Imperial College London

Emeritus ProfessorJeremyNicholson

Faculty of MedicineDepartment of Metabolism, Digestion and Reproduction

Emeritus Professor of Biological Chemistry
 
 
 
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Contact

 

+44 (0)20 7594 3195j.nicholson Website

 
 
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Assistant

 

Ms Wendy Torto +44 (0)20 7594 3225

 
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Location

 

Office no. 665Sir Alexander Fleming BuildingSouth Kensington Campus

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Summary

 

Publications

Publication Type
Year
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990 results found

Belton PS, Delgadillo I, Holmes E, Nicholls A, Nicholson JK, Spraul Met al., 1996, Use of high-field H-1 NMR spectroscopy for the analysis of liquid foods, JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY, Vol: 44, Pages: 1483-1487, ISSN: 0021-8561

Journal article

Holmes E, Bonner FW, Nicholson JK, 1996, Comparative biochemical effects of low doses of mercury II chloride in the F344 rat and the multimammate mouse (Mastomys natalensis), COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-PHARMACOLOGY TOXICOLOGY & ENDOCRINOLOGY, Vol: 114, Pages: 7-15, ISSN: 0742-8413

Journal article

Sidelmann UG, Nicholls AW, Meadows PE, Gilbert JW, Lindon JC, Wilson ID, Nicholson JKet al., 1996, High-performance liquid chromatography directly coupled to F-19 and H-1 NMR for the analysis of mixtures of isomeric ester glucuronide conjugates of trifluoromethylbenzoic acids, 19th International Symposium on Column Liquid Chromatography, Publisher: ELSEVIER SCIENCE BV, Pages: 377-385, ISSN: 0021-9673

Conference paper

Bollard ME, Holmes E, Blackledge CA, Lindon JC, Wilson ID, Nicholson JKet al., 1996, H-1 and F-19-nmr spectroscopic studies on the metabolism and urinary excretion of mono- and disubstituted phenols in the rat, XENOBIOTICA, Vol: 26, Pages: 255-273, ISSN: 0049-8254

Journal article

Cupid BC, Beddell CR, Lindon JC, Wilson ID, Nicholson JKet al., 1996, Quantitative structure-metabolism relationships for substituted benzoic acids in the rabbit: Prediction of urinary excretion of glycine and glucuronide conjugates, XENOBIOTICA, Vol: 26, Pages: 157-176, ISSN: 0049-8254

Journal article

Lindon JC, Nicholson JK, Wilson ID, 1996, The development and application of coupled HPLC-NMR spectroscopy, ADVANCES IN CHROMATOGRAPHY, VOL 36, Vol: 36, Pages: 315-382, ISSN: 0065-2415

Journal article

Lindon JC, Nicholson JK, Wilson ID, 1996, Direct coupling of chromatographic separations to NMR spectroscopy, PROGRESS IN NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY, Vol: 29, Pages: 1-49, ISSN: 0079-6565

Journal article

Anthony ML, McDowell PCR, Gray TJB, Blackmore M, Nicholson JKet al., 1996, H-1 NMR spectroscopic studies on the characterization of renal cell lines and identification of novel potential markers of in vitro nephrotoxicity, BIOMARKERS, Vol: 1, Pages: 35-43, ISSN: 1354-750X

Journal article

Bollard ME, Holmes E, Blackledge CA, Lindon JC, Wilson ID, Nicholson JKet al., 1996, <sup>1</sup>H and <sup>19</sup>F-nmr spectroscopic studies on the metabolism and urinary excretion of mono- and disubstituted phenols in the rat, Xenobiotica, Vol: 26, Pages: 255-273, ISSN: 0049-8254

