Search PubMed⌕ Search

Biomedical subjects

B A Taylor

Publications and source records attributed to B A Taylor.

At least 127 records · Page 7Linked to original sources
PubMed1989

Membrane peptidases in the pig choroid plexus and on other cell surfaces in contact with the cerebrospinal fluid.

A comprehensive survey of 11 peptidases, all of which are markers for renal microvillar membranes, has been made in membrane fractions prepared from pig choroid plexus. Two fractionation schemes were explored, both depending on a MgCl2-precipitation step, the preferred one having advantages in speed and yield of the activities. The specific activities of the peptidases in the choroid-plexus membranes were, with the exception of carboxypeptidase M, lower than in renal microvillar membranes: those of aminopeptidase N, peptidyl dipeptidase A ('angiotensin-converting enzyme') and gamma-glutamyltransferase were 3-5-fold lower, those of aminopeptidase A and endopeptidase-24.11 were 12-15 fold lower, and those of dipeptidyl peptidase IV and aminopeptidase W were 50-70-fold lower. Carboxypeptidase M had a similar activity in both membranes. Alkaline phosphatase and (Na+ + K+)-activated ATPase were more active in the choroid-plexus membranes. No activity for microsomal dipeptidase, aminopeptidase P and carboxypeptidase P could be detected. Six of the peptidases and (Na+ + K+)-activated ATPase were also studied by immunoperoxidase histochemistry at light- and electron-microscopic levels. Endopeptidase-24.11 and (Na+ + K+)-activated ATPase were uniquely located on the brush border, and the other two peptidases appeared to be much more abundant on the endothelial lining of microvessels. Dipeptidyl peptidase IV and aminopeptidase W were also detected in microvasculature. Pial membranes associated with the brain and spinal cord also stained positively for endopeptidase-24.11, aminopeptidase N and peptidyl dipeptidase A. The immunohistochemical studies indicated the subcellular fractionation did not discriminate between membranes derived from epithelial cells (i.e. microvilli) and those from endothelial cells. The possible significance of these studies in relation to neuropeptide metabolism and the control of cerebrospinal fluid production is discussed.

Animals↗
PubMed1989

Genetic and developmental regulation of the lipoprotein lipase gene: loci both distal and proximal to the lipoprotein lipase structural gene control enzyme expression.

We report here a study of the developmental and genetic control of tissue-specific expression of lipoprotein lipase, the enzyme responsible for hydrolysis of triglycerides in chylomicrons and very low density lipoproteins. Lipoprotein lipase (LPL) mRNA is present in a wide variety of adult rat and mouse tissues examined, albeit at very different levels. A remarkable increase in the levels of LPL mRNA occurs in heart over a period of several weeks following birth, closely paralleling developmental changes in lipase activity and myocardial beta-oxidation capacity. Large increases in LPL mRNA also occur during differentiation of 3T3L1 cells to adipocytes. As previously reported, at least two separate genetic loci control the tissue-specific expression of LPL activity in mice. One of the loci, controlling LPL activity in heart, is associated with an alteration in LPL mRNA size, while the other, controlling LPL activity in adipose tissue, appears to affect the translation or post-translational expression of LPL. To examine whether these genetic variations are due to mutations of the LPL structural locus, we mapped the LPL gene to a region of mouse chromosome 8 using restriction fragment-length polymorphisms and analysis of hamster-mouse somatic cell hybrids. This region is homologous to the region of human chromosome 8 which contains the human LPL gene as judged by the conservation of linked genetic markers. Genetic variations affecting LPL expression in heart cosegregated with the LPL gene, while variations affecting LPL expression in adipose tissue did not. Furthermore, Southern blotting analysis indicates that LPL is encoded by a single gene and, thus, the genetic differences are not a consequence of independent regulation of two separate genes in the two tissues. These results suggest the existence of cis-acting elements for LPL gene expression that operate in heart but not adipose tissue. Our results also indicate that two genetic mutations resulting in deficiencies of LPL in mice, the W mutation on chromosome 5 and the cld mutation on mouse chromosome 17, do not involve the LPL structural gene locus. Finally, we show that the gene for hepatic lipase, a member of a gene family with LPL, is unlinked to the gene for LPL. This indicates that combined deficiencies of LPL and hepatic lipase, observed in humans as well as in certain mutant strains of mice, do not result from focal disruptions of a cluster of lipase genes.

