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Biomedical subjects

C J Taylor

Publications and source records attributed to C J Taylor.

At least 91 records · Page 5Linked to original sources

Molecular analysis of the fructose transporter gene (GLUT5) in isolated fructose malabsorption.

Fructose, a naturally occurring monosaccharide, is increasingly used as an added sweetener in processed foods in the form of high fructose corn syrup. Increased fructose intake combined with the identification of children with clinical evidence of isolated fructose malabsorption (IFM) has stimulated interest in possible disorders of fructose absorption. The intestinal absorption of fructose is carried out by the facilitative hexose transporter, which has been designated as GLUT5. Functional properties and tissue distribution of GLUT5 suggest that IFM might be due to mutations in the GLUT5 gene. To test this hypothesis, we screened the GLUT5 gene for mutations in a group of eight patients with IFM and in one subject with global malabsorption, as compared with 15 healthy parents of subjects and up to 6 unrelated controls. No mutations were found in the protein coding region of this gene in any of the subjects. A single G to A substitution in the 5' untranslated region of exon 1 was identified in the subject with global malabsorption. This subject and her healthy mother were heterozygous for the variant sequence, suggesting that it was unlikely to be clinically significant. In addition, sequence analysis of each of the 12 GLUT5 exons was performed in the index case and confirmed the negative single-strand conformation polymorphism findings. These studies demonstrate that IFM does not result from the expression of mutant GLUT5 protein.

Alleles↗

Twenty-four hour ambulatory gastric and duodenal pH profiles in cystic fibrosis: effect of duodenal hyperacidity on pancreatic enzyme function and fat absorption.

Overt steatorrhoea remains a problem for some patients with cystic fibrosis (CF) despite supraphysiological dosages of pancreatic enzymes. As pancreatin release and enzyme function is influenced by duodenal pH, we have used 24-h ambulatory pH measurements to assess the extent and duration of postprandial hyperacidity. Readings were obtained from the stomach and proximal duodenum in 16 CF patients (aged 6 months to 12 years) using a dual-channel antimony electrode. The fasting gastric and duodenal pH values were normal in all patients (mean pH values of 1.3, and 6.8, respectively). There was, however, a marked drop in duodenal pH in the first postprandial hour, which became more pronounced with successive meals. The total time that duodenal pH was < 5 varied from 15 to 90% of the recording (mean 57%). Overnight the duodenal pH returned to normal levels. A subgroup of five patients were studied before and after treatment with omeprazole, a potent inhibitor of gastric acid secretion. There were significant improvements in both weight gain and fat absorption. This study supports the hypothesis that the postprandial duodenal pH is excessively acid in patients with CF and may be an important element in the continuing fat malabsorption experienced by some patients. This malabsorption may limit the efficacy of the newer high-lipase pancreatic enzyme supplements and lead to delayed enzyme release, a possible factor in the recent reports of proximal colonic strictures.

Absorption↗

Head growth in cystic fibrosis following early diagnosis by neonatal screening.

Growth in length, weight gain, and head circumference were recorded from 3 months to 4 years of age in 25 children with cystic fibrosis diagnosed by neonatal screening. Mean standard deviation (SD) scores at 3 months for length, weight, and head circumference were -0.78, -0.91, and -0.52 respectively. Over the first 2 years length SD scores showed a consistent improvement and stabilised at 0.1 SD below mean from 2 to 4 years. Weight SD scores remained essentially unaltered throughout, approximately 1 SD below the mean. Head circumference, however, after an initial increase from -0.52 at 3 months to -0.25 at 18 months, slowed and fell to 1 SD below the mean at 4 years. The data suggest that head growth continues to lag behind somatic growth in children with cystic fibrosis despite early diagnosis and good nutritional management in early infancy. These data also support functional expression of cystic fibrosis transmembrane conductance regulator in the brain.

Body Height↗

Influence of peppermint oil on absorptive and secretory processes in rat small intestine.

