Publications by authors named "Gregor McCombie"

Contact allergy to Nickel is the most prevalent contact allergy in western societies. This has led to regulation for metallic items that come into prolonged and direct contact with the skin, such as buttons on clothing, belt buckles, jewelry and watches. In Europe, the legal provision is based on a test in which there is a limit to the amount of nickel that may be released from the item to an artificial sweat solution (EN 1811).

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Elastomers are not a uniform class of materials but comprise a broad spectrum of chemically different polymers. Sealing gaskets, gloves, teats, conveyor belts and tubing are examples of elastomers being used as food contact materials (FCMs). Ten elastomer samples were evaluated with respect to the content of extractable compounds, migration of substances into ethanolic food simulants, swelling in food simulants and release of elements in different food simulants.

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There is a significant lack of data on acrylamide in food which is prepared domestically, as obtaining samples of food cooked in people's homes is more complex than taking samples from shops. Rösti is a fried potato dish, which can be a significant contributor to acrylamide exposure, particularly in the German speaking areas of Switzerland. A set of 71 samples was collected from people who cooked the dish at home.

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Swiss control authorities checked the safety assessment of nine major producers of polyolefin granulates for making food contact materials. It was a pilot project to gain experience on the procedure of collecting and evaluating compliance documentation, but also to obtain insight into the quality of compliance work performed by the main plastic producers. It revealed that there are fundamental problems in performing such control.

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Plasticizers in toys are a recurring source of criticism and concern, as consumers feel they may endanger the health of their children. Most of the information available in literature concerns the presence or absence of certain phthalic acid ester plasticizers. Very little information can be found in the public domain with respect to the actually used plasticizers at a given time and place.

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Plasticizers migrate from polyvinylchloride (PVC) infusion systems into lipid emulsions. The aim of this study was to investigate the leaching of different plasticizers from PVC perfusion lines by a selection of lipid emulsions under clinical conditions. Seven PVC perfusion lines with an equal length of 150cm and three internal diameters were perfused with three lipid emulsions: Intralipid 20%, ClinOleic 20% and SMOFlipid 20%, mimicking clinical conditions.

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Rösti, a fried potato product, is a large contributor to acrylamide exposure locally in Switzerland. A survey of 55 dishes prepared by 51 restaurants in the city of Zurich showed that the average rösti contained 702 µg/kg acrylamide. By analysing the content of reducing sugars in the potatoes used for frying, it is shown that with simple measures, the exposure to acrylamide could easily be reduced by factor 2 or more, while even improving the culinary experience.

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The peroxisome proliferator-activated receptor-γ coactivators (PGC-1) are transcriptional coactivators with an important role in mitochondrial biogenesis and regulation of genes involved in the electron transport chain and oxidative phosphorylation in oxidative tissues including cardiac tissue. These coactivators are thought to play a key role in the development of obesity, type 2 diabetes and the metabolic syndrome. In this study we have used a combined metabolomic and lipidomic analysis of cardiac tissue from the PGC-1β null mouse to examine the effects of a high fat diet on this organ.

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Previous studies have shown that a combination of weight loss and fish oil supplementation reduce cardiovascular disease and diabetes risks by increasing adiponectin and reducing triacylglyceride concentrations, while weight loss alone significantly improves insulin sensitivity and reduces inflammation. Here, a metabolomic approach, using a combination of (1)H-Nuclear Magnetic Resonance spectroscopy, and gas and liquid chromatography and mass spectrometry, was employed to elucidate the metabolic changes in blood plasma following weight loss and fish oil supplementation. The intervention study was conducted over 24 weeks, with 93 female subjects randomised to one of three groups.

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In recent years, lipidomics or lipid profiling, an extension of metabolomics where the lipid complement of a cell, tissue or organism is measured, has been the recipient of increasing attention as a research tool in a range of diverse disciplines including physiology, lipid biochemistry, clinical biomarker discovery and pathology. The advancement of the field has been driven by the development of analytical technologies, and in particular advances in liquid chromatography mass spectrometry and chemometric methods. In this review, we give an overview of the current methods with which lipid profiling is being performed.