Adipose Tissue↗
PubMed1989

The histology of anal skin tags in Crohn's disease: an aid to confirmation of the diagnosis.

We have investigated excision biopsy of anal skin tags as an adjunct to rectal biopsy in the diagnosis of Crohn's disease. Twenty-six patients with proven Crohn's disease of the large and/or small bowel were studied. All had perianal skin tags removed under local anaesthesia as outpatients, when rectal biopsies were also obtained. Three sections from each skin tag and three from each rectal biopsy were examined for granulomas. The rectal biopsies were also examined for changes 'suggestive' of Crohn's disease. Anal skin tags from 26 patients without Crohn's disease acted as controls. Of the patients with Crohn's disease, granulomas were found in both anal skin tags and rectal biopsies in five patients, in anal skin tags only in four, and in rectal biopsies only in three. When present, granulomas were more plentiful in anal skin tags than in rectal biopsies, being seen in all 3 sections in 7 of 9 'positive' tags (i.e.: in 31% of 78 sections), compared to only 1 of 8 'positive' rectal biopsies (i.e.: in 13% of 78 sections). No granulomas were seen in control anal skin tags. The procedure provides a simple technique which is complementary to rectal biopsy, by which histological confirmation of Crohn's disease may be obtained.

Adult↗
PubMed1989

Genetic and tissue-specific variation in the expression of a closely linked murine multigene family on chromosome 15 that encodes salivary and lacrimal proteins.

The murine submandibular gland (SMG) produces a novel class of highly acidic salivary proteins encoded by one or more highly abundant mRNA transcripts. In inbred mice, these transcripts are encoded by members of a multigene family comprising approximately 8-12 homologues. Most, and probably all, of these homologues are clustered at a new locus near belted (bt) on chromosome 15, which we designate Spt (salivary protein). Although physically closely linked, Spt genes differ in their patterns of expression both in strains of mice and in their tissues. One gene, Spt-1, is expressed at high levels in the SMG of all inbred strains examined. This gene is also expressed at significant levels in the lacrimal gland. A second gene, Spt-2, appears to be present as a single copy in some strains and as two copies in others. This gene is expressed at high levels only in the SMG of those strains carrying two copies, and Spt-2 mRNA is not detectable in the SMG of strains carrying only one copy. In contrast to Spt-1, the Spt-2 gene is not expressed at detectable levels in the lacrimal gland.

Animals↗
PubMed1989

Prp (proline-rich protein) genes linked to markers Es-12 (esterase-12), Ea-10 (erythrocyte alloantigen), and loci on distal mouse chromosome 6.

The closely linked proline-rich protein (Prp) genes, coding for abundant salivary proteins, are located on distal mouse chromosome 6. They are part of a conserved linkage group that is represented on human chromosome 12p. Two other markers, Ea-10 and Es-12, that were previously unassigned to a chromosome are closely linked to Prp genes in the mouse.

Animals↗
PubMed1989

Linkage of the mouse LDL receptor gene on chromosome 9.

We identified restriction fragment length variants of the mouse low-density lipoprotein receptor gene and used these to map the gene, designated Ldlr, to the proximal region of chromosome 9. An interspecific backcross between strains MEV and CAST/Ei yielded the following gene order and distances in centimorgans: Ldlr-18.8 +/- 5.6-Apoa-4-7.3 +/- 3.5-Mpi-1-10.2 +/- 3.9-Emv-3 or dilute. Analysis of recombinant inbred strains also indicated that Ldlr is tightly linked to a previously unmapped retroviral marker, Xmmv-67.

