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
to

992 results found

Gartland KP, Sanins SM, Nicholson JK, Sweatman BC, Beddell CR, Lindon JCet al., 1990, Pattern recognition analysis of high resolution 1H NMR spectra of urine. A nonlinear mapping approach to the classification of toxicological data., NMR Biomed, Vol: 3, Pages: 166-172, ISSN: 0952-3480

A computer-based pattern recognition (PR) approach has been applied to the interpretation of 1H NMR generated urinalysis data in a variety of experimental toxicity states in the rat. 1H NMR signal intensities for each endogenous metabolite in urine were regarded as coordinates in multi-dimensional space and analysed using computer pattern recognition methods through which the dimensionality was reduced for display and categorization purposes. Initially 17 metabolic dimensions were used which were defined by the scored relative concentrations of a variety of urinary metabolites detected in 1H NMR spectra. By employing the unsupervised learning methods of 2- and 3-dimensional nonlinear mapping (NLM) different types of toxin (hepatotoxins, cortical and papillary nephrotoxins) could be classified according to NMR-detectable biochemical effects in the urine. The robustness of the classification methods, and the influence of the addition of new scored biochemical data reflecting dose response situations, nutritional effects on toxicity, sex differences in biochemical response to toxins and addition of a new toxin class (testicular toxin) to the pattern recognition analysis were also evaluated. We find that the initial training set maps are fundamentally stable to the addition of all data types and that the PR methods correctly 'predicted' the toxicological effects of the test compounds. These results confirm the power and wide applicability of linked PR and 1H NMR urinalysis as an approach to the generation and classification of acute toxicological data.

Journal article

, 1990, Regression dilution bias., Lancet, Vol: 335, Pages: 1230-1231, ISSN: 0140-6736

Journal article

POWELL JJ, GARTLAND KPR, LOMBARD M, SALLIE R, NICHOLSON JK, THOMPSON RPHet al., 1990, PROTON NMR-SPECTROSCOPY OF BILE AS A MARKER OF LIVER-FUNCTION IN LIVER-TRANSPLANT PATIENTS, CLINICAL SCIENCE, Vol: 78, Pages: P13-P13, ISSN: 0143-5221

Journal article

SEQUEIRA S, SO PW, EVERETT JR, ELCOMBE CR, KELVIN AS, NICHOLSON JKet al., 1990, H-1-NMR SPECTROSCOPY OF BIOFLUIDS AND THE INVESTIGATION OF XENOBIOTIC-INDUCED CHANGES IN LIVER BIOCHEMISTRY, JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS, Vol: 8, Pages: 945-949, ISSN: 0731-7085

Journal article

WADE KE, WILSON ID, TROKE JA, NICHOLSON JKet al., 1990, F-19 AND H-1 MAGNETIC-RESONANCE STRATEGIES FOR METABOLIC STUDIES ON FLUORINATED XENOBIOTICS - APPLICATION TO FLURBIPROFEN [2-(2-FLUORO-4-BIPHENYLYL)PROPIONIC ACID], JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS, Vol: 8, Pages: 401-410, ISSN: 0731-7085

Journal article

GARTLAND KPR, BEDDELL CR, LINDON JC, NICHOLSON JKet al., 1990, A PATTERN-RECOGNITION APPROACH TO THE COMPARISON OF PMR AND CLINICAL CHEMICAL-DATA FOR CLASSIFICATION OF NEPHROTOXICITY, JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS, Vol: 8, Pages: 963-968, ISSN: 0731-7085

Journal article

HOLMES E, FOXALL PJD, NICHOLSON JK, 1990, PROTON NMR ANALYSIS OF PLASMA FROM RENAL-FAILURE PATIENTS - EVALUATION OF SAMPLE PREPARATION AND SPECTRAL-EDITING METHODS, JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS, Vol: 8, Pages: 955-958, ISSN: 0731-7085

Journal article

HOLMES E, BONNER FW, GARTLAND KPR, NICHOLSON JKet al., 1990, PROTON NMR MONITORING OF THE ONSET AND RECOVERY OF EXPERIMENTAL RENAL DAMAGE, JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS, Vol: 8, Pages: 959-962, ISSN: 0731-7085