1. 1H and 19F-nmr spectroscopy was used to investigate quantitatively the urinary excretion of the metabolites of 15 substituted phenols in the rat. The compounds studied were: 2-, 3-, and 4-fluorophenols; 2-, 3-, and 4-trifluoromethylphenol; 2,4-, 2,6- and 3,4-difluorophenol; 2-fluoro-5-trifluoromethylphenol, 3-fluoro-5-trifluoromethylphenol, 2-trifluoromethyl-4-fluorophenol; 3-chloro-4-fluorophenol, 3-fluoro-4-chlorophenol, and 3-methyl-4-fluorophenol. All compounds were dosed to the Sprague-Dawley rat (10 mg/kg i.p.) and urine was collected over the periods 0-8, 8-24 and 24-48 h post-dosing and analyzed using nmr spectroscopy. 2. The compounds were excreted in the urine mainly as glucuronide or sulphate conjugates or as the unchanged parent compound. There was considerable variation in the urinary excretion of the compounds over 48 h ranging from 22·1 to 93·6% of the dose. There was no apparent relationship between the molecular weight of compounds or their metabolites and the percentage molar recovery of each in the urine. 3. Ortho-substituted phenols in general showed a greater propensity for glucuronidation than did either meta- or para-substituted compounds, irrespective of the substituent group. The molar glucuronide-to-sulphate ratio for ortho-substituted compounds was found to be 2·2 ± 0·9 whereas the ratio for both meta- and para-substituted compounds was 0·8 ± 0·2 (p < 0·0001). 4. There were characteristic substituent effects of phenolic glucuronidation or sulphation on the 19F-nmr chemical shifts for both F- and CF3-substituted phemols and these substituent effects were a useful aid to metabolite signal assignment. 5. These studies show that nmr spectroscopy provides a rapid and convenient approach to the construction of metabolic databases of simple xenobiotics for the investigation of structure-metabolism relationships.

Journal article

Sidelmann UG, Lenz EM, Spraul M, Hofmann M, Troke J, Sanderson PN, Lindon JC, Wilson ID, Nicholson JKet al., 1996, 750 MHz HPLC-NMR spectroscopic studies on the separation and characterization of the positional isomers of the glucuronides of 6,11-dihydro-11-oxodibenz[b,e]oxepin-2-acetic acid, ANALYTICAL CHEMISTRY, Vol: 68, Pages: 106-110, ISSN: 0003-2700

Journal article

SIDELMANN UG, GAVAGHAN C, CARLESS HAJ, SPRAUL M, HOFMANN M, LINDON JC, WILSON ID, NICHOLSON JKet al., 1995, 750-MHZ DIRECTLY COUPLED HPLC-NMR - APPLICATION TO THE SEQUENTIAL CHARACTERIZATION OF THE POSITIONAL ISOMERS AND ANOMERS OF 2-FLUOROBENZOIC, 3-FLUOROBENZOIC, AND 4-FLUOROBENZOIC ACID GLUCURONIDES IN EQUILIBRIUM MIXTURES, ANALYTICAL CHEMISTRY, Vol: 67, Pages: 4441-4445, ISSN: 0003-2700

Journal article

Holmes E, Sweatman BC, Bollard ME, Blackledge CA, Beddell CR, Wilson ID, Lindon JC, Nicholson JKet al., 1995, Prediction of urinary sulphate and glucuronide conjugate excretion for substituted phenols in the rat using quantitative structure-metabolism relationships, XENOBIOTICA, Vol: 25, Pages: 1269-1281, ISSN: 0049-8254

Journal article

Jones G, Willett P, Glen RC, 1995, A genetic algorithm for flexible molecular overlay and pharmacophore elucidation, JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN, Vol: 9, Pages: 532-549, ISSN: 0920-654X

Journal article

Holmes E, Bonner FW, Nicholson JK, 1995, Comparative studies on the nephrotoxicity of 2-bromoethanamine hydrobromide in the Fischer 344 rat and the multimammate desert mouse (Mastomys natalensis), ARCHIVES OF TOXICOLOGY, Vol: 70, Pages: 89-95, ISSN: 0340-5761

Journal article

ANTHONY ML, HOLMES E, MCDOWELL PCR, GRAY TJB, BLACKMORE M, NICHOLSON JKet al., 1995, H-1-NMR SPECTROSCOPIC STUDIES ON THE REACTIONS OF HALOALKYLAMINES WITH BICARBONATE IONS - FORMATION OF N-CARBAMATES AND 2-OXAZOLIDONES IN CELL-CULTURE MEDIA AND BLOOD-PLASMA, CHEMICAL RESEARCH IN TOXICOLOGY, Vol: 8, Pages: 1046-1053, ISSN: 0893-228X

Journal article

Liu ML, Farrant RD, Gillam JM, Nicholson JK, Lindon JCet al., 1995, Selective inverse-detected long-range heteronuclear J-resolved NMR spectroscopy and its application to the measurement of (3)J(CH), JOURNAL OF MAGNETIC RESONANCE SERIES B, Vol: 109, Pages: 275-283, ISSN: 1064-1866

Journal article

Foxall PJD, Bewley S, Neild GH, Rodeck CH, Nicholson JKet al., 1995, Analysis of fetal and neonatal urine using proton nuclear magnetic resonance spectroscopy, Archives of Disease in Childhood, Vol: 73, ISSN: 0003-9888