Animals↗
PubMed1989

A mouse linkage testing stock possessing multiple copies of the endogenous ecotropic murine leukemia virus genome.

A new linkage testing stock of the laboratory mouse has been constructed. The stock, designated MEV (multiple ecotropic provirus), was developed by inbreeding and selection beginning with the cross of strains C58/J and AKXD-14. Eleven different murine leukemia virus (MuLV) proviruses have been fixed in the MEV/1Ty strain. Nine of these can be uniquely identified by Southern blotting of PvuII-digested DNA and probing with a cloned fragment of the ecotropic viral genome. Two proviruses had been mapped previously to chromosome 7, while single proviruses had been mapped to chromosomes 2, 9, and 11. The mapping of six additional proviruses, derived from C58/J, to chromosomes 1, 3, 5, 10, 18, and 19 is described. Another C58/J provirus was mapped to chromosome 8 and proved to be identical to the previously mapped C58v-1 virus inducibility gene of strain C58/Lw. Three dominant visible markers, hammer-toe (Hm), steel (Sl), and caracul-J (CaJ), located on chromosomes 5, 10, and 15, respectively, have been introduced onto the MEV genetic background by repeated backcrosses to provide additional linkage markers. It is estimated that approximately 50% of the genome can be screened by scoring 50 fully informative gametes from a linkage cross of the MEV-Hm, -Sl, -CaJ stock for the combination of viral and visible markers. A strategy for efficiently mapping new recessive visible mutations by pooling tissues for DNA extraction from mutant homozygotes among F2 progeny is described. Ways of further improving the MEV stock are discussed. The location of the Myb proto-oncogene is defined relative to Sl and one of the C58/J proviruses on chromosome 10.

Animals↗
PubMed1989

Genetic analysis of endogenous xenotropic murine leukemia viruses: association with two common mouse mutations and the viral restriction locus Fv-1.

We have defined 40 endogenous xenotropic virus (Xmv) loci from several common inbred strains of mice by examining provirus-cell DNA junction fragments in recombinant inbred mice. Some inbred strains carried unique proviruses, but most Xmv loci were present in several strains, indicating that many Xmv integration events preexisted modern inbreeding. It was also clear that most Xmv junction fragment variation between inbred strains resulted from independent integration events and not modification or restriction site polymorphism following integration. Chromosomal assignments were determined for 32 Xmv loci by comparing their recombinant inbred strain distribution patterns to those of known genetic markers. The Xmv loci were generally dispersed throughout the genome, but several chromosomal regions contained more than one provirus. Furthermore, several close genetic associations with cellular genes were discovered. Four Xmv loci were closely linked to Fv-1b, a dominant viral resistance gene present in C57BL/6J, BALB/cJ, A/J, and several other strains. Xmv-28 was closely linked to rd (retinal degeneration), and Xmv-10 was closely linked to a (non-agouti), both of which are old mutations as inferred from their broad distribution in mice. We suggest that Xmv integration contributed to genetic diversity in the past and that much of this diversity exists today in common laboratory strains.

Animals↗
PubMed1989

Genetic identification of endogenous polytropic proviruses by using recombinant inbred mice.

Forty-seven endogenous polytropic murine viruses (Pmv) were identified by examination of proviral-cellular DNA junction fragment segregation in recombinant inbred (RI) mice. Most Pmv loci were found in more than one of the seven RI progenitor strains analyzed, but only four were present in all strains. Chromosomal assignments for 41 Pmv loci were determined by comparing their RI strain distribution patterns with those of known genetic markers. Pmv loci were found dispersed throughout the genome, with chromosomes 1, 3, 4, 5, 7, 11, 12, 15, and 16 each carrying three or more proviruses. Linkage analysis in the AKXD RI set suggested that the gene encoding mink cell focus-forming virus resistance (Rcmfr) of DBA/2J mice is probably not a Pmv provirus. It was also deduced that no single, AKR/J-specific Pmv provirus is required as an env gene donor for thymomagenic mink cell focus-forming viruses. In addition, a Pmv provirus was very closely associated with the albino mutation on chromosome 7.