Journal article

GARTLAND KPR, ANTHONY ML, BEDDELL CR, LINDON JC, NICHOLSON JKet al., 1990, PROTON NMR-STUDIES ON THE EFFECTS OF URANYL-NITRATE ON THE BIOCHEMICAL-COMPOSITION OF RAT URINE AND PLASMA, JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS, Vol: 8, Pages: 951-954, ISSN: 0731-7085

Journal article

SANINS SM, NICHOLSON JK, ELCOMBE C, TIMBRELL JAet al., 1990, HEPATOTOXIN-INDUCED HYPERTAURINURIA - A PROTON NMR-STUDY, ARCHIVES OF TOXICOLOGY, Vol: 64, Pages: 407-411, ISSN: 0340-5761

Journal article

GRAY J, NICHOLSON JK, CREASY DM, TIMBRELL JAet al., 1990, STUDIES ON THE RELATIONSHIP BETWEEN ACUTE TESTICULAR DAMAGE AND URINARY AND PLASMA CREATINE CONCENTRATION, ARCHIVES OF TOXICOLOGY, Vol: 64, Pages: 443-450, ISSN: 0340-5761

Journal article

GARTLAND KPR, EASON CT, BONNER FW, NICHOLSON JKet al., 1990, EFFECTS OF BILIARY CANNULATION AND BUTHIONINE SULFOXIMINE PRETREATMENT ON THE NEPHROTOXICITY OF PARA-AMINOPHENOL IN THE FISCHER-344 RAT, ARCHIVES OF TOXICOLOGY, Vol: 64, Pages: 14-25, ISSN: 0340-5761

Journal article

SPURWAY TD, GARTLAND KPR, WARRANDER A, PICKFORD R, NICHOLSON JK, WILSON IDet al., 1990, PROTON NUCLEAR-MAGNETIC-RESONANCE OF URINE AND BILE FROM PARACETAMOL DOSED RATS, JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS, Vol: 8, Pages: 969-973, ISSN: 0731-7085

Journal article

Wade KE, Wilson ID, Troke JA, Nicholson JKet al., 1990, <sup>19</sup>F and <sup>1</sup>H magnetic resonance strategies for metabolic studies on fluorinated xenobiotics: Application to flurbiprofen [2-(2-fluoro-4-biphenylyl)propionic acid], Journal of Pharmaceutical and Biomedical Analysis, Vol: 8, Pages: 401-410, ISSN: 0731-7085

Strategies for the use of 1H and 19F nuclear magnetic resonance (NMR) spectroscopy as an aid to the study of the metabolic fate of fluorinated drugs are discussed with reference to the application of these methods to flurbiprofen metabolism in man. 1H and 19F NMR analysis of untreated urine enabled the detection of two major and eight minor metabolites of the drug. The two major metabolites were identified using a combination of NMR spectroscopy, solid-phase extraction chromatography with 19F and 1H NMR detection and chemical hydrolysis to a flurbiprofen glucuronide and the glucuronide of the 4-hydroxy metabolite. 1H-19F 2D shift correlated spectroscopy and spin-echo difference experiments are discussed in relation to their use in the structural identification of drug metabolites. © 1990.

Journal article

Sequeira S, So PW, Everett JR, Elcombe CR, Kelvin AS, Nicholson JKet al., 1990, <sup>1</sup>H-NMR spectroscopy of biofluids and the investigation of xenobiotic-induced changes in liver biochemistry, Journal of Pharmaceutical and Biomedical Analysis, Vol: 8, Pages: 945-949, ISSN: 0731-7085

Journal article

Glen RC, 1990, Recent progress in computational chemistry and molecular graphics applied to drug design, Drug News and Perspectives, Vol: 3, Pages: 332-336, ISSN: 0214-0934

Journal article

GHAURI FYK, BLACKLEDGE CA, WILSON ID, NICHOLSON JKet al., 1990, STUDIES ON THE METABOLISM OF FLUORINATED XENOBIOTICS IN THE RAT USING F-19-NMR AND H-1-NMR SPECTROSCOPY, JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS, Vol: 8, Pages: 939-944, ISSN: 0731-7085

