant in a set of RI strains to the centromere of Chromosome 7. The minor satellite arrays are very close to the centromeric telomere and physical linkage with terminal repeat sequences can readily be detected, placing many minor satellite arrays on terminal restriction fragments smaller than 1 Mb. The apparent lack of any sizable amount of nonsatellite DNA between the minor satellite and the terminal repeat arrays indicates that many mouse chromosomes are truly telocentric.

Alleles↗
PubMed1991

Mapping genes encoding drug-metabolizing enzymes in recombinant inbred mice.

Probes for cytochrome P450IVA (P450IVA), alpha- and pi-class glutathione S-transferases (GST), and phenol-metabolizing UDP-glucuronyltransferase (UDPGT-K39) detected restriction fragment length variants (RFLVs) between C57BL/6J and DBA/2J mice. These variants were used to map the P450IVA genes (Cyp4 alpha) to chromosome 4, close to Mtv-13 and Pmv-19, midway between brown (b) and Gpd-1; GST alpha genes were mapped to chromosome 9, with a cross-hybridizing sequence mapping to another chromosome; the GST pi genes were mapped to the distal end of chromosome 1 near Pmv-21; one UDPGT-K39 variant to chromosome 1, between Acrg and Emv-17, and another showed linkage to Odc-10 on an unidentified chromosome. No RFLVs were detected with probes for P450IID, P450 reductase, androsterone-metabolizing UDPGT, GST mu, or microsomal GST.

Animals↗
PubMed1991

Characterization of the murine homing receptor gene reveals correspondence between protein domains and coding exons.

Lymphocytes and other leukocytic cells traffic to diverse lymphoid organs and sites of inflammation by utilizing an adhesion molecule termed the homing receptor. Characterization of the cDNAs encoding the murine lymphocyte homing receptor has revealed an interesting mosaic structure containing three well-known protein motifs: a C-type lectin domain, an epidermal growth factor-like domain, and two exact copies of a short consensus repeat sequence homologous to those found in a family of complement regulatory proteins, in addition to a signal sequence, a transmembrane anchor, and a short cytoplasmic tail. Characterization of genomic clones encoding the murine homing receptor gene has revealed a high degree of correlation between these various structure/function motifs and exons that specify them. Interestingly, comparison of the exons encoding the two identical copies of the complement regulatory motif revealed that short intronic regions 5' and 3' of these exactly repeated exons are also identical. The gene was found to map to a region of chromosome 1, very near a site previously shown to contain the genes for the family of complement regulatory proteins which encode short consensus repeats similar to those found in the homing receptor, implying that these diverse proteins may have evolved in part by repeated duplications.

Animals↗
PubMed1991

Isolation, characterization, and chromosomal mapping of mouse P450 17 alpha-hydroxylase/C17-20 lyase.

Cytochrome P450 17 alpha-hydroxylase/C17-20 lyase (P45017 alpha) catalyzes the conversion of C-21 steroids to C-19 steroids in gonads. A full-length mouse cDNA encoding P450 17 alpha was isolated from a mouse Leydig cell library and characterized by restriction mapping and sequencing. The predicted amino acid sequence has 83% homology to rat, 66% homology to human, and 62% homology to bovine P45017 alpha amino acid sequences. The protein is 507 amino acids in length, which is 1 amino acid shorter than the human protein and 2 amino acids shorter than the bovine protein. The structural gene encoding P450 17 alpha (Cyp17) was localized utilizing an interspecific testcross to mouse chromosome 19, distal to Got-1. Another cytochrome P450, P4502c (Cyp2c), also is located at the distal end of chromosome 19. CYP17, CYP2c, and GOT1 have been mapped to human chromosome 10, with CYP2C and GOT1 mapped to the distal region, q24.3 and q25.3, respectively. The data in the present study indicate conserved syntenic loci on mouse chromosome 19 and human chromosome 10 and predict that the structural gene encoding P45017 alpha will be found distal to GOT1 on human chromosome 10.

Amino Acid Sequence↗
PubMed1991

Inter-relationships between platelet count, platelet IgG, serum IgG, immune complexes and severity of liver disease.

Thrombocytopenia is a common finding in subjects with chronic liver diseases. A variety of mechanisms may underlie this. Immunological disturbances are commonly a feature in chronic liver disease, including hyperglobulinaemia and the presence of autoantibodies and circulating immune complexes and immune mechanisms could therefore contribute to thrombocytopenia. We have investigated the relationships between blood platelet count, serum IgG and IgG immune complexes and IgG associated with platelets in 92 subjects with chronic liver disease (27 with chronic active hepatitis, 38 with primary biliary cirrhosis and 27 with alcoholic liver disease). Severity of liver impairment was a major determinant of degree of thrombocytopenia. Also, an inverse relationship was demonstrated between platelet count and platelet-associated IgG. In subjects with chronic active hepatitis the relationships between platelet count, serum IgG immune complexes and platelet-associated IgG were consistent with a role for immune mechanisms in general and immune complexes in particular as mediators of the thrombocytopenia.

