Search Results - (Author, Cooperation:D. G. Watson)

2011-08-19

Nature Publishing Group (NPG)

0028-0836

1476-4687

Biology

Chemistry and Pharmacology

Medicine

Natural Sciences in General

Physics

Animals ; Bilirubin/metabolism ; Cell Line ; Cells, Cultured ; Citric Acid Cycle ; Computer Simulation ; Fumarate Hydratase/deficiency/*genetics/*metabolism ; Fumarates/metabolism ; Genes, Lethal/*genetics ; *Genes, Tumor Suppressor ; Glutamine/metabolism ; Heme/metabolism ; Heme Oxygenase (Decyclizing)/antagonists & inhibitors/*genetics/*metabolism ; Kidney Neoplasms/drug therapy/enzymology/genetics/metabolism ; Leiomyomatosis/congenital/drug therapy/enzymology/genetics/metabolism ; Mice ; Mitochondria/metabolism ; Mutation/*genetics ; NAD/metabolism ; Neoplastic Syndromes, Hereditary ; Skin Neoplasms ; Uterine Neoplasms

1471-4159

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

Abstract: Acidic metabolites of a number of biogenic amines have been identified and quantified by reaction with either acetic or propionic anhydride in the aqueous phase followed by extraction into ethyl acetate, esterification of carboxyl groups with ditrifluoromethylbenzyl bromide (DTFMBzBr), and then conversion of the remaining free hydroxyl groups to acetates. Subsequent analysis of these derivatives revealed that most (〉60%) of the ion current was carried by the ion resulting from the loss of DTFMBz from the molecular ion. This made the method highly specific and practical—limits of detection were established at ∼200 pg with a potential limit of detection below the picogram level. This method establishes unequivocally that the metabolites of tyramine. dopamine, and adrenaline/noradrenaline (4-hydroxyphenylacetic acid, 3,4-dihydroxyphenylacetic acid, and dihydroxymandelic acid, respectively) are present in bovine retina and in vitreous and aqueous humour. In addition, high concentrations of the dopamine metabolite homovanillic acid were found in retina and vitreous, but not in aqueous humour. p-Hydroxymandelic acid, the acidic metabolite of p-octopamine-p-synephrine, was identified in vitreous and in aqueous humour.

Electronic Resource

1471-4159

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

Abstract: The expression of MARCKS, a major protein kinase C (PKC) substrate, was examined in the immortalized hippocampal cell line HN33, following differentiation using phorbol esters or retinoic acid. In cells exposed to phorbol esters, MARCKS protein levels were reduced through an apparent PKC-dependent mechanism. Exposure to 1 µM phorbol 12-myristate 13-acetate (PMA) for 10 min resulted in a rapid loss of PKC activity in the soluble fraction with a concurrent increase in membrane-associated PKC activity. PKC activity was reduced to 〈20% of control values in both soluble and membrane fractions following 1 h of PMA exposure. Significant reductions in MARCKS protein levels were initially observed in membrane and soluble fractions following PMA exposure for 4 and 8 h, respectively. The reduction in MARCKS protein levels was maximal following 24 h of PMA exposure. MARCKS protein expression was also down-regulated in a dose-dependent manner on exposure of HN33 cells to retinoic acid. In cells exposed to 10 µM retinoic acid, the MARCKS protein level was reduced in the membrane fraction within 4 h. Reduction of MARCKS protein levels was maximal (〉90%) by 12 h with no evidence for any alteration in PKC activity. Reduced levels of MARCKS protein were also observed in the soluble fraction of retinoic acid-exposed cells, but to a significantly lesser extent. Addition of the PKC inhibitor GF109203X blocked the down-regulation of MARCKS protein in PMA-treated cultures but not in retinoic acid-treated cells. These findings suggest that the down-regulation of MARCKS may play an important role in both phorbol ester- and retinoic acid-induced differentiation in cells of neuronal origin.