Journal article

WILSON ID, WADE KE, NICHOLSON JK, 1989, ANALYSIS OF BIOLOGICAL-FLUIDS BY HIGH-FIELD NUCLEAR MAGNETIC-RESONANCE SPECTROSCOPY, TRAC-TRENDS IN ANALYTICAL CHEMISTRY, Vol: 8, Pages: 368-374, ISSN: 0165-9936

Journal article

FOXALL PJD, BENDING MR, GARTLAND KPR, NICHOLSON JKet al., 1989, ACUTE RENAL-FAILURE FOLLOWING ACCIDENTAL CUTANEOUS ABSORPTION OF PHENOL - APPLICATION OF NMR URINALYSIS TO MONITOR THE DISEASE PROCESS, HUMAN TOXICOLOGY, Vol: 8, Pages: 491-496, ISSN: 0144-5952

Journal article

Dyer AR, Elliott P, 1989, The INTERSALT study: relations of body mass index to blood pressure. INTERSALT Co-operative Research Group., J Hum Hypertens, Vol: 3, Pages: 299-308, ISSN: 0950-9240

In INTERSALT, the relationship between body mass index (kg/m2) and blood pressure was studied in 10,079 men and women aged 20-59, sampled from 52 centres around the world, based on a standardised protocol with central training of observers, a central laboratory and extensive quality control. Body mass index-blood pressure relationships were first studied in men and women within each centre, and results of these regression analyses were then pooled for all 52 centres. With adjustment for age, alcohol intake, smoking, and sodium and potassium excretion, body mass index was positively associated with systolic blood pressure among men in 51 of 52 centres and among women in 47, significantly so in 24 and 27, respectively. Body mass index was positively associated with diastolic blood pressure in 51 and 49 centres in men and women, respectively, significantly so in 33 and 31. When the within centre regression coefficients were pooled, the pooled coefficients were highly significant in all analyses (P less than 0.001), and were similar for those aged 20-39 and 40-59. Overall, a 10 kg difference in body weight was associated on average with a 3.0 mmHg difference in systolic and a 2.2 mmHg difference in diastolic pressure. In further analyses across centres, median body mass index was related significantly to median systolic blood pressure, median diastolic pressure and the prevalence of hypertension in both men and women. Body mass index was related to the slopes of systolic and diastolic blood pressure with age in women, but not in men. These INTERSALT findings confirm the importance of the association between body weight and blood pressure. Differences of 2-3 mmHg in systolic blood pressure on a population basis have been shown to be associated with differences in stroke mortality rates of 6-9 per cent and in coronary death rates of 4-6 per cent.

Journal article

CARVALHO JJM, BARUZZI RG, HOWARD PF, POULTER N, ALPERS MP, FRANCO LJ, MARCOPITO LF, SPOONER VJ, DYER AR, ELLIOTT P, STAMLER J, STAMLER Ret al., 1989, BLOOD-PRESSURE IN 4 REMOTE POPULATIONS IN THE INTERSALT STUDY, HYPERTENSION, Vol: 14, Pages: 238-246, ISSN: 0194-911X

Journal article

NICHOLSON JK, HIGHAM DP, TIMBRELL JA, SADLER PJet al., 1989, QUANTITATIVE HIGH-RESOLUTION H-1-NMR URINALYSIS STUDIES ON THE BIOCHEMICAL EFFECTS OF CADMIUM IN THE RAT, MOLECULAR PHARMACOLOGY, Vol: 36, Pages: 398-404, ISSN: 0026-895X

Journal article

Nicholson JK, Gartland KP, 1989, 1H NMR studies on protein binding of histidine, tyrosine and phenylalanine in blood plasma., NMR Biomed, Vol: 2, Pages: 77-82, ISSN: 0952-3480