Antigen-Antibody Complex↗
PubMed1991

Localization of the gene encoding insulin-like growth factor I on mouse chromosome 10.

The peptide hormone, insulin-like growth factor I (IGF-I), is a major determinant of growth in mammals, and also plays a role in differentiation of adipocytes and other cells (Van Wyk, 1984). Although IGF-I is synthesized in many cell types, the liver appears to be the principal organ in which IGF-I is synthesized in response to pituitary growth hormone. In mice, there is a spurt of IGF-I synthesis in liver at about three weeks of age. In human pygmies, the absence of a growth spurt at adolescence is associated with the absence of an increase in serum levels of IGF-I (Merimee et al., 1981). Thus deficiency of IGF-I may be the primary determinant of short stature in pygmies and in other isolated cases of growth hormone resistant dwarfism. Although the murine Igf-1 locus has not been assigned to a chromosome, the human homolog (IGF1) has been mapped to chromosome region 12q22----q24.1 (Francke et al., 1986). Since there appears to be extensive homology between this human chromosomal segment and the distal part of murine Chromosome 10, linkage to this chromosome was suspected. Because the growth deficient mutation of the mouse, pygmy (pg), has also been mapped to Chromosome 10 (Falconer and Isaacson, 1965), we were interested in localizing Igf-1 in order to investigate the possibility that pg might be allelic to Igf-1. We show that the Igf-1 locus is located in the central part of Chromosome 10, a considerable distance from pg.

Blotting, Southern↗
PubMed1990

Clustering of cytokine genes on mouse chromosome 11.

The presence of positionally conserved amino acid residues suggests that the mouse proteins TCA3, P500, MIP1-alpha, MIP1-beta, and JE are members of a single gene family. These proteins are activation specific and can be expressed by both myeloid and lymphoid cells. MIP1-alpha/MIP1-beta and MCAF (the putative human homologue of JE) act as chemotactic and activating agents for neutrophils and macrophages, respectively. The functions of TCA3 and P500 are unknown. We have used interspecies somatic cell hybrids and recombinant inbred mouse strains to show that the genes encoding TCA3, MIP1-alpha, MIP1-beta, and JE (provisionally termed Tca3, Mip-1a, Mip-1b, and Sigje, respectively) map as a cluster on the distal portion of mouse chromosome 11 near the Hox-2 gene complex. DNA sequence analysis indicates that the P500 and TCA3 proteins are encoded by alternative splicing products of one genomic gene. Additionally, the genes encoding TCA3 and JE are found to be strikingly similar with respect to the positions of intron-exon boundaries. Together, these data support the model that the cytokines TCA3, P500, MIP1-alpha, MIP1-beta, and JE are encoded by a single cluster of related genes. The gene encoding IL-5 (Il-5), which acts as a T cell-replacing factor, a B cell growth factor, and an eosinophil differentiation factor, is also mapped to mouse chromosome 11.Il-5 maps approximately 25 cM proximal to the Tca-3 gene and appears tightly linked to a previously described gene cluster that includes Il-3, Il-4, and Csfgm. We discuss the potential relevance of the two cytokine gene clusters described here with particular attention to specific human hematologic malignancies associated with chromosomal aberrations at corresponding locations on human chromosomes 5 and 17.

Amino Acid Sequence↗
PubMed1990

The murine situs inversus viscerum (iv) gene responsible for visceral asymmetry is linked tightly to the Igh-C cluster on chromosome 12.

The iv gene controls left-right determination during murine organogenesis. To map this gene, we analyzed backcross progeny produced by mating (C57BL/6J X MEV/Ty)F1-iv/+heterozygotes to C57BL/6J-iv homozygotes. Hybridization of a murine ecotropic virus probe and several homeotic box gene probes coupled with analysis of dominant visible markers enabled us to exclude the iv locus from much of the mouse genome. Spurred by a recent report that mapped the iv gene to mouse chromosome 12 which was not excluded by our previous work, we used the polymerase chain reaction on our larger cohort to determine that the iv gene is indeed linked tightly to the Igh-C locus on this chromosome: we observed 0/156 recombinants between the iv and Igh-C loci. Combining data from the two studies demonstrates that the murine iv gene is close (1/201 recombinants) to the Igh-C cluster on chromosome 12.

Animals↗