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Biomedical subjects

B A Taylor

Publications and source records attributed to B A Taylor.

At least 73 records · Page 4Linked to original sources

Colonic mucin synthesis is increased by sodium butyrate.

The effects of sodium butyrate and sodium bromo-octanoate (an inhibitor of beta oxidation) on colonic mucus glycoprotein (mucin) synthesis have been assessed using tissue from colonic resection samples. Epithelial biopsy specimens were incubated for 16 hours in RPMI 1640 with glutamine, supplemented with 10% fetal calf serum and N-acetyl-[3H]-glucosamine ([3H]-Glc NAc), and differing concentrations of sodium butyrate. Incorporation of [3H] Glc NAc into mucin by normal epithelium at least 10 cm distant from colonic cancer was increased in the presence of sodium butyrate in a dose dependent manner, with maximum effect (476%) at a concentration of 0.1 mM (number of specimens = 24 from six patients, p < 0.001). The increase in response to butyrate was not seen when specimens were incubated in the presence of the beta oxidation inhibitor sodium bromo-octanoate 0.05 M. The striking increase in mucin synthesis that results when butyrate is added to standard nutrient medium suggests that this may be an important mechanism affecting the rate of mucin synthesis in vivo and may also explain the therapeutic effect of butyrate in colitis.

Adult↗

Octreotide, the reticuloendothelial system, and experimental liver tumour.

The inhibitory effect of octreotide on the growth of liver tumour is probably mediated (at least in part) by stimulation of the hepatic reticuloendothelial system (RES) activity. This study therefore investigated the effect of octreotide on the hepatic and splenic RES (assessed by the uptake of technetium 99m labelled albumin colloid, 99mTc-AC) in normal and tumour bearing rats and in animals treated with gadolinium chloride. The effects of gadolinium chloride and octreotide alone or in combination on the growth of liver tumour were also studied. Octreotide significantly stimulates both hepatic and splenic uptake of 99mTc-AC in normal rats and tumour bearing rats. In controls, the uptake of 99mTc-AC was significantly reduced by gadolinium chloride and was not changed by octreotide. RES blockade with gadolinium chloride significantly increased (p < 0.001) tumour growth compared with controls (hepatic replacement 42%; 95% confidence intervals (CI), 27.6 to 56.4 v 16.7%, 95% CI, 11.1 to 21.3%) whereas octreotide significantly inhibited (p < 0.001) the percentage hepatic replacement by tumour (0.7%; 95% CI, 0 to 2.3 v 16.7%; 95% CI, 11.1 to 21.3). This study highlights the importance of the RES in the development of liver tumour. Furthermore, octreotide inhibited the growth of liver tumour in rats with RES blockade, albeit to a lesser degree than in normal animals. These findings suggest that octreotide inhibits the growth of hepatic tumour by mechanisms other than stimulation of RES activity.

Animals↗

Teaching children with autism to seek information: acquisition of novel information and generalization of responding.

A time delay procedure was used to teach 3 children with autism to ask the question "What's that?" when novel stimuli were presented during an instructional task. Once the ability to ask the question was acquired, the children's ability to learn novel information by asking the question was assessed. The children were then taught to ask the question within a less structured context. All three studies used a multiple baseline across participants. Generalization was assessed in a different room, to a new person, and to novel stimuli. All of the children learned to ask the question within the instructional context, while on a walk in the school building, and to request information about three-dimensional objects. The acquisition of novel information was consistent for receptive and expressive tests for 2 of the children, with varied results for the 3rd. These studies indicate that children with autism can be taught to ask questions that lead to the acquisition of new information.

Attention↗

General anesthetic effects on compound muscle action potentials elicited by single or dual spinal cord stimulation.