The binding of histidine (His), phenylalanine (Phe) and tyrosine (Tyr) to macromolecules in blood plasma and serum has been investigated by high resolution 1H NMR spectroscopy. In single pulse and spin-echo spectra of quality control bovine serum and normal human plasma, there are no resonances in the chemical shift range to high frequency of delta = 5.3 ppm when measured in the pH* (meter reading, uncorrected for the presence of 2H2O) range 3 to 8.5. On acidification of the plasma to pH* less than 2.5, resonances from His and Phe are observable. In plasma from patients with Wilson's disease, weak signals from His and Tyr are seen in spin-echo spectra at pH* 7.6, but increase in strength on acidification and signals from Phe appear at pH* 1.8. Addition of standard solutions containing Tyr, His and especially Phe and Trp to plasma at neutral pH* results in poor recovery of their expected signal intensity in spin-echo spectra. Addition of 2 M urea to bovine plasma at pH* 4.5 results in the appearance of Phe signals. These data are consistent with Phe and Tyr (and to a lesser extent His) being bound in or to a macromolecular structure at neutral pH from which there is relatively slow exchange with the free solution environment. Experiments with model solutions suggest that serum albumin has a high capacity for binding aromatic amino acids (stabilized by hydrophobic interactions) at neutral pH and this is responsible for the NMR-invisibility of Tyr and Phe in blood plasma.

Journal article

JOHNSON AM, WADSWORTH J, ELLIOTT P, PRIOR L, WALLACE P, BLOWER S, WEBB NL, HEALD GI, MILLER DL, ADLER MW, ANDERSON RMet al., 1989, A PILOT-STUDY OF SEXUAL LIFESTYLE IN A RANDOM SAMPLE OF THE POPULATION OF GREAT-BRITAIN, AIDS, Vol: 3, Pages: 135-141, ISSN: 0269-9370

Journal article

GARTLAND KPR, BONNER FW, NICHOLSON JK, 1989, INVESTIGATIONS INTO THE BIOCHEMICAL EFFECTS OF REGION-SPECIFIC NEPHROTOXINS, MOLECULAR PHARMACOLOGY, Vol: 35, Pages: 242-250, ISSN: 0026-895X

Journal article

NICHOLSON JK, WILSON ID, 1989, HIGH-RESOLUTION PROTON MAGNETIC-RESONANCE SPECTROSCOPY OF BIOLOGICAL-FLUIDS, PROGRESS IN NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY, Vol: 21, Pages: 449-501, ISSN: 0079-6565

Journal article

GARTLAND KPR, EASON CT, WADE KE, BONNER FW, NICHOLSON JKet al., 1989, PROTON NMR-SPECTROSCOPY OF BILE FOR MONITORING THE EXCRETION OF ENDOGENOUS AND XENOBIOTIC METABOLITES - APPLICATION TO PARA-AMINOPHENOL, JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS, Vol: 7, Pages: 699-707, ISSN: 0731-7085

Journal article

TULIP K, NICHOLSON JK, TIMBRELL JA, 1989, A STUDY OF THE METABOLISM OF DIMETHYLFORMAMIDE IN THE RAT BY HIGH-RESOLUTION PROTON NMR-SPECTROSCOPY, JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS, Vol: 7, Pages: 499-505, ISSN: 0731-7085

Journal article

GARTLAND KPR, BONNER FW, TIMBRELL JA, NICHOLSON JKet al., 1989, BIOCHEMICAL-CHARACTERIZATION OF PARA-AMINOPHENOL-INDUCED NEPHROTOXIC LESIONS IN THE F344 RAT, ARCHIVES OF TOXICOLOGY, Vol: 63, Pages: 97-106, ISSN: 0340-5761

Journal article

Marmot MG, Elliott P, 1989, Public health measures for blood pressure control in the whole community., Clin Exp Hypertens A, Vol: 11, Pages: 1171-1186, ISSN: 0730-0077

One approach to the prevention of blood pressure-associated cardiovascular disease is to find increased numbers of "hypertensives" and bring them under treatment. A complementary approach is to attempt to change the blood pressure distribution of the whole population. It can be calculated that, if the association between blood pressure level and mortality were reversible, a reduction of diastolic blood pressure of 5 mmHg in the population mean would be associated with a substantial reduction in cardiovascular mortality. The assumption of reversibility of risk of coronary heart disease may be more reasonable in the long than in the short term. The evidence from INTERSALT and other studies suggests that readily achievable changes in sodium and potassium intake, in body mass index and in alcohol intake, could lead to average blood pressure change across a whole population of 5 mmHg. A major task for public health is the implementation of such life-style changes among different social class and ethnic groups.

Journal article

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