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Biomedical subjects

Andrew Craig

Publications and source records attributed to Andrew Craig.

7 recordsLinked to original sources
PubMed2005

Statistical total correlation spectroscopy: an exploratory approach for latent biomarker identification from metabolic 1H NMR data sets.

We describe here the implementation of the statistical total correlation spectroscopy (STOCSY) analysis method for aiding the identification of potential biomarker molecules in metabonomic studies based on NMR spectroscopic data. STOCSY takes advantage of the multicollinearity of the intensity variables in a set of spectra (in this case 1H NMR spectra) to generate a pseudo-two-dimensional NMR spectrum that displays the correlation among the intensities of the various peaks across the whole sample. This method is not limited to the usual connectivities that are deducible from more standard two-dimensional NMR spectroscopic methods, such as TOCSY. Moreover, two or more molecules involved in the same pathway can also present high intermolecular correlations because of biological covariance or can even be anticorrelated. This combination of STOCSY with supervised pattern recognition and particularly orthogonal projection on latent structure-discriminant analysis (O-PLS-DA) offers a new powerful framework for analysis of metabonomic data. In a first step O-PLS-DA extracts the part of NMR spectra related to discrimination. This information is then cross-combined with the STOCSY results to help identify the molecules responsible for the metabolic variation. To illustrate the applicability of the method, it has been applied to 1H NMR spectra of urine from a metabonomic study of a model of insulin resistance based on the administration of a carbohydrate diet to three different mice strains (C57BL/6Oxjr, BALB/cOxjr, and 129S6/SvEvOxjr) in which a series of metabolites of biological importance can be conclusively assigned and identified by use of the STOCSY approach.

Amines↗
PubMed2005

Evaluation of the orthogonal projection on latent structure model limitations caused by chemical shift variability and improved visualization of biomarker changes in 1H NMR spectroscopic metabonomic studies.

In general, applications of metabonomics using biofluid NMR spectroscopic analysis for probing abnormal biochemical profiles in disease or due to toxicity have all relied on the use of chemometric techniques for sample classification. However, the well-known variability of some chemical shifts in 1H NMR spectra of biofluids due to environmental differences such as pH variation, when coupled with the large number of variables in such spectra, has led to the situation where it is necessary to reduce the size of the spectra or to attempt to align the shifting peaks, to get more robust and interpretable chemometric models. Here, a new approach that avoids this problem is demonstrated and shows that, moreover, inclusion of variable peak position data can be beneficial and can lead to useful biochemical information. The interpretation of chemometric models using combined back-scaled loading plots and variable weights demonstrates that this peak position variation can be handled successfully and also often provides additional information on the physicochemical variations in metabonomic data sets.

3-Hydroxybutyric Acid↗
PubMed2004

Good management. Corporate governance: 'the hospital is listening'.

Homerton University Hospital trust, a first-wave foundation, commissioned a specialist consultancy to devise an induction programme for the governors. It was vital to tailor activities to individual needs while retaining overall consistency. A concluding exercise demonstrated that the majority agreed they had overcome initial hesitancy.

Community-Institutional Relations↗
PubMed2004

Cell-to-cell adhesion modulates Stat3 activity in normal and breast carcinoma cells.

Stat3 (signal transducer and activator of transcription-3) activity is required for transformation by a number of oncogenes, while a constitutively active form of Stat3 alone is sufficient to induce neoplastic transformation. Although in most instances Stat3 is growth-promoting, the impact of cell density on Stat3 activation status and the biological importance of Stat3 during growth arrest have not been characterized. Previous results indicated that cell density alters tyrosine phosphorylation levels of cultured cells. Since signalling through Stat3 is determined by a key phosphorylation at tyr705, we examined the effects of cell density upon Stat3 activity in normal breast epithelial cells, breast carcinoma lines and normal mouse fibroblasts. Intriguingly, the results revealed a dramatic increase in Stat3, tyr705 phosphorylation and activity with cell density, which gradually declined at later stages. This activation was dependent upon cell-cell contact, since it was eliminated if cell adhesion was disrupted through calcium chelation, while it was reinstated through cell aggregation. Furthermore, this activation was suppressed following inhibition of JAKs (Janus kinases) but not inhibition of Fer, IGF1-R, or kinases of the c-Src family. On the other hand, constitutively active Stat3 in carcinoma lines, known to harbor activated Src, was blocked by pharmacological inhibitors of Src as well as JAKs. These results point to the existence of two distinct pathways of Stat3 activation in breast carcinomas, based on Src dependence. More importantly, our results suggest that Stat3 activity is upregulated during the confluence-mediated growth arrest by a signalling mechanism that requires JAKs.

Animals↗
PubMed2003

Quantitative analysis of perinatal rodent oligodendrocyte lineage progression and its correlation with human.

The development of a rodent model in the perinatal rat or mouse that reproduces the principal features of human perinatal white matter injury (periventricular leukomalacia) has been hampered by uncertainty about the developmental window in the rodent that coincides temporally with cerebral white matter development in the premature infant. We recently determined oligodendrocyte (OL) lineage progression in human cerebral white matter and found that the late OL progenitor (preOL) predominates throughout the high-risk period for periventricular leukomalacia [J. Neurosci. 21(2001), 1302-1312]. Here, we determined in the perinatal rat and mouse when each species displays a distribution of OL stages that is similar to the premature human cerebral white matter. PreOLs are abundant in the rat and mouse at P2. By P7, extensive OL maturation occurs in both species and coincides with the onset of early myelination. PreOLs and immature OLs mature in the P2 white matter along a medial to lateral gradient. This may provide an explanation for regional variation in the susceptibility of perinatal white matter to injury. We propose that the sequence of OL lineage progression is a useful means to estimate developmental windows of white matter maturation in perinatal rodents that coincide with those of developing human cerebral white matter. These studies support that the vulnerable period for white matter injury in the rodent is centered around P2 and should decline thereafter, coincident with the onset of myelination.

Animals↗