Search PubMed⌕ Search

Biomedical subjects

S J Barton

Publications and source records attributed to S J Barton.

At least 19 recordsLinked to original sources
PubMed2006

The cysteinyl-leukotriene type 1 receptor polymorphism 927T/C is associated with atopy severity but not with asthma.

BACKGROUND: The cysteinyl-leukotriene receptor type 1 (CysLT1) mediates the bronchoconstrictor and pro-inflammatory actions of cysteinyl-leukotrienes (LTC4, LTD4, LTE4) in asthma and is the molecular target of the lukast class of oral anti-leukotriene drugs. We screened the CYSLTR1 gene on chromosome Xq13-21 for coding region polymorphisms, and investigated their associations with allergy and asthma. METHODS: Solid-phase chemical cleavage was used to screen polymorphisms in the coding region of CYSLTR1. A TaqMan allelic discrimination assay was used to genotype a 927T/C SNP and oligonucleotide ligation assays were used to genotype the previously reported 617T/C and 898G/A SNPs of CYSLTR1 in 341 asthmatic families from the UK. Associations with asthma diagnosis, atopic status, serum-specific IgE and severity of allergy and asthma were examined. RESULTS: Family-based association tests showed that the 927 T allele was associated with atopy severity, especially in female subjects, but not with asthma diagnosis or severity, atopic status, bronchial hyper-responsiveness to methacholine or forced expiratory volume in 1 s. CONCLUSION: Mutation screening identified only one polymorphism, 927T/C, in the coding region of the CysLT1 receptor. This polymorphsim is predictive of atopy severity, but not associated with asthma.

Adolescent↗
PubMed2005

Hyperactive striatal neurons in symptomatic Huntington R6/2 mice: variations with behavioral state and repeated ascorbate treatment.

Membrane and morphological abnormalities occur in the striatum of R6/2 transgenics, a widely used mouse model of Huntington's disease. To assess changes in behavior-related neuronal activity, we implanted micro-wire bundles in the striatum of symptomatic R6/2 mice and wild-type controls. Unit activity was recorded in an open-field arena once weekly for the next several weeks. For each recording session, firing rate was monitored before, during, and after a period of light anesthesia to assess the influence of behavioral arousal. Because low ascorbate in striatal extracellular fluid may contribute to Huntington's disease symptoms, all animals received an injection of either 300 mg/kg sodium ascorbate or vehicle for three consecutive days prior to each recording session. In R6/2 mice, regardless of treatment, striatal unit activity was significantly faster than in wild-type controls. The difference in mean (+/-S.E.M.) firing was most apparent during wakefulness (6.4+/-0.8 vs. 3.5+/-0.3 spikes/s) but also persisted during anesthesia (2.0+/-0.3 vs. 0.7+/-0.1 spikes/s). Assessment of treatment duration indicated that R6/2 mean waking discharge rate was significantly slower after three weeks than after one week of ascorbate treatment (3.1+/-0.6 vs. 10.2+/-2.7 spikes/s). Vehicle-treated R6/2s showed no such decline in striatal activity ruling out an age- or injection-related effect. Slow-scan voltammetry in separate animals confirmed that ascorbate-injections returned the level of striatal extracellular ascorbate in R6/2 mice to that of wild-type controls. Our results indicate that although striatal neurons modulate firing in relation to behavioral state, impulse activity is consistently elevated in transgenic relative to wild-type mice. Restoring extracellular ascorbate to the wild-type level reverses this effect suggesting a role for ascorbate in normalizing neuronal function in Huntington's disease striatum.

Anesthesia↗
PubMed2005

An unusual presentation of metastatic testicular tumour.

We report a unique case of metastatic malignant teratoma from an undescended testis which presented with acute pulmonary embolism. After chemotherapy, the undescended right testicle was resected along with a cord of non- obstructing inferior venal caval tumour which extended into the right atrium with tumour floating free within the atrium at the end of the cord of tumour. The presentation, diagnosis and treatment of testicular tumours is described and the literature pertaining to testicular tumours in military personnel reviewed.

Adult↗
PubMed2004

Toll-like receptor 4 polymorphism and severity of atopy in asthmatics.

