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Biomedical subjects

B A Taylor

Publications and source records attributed to B A Taylor.

At least 91 records · Page 5Linked to original sources

The MEV mouse linkage testing stock: mapping 30 novel proviral insertions and establishment of an improved stock.

Continuing efforts to improve the MEV linkage testing stock are described. The MEV stock carries multiple copies of the ecotropic murine leukemia virus genome. These proviruses are individually detectable in Southern blots, making it possible to follow the segregation of many loci simultaneously in genetic crosses. About 50 novel proviral insertions have been detected in this stock and propagated to homozygosity in a number of sublines. Many of the proviruses were first observed in individuals that were somatic and germinal mosaics. From the minimum frequency of primary transmission of proviruses to offspring, it is estimated that about 7 embryonic cells contribute to the pool of germ cells that populate the gonads. Thirty of the proviruses have been mapped to 15 different chromosomes in intercrosses between MEV sublines and the inbred Mus musculus castaneus strain CAST/Ei or in other crosses. Mapped insertions appear to be randomly distributed among chromosomes, but possibly clustered within chromosomes. Several of the mapped insertions are located such that their inclusion in improved MEV stocks would permit the screening of additional regions of the genome. An improved MEV stock that is homozygous for 12 proviruses on 11 chromosomes, including novel insertions on Chromosomes 17 and 19 is described. The stock also carries four dominant visible markers on 4 additional chromosomes. This stock is estimated to sweep approximately 68% of the autosomal genome.

Alleles↗

mnd2: a new mouse model of inherited motor neuron disease.

The autosomal recessive mutation mnd2 results in early onset motor neuron disease with rapidly progressive paralysis, severe muscle wasting, regression of thymus and spleen, and death before 40 days of age. mnd2 has been mapped to mouse chromosome 6 with the gene order: centromere-Tcrb-Ly-2-Sftp-3-D6Mit4-mnd2-D6Mit 6, D6Mit9-D6Rck132-Raf-1, D6Mit11-D6Mit12-D6Mit14, mnd2 is located within a conserved linkage group with homologs on human chromosome 2p12-p13. Spinal motor neurons of homozygous affected animals are swollen and stain weakly, and electromyography revealed spontaneous activity characteristic of muscle denervation. Myelin staining was normal throughout the neuraxis. The clinical observations are consistent with a primary abnormality of lower motor neuron function. This new animal model will be of value for identification of a genetic defect responsible for motor neuron disease and for evaluation of new therapies.

Animals↗

Typing recombinant inbred mouse strains for microsatellite markers.

In total, 41 different microsatellite variants have been typed in one or more of four different sets of recombinant inbred (RI) mouse strains. Microsatellite variants were selected that were located in chromosomal regions previously lacking markers. These markers extend the regions swept in these RI strains.

Animals↗

Mapping of multiple mouse loci related to the farnesyl pyrophosphate synthetase gene.

The prenyltransferases are a class of enzymes involved in the synthesis of sterol and nonsterol isoprene compounds. We report here the chromosomal mapping of nine loci in the mouse that hybridize to the cDNA for the enzyme farnesyl pyrophosphate synthetase (FPS), a prenyltransferase that catalyzes the synthesis of an intermediate common to both the sterol and nonsterol branches of the isoprene biosynthetic pathway. Mapping was performed with genomic DNA from a mouse-hamster somatic cell hybrid panel, and by linkage analysis with recombinant inbred strains and the progeny of an interspecific backcross. The mapped loci have been designated farnesyl pyrophosphate synthetase-like-1 (Fpsl-1) on mouse Chromosome (Chr) 3; Fpsl-2 on Chr 4; Fpsl-3, Fpsl-4, and Fpsl-5, dispersed on Chr 10; Fpsl-6 on Chr 12; Fpsl-7 on Chr 13; Fpsl-8 on Chr 17; and Fpsl-9 on Chr X. It is presently unclear which of these loci encode active prenyltransferases and which may correspond to pseudogenes. The strongly hybridizing loci provide convenient genetic markers for seven mouse chromosomes.

Animals↗

Reticuloendothelial stimulation: levamisole compared.

PURPOSE: Levamisole in combination with 5-fluorouracil is an effective adjuvant for the treatment of resected Dukes stage C colon cancer. Since the mechanism of action of levamisole is not known, we have investigated its effects on hepatic and splenic reticuloendothelial system (RES) activity in the rat and compared the effect of levamisole with other known RES stimulators. METHODS: The hepatic and splenic uptake of an intravenous dose of technetium-99m-sulfur colloid has been used to measure RES activity in rats treated with levamisole, glucan, zymosan, chlormethiazole, octreotide, and saline. RESULTS: Levamisole significantly increased the hepatic uptake of technetium-99m-sulfur colloid and is comparable in its effect to the other RES stimulators. In contrast, levamisole has no effect on splenic RES activity. CONCLUSION: RES function is considered to be a potentially important factor in the development of liver metastases, and the stimulatory effect of levamisole on the hepatic RES may partly explain its efficacy as an adjuvant treatment in colon cancer.