Aim: To use high field proton nuclear magnetic resonance spectroscopy (1H NMR) to characterise the low molecular weight metabolite composition of neonatal and fetal urine in relation to gestational age and perinatal outcome. Methods: The first urine passed by two neonatal groups, six full term and five preterm infants with normal renal function, was analysed by 1H NMR and compared with fetal urine from 14 cases with obstructive uropathy. Results: The mean ratios of taurine, myo-inositol, and trimethylamine-N-oxide (TMAO) to creatinine were 4.3, 10.1, and 14.1 times higher, respectively, in the preterm group when compared with those of the full term group. Fetal obstructive uropathy was characterised by glycosuria, amino and organic aciduria, regardless of gestational age (13-30 weeks). Conclusions: Samples of the first urine passed - that is, urine produced in fetal life - by normal preterm infants are useful controls for cases of obstructive uropathy detected in the third trimester. 1H NMR will become a clinically useful tool for monitoring renal development and abnormalities in utero.

Journal article

LINDON JC, FARRANT RD, SANDERSON PN, DOYLE PM, GOUGH SL, SPRAUL M, HOFMANN M, NICHOLSON JKet al., 1995, SEPARATION AND CHARACTERIZATION OF COMPONENTS OF PEPTIDE LIBRARIES USING ON-FLOW COUPLED HPLC-NMR SPECTROSCOPY, MAGNETIC RESONANCE IN CHEMISTRY, Vol: 33, Pages: 857-863, ISSN: 0749-1581

Journal article

FOXALL PJD, BEWLEY S, NEILD GH, RODECK CH, NICHOLSON JKet al., 1995, ANALYSIS OF FETAL AND NEONATAL URINE USING PROTON NUCLEAR-MAGNETIC-RESONANCE SPECTROSCOPY, ARCHIVES OF DISEASE IN CHILDHOOD, Vol: 73, Pages: F153-F157, ISSN: 0003-9888

Journal article

SIDELMANN UG, GAVAGHAN C, CARLESS HAJ, FARRANT RD, LINDON JC, WILSON ID, NICHOLSON JKet al., 1995, IDENTIFICATION OF THE POSITIONAL ISOMERS OF 2-FLUOROBENZOIC ACID 1-O-ACYL GLUCURONIDE BY DIRECTLY COUPLED HPLC-NMR, ANALYTICAL CHEMISTRY, Vol: 67, Pages: 3401-3404, ISSN: 0003-2700

Journal article

Dyer AR, Stamler R, Elliott P, Stamler Jet al., 1995, Dietary salt and blood pressure., Nat Med, Vol: 1, Pages: 994-996, ISSN: 1078-8956

Journal article

FOXALL PJD, BEWLEY S, KINGDOM JCP, RODECK CH, NEILD GH, NICHOLSON JKet al., 1995, THE EFFECT OF GESTATIONAL-AGE ON THE URINARY-EXCRETION OF ORGANIC OSMOLYTES, JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, Vol: 6, Pages: 361-361, ISSN: 1046-6673

Journal article

ANTHONY ML, FOXALL PJD, WHITE SJ, NICHOLSON JK, WOOLF ASet al., 1995, WITHDRAWAL OF AN IMMORTALIZING GENE CONFERS A MORE DIFFERENTIATED PHENOTYPE IN ADULT RENAL EPITHELIAL-CELLS, JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, Vol: 6, Pages: 358-358, ISSN: 1046-6673

Journal article

GLEN RC, MARTIN GR, HILL AP, HYDE RM, WOOLLARD PM, SALMON JA, BUCKINGHAM J, ROBERTSON ADet al., 1995, COMPUTER-AIDED-DESIGN AND SYNTHESIS OF 5-SUBSTITUTED TRYPTAMINES AND THEIR PHARMACOLOGY AT THE 5-HT1D RECEPTOR - DISCOVERY OF COMPOUNDS WITH POTENTIAL ANTIMIGRAINE PROPERTIES, JOURNAL OF MEDICINAL CHEMISTRY, Vol: 38, Pages: 3566-3580, ISSN: 0022-2623

Journal article

FARRANT RD, SPRAUL M, WILSON ID, NICHOLLS AW, NICHOLSON JK, LINDON JCet al., 1995, ASSIGNMENT OF THE 750 MHZ H-1-NMR RESONANCES FROM A MIXTURE OF TRANSACYLATED ESTER GLUCURONIC-ACID CONJUGATES WITH THE AID OF OVERSAMPLING AND DIGITAL FILTERING DURING ACQUISITION, JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS, Vol: 13, Pages: 971-977, ISSN: 0731-7085