Endotoxin exposure may have a protective effect against asthma and atopy. An Asp299Gly polymorphism in the Toll-like receptor 4 (TLR4) gene reduces responsiveness to endotoxin. This study determined the effect of TLR4 polymorphism on the risk and severity of asthma and atopy. In all, 336 UK Caucasian families with > or = 2 affected sibs (physician's diagnosis of asthma and current medication use) and 179 Caucasians without asthma or a family history of asthma were genotyped using ARMS-PCR. No association of the TLR4 polymorphism was found with the risk of developing asthma, either in parent-affected sibling trios, or in case-control analyses (P>0.05). In the first affected asthmatic siblings, the atopy severity score (based on size and number of positive skin-prick tests and specific IgE) was higher in those with the Asp/Gly or Gly/Gly genotypes (mean 1.8, s.d. 1.1, n=39) compared to those with the Asp/Asp genotype (mean 1.2, s.d. 1.0, n=279) (P=0.003, t-test). No associations were found with total IgE, FEV(1) % predicted, slope of FEV(1) response to methacholine or asthma severity score (P>0.05). This study confirms the previously observed lack of association of TLR4 polymorphisms with asthma. In contrast, the findings suggest that genetically determined hyporesponsiveness to endotoxin may increase atopy severity.

Amino Acid Substitution↗
PubMed2004

Lack of association of HLA class I genes and TNF alpha-308 polymorphism in toluene diisocyanate-induced asthma.

BACKGROUND: Toluene diisocyanate (TDI)-induced asthma is a common cause of occupational asthma and it affects 5-15% of the exposed population suggesting an underlying genetic susceptibility. METHODS: To investigate the role of genetic factors in the development of TDI-induced asthma, we analyzed the distribution of human leukocyte antigen (HLA) class I genes and of tumor necrosis factor (TNF)-alpha A-308G polymorphism in 142 patients with TDI-induced asthma and in 50 asymptomatic exposed subjects. RESULTS: Neither the distribution of HLA class I antigens nor the distribution of TNF-alpha A-308G polymorphism was different between patients with TDI-induced asthma and asymptomatic exposed subjects. CONCLUSIONS: These results suggest that HLA class I antigens and TNF-alpha A-308G are not associated with susceptibility or resistance to the development of TDI-induced asthma.

Adult↗
PubMed2004

Polymorphism of the mast cell chymase gene (CMA1) promoter region: lack of association with asthma but association with serum total immunoglobulin E levels in adult atopic dermatitis.

BACKGROUND: Mast cell chymase has the potential to be an important mediator of inflammation and remodelling in the asthmatic lung. Previous studies have examined association between promoter polymorphism of the chymase gene (CMA1) and allergic phenotypes but the significance of this polymorphism is unclear. We have examined association of a CMA1 variant in relation to asthma in a large UK Caucasian family cohort. METHODS: A polymorphism of the CMA1 gene promoter (-1903G/A) was genotyped in 341 asthmatic families and in 184 non-asthmatic adults recruited from the UK PCR-RFLP based genotyping. Association with asthma diagnosis, atopy, specific and total IgE, and atopy and asthma severity was examined. RESULTS: Case-control studies did not reveal a significant difference in allele frequency between asthmatics and controls. A significant association was found between CMA1 genotypes and total IgE levels in subjects with self-reported eczema that remained significant after correction for multiple testing (median total serum IgE GG 297 kU/L, GA 144 kU/L, AA 48.4 kU/L, Pc=0.0032). CONCLUSION: These data suggest that CMA1 promoter polymorphism does not contribute to asthma susceptibility or severity but may be involved in regulating IgE levels in patients with eczema.

Adolescent↗
PubMed2003

Metabolic profiles of human brain tumors using quantitative in vivo 1H magnetic resonance spectroscopy.