BACKGROUND: Peppermint oil is used to relieve the symptoms of irritable bowel syndrome, relaxing intestinal smooth muscle by reducing the availability of calcium, but its effects on intestinal transport are unknown. AIMS: To determine the effect of peppermint oil on intestinal transport processes. METHODS: The influence of peppermint oil on intestinal transport was investigated in rat jejunum using both intestinal sheets mounted in Ussing chambers and brush border membrane vesicles. RESULTS: Mucosal peppermint oil (1 and 5 mg/ml) had no significant effect on basal short circuit current, but inhibited the increase associated with sodium dependent glucose absorption. The increased short circuit current induced by serosal acetylcholine, a reflection of calcium mediated electrogenic chloride secretion, was unaffected by mucosal peppermint oil (5 mg/ml). In contrast, serosal peppermint oil (1 mg/ml) inhibited the response to acetylcholine without reducing the effect of mucosal glucose. In brush border membrane vesicles active glucose uptake was inhibited by extravesicular peppermint oil at concentrations of 0.5 and 1 mg/ml. CONCLUSIONS: Peppermint oil in the intestinal lumen inhibits enterocyte glucose uptake via a direct action at the brush border membrane. Inhibition of secretion by serosal peppermint oil is consistent with a reduced availability of calcium.

Absorption↗

Modification of nasal membrane potential difference with inhaled amiloride and loperamide in the cystic fibrosis (CF) mouse.

BACKGROUND: In the airway of subjects with cystic fibrosis (CF) the combination of defective cAMP mediated chloride secretion and enhanced sodium absorption leads to dehydration of mucosal mucus and is reflected in an increased trans-epithelial potential difference (PD). The airway secretions may be less viscid and easier to expectorate if sodium (and water) reabsorption is inhibited. METHODS: To evaluate the response to sodium blocking agents, changes in the nasal PD in 20 transgenic CF mice were compared with 14 control mice (MF1 strain) before and after administration of nebulised amiloride and loperamide (both in a concentration of 1 mmol/l). The duration of action for both drugs was also determined after a single inhaled dose of 1 mmol/l for two minutes. RESULTS: The median basal PD was -24 mV in controls and -28 mV in CF mice (p < 0.01). This fell in CF mice after amiloride and loperamide administration by 15 mV and 14 mV, respectively, compared with a decrease of 7 mV and 5.5 mV in controls (p < 0.01). There was no further change in PD when loperamide was given after amiloride. This suggests that loperamide and amiloride may act on sodium absorption via similar mechanisms. Loperamide had a longer duration of action after a single administration than amiloride. CONCLUSION: The administration of amiloride and loperamide reduces the transepithelial potential and inhibits sodium reabsorption in the CF mouse airway. Further studies are required to determine if the more prolonged action of loperamide could be of therapeutic use.

Amiloride↗

Characterization of a lipopolysaccharide O antigen containing two different trisaccharide repeating units from Burkholderia cepacia serotype E (O2).

The O antigen of the lipopolysaccharide of Burkholderia cepacia serotype E (O2) was shown by a combination of methylation analysis, partial hydrolysis, NMR, and mass spectrometric methods to be a high molecular weight polysaccharide composed of two different trisaccharide repeating units in the ratio 2:1. The major trisaccharide component is composed of two alpha-D-mannopyranosyl and one beta-D-galactopyranosyl residues with the structure, [-->2)-alpha-D-Man p-(1-->2)-alpha-D-Man p-(1-->4)-beta-D-Gal p-(1-->]n The minor trisaccharide component is a D-mannan composed of two alpha- and one beta-D-mannopyranosyl residues with the structure, [-->2)-alpha-D-Man p-(1-->2)-alpha-D-Man p-(1-->3)-beta-D-Man p-(1-->]n

Carbohydrate Conformation↗

Structures of the two polymers present in the lipopolysaccharide of Burkholderia (Pseudomonas) cepacia serogroup O4.