Electronic Resource

1471-4159

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

Abstract: Biogenic amines in bovine retina have been identified and quantified by an extraction-derivatisation procedure involving their reaction with 3,5-di(trifluoromethyl)benzoyl chloride (DTFMBCl) in the aqueous phase followed by extraction into an organic solvent, hydrolysis of phenolic esters, and conversion of free hydroxyl groups to trimethylsilyl ethers. Subsequent analysis of these DTFMB-trimethylsilyl derivatives by gas chromatography-negative ion chemical ionisation mass spectrometry revealed that the molecular ion carried most (〉60%) of the ion current, which made the method highly specific and gave a potential limit of detection below the picogram level. This method establishes unequivocally that the principal amines in bovine retina are p-tyra-mine, dopamine, and 5-hydroxytryptamine

Electronic Resource

1476-4687

Nature Archives 1869 - 2009

Biology

Chemistry and Pharmacology

Medicine

Natural Sciences in General

Physics

[Auszug] The three dimensional structure of adenosine triphosphate in the hydrated disodium salt is reported to a resolution of 0.9 ...

Electronic Resource

1420-9071

Springer Online Journal Archives 1860-2000

Biology

Medicine

Zusammenfassung Die Struktur desepi-Limonol-jodoacetates (C26H31O8) COCH2I, wurde durch dreidimensionale Röntgenanalyse bestimmt. Es gelang, die Lage sämtlicher Atome in zwei kristallographisch unabhängigen, jedoch chemisch identischen Molekeln zu ermitteln. Dieses Resultat stellt eine vollständige Bestimmung der Konstitution und der Stereochemie des Limonins dar.

Electronic Resource

1432-0843

Key words Bioavailability ; 5-Fluorouracil ; Subcutaneous administration ; Colorectal cancer

Springer Online Journal Archives 1860-2000

Medicine

Abstract  The optimal schedule for the administration of 5-fluorouracil (5-FU) in the management of advanced colorectal cancer remains to be determined. It has been suggested that this drug may be given by the subcutaneous route and that following a short infusion the bioavailability is similar to that observed after intravenous administration. We report the results we obtained in a patient treated with an intravenous bolus of 5-FU followed by a 22-h subcutaneous infusion. In this patient the bioavailability of 5-FU given by subcutaneous infusion was 0.94. The steady-state plasma levels of 5-FU reached during subcutaneous infusion were comparable with those achieved during intravenous infusion. Following four cycles of subcutaneous therapy, painless blistering was noted at the infusion sites, which healed following the cessation of subcutaneous therapy. Further studies are required to evaluate this route of therapy as an alternative to protracted intravenous therapy. The main dose-limiting side effect appears to be local skin toxicity.

Electronic Resource

1432-1351

Cobalt staining ; Gas chromatography-mass spectrometry ; Immunohistochemistry ; Insect ; Neuromodulation

Springer Online Journal Archives 1860-2000

Biology

Medicine

Abstract The two Protocerebral-Medulla 4 neurons (PM4a and b) in the locust brain have adjacent cell bodies in the medial deutocerebrum. They project through the posterior protocerebrum, forming limited arborisations en route, and enter the lobula and medulla of the ipsilateral optic lobe, where they form extensive, overlapping arborisations. The PM4a and b neurons are octopamine immunoreactive. Their octopamine content (approximately 25 pg per cell) is confirmed by gas chromatography-mass spectrometry; each cell contains approximately 25 pg p-octopamine. Simultaneous intracellular recording from exposed PM4a and b cell bodies reveals that the two cells are physiologically indistinguishable. They receive multimodal sensory inputs. Tactile/mechanosensory stimuli to much of the animal's body and head, acoustic stimuli, and simple visual stimuli all give rise to e.p.s.p.s and action potentials in the PM4 cell body. Simultaneous recording from the cell body in the deutocerebrum and the axon in the lobula demonstrates that action potentials are predominantly initiated in the deutocerebrum and propagate centrifugally, towards the optic lobe. Occasionally, bright light flashes will initiate an action potential in the axon in the optic stalk, which probably propagates bidirectionally: centripetally to the cell body, and centrifugally into the optic lobe. The extensive arborisations in the lobula and medulla are therefore likely to be sites of octopamine release. Because PM4 neurons are octopaminergic, project to the optic lobe, and receive modalities of sensory input known to dishabituate the Descending Contralateral Movement Detector (DCMD) visual interneuron, it is proposed that PM4 neurons are neuromodulatory — mediating dishabituation or arousal of the visual system.