Proton spectroscopy can noninvasively provide useful information on brain tumor type and grade. Short- (30 ms) and long- (136 ms) echo time (TE) (1)H spectra were acquired from normal white matter (NWM), meningiomas, grade II astrocytomas, anaplastic astrocytomas, glioblastomas, and metastases. Very low myo-Inositol ([mI]) and creatine ([Cr]) were characteristic of meningiomas, and high [mI] characteristic of grade II astrocytomas. Tumor choline ([Cho]) was greater than NWM and increased with grade for grade II and anaplastic astrocytomas, but was highly variable for glioblastomas. Higher [Cho] and [Cr] correlated with low lipid and lactate (P < 0.05), indicating a dilution of metabolite concentrations due to necrosis in high-grade tumors. Metabolite peak area ratios showed no correlation with lipids and mI/Cho (at TE = 30 ms), and Cr/Cho (at TE = 136 ms) best correlated with tumor grade. The quantified lipid, macromolecule, and lactate levels increased with grade of tumor, consistent with progression from hypoxia to necrosis. Quantification of lipids and macromolecules at short TE provided a good marker for tumor grade, and a scatter plot of the sum of alanine, lactate, and delta 1.3 lipid signals vs. mI/Cho provided a simple way to separate most tumors by type and grade.

Alanine↗
PubMed1999

Comparison of in vivo 1H MRS of human brain tumours with 1H HR-MAS spectroscopy of intact biopsy samples in vitro.

High resolution magic angle spinning (MAS) 1H nuclear magnetic resonance (NMR) spectroscopy has been employed to study intact human brain tumour tissue and comparison with the corresponding in vivo spectrum has been made. Two dimensional 1H MAS-NMR measurements, including J-resolved and homonuclear shift correlation spectra, were obtained to aid metabolite signal assignment. MAS gave greatly improved line-shape and reduced line-width in comparison to conventional high resolution in vivo 1H MRS of intact tissue, permitting the simultaneous detection of cellular lipids and metabolites. The technique provides the most direct method for comparison of in vivo spectra with high resolution spectra in vitro and hence allows more reliable peak assignment of in vivo 1H MRS spectra.

Astrocytoma↗
PubMed1998

Foster parents of cocaine-exposed infants.

The purpose of this study was to describe the experience of foster parents of cocaine-exposed infants. A qualitative approach was selected because of the paucity of knowledge on the topic. Results showed foster parents observed alterations in physiological and behavioral health, developmental problems, and variability among infants related to these problems. Foster parents were concerned about the future development of infants. They felt the experience of living with a cocaine-exposed infant gave them a unique view of the effects of exposure. Parents found difficulties obtaining social services. Foster parents reported problems with access to and appropriateness of health care and identified difficulties arising from community reaction to foster parenting. Recommendations focused on the need for more research on social, developmental, and behavioral effects of cocaine exposure and increased attention to the needs and concerns of foster parents.

Adult↗
PubMed1997

Nuclear magnetic resonance spectroscopy of cancer.

Nuclear magnetic resonance spectroscopy (MRS) offers a non-invasive approach for studying tumour biochemistry and physiology. This review highlights NMR nuclei (31P, 1H, 19F, 13C, 2H) that have been observed in both pre-clinical and clinical spectroscopic studies of cancer.

Carbon Isotopes↗
PubMed1988

Reproductive toxicity studies of ademetionine.

S-Adenosyl-L-methionine sulphate-p-toluene sulphonate (ademetionine, SAMe), a donor of methyl groups, was examined for effects upon embryofoetal toxicity following both premating treatment and treatment during pregnancy and for peri- and post-natal toxicity in the rat at dosages of 0, 100, 200 and 400 mg/kg/d SAMe ion by subcutaneous or intravenous administration. Embryofoetal toxicity was also examined in the New Zealand White rabbit at dosages of 0, 10, 20 and 40 mg/kg/d SAMe by intravenous administration. Treatment was considered to be without adverse effect upon any of the reproductive parameters examined on either F0 or on the untreated F1 generations. There was no indication that treatment adversely affected the litter parameters including the incidences of malformations, anomalies and skeletal variants. Some slight changes in the activity of the F1 females derived from F0 animals given 400 mg/kg/d were considered to be of minimal importance. In contrast to the above, adverse effects upon the parents were noted at 400 mg/kg/d including local tissue reaction at the injection sites and retardation of body weight gain. In the intravenous studies some rigidity and dyspnoea were noted following administration. Following subcutaneous premating treatment there was also evidence of histopathological change to the kidney of the female rat. Increased water consumption was noted in this latter study and amongst females rearing offspring in the embryo foetal toxicity study in which the compound was administered intravenously. At the lower dosages administered to the rat some local tissue reaction was evident as was some retardation of body weight gain, minimal at the lowest intravenous dose.(ABSTRACT TRUNCATED AT 250 WORDS)

Abnormalities, Drug-Induced↗
PubMed1987

Delineation of human prometaphase paracentromeric regions using sequential GTG- and C-banding.