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Label-free molecular imaging by mass spectrometry allows simultaneous mapping of multiple analytes in biological tissue sections. In this chapter, the application of this new technology to the detection Abeta peptides in mouse brain sections is discussed.

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The identification of biomarkers from serum or plasma is often hindered by a few proteins present at high concentrations, which may obscure less abundant proteins. Ideal serum depletion strategies would be flexible as regards the proteins to be removed, and would feature the use of reagents with long shelf-lives. In this article, we describe a novel protein depletion methodology based on the incubation of serum samples with phage-derived recombinant antibody fragments, which are able to bind to staphylococcal Protein A, and which carry a C-terminal peptide tag capable of streptavidin binding.

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Electrosprayed spots of varying thickness were evaluated for use as reproducible, homogenous, high efficiency MALDI samples. Thin samples on stainless steel plates were found to give exceptionally strong signals, as did the last layers of thick samples, when ablated down to the steel substrate. A small enhancement was also observed for thin samples on a gold substrate, and with a few-nanometer gold coating on top of a thick sample.

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Matrix-assisted laser desorption/ionization mass spectrometry imaging is a technique for direct analysis of tissue sections without the use of molecular tags or contrast agents. The combination of spatial and mass resolution results in large and complex data sets that require powerful and efficient analysis and interpretation tools. Conventional images, derived from a specific analyte mass, do not identify the spatially localized correlations between analytes that are latent in the data.

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The high mass accuracy and resolution of Fourier transform (FT)-ion cyclotron resonance (ICR) mass spectrometry are making it an increasingly useful tool in drug discovery and development. The basics of FT-ICR are described here, including modern ion sources and fragmentation methods. Although FT-ICR is not a high-throughput method in the traditional sense, previously difficult and complex problems are being efficiently approached using steadily improving instruments and magnets.

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The matrix suppression effect (MSE) can lead to high-quality MALDI mass spectra: strong analyte signals and weak or negligible matrix background peaks. Experiment and theory suggest that MSE should be widespread and, therefore, generally applicable to measurement of low molecular weight (LMW) substances. These are otherwise impractical with MALDI due to interference from matrix.

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The central nervous system myelin components oligodendrocyte-myelin glycoprotein, myelin-associated glycoprotein and the Nogo-66 domain of Nogo-A inhibit neurite outgrowth by binding the neuronal glycosyl-phosphatidylinositol-anchored Nogo-66 receptor (NgR) that transduces the inhibitory signal to the cell interior via a transmembrane co-receptor, p75NTR. Here, we demonstrate that human NgR expressed in human neuroblastoma cells is constitutively cleaved in a post-ER compartment to generate a lipid-raft associated C-terminal fragment that is present on the cell surface and a soluble N-terminal fragment that is released into the medium. Mass spectrometric analysis demonstrated that the N-terminal fragment terminated just after the C-terminus of the ligand-binding domain of NgR.

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Electrospray time-of-flight mass spectrometry was used to quantitatively determine the dissociation constant of chorismate mutase and a transition state analogue inhibitor. This system presents a fairly complex stoichiometry because the native protein is a homotrimer with three equal and independent substrate binding sites. We can detect the chorismate mutase trimer as well as chorismate mutase-inhibitor complexes by choosing appropriate conditions in the ESI source.

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Noncovalent complexes between chicken muscle adenylate kinase and two inhibitors, P(1),P(4)-di(adenosine-5')tetraphosphate (Ap4A) and P(1),P(5)-di(adenosine-5') pentaphosphate (Ap5A), were investigated with electrospray ionization mass spectrometry under non-denaturing conditions. The nonconvalent nature and the specificity of the complexes are demonstrated with a number of control experiments. Titration experiments allowed the association constants for inhibitor binding to be determined.

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