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Biomedical subjects

J C Taylor

Publications and source records attributed to J C Taylor.

At least 19 recordsLinked to original sources
PubMed2007

Optical adjuncts for enhanced colonoscopic diagnosis.

BACKGROUND: Optical techniques using previously unexploited properties of light interaction with tissue may be valuable in the detection, diagnosis and staging of colorectal neoplasia. METHODS: A Medline search (1990 to present) was conducted on optical diagnostics in the detection of colorectal neoplasia. The reference list of each identified article was reviewed for further relevant papers. RESULTS AND CONCLUSION: Chromoendoscopy is the only optical adjunct to colonoscopy that has been tested in large randomized clinical trials. It improves the detection of small and flat colorectal adenomas, and of neoplasia in chronic ulcerative colitis and hereditary non-polyposis colorectal cancer. All other techniques are the subject of ongoing research and the practicality of population screening with any of the methods has yet to be established. Optical techniques may, however, permit immediate clinical diagnosis, removing the need for histological analysis. They may also improve the diagnosis of early colonic neoplasia.

Colonoscopy↗
PubMed2005

A genome-wide screen in 1119 relative pairs with autoimmune thyroid disease.

CONTEXT: Autoimmune thyroid diseases (AITD), comprising Graves' disease and autoimmune hypothyroidism, are characterized by loss of immunological self-tolerance to thyroid antigens. These are complex diseases arising from a combination of genetic and environmental factors. An understanding of the genetic susceptibility factors for AITD could help to target treatments more effectively and identify people at risk for these conditions. OBJECTIVE: The objective of this study was to identify regions of genetic linkage to AITD that could potentially harbor genetic susceptibility factors for these conditions. DESIGN: The study design was a genome-wide screen performed on affected relative pairs with AITD. SETTING: Patients were recruited through hospital endocrinology clinics. PARTICIPANTS: Some 1119 Caucasian relative pairs affected with AITD (Graves' disease or autoimmune hypothyroidism) were recruited into the study. INTERVENTION: Blood samples were obtained from each participant for DNA analysis, and clinical questionnaires were completed. MAIN OUTCOME MEASURE: The study aimed to identify regions of genetic linkage to AITD. RESULTS: Three regions of suggestive linkage were obtained on chromosomes 18p11 (maximum LOD score, 2.5), 2q36 (maximum LOD score, 2.2), and 11p15 (maximum LOD score, 2.0). No linkage to human leukocyte antigen was found. CONCLUSIONS: The absence of significant evidence of linkage at any one locus in such a large dataset argues that genetic susceptibility to AITD reflects a number of loci, each with a modest effect. Linkage analysis may be limited in defining such loci, and large-scale association studies may prove to be more useful in identifying genetic susceptibility factors for AITD.

Chromosome Mapping↗
PubMed2004

Late survival after elective repair of aortic aneurysms detected by screening.

BACKGROUND: The aim of this study was to examine whether there was any survival advantage in men following elective repair of an abdominal aortic aneurysm (AAA) detected by ultrasound screening compared to those with an AAA detected incidentally. METHODS: A total of 424 men underwent elective AAA repair between 1990 and 1998; 181 were detected in an aneurysm screening programme and 243 were diagnosed incidentally. Follow-up survival data were collected until 2003 (minimum 5 years) and survival curves were compared using regression analysis. RESULTS: The postoperative 30-day mortality rate was significantly lower in men whose aneurysms were detected by screening (4.4%), compared with those detected incidentally (9.0%). Similarly, 5-year survival (78% vs. 65%) and 10-year survival rates (63% vs. 40%) were better after repair of a screen-detected AAA (p<0.0003 at all time intervals, by log rank testing). Multivariate analysis showed that this was largely due to the older age of men who had repair of an incidental AAA (71.2 vs. 67.1 years). CONCLUSION: Men who had elective repair of an AAA detected by screening had a better late survival rate than men whose aneurysm was discovered incidentally because they were younger at the time of surgery.

Aged↗
PubMed2004

Determination of residues of propamocarb in wine by liquid chromatography-electrospray mass spectrometry with direct injection.