The centromeric-paracentromeric regions of high-resolution human chromosomes have not been examined in detail. It is not clear which bands in the paracentromeric regions are included within the heterochromatin and are therefore not clinically meaningful, and which bands are excluded. This makes breakpoint analysis in these regions difficult. Using sequential G- and C-banding of high-resolution chromosome preparations from four clinically normal subjects and from one patient with a very small interstitial deletion of the chromosome 16 long arm, we have made a detailed analysis of the centromeric-paracentromeric regions of each chromosome and of the entire Y chromosome at the 400, 550, and 800-850 band stages. We present here the results of analysis of preparations at the 800-850 band stage.

Amino Acid Metabolism, Inborn Errors↗
PubMed1987

Reproductive toxicity studies of rentiapril.

(2R,4R)-2-(o-Hydroxyphenyl)-3-(3-mercaptopropionyl)-4- thiazolidinecarboxylic acid (rentiapril, SA 446), an orally active inhibitor of angiotensin converting enzyme, was examined for effects upon general reproductive performance, for embryofoetal toxicity and for peri- and postnatal toxicity in the rat at dosages of 0, 20, 100 and 500 mg/kg/d. Embryofoetal toxicity was also examined in the New Zealand White rabbit at dosages of 0, 1, 2 and 4 mg/kg/d. The compound was administered by gastric intubation. Prolonged treatment at 100 and 500 mg/kg/d during the fertility study was associated with some slight depression of body weight gain of males. Body weight gain of females during gestation was significantly depressed at 500 mg/kg/d. There was salivation in both sexes at 500 mg/kg/d and also in males receiving 100 mg/kg/d. Following this prolonged treatment in the fertility study. Fo male and female kidney weights were increased at all dosages. Although there was no obvious effect upon fertility there was an increased incidence of total litter loss at 500 mg/kg/d and mean pup weights to day 21 post partum were reduced at this dosage and at 100 mg/kg/d with delays in the attainment of some of the developmental landmarks. In the rat treatment at 500 mg/kg/d from day 7 to 17 of pregnancy did not adversely effect embryofoetal development. Subsequent development and reproductive performance of the F1 offspring was also unimpaired. During this treatment period signs of salivation were seen at 500 mg/kg/d. Slight retardation of maternal body weight gain was noted at 500 mg/kg/d and at 100 mg/kg/d but not at 20 mg/kg/d.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Mercaptopropionic Acid↗
PubMedDate not supplied

Infant feeding practices of low-income rural mothers.

PURPOSE: To examine infant feeding practices at 1 to 2 months of age and at 4 to 6 months in a rural population of infants at risk for failure to thrive. DESIGN: A descriptive/exploratory study with 52 mothers who were interviewed twice during the infant's first 6 months of life. Mothers were recruited from health care facilities in rural southeastern Kentucky. Mothers participated in two structured interviews about feeding practices conducted in health care clinics or in the home. RESULTS: At birth 52% of mothers chose to use formula, 41.2% chose breastfeeding, and 8% were both breastfeeding and formula feeding. By 1 month, 71% of mothers were formula feeding and only 29% were breastfeeding. At 4 to 6 months postpartum 80% of mothers were formula feeding and 20% were breastfeeding. Mothers with more children, higher family income, and more education were more likely to breastfeed. Almost all mothers began solid foods before the infant was 4 months old. Infants were fed table foods including mashed potatoes and gravy, and beverages such as apple juice, fruit juices, and soda. Mothers relied on health professionals for support for feeding decisions at the first interview; however, they relied more on the grandmother for support at the time of the second interview. CONCLUSIONS AND CLINICAL IMPLICATIONS: Breastfeeding mothers need additional support to continue breastfeeding beyond the first month. Mothers and grandmothers need education to discourage the practice of early introduction of inappropriate solid foods, including the practice of thickening bottles of formula with cereal. Nutrition teaching should be provided to mothers and grandmothers including how to select high nutrient, lower fat-weaning foods, and limiting infant intake of high-calorie drinks.

Bottle Feeding↗