Animals↗

Pin placement in pelvic external fixation.

Early external fixation of major pelvic fractures reduces haemorrhage and mortality. The best site and method for pin placement remains unresolved. The superior iliac crest is biomechanically disadvantageous and hinders access to the abdomen. Low pin placement between the anterior iliac spines has been proposed as a better solution. A case-controlled study was performed on cadavers using a jig designed to place external fixator pins accurately in the pelvis; the study tested the safety of pin placement and the mechanical strength of the two placement sites. The results showed that pins could be placed safely using this method and that low placement in cadaveric bone is as strong as that of the conventional placement.

Biomechanical Phenomena↗

The role of the cell-cell adhesion molecule E-cadherin in large bowel tumour cell invasion and metastasis.

It has been suggested that the selective loss of E-cadherin expression can generate invasiveness in human carcinoma cells and might be a predictor of metastasis. Frozen sections of samples from 44 patients, 43 with suspected large bowel cancer and one with a liver recurrence were examined for E-cadherin expression using the antibody 6F9 specific for the human E-cadherin molecule. Twelve of the 40 patients with carcinoma already had lymph node involvement at the time of surgery. Samples from the primary carcinomas of only nine of these 12 patients showed reduced E-cadherin expression. However, the one lymph node with metastatic spread examined did show reduced E-cadherin expression. Four of the 40 carcinoma patients had liver involvement at the time of surgery. The primary carcinoma samples from only three of these four patients showed reduced E-cadherin expression. In addition only two out of the three liver metastases examined showed reduced expression. The primary carcinoma samples from seven patients with no evidence of tumour spread also exhibited reduced expression. Overall, analysis of the data suggests that there is no absolute correlation between reduced E-cadherin expression and tumour spread in carcinomas of the large bowel.

Adenocarcinoma↗

Susceptibility of AKXD recombinant inbred mouse strains to lymphomas.

We analyzed the susceptibility of 10 AKXD recombinant inbred (RI) mouse strains to lymphomas. These strains were derived from crosses of AKR/J, a highly lymphomatous strain, and DBA/2J, a weakly lymphomatous strain. Of the 10 strains analyzed, nine showed a high incidence of lymphoma development. As with the other 13 AKXD strains analyzed previously (M. L. Mucenski, B. A. Taylor, N. A. Jenkins, and N. G. Copeland, Mol. Cell. Biol. 6:4236-4243, 1986), the mean age at onset of lymphomas and lymphoma types varied among the strains. Whereas some strains were susceptible to T-cell lymphomas, as was the AKR/J parent, other strains were susceptible to B-cell lymphomas or to a combination of T- and B-cell lymphomas. Somatic mink cell focus-forming proviruses appeared causally associated with T-cell lymphomas, whereas somatic ecotropic proviruses appeared causally associated with B-cell lymphomas. Mice with T-cell lymphomas died significantly earlier than mice with other lymphoma types (stem, pre-B, or B cell and myeloid). The numbers of effective loci influencing the mean age at onset of lymphomas, the presence or absence of mink cell focus-forming viruses in tumors, and the frequency of T-cell lymphomas were estimated to be 3.9, 1.8, and 2.7, respectively. Tests of association with marker loci already typed in the AKXD RI strains suggested that two loci, Rmcf and Pmv-25 (or a locus linked to Pmv-25), influence all three trait variables. Finally, D21S16h, a marker locus on distal chromosome 16, showed 50% probability of linkage to a locus that influences the mean age at onset of lymphomas. Additional studies in combination with classical genetic crosses should be helpful in confirming these linkages and in identifying other loci influencing tumor susceptibility in AKXD RI strains.

Age Factors↗

Ileal and colonic epithelial metabolism in quiescent ulcerative colitis: increased glutamine metabolism in distal colon but no defect in butyrate metabolism.

Previous studies have shown that butyrate is an important energy source for the distal colon, and that its metabolism may be defective in ulcerative colitis (UC). A similar metabolic defect in the ileum might account for the occurrence of 'pouchitis' in UC patients after colectomy. A method has been developed that allows the measurement of metabolism in ileocolonoscopic biopsy specimens, and this has been used to assess butyrate and glutamine metabolism in quiescent UC and controls. Preliminary experiments showed optimal metabolism of butyrate at 1 mmol/l. In controls glutamine metabolism was greater in the ascending (mean (SD)) (4.9 (3.2) nmol/h/micrograms protein) than in the descending colon (1.4 0.7)) (p < 0.05, Mann-Whitney U test), but butyrate metabolism was similar in the two regions (ascending 62.6 (44.2), descending 51.5 (32.0)). Consequently ratios of butyrate/glutamine metabolism were higher in the descending colon (20.6 (14.3)) than in the ascending colon (14.3 (9.6)) (p < 0.05). In UC, rates of butyrate metabolism were similar in the ascending (92.5 (58.3) nmol/h/micrograms protein) and descending (93.3 (115)) colon, and these were not significantly different from controls. In UC, glutamine metabolism was similar in the ascending (6.2 (7.7) nmol/h/micrograms protein) and descending colon (7.8 (7.9)); the metabolism in the descending colon was significantly greater than in controls (p < 0.01). Butyrate (135 (56) nmol/h/microgram protein) and glutamine (24.1 (16.2)) metabolism in the ileum in UC, were not significantly different from control values (butyrate 111 (57), glutamine 15.5 (15.6)). These results confirm that there is regional variation of nutrient utilisation throughout the colon, but they do not support the hypothesis that UC is caused by a deficiency of butyrate metabolism.