The aim of this study was to determine the optimal conditions, during general anesthesia, to obtain reproducible monitoring of compound muscle action potentials (CMAPs) as a means to evaluate motor tract integrity. The CMAPs were recorded in the soleus muscle of cats and were elicited by either single or double pulse stimulations (with various amplitudes and interpulse durations) of the spinal cord via an epidural electrode. The effects of various depths of general anesthesia with halothane, enflurane, isoflurane, or propofol on such recordings were also determined. For each agent, the CMAP amplitudes were significantly greater following double pulse stimulations (2-ms optimal interpulse duration) relative to single pulses. The CMAP amplitudes elicited by double pulse stimulations were the same at propofol concentrations of 50, 100, 150, and 200 micrograms/kg/min, whereas those for each volatile anesthetic, at all concentrations studied (0.5%, 1.0%, 1.5%, or 2.0%), were significantly lower. It was concluded that to obtain reliable CMAP amplitudes, general anesthesia with propofol should be employed and the potentials should be evoked by double pulse stimulations.

Action Potentials↗

Mouse cellular nucleic acid binding proteins: a highly conserved family identified by genetic mapping and sequencing.

Human cellular nucleic acid binding protein (CNBP) is a zinc finger DNA binding protein of unknown function. The human CNBP cDNA was used as a probe to isolate four structurally distinct but highly homologous mouse liver cDNA clones. Each of the mouse clones exhibited extraordinary sequence conservation with human CNBP cDNA, and the predicted mouse amino acid sequence identities with human CNBP protein ranged from 99 to 100%. Genetic mapping of CNBP genes in interspecific and intersubspecific mouse backcrosses revealed two loci that hybridize to CNBP cDNA at high stringency, located on chromosomes 5 and 6. The subcellular distribution of the CNBP protein was characterized with a specific polyclonal antibody generated against a synthetic peptide from the carboxyl terminus. CNBP was found in the cytosol and the endoplasmic reticulum in subcellular fractions from mouse liver, but was undetectable in nuclear fractions. These data suggest that CNBP is a member of a highly conserved family of cytosolic proteins that may be encoded by multiple dispersed genes.

Amino Acid Sequence↗

Syringomyelia. A potential risk factor in scoliosis surgery.

STUDY DESIGN: An 18-year-old patient with "idiopathic" adolescent scoliosis is presented. A thoracic syrinx was detected as an incidental finding during magnetic resonance imaging of the spine. OBJECTIVES: Syringomyelia may be a risk factor for neurologic injury during correction of scoliosis, and in these cases, spinal cord monitoring may be of particular value. BACKGROUND DATA: Spinal distraction and instrumentation carry a risk of neurologic damage in patients with scoliosis and associated syringomyelia. Syringomyelia is a cause of scoliosis, and although neurologic problems are the usual symptom, scoliosis may be the only sign at initial examination. A higher risk of neurologic injury has been reported in corrective surgical treatment of patients with syringomyelia. The mechanism of cord damage is unclear. Monitoring of spinal cord function is recommended to detect intraoperative neurological injury, which may be reversed on removing distraction and implants. RESULTS: Intraoperative somatosensory-evoked potential (SSEP) spinal cord monitoring detected possible cord damage during outrigger distraction. Reduction of distraction led to a recovery of SSEPs and a satisfactory operative outcome. CONCLUSION: Syringomyelia may be a risk factor for neurologic injury during correction of scoliosis, and SSEP spinal cord monitoring may identify and prevent intraoperative spinal cord injury.

Adolescent↗

Delayed postoperative paraplegia with hypotension in adult revision scoliosis surgery.

The clear and reversible relationship of spinal cord function to postoperative hypotension is illustrated in a case of revision scoliosis surgery in an adult patient. The correlation of spinal cord monitoring by both magnetic cortical motor evoked potentials and spinal somatosensory evoked potentials to the clinical status is shown, and the importance of close postoperative observation of the adult revision case is emphasized.

Adult↗

Pelvic ileal reservoirs: the options.