Animals↗
PubMed1988

Mapping of mouse gamma crystallin genes on chromosome 1.

Restriction fragments analysis of DNA from mouse-hamster somatic-cell hybrid clones revealed that a mouse gamma crystallin cDNA hybridized to genomic sequences located on mouse chromosome 1. Identification of restriction fragment length polymorphisms (RFLPs) in the gamma crystallin sequences of inbred strains of mice permitted the further localization of the gamma crystallin genes (Cryg) to the proximal region of chromosome 1 closely linked to the loci encoding isocitrate dehydrogenase (Idh-1), a low molecular weight (LM) crystallin protein polymorphism (Len-1), and fibronectin (Fn-1). A single recombinant was observed between Len-1 and an RFLP in the gamma crystallin gene family, consistent with the hypothesis that Len-1 is one of the several structural loci encoding gamma crystallin genes. Len-1 is probably located on the centromeric end of the Cryg gene family. Linkage of Idh-1, Cryg, and Fn-1 in mice extends the syntenic relationship of those loci to the human, bovine, and rodent genomes and may define a chromosomal region that is generally conserved among mammals. The map position of Cryg, near the eye lens obsolescence (Elo) locus, was confirmed by the discovery that the restriction fragment patterns of gamma crystallin sequences differed between strain C3H/HeJ and the congenic anophthalmic mutant strain, C3H.Elo. Therefore, the gamma crystallin genes were cotransferred with the mutant Elo gene in the derivation of C3H.Elo. The results establish that LEN-1 is a marker for the gamma crystallin gene family, position the gamma crystallin gene family relative to other markers on mouse chromosome 1, and provide additional evidence that the Elo mutation is encoded at a locus closely linked to the gamma crystallin gene cluster. This study found no evidence of recombination hot spots within the gamma crystallin gene cluster.

Animals↗
PubMed1988

Perianal metastasis from a sigmoid carcinoma--objective evidence of a clonal origin. Report of a case.

A case is described in which flow cytometric DNA analysis of a sigmoid cancer and a subsequently diagnosed anal malignancy demonstrated the same DNA aneuploid pattern in both tumors. The ability to show, by this technique of DNA analysis, that an anal malignancy has seeded from a colon cancer could be important for future therapy. This is because the positive identification of such a deposit as a "dropped" metastasis would prevent inappropriately radical surgery.

Adenocarcinoma↗
PubMed1988

Ileal pouch-anal anastomosis for chronic ulcerative colitis and familial polyposis coli complicated by adenocarcinoma.

Of 518 patients undergoing the ileal pouch-anal anastomosis (IPAA), 17 (13 with chronic ulcerative colitis [CUC] and four with familial polyposis coli [FPC] ) also had a total of 22 cancers of the colorectum. Tumors were concentrated distally (rectum 6; sigmoid colon 5; proximal colon 11) and were diagnosed preoperatively in eight patients. Histologic grade and stage were as follows: grade I, 36 percent; II, 23 percent; III, 23 percent; IV, 18 percent; stage A, 5 percent; B1, 32 percent; B2, 18 percent; C1 and C2, 45 percent. Median hospital stay was 17 days with no operative mortality. Relaparotomy was required in 35 percent (sepsis in four patients; obstruction in two) and minor procedures were done in 12 percent (anastomotic dilatation in one; rectovaginal fistula in one). Mean frequency of defecation was 6.4/day, 1.0/night; incidence of minor seepage, 17 percent (day), 50 percent night); incidence of pouchitis, 8 percent; intermittent dyspareunia, 17 percent of six women. One patient died from hepatic metastases nine months after operation. IPAA should be considered in favorable cancers complicating CUC or FPC, although it may be contraindicated in advanced rectal cancer, and may be unsuitable in advanced proximal cancer.

Adenocarcinoma↗
PubMed1988

Local depot methylprednisolone injection for painful anal Crohn's disease.