Electronic Resource

1476-4687

Nature Archives 1869 - 2009

Biology

Chemistry and Pharmacology

Medicine

Natural Sciences in General

Physics

[Auszug] We now find that our preliminary structure is wrong, or at least it constitutes only half the truth, and the structure must in fact be disordered, as postulated by G nthard. This is one of the most remarkable examples that we have encountered of a preliminary structure based on data from three ...

Electronic Resource

1573-6903

Trace amines ; catecholamines ; 5HT ; plasma ; hypertensives ; GC-MS

Springer Online Journal Archives 1860-2000

Medicine

Abstract Procedures were developed for the determination of 17 circulating amines using gas chromatography-negative ion chemical ionisation mass spectrometry. The amines were quantified against their appropriate deuterated isotopomers. The mean concentrations and ranges of catecholamines and trace amines were high compared with previous studies. In comparison with nonhypertensives, plasma from hypertensives had higher concentrations of the following amines: noradrenaline (t=4.0%); normetanephrine (t=6.1%) and metanephrine (t=1.9%). There were no significant differences between 5HT levels in plasma from hypertensives and controls. The following trace amine could be detected in variable amounts in plasma:p-tyramine,m-tyramine,p-octopamine,m-octopamine,p-synephrine,m-synephrine, and salsolinol. The trace amines melatonin,N-acetyl 5HT, tryptamine, 6-hydroxymelatonin and 5-methoxytryptamine could not be detected in plasma with limits of detection lying in the range 20–100 pg ml−1.

Electronic Resource

1573-6903

Hydroxydopamines ; gas chromatography-mass spectrometry ; Parkinson's disease

Springer Online Journal Archives 1860-2000

Medicine

Abstract 5- and 6-Hydroxydopamine, which we had earlier identified as naturally occurring amines in human urine, were quantified in Parkinson's patients treated with L-DOPA, Parkinson's patients whose treatment did not include L-DOPA and in age matched controls. Analysis was carried out by GCMS of the ditrifluoromethylbenzoyl-trimethylsilyl (DTFMB-TMS) derivatives of the compounds. The concentrations of 5- and 6-hydroxydopamine in the urine of DOPA treated Parkinson's patients were significantly higher than the concentrations from patients not treated and from normal controls. Urinary dopamine levels were greatly elevated in DOPA treated Parkinson's patients whilep-tyramine levels were suppressed. No marked differences were seen between the three groups in terms of the urinary concentrations of any of the other amines measured.

Electronic Resource

0887-6134

Chemistry ; Analytical Chemistry and Spectroscopy

Wiley InterScience Backfile Collection 1832-2000

Chemistry and Pharmacology

An extraction-derivatization method suitable for the analysis of subnanogram amounts of biogenic amines in aqueous solution has been developed. The most satisfactory procedure for the analysis of these compounds was reaction with 3,5-ditrifluorobenzoylchloride (DTFMBCl) in phosphate buffer at pH 7.2 followed by extraction of the resultant amide esters into ethyl acetate. This was followed by hydrolysis of the phenolic ester functionalities by shaking the organic layer with 10 M ammonium hydroxide. The phenolic and alcoholic hydroxyl groups were then reacted with bistrimethylsilylacetamide and the trimethylsilyl-DTFMB amides were then analysed by gas chromatography/mass spectrometry in the negative ion chemical ionization mode with methane as reagent gas. The limits of detection for these derivatives was 〈1 pg and the method was readily applicable to the extraction and analysis of 0.5 ng of a given biogenic amine.

7 Ill.

Electronic Resource

0887-6134

Chemistry ; Analytical Chemistry and Spectroscopy

Wiley InterScience Backfile Collection 1832-2000

Chemistry and Pharmacology

Prednisolone, dexamethasone and betamethasone were labelled with deuterium via a simple synthetic procedure and used as internal standards in the gas chromatographic/mass spectrometric analysis of the corresponding undeuterated compounds. The mass spectrometer was used in the negative chemical ionization mode, which gave fragmentation of the methoxime trimethylsilyl ether derivatives favourable for their quantification. The method was applicable to the quantification of synthetic corticosteroids contained in human aqueous humour in the 0.1-10-ng range.