Restorative proctocolectomy has become an established surgical option for patients with chronic ulcerative colitis and familial adenomatous polyposis. However, despite a large number of different reservoir designs there is so far no acknowledged ideal configuration. This paper reviews the advantages and disadvantages of the different types of pelvic ileal reservoir so far studied.

Adenomatous Polyposis Coli↗

PCR-amplification of simple sequence repeat variants from pooled DNA samples for rapidly mapping new mutations of the mouse.

A novel strategy for rapidly mapping new mutations of the mouse is presented and tested. The inbred Mus musculus castaneus strain CAST/Ei is used as a tester stock. Separate DNA pools are made from mutant and wildtype intercross (F2) progeny and analyzed using simple sequence repeat (SSR) variants detected using PCR amplification. Linkage is indicated if the mutant DNA pool is enriched for the mutant-strain SSR allelic fragment in comparison with the wildtype pool and controls. The expected contributions of the tester stock to mutant and wildtype pools as a function of recombination frequency are derived for both intercross and backcross progeny segregating for a recessive mutant gene. The sensitivity and reliability of this method is investigated using arbitrary DNA mixtures and also mutant and wildtype pools from a (CAST/Ei x MEV) intercross segregating for the dilute coat color mutation. It is concluded that linkages as great as 20 cM can be reliably detected by this method provided that sufficient progeny contribute to the pools. A set of 39 SSR variants, resolvable by agarose gel electrophoresis and suitable for pooled-SSR analysis, is identified. These are expected to screen 94% of the autosomal genome in crosses between CAST/Ei and common laboratory strains.

Animals↗

Mouse centromere mapping using oligonucleotide probes that detect variants of the minor satellite.

Cytologically, the centromere is found at the very end of most Mus musculus chromosomes, co-localizing with an array of minor satellite sequences. It is separated from the euchromatin of the long arm by a large domain of heterochromatin, composed in part of arrays of major satellite sequences. We used oligonucleotide probes that specifically detect regions of sequence variation found in certain cloned minor satellite sequences. They detect a limited subset of the minor satellite arrays in the mouse genome, based on both pulsed-field gel electrophoresis and in situ hybridization data, and provide direct molecular genetic markers for individual centromeres in some inbred mouse strains. Array size polymorphisms detected by these probes map to positions consistent with the centromeres of chromosomes 1 and 14 in the BXD recombinant inbred (RI) strains. The genetic distances between these minor satellite arrays and loci on the long arms of chromosomes 1 and 14 are consistent with repression of meiotic recombination in the heterochromatic domains separating them. The existence of chromosome-specific minor satellite sequences implies that the rate of sequence exchange between non-homologous chromosomes relative to the rate between homologous chromosomes is much lower than has previously been postulated. We suggest that the high degree of sequence homogeneity of mouse satellite sequences may instead reflect recent common ancestry.

Animals↗

Genetic epilepsy model derived from common inbred mouse strains.

The recombinant inbred mouse strain, SWXL-4, exhibits tonic-clonic and generalized seizures similar to the commonest epilepsies in humans. In SWXL-4 animals, seizures are observed following routine handling at about 80 days of age and may be induced as early as 55 days by rhythmic gentle tossing. Seizures are accompanied by rapid, bilateral high frequency spike cortical discharges and followed by a quiescent post-ictal phase. Immunohistochemistry of the immediate early gene products c-Fos and c-Jun revealed abnormal activation within cortical and limbic structures. The seizure phenotype of SWXL-4 can be explained and replicated fully by the inheritance of susceptibility alleles from its progenitor strains, SWR/J and C57L/J. Outcrosses of SWXL-4 with most other common inbred strains result in F1 hybrids that have seizure at least as frequently as SWXL-4 itself. Quantitative trait locus mapping reveals a seizure frequency determinant, Szf1, near the pink-eyed dilution locus on chromosome 7, accounting for up to 32% of the genetic variance in an F2 intercross between SWXL-4 and the linkage testing strain ABP/Le. These studies demonstrate that common strains of mice such as SWR and C57L contain latent epilepsy susceptibility alleles. Although the inheritance of susceptibility may be complex, these results imply that a number of potentially important and practical, noninvasive models for this disorder can be constructed and studied in crosses between common mouse strains.