Treatment, by local depot methylprednisolone injection, of severe anal pain in Crohn's disease not associated with overt sepsis is reported. It has given dramatic relief in 5 patients, but has not been successful in 2 patients where anal disease was in continuity with severe rectal involvement. Treatment has been effective for greater than 1 yr, and no complication of the technique has been found on regular follow-up. When compared with previous attempts at treatment, the beneficial results attained with methylprednisolone injection suggest that the effect is more than a placebo response. Careful patient selection to exclude overt sepsis or severe rectal disease is recommended before proceeding to steroid injection.

Adult↗
PubMed1988

Comparative mapping of DNA markers from the familial Alzheimer disease and Down syndrome regions of human chromosome 21 to mouse chromosomes 16 and 17.

Mouse trisomy 16 has been proposed as an animal model of Down syndrome (DS), since this chromosome contains homologues of several loci from the q22 band of human chromosome 21. The recent mapping of the defect causing familial Alzheimer disease (FAD) and the locus encoding the Alzheimer amyloid beta precursor protein (APP) to human chromosome 21 has prompted a more detailed examination of the extent of conservation of this linkage group between the two species. Using anonymous DNA probes and cloned genes from human chromosome 21 in a combination of recombinant inbred and interspecific mouse backcross analyses, we have established that the linkage group shared by mouse chromosome 16 includes not only the critical DS region of human chromosome 21 but also the APP gene and FAD-linked markers. Extending from the anonymous DNA locus D21S52 to ETS2, the linkage map of six loci spans 39% recombination in man but only 6.4% recombination in the mouse. A break in synteny occurs distal to ETS2, with the homologue of the human marker D21S56 mapping to mouse chromosome 17. Conservation of the linkage relationships of markers in the FAD region suggests that the murine homologue of the FAD locus probably maps to chromosome 16 and that detailed comparison of the corresponding region in both species could facilitate identification of the primary defect in this disorder. The break in synteny between the terminal portion of human chromosome 21 and mouse chromosome 16 indicates, however, that mouse trisomy 16 may not represent a complete model of DS.

Alzheimer Disease↗
PubMed1988

Chromosomal organization of the cytochrome P450-2C gene family in the mouse: a locus associated with constitutive aryl hydrocarbon hydroxylase.

Cytochromes P-450 represent a superfamily of enzymes with a central role in the metabolism of drugs, chemical toxins, and carcinogens. We have used genetic analysis to establish the complexity and catalytic function of a recently identified constitutively expressed murine hepatic cytochrome P-450 encoded by P450-2C. Southern blotting analysis shows that there are at least seven or eight genes within this family in the mouse and rat and that DNA restriction fragment length variants between different mouse inbred strains are observed. Analysis of recombinant inbred strains derived from these parent strains shows (i) these genes are clustered within 1 centimorgan, (ii) this gene family does not correspond to any of the known cytochrome P-450 loci or map near any well-characterized genomic markers, and (iii) this gene family segregates to within 1-2 centimorgans of a locus controlling constitutive aryl hydrocarbon hydroxylase activity in mice. With use of Chinese hamster/mouse somatic cell hybrids, the P450-2C locus was assigned to a region of mouse chromosome 19 that appears to be syntenic with the previously mapped human P450C2C locus on human chromosome 10. By in situ hybridization to mitotic mouse chromosomes, we have localized this region to the tip of chromosome 19. These results are discussed in relation to the physiological roles of this P-450 family in foreign compound metabolism and steroid oxidations.

Animals↗
PubMed1988

The Hox-2 homeo box gene complex on mouse chromosome 11 is closely linked to Re.

Restriction fragment length polymorphisms have been identified between inbred strains of mice for the homeo box gene complex Hox-2. These genetic markers were used to follow the segregation of different Hox-2 alleles among recombinant inbred strains of mice and among the progeny of a three point genetic cross. The results place the Hoax-2 locus approximately 1 cM from the rex (Re) locus on mouse chromosome 11.

Alleles↗