Adolescent↗

Temporal summation--the key to motor evoked potential spinal cord monitoring in humans.

Spinal motor evoked potentials (SMEP) were recorded from tibialis anterior muscle after epidural stimulation of the spinal cord at the low cervical or high thoracic level during scoliosis surgery. By using a double stimulus pulse to produce temporal summation within the spinal cord a maximal CMAP response was readily achieved despite good surgical anaesthesia.

Anesthesia, Epidural↗

Control of the human ileocaecal junction: an in vitro analysis of adrenergic and non-adrenergic non-cholinergic mechanisms.

Circular muscle strips from the human ileocaecal junction developed myogenic tone (sustained resting tension) in vitro and showed an obvious component of relaxation in response to electrical field stimulation. These features are considered typical of sphincteric muscle because circular muscle strips from terminal ileum 1-2 cm proximal to the junction and from the caecum or ascending colon 1-2 cm distal to the junction developed little or no tone and showed predominantly contractile responses to electrical-field stimulation. In 18 out of 29 specimens, junctional strips showed excitatory responses to adrenaline or noradrenaline. The relaxation of junctional strips was non-adrenergic non-cholinergic (NANC) in nature. Nitric oxide appears to be involved in the NANC relaxation.

Electric Stimulation↗

Physiological and genetic analyses of inbred mouse strains with a type I iodothyronine 5' deiodinase deficiency.

Inbred mouse strains differ in their capacity to deiodinate iododioxin and iodothyronines, with strains segregating into high or low activity groups. Metabolism of iododioxin occurs via the type I iodothyronine 5'deiodinase (5'DI), one of two enzymes that metabolize thyroxine (T4) to 3,5,3'-triiodothyronine (T3). Recombinant inbred strains derived from crosses between high and low activity strains exhibit segregation characteristic of a single allele difference. Hepatic and renal 5'DI mRNA in a high (C57BL/6J) and low (C3H/HeJ) strain paralleled enzyme activity and concentration, in agreement with a recent report. 5'DI-deficient mice had twofold higher serum free T4 but normal free T3 and thyrotropin. Brown adipose tissue 5'DII was invariant between the two strains. Southern analyses using a 5'DI probe identified a restriction fragment length variant that segregated with 5'DI activity in 33 of 35 recombinant inbred strains derived from four different pairs of high and low activity parental strains. Recombination frequencies using previously mapped loci allowed assignment of the 5'DI gene to mouse chromosome 4 and identified its approximate chromosomal position. We propose the symbol Dio1 to denote the mouse 5'DI gene. Conserved linkage between this segment of mouse chromosome 4 and human HSA1p predicts this location for human Dio1.

Animals↗

Youth coping with sexual orientation issues.

Youth who are struggling with the issue of sexual orientation often are aware of hostile attitudes within their families, schools, communities and among their peers, but are unable to find help. These young people are subject to humiliation, rejection, social isolation, and physical assaults, as well as life-threatening STDs and HIV. Resultant emotional and behavioral symptoms may bring them to the attention of the school nurse, who is often perceived as the most accepting and accessible resource within the school setting. This article provides background information on homosexuality, suggestions for leadership in providing intervention, and resources to help the school nurse reach out to these unserved youth.

Acquired Immunodeficiency Syndrome↗

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↗

Close linkage of Mdm-1, a gene amplified and overexpressed in a transformed 3T3 cell line, with gamma interferon (Ifg) on chromosome 10 of the mouse.

The Mdm-1 gene was mapped to the distal end of Chromosome (Chr) 10. An extensive series of restriction fragment variants was identified among conventional and exotic inbred strains of mice. Mapping was carried out with recombinant inbred strains and an intersubspecific testcross. No recombinants were observed between Mdm-1 and the gamma interferon locus (Ifg). These two loci appear to be in linkage disequilibrium among inbred strains. Data from the testcross place Mdm-1 approximately 11 centimorgans distal to the steel (Sl) locus. Because of its extensive polymorphism, Mdm-1 is a useful genetic marker for distal Chr 10.

3T3 Cells↗