Animals↗

Chromosomal mapping and expression levels of a mouse soluble epoxide hydrolase gene.

The chromosomal location of a murine soluble epoxide hydrolase gene was determined using in situ mapping, restriction fragment length polymorphism (RFLP) and simple sequence length polymorphism (SSLP) analysis. In situ hybridization to mouse metaphase chromosomes using a soluble epoxide hydrolase cDNA probe showed that soluble epoxide hydrolase maps at band D of chromosome 14. An RFLP found between Mus castaneus (CAST) and Mus musculus (MEV) was used to map the soluble epoxide hydrolase gene in CAST x MEV intersubspecific testcross progeny to 14 cM from the Np-1 locus on mouse chromosome 14. SSLP markers were then used to confirm the location of soluble epoxide hydrolase at 14.0 +/- 3.7 cM distal to Np-1 and 19.2 +/- 4.3 cM proximal to D14Mit7. This region of mouse chromosome 14 is homologous with human chromosomes 8, 13 and 14. Enzyme assays and immunoblotting results suggest significant quantitative differences in expression of soluble epoxide hydrolase among three mouse strains. Northern blotting analysis showed that soluble epoxide hydrolase mRNA levels were correlated with the relative level of soluble epoxide hydrolase enzyme activity and soluble epoxide hydrolase protein in all three mouse strains.

Animals↗

The genes encoding gonadal and nongonadal forms of 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4 isomerase are closely linked on mouse chromosome 3.

The biosynthesis of steroid hormones in the gonads and adrenal glands requires the activities of the enzyme 3 beta-hydroxysteroid dehydrogenase/isomerase (3 beta HSD) which catalyzes the NAD(+)-dependent dehydrogenation and subsequent delta 5-->delta 4 isomerization of delta 5-3 beta-hydroxysteroids to delta 4-3-ketosteroids. The mouse expresses four isoforms of 3 beta HSD. 3 beta HSD I is expressed in gonads and adrenal glands and appears to be the major steroidogenic form, 3 beta HSDs II and III are expressed in both liver and kidneys, and 3 beta HSD IV has been detected only in kidneys. To determine the genetic relationship between the 3 beta HSD isoforms, we have mapped the chromosomal locations of the four genes by linkage analysis using gene-specific probes derived from the 3' untranslated regions of 3 beta HSD cDNA clones. The four 3 beta HSD structural genes (Hsd3b) are closely linked within a segment of chromosome 3 that is conserved on human chromosome 1. The order of markers on Chr 3 surrounding Hsd3b is: centromere-Gba-(4.4 +/- 2.2)-Hsd3b-(3.3 +/- 1.9)-Tshb-(6.7 +/- 2.7)-Amy-1.

Animals↗

Identification of the mutation in murine histidinemia (his) and genetic mapping of the murine histidase locus (Hal) on chromosome 10.

We cloned a mouse histidase cDNA to identify the mutation in histidinemic mice (his/his) and to determine the relationship of the histidase locus (Hal) both to Chromosome 10 markers and to Hsd, the histidase activity variant locus. The his mutation, a G to A transition at nucleotide +965, changes Arg-322 to Gln (R322Q). Expression of the R322Q allele in COS cells resulted in proportionately reduced amounts of histidase protein and activity compared to the wildtype allele. Hal maps approximately 4 cM distal to the insulin-like growth factor-1 locus and approximately 10 cM proximal to steel. Hsd was found to be tightly linked to Hal, and the low-histidase-activity Hsd allele was associated with reduced histidase mRNA. These studies indicate that the R322Q allele reduces the stability of histidase, position Hal on the Chromosome 10 linkage map, and provide further evidence that Hsd is allelic to Hal.

Amino Acid Metabolism, Inborn Errors↗