7 Ill.

Electronic Resource

0887-6134

Chemistry ; Analytical Chemistry and Spectroscopy

Wiley InterScience Backfile Collection 1832-2000

Chemistry and Pharmacology

Pentafluorobenzyl hydroxylamine has been used as a derivatization reagent in the analysis of corticosteroids by gas chromatography/negative ion chemical ionization (GC/NICI) mass spectrometry. The resulting pentafluorobenzyloxime-trimethylsilyl (PFBO/TMS) derivatives were generally formed in moderate yield but, despite this, the use of these derivatives resulted in a ∼ 10-fold improvement in the capability of identification of corticosteroids by GC/NICI mass spectrometry in comparison with the methoxime/TMS derivatives previously employed. The NICI mass spectra of PFBO/TMS derivatives were simple, with most of the ion current being carried by the [M - C6F6CH2]-. or [M - PFB]-. ion and by a reagent-specific peak at m/z 196. The derivatives have been employed in the quantification of ∼400 pg amounts of endogenous hydrocortisone present in samples of human aqueous humour and are readily applicable to the determination of low-picogram amounts of these compounds in biological media.

5 Ill.

Electronic Resource

0951-4198

Chemistry ; Analytical Chemistry and Spectroscopy

Wiley InterScience Backfile Collection 1832-2000

Physics

5 Ill.

Electronic Resource

0951-4198

Chemistry ; Analytical Chemistry and Spectroscopy

Wiley InterScience Backfile Collection 1832-2000

Physics

Thiocarbamides were converted to their di-N-pentafluorobenzyl (PFB) derivaties and analysed by gas chromatography/negative-ion chemical-ionization mass spectrometry with methane as reagent gas. The PFB derivatives of the 2-thiouracils gave mass spectra in which the ion current was carried largely by an ion arising from [M=PFB]-. The derivative was used in the determination of the uptake and metabolism of thiocarbamides by cultures of melanoma cells.

3 Ill.

Electronic Resource

0951-4198

Chemistry ; Analytical Chemistry and Spectroscopy

Wiley InterScience Backfile Collection 1832-2000

Physics

Oxazolidinone derivatives of glycine, phenylalanine and tyrosine were prepared by their reaction with dichlorotetrafluoroacetone. The derivatives were analyzed by gas chromatography/negative-ion chemicalionization mass spectrometry with methane as the reagent gas. The mass spectra under these conditions were composed of a few ions resulting largely from the addition of a chlorine radical to the molecular ion and successive losses of up to two HCl moieties from the molecular ion; loss of CO2 was also observed. Comparison of the mass spectrum of glycine and [2H2]glycine indicated that the protons involved in the loss of HCl from the molecular ion were derived in the first instance from the CH2 group in the derivative and secondly from the NH group. The derivatives were applied to the analysis of the amino acid precursors of biogenic amines in nervous tissue from the locust.

7 Ill.

Electronic Resource

0142-2421

Chemistry ; Polymer and Materials Science

Wiley InterScience Backfile Collection 1832-2000

Physics

Depth profiles calculated using simple peak-to-peak or peak height or area measurements are subject to inaccuracies caused by spectral noise, sloping backgrounds and possibly by overlapping spectra of different elements or chemical species. An automated program that reduces or eliminates the effects of these potential sources of error in the peak heights and areas calculated from electron spectra has been developed. The program uses linear least-squares fitting of one or more basis spectra to determine the peak height or area for each spectrum recorded during the profile. The program selects the basis spectra from the energy region data set without operator intervention. The number of unique lineshapes is determined by the program, again without operator intervention, and a profile is calculated for each species. The fit method of intensity determination was found to increase the dynamic range by reducing false contributions to the calculated intensities; this observation holds when a single basis spectrum is sufficient to model the data. Contributions from overlapping spectra are resolved if an example of each pure species lineshape is available in the regional data set. The method is demostrated by practical example.

7 Ill.

Electronic Resource