A simple, sensitive and reliable liquid chromatography-mass spectrometry method with direct injection of diluted samples is reported for the determination of propamocarb residues in wine. Red and white wines were diluted 40- and 20-fold, respectively, using water. Liquid chromatography was performed with a mobile-phase gradient and detection was by electrospray mass spectrometry in a positive ionization mode. Propamocarb was detected as the protonated molecular species at m/z 189. Using matrix-matched calibrant solutions, a calibrated range equivalent to 0.05-2.0 mg kg(-1) in red and white wines and limits of detection of 0.025 mg kg(-1) for white wine and of 0.05 mg kg(-1) for red wine (0.00125 microg ml(-1) of sample solution injected) were readily achievable. Recovery of propamocarb hydrochloride from wine spiked before dilution was in the range 91-115%. The chromatograms were free of isobaric interferences. In a small wine survey (72 samples), no residues of propamocarb were detected above 0.1 mg kg(-1).

Carbamates↗
PubMed2002

Psychological, social and health behaviour risk factors for deaths certified as asthma: a national case-control study.

BACKGROUND: Uncontrolled studies suggest that psychosocial factors and health behaviour may be important in asthma death. METHODS: A community based case-control study of 533 cases, comprising 78% of all asthma deaths under age 65 years and 533 hospital controls individually matched for age, district and asthma admission date corresponding to date of death was undertaken in seven regions of Britain (1994-98). Data were extracted blind from anonymised copies of primary care records for the previous 5 years and non-blind for the earlier period. RESULTS: 60% of cases and 63% of controls were female. The median age in both groups was 53. Cases had an earlier age of asthma onset, more chronic obstructive lung disease, and were more obese. 48% of cases and 42% of controls had a health behaviour problem; repeated non-attendance/poor inhaler technique was related to increased risk of death. Overall, 85% and 86%, respectively, had a psychosocial problem. Four psychosocial factors were associated with increased risk of death (psychosis, alcohol/drug abuse, financial/employment problems, learning difficulties) and two with reduced risk (anxiety/prescription of antidepressant drugs and sexual problems). While alcohol/drug abuse lost significance after adjustment for psychosis, other associations appeared independent of each other and of indicators of severity and co-morbidity. None of the remaining 13 factors including family problems, domestic abuse, bereavement, and social isolation were significantly related to risk of asthma death. CONCLUSION: There was an apparently high burden of psychosocial problems in both cases and controls. The associations between health behaviour, psychosocial factors, and asthma death are varied and complex with a limited number of factors showing positive relationships.

Adolescent↗
PubMed2001

The multidrug resistance P-glycoprotein. Oligomeric state and intramolecular interactions.

The human multidrug resistance P-glycoprotein (P-gp), a member of the ATP-binding cassette (ABC) superfamily of transporters, is frequently responsible for the failure of chemotherapy by virtue of its ability to export hydrophobic cytotoxic drugs from cells. Elucidating the inter- and intramolecular interactions of this protein is critical to understanding its cellular function and mechanism of action. Toward this end, we have used both biochemical and genetic techniques to probe potential oligomerization interactions of P-gp. Differentially epitope-tagged P-gp molecules did not co-immunoprecipitate when co-expressed in HEK293 cells or when co-translated in vitro, demonstrating that P-gp is monomeric in both the presence and absence of detergents. The two cytoplasmic domains of P-gp did not interact with each other in vivo when co-expressed as gene fusions in yeast. In contrast, the homologous domains of the transporter associated with antigen processing (TAP), which reside on separate polypeptides and must form a heterodimeric transporter (TAP1/TAP2), did interact in this system, suggesting a role for these domains in TAP dimerization. Implications for understanding the subunit organization of ABC transporters are discussed.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2001

Opinions and experiences in general practice on osteoporosis prevention, diagnosis and management.

We determined to survey the general practice population regarding their attitudes to and knowledge of osteoporosis as a baseline prior to publication of national guidelines for the management of osteoporosis. All 2515 general practitioners registered in the 10 Health Authorities of the North Thames region, London, UK were surveyed by a postal questionnaire. Responses relating to epidemiology, public health and education on osteoporosis were analyzed. The overall response was 1153 (46%). General practitioners who responded were younger, predominantly female and in group practice. There is considerable awareness of the importance of preventing osteoporosis. General practitioners are active in identifying groups at risk, particularly those who are aged 40 years and older. A prevention strategy for osteoporosis is viewed as effective. However, two thirds of general practitioners remain unconvinced about the efficacy of drug therapy. Education on osteoporosis is considered inadequate. General practitioners would welcome further information on management issues and access to osteoporosis services. In conclusion, educational initiatives will be important both at undergraduate and postgraduate levels to increase awareness and knowledge of osteoporosis. General practitioners are aware of the public health impact of this condition and express a preference for educational material of direct relevance to the care of their patients. Therefore better cooperation between primary and secondary care should lead to ways of breaking down barriers to change in clinical practice and promoting fully integrated care of patients with osteoporosis.