Like several other strains of Burkholderia (Pseudomonas) cepacia, the reference strain for serogroup O4 in the French typing scheme [Heidt, A., Monteil, H. & Richard, C. (1983) J. Clin. Microbiol. 18, 738-740] produces a lipopolysaccharide containing two distinct polymers. Attempts to separate the polymers chromatographically were unsuccessful, but the periodate-resistant major polymer could be isolated by application of the Smith degradation technique to the mixture. By means of chemical and NMR spectroscopic analysis, the following structure could be assigned to the repeating unit of the major polymer: -->3)-alpha-D-Galp-(1-->3)-beta-D-Galp-(1-->3)-beta-D-GalpNAc-(1-->. The following structure of the repeating unit of the minor polymer was established from similar studies of its degradation product, resulting from the oxidation of L-rhamnose (Rha), and of the original mixture: -->3)-alpha-D-GalpNAc-(1-->3)-beta-D-GalpNAc-(1-->4)-alpha-L-Rhap- (1-->. Individually, the polymers have recently been found in related strains of B. cepacia. The minor polymer was identified as the O-antigen in serotype A of a Canadian typing scheme [Beynon, L. M. & Perry, M. B. (1993) Biochem. Cell Biol. 71, 417-420], and the major polymer in serotype C of a Japanese typing scheme [Paramonov, N. A., Shashkov, A. S., Knirel, Y. A., Soldatkina, M. A. & Zakharova, I. Y. (1994) Bioorg. Khim. 20, 984-993]. In the case of the O4 strain studied here, both polymers were produced under a variety of growth conditions.

Biopolymers↗

Continuous performance tests: a comparison of modalities.

Continuous Performance Tests (CPTs) are popular instruments for the assessment of sustained attention and impulsivity in individuals thought to have attentional deficits. CPTs used in research and clinical practice rely on visual presentations of stimulus material with little consideration given to the effects on CPT performance when stimuli are presented in an auditory mode. This study examined CPT performance in normal adult subjects. The mode of presentation (visual or auditory) and the type of task (vigilance or distractibility) were varied and their effects on performance measured. Data were collected on 82 subjects; results indicated that auditory presentation of stimuli increased the difficulty of both tasks. Results also showed that distractibility tasks were more difficult than vigilance tasks.

Acoustic Stimulation↗

Technegas and Pertechnegas particle size distribution.

Technegas and Pertechnegas are radioactive aerosols produced in a commercial generator and used for lung scintigraphy. The aerosols are produced by first evaporating to dryness standard technetium-99m generator eluate (99mTcO4 in normal saline) in a graphite crucible (the simmer stage) and then heating this to 2500 degrees C (the "burn" stage). The aim of this work was to measure the particle size distributions of these agents and relate this to regional lung deposition. Factors that may vary during production of the aerosol in routine use were investigated to determine whether they influenced the particle size. Activity size distributions were measured using a serial wire-screen diffusion battery. The Technegas size distribution was approximately log-normal with an activity median diameter of 158 nm and a geometric standard deviation of 1.5. The results for Pertechnegas were similar. The median size increased with the number of simmers and with the time from generation. The increase in size with the number of simmers is thought to be due to the increased salt content in the crucible prior to the "burn". The predicted lung deposition is 37% in the alveolar region and 5% in the bronchial region. Significant changes in deposition are not predicted over the range of particle sizes measured.

Aerosols↗

Texture analysis of technegas lung ventilation images.

