Taylor R

References (7)

Title : Hepatic cholesteryl ester accumulation in lysosomal acid lipase deficiency: non-invasive identification and treatment monitoring by magnetic resonance - Thelwall_2013_J.Hepatol_59_543
Author(s) : Thelwall PE , Smith FE , Leavitt MC , Canty D , Hu W , Hollingsworth KG , Thoma C , Trenell MI , Taylor R , Rutkowski JV , Blamire AM , Quinn AG
Ref : Journal of Hepatology , 59 :543 , 2013
Abstract : BACKGROUND & AIMS: Lysosomal Acid Lipase (LAL) deficiency is a rare metabolic storage disease, caused by a marked reduction in activity of LAL, which leads to accumulation of cholesteryl esters (CE) and triglycerides (TG) in lysosomes in many tissues. We used (1)H magnetic resonance (MR) spectroscopy to characterize the abnormalities in hepatic lipid content and composition in patients with LAL deficiency, and in ex vivo liver tissue from a LAL deficiency rat model. Secondly, we used MR spectroscopy to monitor the effects of an enzyme replacement therapy (ERT), sebelipase alfa (a recombinant human lysosomal acid lipase), on hepatic TG and CE content in the preclinical model.
METHODS: Human studies employed cohorts of LAL-deficient patients and NAFLD subjects. Rat experimental groups comprised ex vivo liver samples of wild type, NAFLD, LAL-deficient, and LAL-deficient rats receiving 4weeks of sebelipase alfa treatment. Hepatic (1)H MR spectroscopy was performed using 3T (human) and 7T (preclinical) MRI scanners to quantify hepatic cholesterol and triglyceride content.
RESULTS: CE accumulation was identified in LAL deficiency in both human and preclinical studies. A significant decrease in hepatic CE was observed in LAL-deficient rats following treatment with sebelipase alfa.
CONCLUSIONS: We demonstrate an entirely non-invasive method to identify and quantify the hepatic lipid signature associated with a rare genetic cause of fatty liver. The approach provides a more favorable alternative to repeated biopsy sampling for diagnosis and disease progression / treatment monitoring of patients with LAL deficiency and other disorders characterised by increased free cholesterol and/or cholesteryl esters.
ESTHER : Thelwall_2013_J.Hepatol_59_543
PubMedSearch : Thelwall_2013_J.Hepatol_59_543
PubMedID: 23624251

Title : Novel piperidinium and pyridinium agents as water-soluble acetylcholinesterase inhibitors for the reversal of neuromuscular blockade - Palin_2002_Bioorg.Med.Chem.Lett_12_2569
Author(s) : Palin R , Clark JK , Cowley P , Muir AW , Pow E , Prosser AB , Taylor R , Zhang MQ
Ref : Bioorganic & Medicinal Chemistry Lett , 12 :2569 , 2002
Abstract : A series of piperidinium and pyridinium agents containing a common structural fragment of 5,6-dimethoxybenzothiophene have been synthesised as water-soluble acetylcholinesterase inhibitors. Several compounds, for example 42 (AChE IC(50) 0.03 microM) have been found to reverse the neuromuscular blockade induced by vecuronium bromide in vitro and in vivo. Coupled with their high water solubility (up to 30-60 mg/mL), these compounds are potentially useful as intravenous reversal agents of neuromuscular blocking agents in surgical anaesthesia.
ESTHER : Palin_2002_Bioorg.Med.Chem.Lett_12_2569
PubMedSearch : Palin_2002_Bioorg.Med.Chem.Lett_12_2569
PubMedID: 12182862

Title : Quaternary salts of E2020 analogues as acetylcholinesterase inhibitors for the reversal of neuromuscular block - Clark_2002_Bioorg.Med.Chem.Lett_12_2565
Author(s) : Clark JK , Cowley P , Muir AW , Palin R , Pow E , Prosser AB , Taylor R , Zhang MQ
Ref : Bioorganic & Medicinal Chemistry Lett , 12 :2565 , 2002
Abstract : A series benzylpiperidinium and benzylpyridinium quaternary salts have been synthesised and tested for inhibition of acetylcholinesterase and reversal of neuromuscular block induced by vecuronium. Several potent reversal agents have been identified and their haemodynamic effects measured.
ESTHER : Clark_2002_Bioorg.Med.Chem.Lett_12_2565
PubMedSearch : Clark_2002_Bioorg.Med.Chem.Lett_12_2565
PubMedID: 12182861