Attitude of Health Personnel↗
PubMed2001

Associations of past conduct disorder with personality disorders in 'non-psychotic' psychiatric inpatients.

The aim was to investigate associations of a history of features of DSM-III-R conduct disorder (CD) with features of DSM-III-R personality disorders (PDs) and psychopathy, in inpatient psychiatric practice. Fifty-six psychiatric inpatients, without a history of specified 'psychoses', were assessed by the SCID structured interview for DSM-III-R PDs and the 'Psychopathy Checklist Revised' (PCL-R). In a sample in which 59% had borderline PD, significant associations between a history of CD criteria and the adult features of antisocial PD (APD) were relatively specific compared with other PDs, but were weaker in women. However, significant correlations between the number of positive CD criteria and PCL-R scores were similar in both genders. The relatively specific associations between CD and adult features of APD are likely to be relevant to psychiatric patients who show various presentations of PD, if these include some adult features of APD. The findings inform the understanding of the development and classification of PDs.

Adolescent↗
PubMed2000

The bifunctional active site of S-adenosylmethionine synthetase. Roles of the basic residues.

S-adenosylmethionine (AdoMet) synthetase catalyzes a unique two-step enzymatic reaction leading to formation of the primary biological alkylating agent. The crystal structure of Escherichia coli AdoMet synthetase shows that the active site, which lies between two subunits, contains four lysines and one histidine as basic residues. In order to test the proposed charge and hydrogen bonding roles in catalytic function, each lysine has been changed to an uncharged methionine or alanine, and the histidine has been altered to asparagine. The resultant enzyme variants are all tetramers like the wild type enzyme; however, circular dichroism spectra show reductions in helix content for the K245*M and K269M mutants. (The asterisk denotes that the residue is in the second subunit.) Four mutants have k(cat) reductions of approximately 10(3)-10(4)-fold in AdoMet synthesis; however, the k(cat) of K165*M variant is only reduced 2-fold. In each mutant, there is a smaller catalytic impairment in the partial reaction of tripolyphosphate hydrolysis. The K165*A enzyme has a 100-fold greater k(cat) for tripolyphosphate hydrolysis than the wild type enzyme, but this mutant is not activated by AdoMet in contrast to the wild type enzyme. The properties of these mutants require reassessment of the catalytic roles of these residues.

Binding Sites↗
PubMed2000

Considerations in measuring the electrical potentials of metallic restorations in vivo.

Many variables are believed to affect the accurate measuring of metallic restoration electrical potentials. This study examined the effects of intra- versus extra-oral location of the reference electrode, the type of metallic probe used to make contact with the restoration, and scratching and brushing of the restoration surface. Dental amalgam restorations were measured in 40 human subjects. Results showed that only the location of the reference electrode affected the central tendency of the potential. The study discusses the significance of some experimental variables in the accurate measuring of metallic potentials and the need to consider individual subject differences when statistically analysing for the central tendency of a sample.

Adult↗
PubMed2000

The I gene of bean: a dosage-dependent allele conferring extreme resistance, hypersensitive resistance, or spreading vascular necrosis in response to the potyvirus Bean common mosaic virus.

The resistance to the potyvirus Bean common mosaic virus (BCMV) conferred by the I allele in cultivars of Phaseolus vulgaris has been characterized as dominant, and it has been associated with both immunity and a systemic vascular necrosis in infected bean plants under field, as well as controlled, conditions. In our attempts to understand more fully the nature of the interaction between bean with the I resistance allele and the pathogen BCMV, we carefully varied both I allele dosage and temperature and observed the resulting, varying resistance responses. We report here that the I allele in the bean cultivars we studied is not dominant, but rather incompletely dominant, and that the system can be manipulated to show in plants a continuum of response to BCMV that ranges from immunity or extreme resistance, to hypersensitive resistance, to systemic phloem necrosis (and subsequent plant death). We propose that the particular phenotypic outcome in bean results from a quantitative interaction between viral pathogen and plant host that can be altered to favor one or the other by manipulating I allele dosage, temperature, viral pathogen, or plant cultivar.

Fabaceae↗
PubMed1999

The bifunctional active site of s-adenosylmethionine synthetase. Roles of the active site aspartates.

S-Adenosylmethionine (AdoMet) synthetase catalyzes the biosynthesis of AdoMet in a unique enzymatic reaction. Initially the sulfur of methionine displaces the intact tripolyphosphate chain (PPP(i)) from ATP, and subsequently PPP(i) is hydrolyzed to PP(i) and P(i) before product release. The crystal structure of Escherichia coli AdoMet synthetase shows that the active site contains four aspartate residues. Aspartate residues Asp-16* and Asp-271 individually provide the sole protein ligand to one of the two required Mg(2+) ions (* denotes a residue from a second subunit); aspartates Asp-118 and Asp-238* are proposed to interact with methionine. Each aspartate has been changed to an uncharged asparagine, and the metal binding residues were also changed to alanine, to assess the roles of charge and ligation ability on catalytic efficiency. The resultant enzyme variants all structurally resemble the wild type enzyme as indicated by circular dichroism spectra and are tetramers. However, all have k(cat) reductions of approximately 10(3)-fold in AdoMet synthesis, whereas the MgATP and methionine K(m) values change by less than 3- and 8-fold, respectively. In the partial reaction of PPP(i) hydrolysis, mutants of the Mg(2+) binding residues have >700-fold reduced catalytic efficiency (k(cat)/K(m)), whereas the D118N and D238*N mutants are impaired less than 35-fold. The catalytic efficiency for PPP(i) hydrolysis by Mg(2+) site mutants is improved by AdoMet, like the wild type enzyme. In contrast AdoMet reduces the catalytic efficiency for PPP(i) hydrolysis by the D118N and D238*N mutants, indicating that the events involved in AdoMet activation are hindered in these methionyl binding site mutants. Ca(2+) uniquely activates the D271A mutant enzyme to 15% of the level of Mg(2+), in contrast to the approximately 1% Ca(2+) activation of the wild type enzyme. This indicates that the Asp-271 side chain size is a discriminator between the activating ability of Ca(2+) and the smaller Mg(2+).

Adenosine Triphosphate↗
PubMed1999

The equilibrium and kinetic drug binding properties of the mouse P-gp1a and P-gp1b P-glycoproteins are similar.

The gene encoding the multidrug resistance P-glycoprotein (P-gp) is duplicated in rodent species and the functional basis for this remains unresolved. Despite a high sequence similarity, the mouse P-gp1a and P-gp1b isoforms show distinct patterns of tissue distribution which suggest a specific role of the P-gp1b isoform in steroid transport. In the present study possible biochemical differences between the isoforms were directly investigated at the level of drug interaction. There was no detectable difference in the affinity or binding capacity of the two isoforms towards [3H]vinblastine at equilibrium. Similarly, the rate at which [3H]vinblastine associates with P-gp was indistinguishable between the two isoforms. Some modest differences were observed in the relative abilities of the multidrug-resistant (MDR) reversing agents CP100-356, nicardipine and verapamil to displace equilibrium [3H]vinblastine binding to P-gp1a and P-gp1b. The steroid hormone progesterone displayed a low affinity (Ki = 1.2 +/- 0.2 microM for P-gp1a and 3.5 +/- 0.5 microM for P-gp1b), suggesting an unlikely role as a physiological substrate. Thus the mouse isoforms do not appear to exhibit functional differences at the level of initial substrate interaction with protein.

ATP Binding Cassette Transporter, Subfamily B↗
PubMed1999

Determination of residues of the plant growth regulator chlormequat in pears by ion-exchange high performance liquid chromatography-electrospray mass spectrometry.

We report a method which we have used routinely for the determination of chlormequat residues in pears. After extraction with methanol, determination was performed, without clean-up, by ion-exchange HPLC using an SCX column eluted with aqueous ammonium formate-methanol, and HPLC-MS with an electrospray interface. MS and MS-MS were employed concurrently, using selected ion monitoring and selected reaction monitoring, respectively, of the 35Cl and 37Cl isotopes of the chlormequat cation and the CID transitions of each of these precursors to the common product ion at m/z 58. The method was suitable for determinations at concentrations of chlormequat cation of 0.04 mg kg-1. Concentrations determined using the four signals were in good agreement (mean RSD 3%). The mean recovery of chlormequat cation at 0.16 mg kg-1, measured using the m/z 122-->58 signal, was 86% (RSD 7%) under repeatability conditions and 88% (RSD 15%) in routine application of the method over a 3 month period. Analysis of an in-house reference sample of pears, similarly analysed over the 3 month period, gave an RSD of 10% with a mean of 0.14 mg kg-1. Mean recovery at 0.016 mg kg-1, under repeatability conditions on two occasions, was 101% (RSD 6%) and 56% (RSD 12%).

Chlormequat↗
PubMed1999

Effects of endotoxin on surfactant protein A and D stimulation of NO production by alveolar macrophages.

Surfactant protein (SP) A and SP-D affect numerous functions of immune cells including enhancing phagocytosis of bacteria and production of reactive species. Previous studies have shown that SP-A and SP-D bind to a variety of bacteria and to the lipopolysaccharide (LPS) components of their cell walls. In addition, purified preparations of SPs often contain endotoxin. The goals of this study were 1) to evaluate the effects of SP-A and SP-D and complexes of SPs and LPS on the production of nitric oxide metabolites by rat alveolar macrophages and 2) to evaluate methods for the removal of endotoxin with optimal recovery of SP. Incubation of SP-A or SP-D with polymyxin, 100 mM N-octyl-beta-D-glucopyranoside, and 2 mM EDTA followed by dialysis was the most effective method of those tested for reducing endotoxin levels. Commonly used storage buffers for SP-D, but not for SP-A, inhibited the detection of endotoxin. There was a correlation between the endotoxin content of the SP-A and SP-D preparations and their ability to stimulate production of nitrite by alveolar macrophages. SP-A and SP-D treated as described above to remove endotoxin did not stimulate nitrite production. These studies suggest that the functions of SP-A and SP-D are affected by endotoxin and illustrate the importance of monitoring SP preparations for endotoxin contamination.

Animals↗
PubMed1998

The active-site arginine of S-adenosylmethionine synthetase orients the reaction intermediate.

S-Adenosylmethionine (AdoMet) synthetase catalyzes the formation of AdoMet and tripolyphosphate (PPPi) from ATP and L-methionine and the subsequent hydrolysis of the PPPi to PPi and Pi before product release. Little is known about the roles of active-site residues involved in catalysis of the two sequential reactions that occur at opposite ends of the polyphosphate chain. Crystallographic studies of Escherichia coli AdoMet synthetase showed that arginine-244 is the only arginine near the polyphosphate-binding site. Arginine-244 is embedded as the seventh residue in the conserved sequence DxGxTxxKxI which is also found at the active site of inorganic pyrophosphatases, suggesting a potential pyrophosphate-binding motif. Chemical modification of AdoMet synthetase by the arginine-specific reagents phenylglyoxal or p-hydroxyphenylglyoxal inactivates the enzyme. ATP and PPPi protect the enzyme from inactivation, consistent with the presence of an important arginine residue in the vicinity of the polyphosphate-binding site. Site-specific mutagenesis has been used to change the conserved arginine-244 to either leucine (R244L) or histidine (R244H). In the overall reaction, the R244L mutant has the kcat reduced approximately 10(3)-fold, with a 7 to 10-fold increase in substrate Km values; the R244H mutant has an approximately 10(5)-fold decrease in kcat. In contrast, the kcat values for hydrolysis of added PPPi by the R244L and R244H mutants have been reduced by less than 2 orders of magnitude. In contrast to the wild-type enzyme in which 98% of the Pi formed originates as the gamma-phosphoryl group of ATP, in the R244L mutant the orientation of the PPPi intermediate equilibrates at the active site yielding equal amounts of Pi from the alpha- and gamma-phosphoryl groups of ATP. Thus, the active-site arginine has a profound role in the cleavage of PPPi from ATP during AdoMet formation and in maintaining the orientation of PPPi in the active site, while playing a lesser role in the subsequent PPPi hydrolytic reaction.

Amino Acid Substitution↗