Technegas lung ventilation images sometimes have 'hot spots', particularly in patients with respiratory disease. A novel technique is presented for quantifying this 'spottiness' using morphological texture analysis. A set of 32 images from patients with various respiratory diseases is studied. Images are filtered at a range of scales using morphological opening, and the slopes of image metrics versus structuring element size are used as texture parameters. The results are compared with the opinions of three experienced nuclear medicine physicians who have classified the images into two groups, 'spotty' and 'non-spotty', and have ranked the former. For the spotty images, the computer and observer ranks are compared; the highest correlation is rs = 0.66 (p = 0.01) for a single parameter, and rs = 0.71 (p < 0.01) for a combination of two parameters. Using a pair of parameters, 83% and 90% correct classification rates are obtained for the spotty and non-spotty classes, respectively. It is concluded that these texture parameters provide a useful measure of image spottiness, and it is demonstrated that this technique is superior to previously published methods. The practical value of the technique is illustrated using two applications.

Humans↗

Disproportionate head growth retardation in cystic fibrosis.

Monthly increments of length, weight gain, and head circumference were recorded from birth to 4 years of age in 52 children with cystic fibrosis. At birth the children showed stunting. Standard deviation (SD) scores at birth for height, weight, and head circumference were -1.24, -0.72, and -1.82 respectively. Over the first four years, length and weight SD scores showed a consistent improvement. However, there was very limited improvement in head circumference, which stabilised 1 SD below the mean from 1.5 years to 4 years. Our data suggest that head growth lags behind gain in height and weight in children with cystic fibrosis despite good nutritional management in early infancy. The data may also support the expression of cystic fibrosis transmembrane conductance regulator in choroid plexus and ependyma.

Body Height↗

Serum glutathione S-transferase B1 activity as an index of liver function in cystic fibrosis.

AIMS: To evaluate serum glutathione S-transferase B1 (GST B1), a highly sensitive test of hepatocellular function, as a means of identifying liver disease in patients with cystic fibrosis (CF). METHODS: The presence of liver disease was sought over a three year period in 60 children with CF, using a combination of clinical assessment, ultrasound examination, conventional biochemical tests of liver function (LFTs), and measurement of GST B1. RESULTS: Reference ranges for serum GST B1 were established in a paediatric control population. The 95% value (4.55 micrograms/l) was similar to the upper limit of normal previously derived in adults. Mean (SE) serum GST B1 activities were higher in the CF population (9.0 (1.14) micrograms/l) than in age matched controls (2.4 (0.15) micrograms/l). Ten patients with CF showed clinical signs of liver dysfunction. All but one had a serum GST B1 > 4.55 micrograms/l. Twelve other patients had elevated LFTs without clinically evident liver dysfunction, six had abnormal ultrasound scans and two showed both of these anomalies. Thirty patients with CF had neither biochemical, ultrasonographic nor clinical signs of liver disease. On review three years later, clinically important liver disease was reaffirmed in eight of the 10 index cases and had become apparent in a further eight, all of whom had elevated GST B1 activities. Five (36%) of the patients with elevated LFTs and two (33%) with isolated ultrasound changes continued to show these abnormalities. CONCLUSIONS: The limitations of conventional LFTs and ultrasound scans were evident from this study. The results suggest that elevated GST B1 activities may be a better predictor of hepatic dysfunction in CF than conventional LFTs.

Adolescent↗

Off-resonance binomial composite pulses in 2D and 3D fat/water imaging at 0.5 T.

A new method of acquiring two-dimensional (2D) and three-dimensional (3D) fat/water decomposed images on a 0.5 T magnetic resonance (MR) imaging system is described. The method uses a gradient-recalled echo (GRE) sequence incorporating a composite 121 pulse, originally used for magnetization transfer contrast (MTC) experiments, for frequency-selective pre-saturation. By applying the 121 pulse off resonance, a sharp discrimination between the chemically shifted water and fat signals may be obtained using a composite pulse as short as 4 ms. Phantom studies demonstrate that suppression ratios as high as 50:1 are achievable. The new method has been applied to volunteers and patients, and good fat/water images of limb, abdomen, head and neck obtained. The new method can be incorporated into other pulse sequences related to GRE, such as phase contrast (PC) and time-of-flight (TOF), and represents the first practical (i.e. rapid) method for 3D fat/water imaging at an operating field as low as 0.5 T.

Adipose Tissue↗