Title : The DNA sequence and comparative analysis of human chromosome 20 - Deloukas_2001_Nature_414_865
Author(s) : Deloukas P , Matthews LH , Ashurst J , Burton J , Gilbert JG , Jones M , Stavrides G , Almeida JP , Babbage AK , Bagguley CL , Bailey J , Barlow KF , Bates KN , Beard LM , Beare DM , Beasley OP , Bird CP , Blakey SE , Bridgeman AM , Brown AJ , Buck D , Burrill W , Butler AP , Carder C , Carter NP , Chapman JC , Clamp M , Clark G , Clark LN , Clark SY , Clee CM , Clegg S , Cobley VE , Collier RE , Connor R , Corby NR , Coulson A , Coville GJ , Deadman R , Dhami P , Dunn M , Ellington AG , Frankland JA , Fraser A , French L , Garner P , Grafham DV , Griffiths C , Griffiths MN , Gwilliam R , Hall RE , Hammond S , Harley JL , Heath PD , Ho S , Holden JL , Howden PJ , Huckle E , Hunt AR , Hunt SE , Jekosch K , Johnson CM , Johnson D , Kay MP , Kimberley AM , King A , Knights A , Laird GK , Lawlor S , Lehvaslaiho MH , Leversha M , Lloyd C , Lloyd DM , Lovell JD , Marsh VL , Martin SL , McConnachie LJ , McLay K , McMurray AA , Milne S , Mistry D , Moore MJ , Mullikin JC , Nickerson T , Oliver K , Parker A , Patel R , Pearce TA , Peck AI , Phillimore BJ , Prathalingam SR , Plumb RW , Ramsay H , Rice CM , Ross MT , Scott CE , Sehra HK , Shownkeen R , Sims S , Skuce CD , Smith ML , Soderlund C , Steward CA , Sulston JE , Swann M , Sycamore N , Taylor R , Tee L , Thomas DW , Thorpe A , Tracey A , Tromans AC , Vaudin M , Wall M , Wallis JM , Whitehead SL , Whittaker P , Willey DL , Williams L , Williams SA , Wilming L , Wray PW , Hubbard T , Durbin RM , Bentley DR , Beck S , Rogers J
Ref : Nature , 414 :865 , 2001
Abstract : The finished sequence of human chromosome 20 comprises 59,187,298 base pairs (bp) and represents 99.4% of the euchromatic DNA. A single contig of 26 megabases (Mb) spans the entire short arm, and five contigs separated by gaps totalling 320 kb span the long arm of this metacentric chromosome. An additional 234,339 bp of sequence has been determined within the pericentromeric region of the long arm. We annotated 727 genes and 168 pseudogenes in the sequence. About 64% of these genes have a 5' and a 3' untranslated region and a complete open reading frame. Comparative analysis of the sequence of chromosome 20 to whole-genome shotgun-sequence data of two other vertebrates, the mouse Mus musculus and the puffer fish Tetraodon nigroviridis, provides an independent measure of the efficiency of gene annotation, and indicates that this analysis may account for more than 95% of all coding exons and almost all genes.
ESTHER : Deloukas_2001_Nature_414_865
PubMedSearch : Deloukas_2001_Nature_414_865
PubMedID: 11780052
Gene_locus related to this paper: human-ABHD12 , human-ABHD16B , human-CTSA , human-NDRG3 , human-RBBP9