Journal article

HOLMES E, CADDICK S, LINDON JC, WILSON ID, KRYVAWYCH S, NICHOLSON JKet al., 1995, H-1 AND H-2 NMR SPECTROSCOPIC STUDIES ON THE METABOLISM AND BIOCHEMICAL EFFECTS OF 2-BROMOETHANAMINE IN THE RAT, BIOCHEMICAL PHARMACOLOGY, Vol: 49, Pages: 1349-1359, ISSN: 0006-2952

Journal article

Holmes E, Caddick S, Undon JC, Wilson ID, Kryvawych S, Nicholson JKet al., 1995, <sup>1</sup>H and <sup>2</sup>H NMR spectroscopic studies on the metabolism and biochemical effects of 2-bromoethanamine in the rat, Biochemical Pharmacology, Vol: 49, Pages: 1349-1359, ISSN: 0006-2952

Male Fischer 344 rats were dosed with 2-bromoethanamine hydrobromide (BEA, N = 6) or [1,1,2,2,-2H4]-bromoethanamine hydrobromide (BEA-d4, N = 6) at 150 mg/kg i.p. and urine was collected -24 to 0 hr pre-dose and at 0-2 hr, 2-4 hr, 4-8 hr and 8-12 hr post-dose (p.d.). Urine samples were analysed directly using 500 and 600 MHz 1H NMR and 92.1 MHz 2H NMR spectroscopy. The major observed effect of BEA treatment was the induction of transient elevations in urinary glutaric acid (GTA) and adipic acid (ADA) excretion lasting up to 24 hr p.d. Most of the GTA was excreted in the 0-8 hr p.d. with maximal rates of 100-120 μM/hr for each rat occurring between 4 and 8 hr p.d. in animals treated with BEA or BEA-d4. GTA and ADA were shown to be of endogenous origin as there was no detectable incorporation of the 2H label into either compound following treatment of rats with BEA-d4. Following BEA-treatment there was an initial decrease in the levels of urinary citrate, succinate, 2-oxoglutarate and trimethylamine-N-oxide. A subsequent recovery of citrate and succinate was noted following the onset of medullary nephropathy. The abnormal urinary metabolite profiles were similar to that observed in the urine of humans with glutaric aciduria type II (an inborn error of metabolism) caused by a lack of mitochondrial fatty acyl coenzyme A dehydrogenases indicating that BEA or its metabolites have similar metabolic consequences. The BEA metabolite aziridine was detected by 1H and 2H NMR spectroscopy of the urine 8 hr p.d. together with BEA itself and two novel metabolites 2-oxazolidone (OX) and 5-hydroxy-2-oxazolidone (HOX). The formation of OX requires the reaction of BEA with endogenous bicarbonate followed by a cyclisation reaction eliminating HBr. Dosing rats with authentic OX resulted in the excretion of HOX but did not cause glutaric or adipic aciduria indicating that either aziridine or BEA itself was responsible for the presumed defect in mitochondrial metabolism. © 1995.

Journal article

NICHOLLS AW, CADDICK S, WILSON ID, FARRANT RD, LINDON JC, NICHOLSON JKet al., 1995, HIGH-RESOLUTION NMR SPECTROSCOPIC STUDIES ON THE METABOLISM AND FUTILE DEACETYLATION OF 4-HYDROXYACETANILIDE (PARACETAMOL) IN THE RAT, BIOCHEMICAL PHARMACOLOGY, Vol: 49, Pages: 1155-1164, ISSN: 0006-2952

Journal article

LIU M, FARRANT RD, SWEATMAN BC, NICHOLSON JK, LINDON JCet al., 1995, OBSERVATION OF SEPARATE J-RESOLVED H-1-NMR SPECTRA FROM CH, CH2, AND CH3 GROUPS USING A MAXIMUM-QUANTUM FILTER, JOURNAL OF MAGNETIC RESONANCE SERIES A, Vol: 113, Pages: 251-256, ISSN: 1064-1858

Journal article

GLEN RC, PAYNE AWR, 1995, A GENETIC ALGORITHM FOR THE AUTOMATED GENERATION OF MOLECULES WITHIN CONSTRAINTS, JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN, Vol: 9, Pages: 181-202, ISSN: 0920-654X

Journal article

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