Title : A structure-based design approach to the development of novel, reversible AChE inhibitors - Doucet-Personeni_2001_J.Med.Chem_44_3203
Author(s) : Doucet-Personeni C , Bentley PD , Fletcher RJ , Kinkaid A , Kryger G , Pirard B , Taylor A , Taylor R , Taylor J , Viner R , Silman I , Sussman JL , Greenblatt HM , Lewis T
Ref : Journal of Medicinal Chemistry , 44 :3203 , 2001
Abstract : Chimeras of tacrine and m-(N,N,N-Trimethylammonio)trifluoroacetophenone (1) were designed as novel, reversible inhibitors of acetylcholinesterase. On the basis of the X-ray structure of the apoenzyme, a molecular modeling study determined the favored attachment positions on the 4-aminoquinoline ring (position 3 and the 4-amino nitrogen) and the favored lengths of a polymethylene link between the two moieties (respectively 5-6 and 4-5 sp(3) atoms). Seven compounds matching these criteria were synthesized, and their inhibitory potencies were determined to be in the low nanomolar range. Activity data for close analogues lacking some of the postulated key features showed that our predictions were correct. In addition, a subsequent crystal structure of acetylcholinesterase complexed with the most active compound 27 was in good agreement with our model. The design strategy is therefore validated and can now be developed further.
ESTHER : Doucet-Personeni_2001_J.Med.Chem_44_3203
PubMedSearch : Doucet-Personeni_2001_J.Med.Chem_44_3203
PubMedID: 11563919
Gene_locus related to this paper: torca-ACHE

Title : Lipoprotein lipase D9N, N291S and S447X polymorphisms: their influence on premature coronary heart disease and plasma lipids - van Bockxmeer_2001_Atherosclerosis_157_123
Author(s) : van Bockxmeer FM , Liu Q , Mamotte C , Burke V , Taylor R
Ref : Atherosclerosis , 157 :123 , 2001
Abstract : Lipoprotein lipase (LPL) plays a pivotal role in lipoprotein metabolism. Three recently described exonic polymorphisms of the gene, D9N, N291S and S447X, have been variably found to influence plasma lipids while effects on coronary heart disease (CHD) are less well documented. Two predominantly Caucasian groups were studied: CHD patients <50 years of age, with angiographically documented CHD; and a randomly recruited community control group without a history of heart disease. The 9N allele of the D9N polymorphism was present in 25 of 428 (5.8%) of Caucasian males with CHD and in seven of 291 (2.4%) of corresponding community subjects (odds ratio, 2.5; 95% confidence interval (CI), 1.1-5.9; P=0.03) and was also significantly over-represented in the Caucasian males with myocardial infarction (MI) (21 of 308 or 6.8%; odds ratio, 2.6; 95% CI, 1.1-5.9; P=0.01). The distributions of the other two polymorphisms were similar in the CHD and community groups. In multivariate models adjusted for age, sex, diabetes, body mass index, smoking, lipid levels and race, the D9N polymorphism remained significantly related to both CHD and MI, with an odds ratio >2. There were, generally, trends to more adverse fasting plasma high-density lipoprotein (HDL) cholesterol and triglycerides in carriers of the 291S and 9N alleles, and the opposite trends for triglycerides in 447X carriers. In the community group, male carriers of 291S (n=13) had significantly (20%) lower HDL cholesterol than corresponding non-carriers (n=323), 0.98+/-0.07 mmol/l (mean+/-S.E.) versus 1.22+/-0.02 mmol/l (P<0.005), while HDL cholesterol was not different in male carriers (n=8) and non-carriers (n=296) of 9N (1.23+/-0.13 mmol/l versus 1.22+/-0.02 mmol/l). Multivariate analysis confirmed that the 291S allele carrier status conferred a significantly lower HDL cholesterol (P=0.001) and the 447X allele lower triglyceride (P<0.01) in the community group. In conclusion, LPL 9N carrier status was unequivocally related to premature CHD and to MI in males, strongly supporting recent results in older aged males. The somewhat different effects of the D9N and N291S polymorphisms on plasma lipids, and the absence of a clear effect of the N291S on CHD, raise the possibility that the effect of 9N carrier status might be mediated through effects on LPL function in addition to those influencing fasting plasma lipids.
ESTHER : van Bockxmeer_2001_Atherosclerosis_157_123
PubMedSearch : van Bockxmeer_2001_Atherosclerosis_157_123
PubMedID: 11427211

Title : Mutations in the Housefly Acetylcholinesterase Gene that Confer Resistance to Insecticides -
Author(s) : Williamson MS , Moores GD , Walsh S , Dolden T , Mullaley A , Taylor R , Devonshire AL
Ref : In: Structure and Function of Cholinesterases and Related Proteins - Proceedings of Sixth International Meeting on Cholinesterases , (Doctor, B.P., Taylor, P., Quinn, D.M., Rotundo, R.L., Gentry, M.K. Eds) Plenum Publishing Corp. :548 , 1998
PubMedID: