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R Goodacre

Publications and source records attributed to R Goodacre.

At least 37 records · Page 2Linked to original sources

Quantitative analysis of multivariate data using artificial neural networks: a tutorial review and applications to the deconvolution of pyrolysis mass spectra.

The implementation of artificial neural networks (ANNs) to the analysis of multivariate data is reviewed, with particular reference to the analysis of pyrolysis mass spectra. The need for and benefits of multivariate data analysis are explained followed by a discussion of ANNs and their optimisation. Finally, an example of the use of ANNs for the quantitative deconvolution of the pyrolysis mass spectra of Staphylococcus aureus mixed with Escherichia coli is demonstrated.

Escherichia coli↗

Rapid and quantitative analysis of recombinant protein expression using pyrolysis mass spectrometry and artificial neural networks: application to mammalian cytochrome b5 in Escherichia coli.

Recombinant Escherichia coli clones encoding between 0 and 6 copies of the mammalian cytochrome b5 gene were subjected to pyrolysis mass spectrometry (PyMS). To deconvolute the pyrolysis mass spectra so as to obtain quantitative information on the amount of cytochrome b5 produced fully-interconnected feedforward artificial neural networks (ANNs) were studied. It was found that the combination of PyMS and ANNs could be used to predict the amount of cytochrome b5 expressed in E. coli. PyMS is a novel, convenient and rapid method for the screening and analysis of microbial and other cultures producing recombinant proteins.

Animals↗

Rapid identification of species within the Mycobacterium tuberculosis complex by artificial neural network analysis of pyrolysis mass spectra.

An artificial neural network (ANN) was trained to distinguish between Mycobacterium tuberculosis and M. bovis with averaged pyrolysis mass spectra from duplicate subcultures of four strains of each of these species, each pyrolysed in triplicate. Once trained, the ANN was interrogated with spectrum data from the original organisms (the "training set") and from 26 other mycobacterial isolates (the "challenge set") of the M. tuberculosis complex (MTBC). Eight strains of M. bovis and 13 of M. tuberculosis, whether sensitive or variously resistant to antituberculosis drugs, were identified in agreement with conventional identification. Four strains of "M. africanum" were identified as M. bovis. Of two atypical M. tuberculosis strains from South India, one was identified as M. tuberculosis and the other as M. bovis. Six strains of BCG proved heterogeneous; two gave equivocal identifications, three were identified as M. bovis and one was identified as M. tuberculosis.

Humans↗

Rapid identification using pyrolysis mass spectrometry and artificial neural networks of Propionibacterium acnes isolated from dogs.

Curie-point pyrolysis mass spectra were obtained from reference Propionibacterium strains and canine isolates. Artificial neural networks (ANNs) were trained by supervised learning (with the back-propagation algorithm) to recognize these strains from their pyrolysis mass spectra; all the strains isolated from dogs were identified as human wild type P. acnes. This is an important nosological discovery, and demonstrates that the combination of pyrolysis mass spectrometry and ANNs provides an objective, rapid and accurate identification technique. Bacteria isolated from different biopsy specimens from the same dog were found to be separate strains of P. acnes, demonstrating a within-animal variation in microflora. The classification of the canine isolates by Kohonen artificial neural networks (KANNs) was compared with the classical multivariate techniques of canonical variates analysis and hierarchical cluster analysis, and found to give similar results. This is the first demonstration, within microbiology, of KANNs as an unsupervised clustering technique which has the potential to group pyrolysis mass spectra both automatically and relatively objectively.

Animals↗

Characterization of exopolymers of aquatic bacteria by pyrolysis-mass spectrometry.

Exopolymers from a diverse collection of marine and freshwater bacteria were characterized by pyrolysis-mass spectrometry (Py-MS). Py-MS provides spectra of pyrolysis fragments that are characteristic of the original material. Analysis of the spectra by multivariate statistical techniques (principal component and canonical variate analysis) separated these exopolymers into distinct groups. Py-MS clearly distinguished characteristic fragments, which may be derived from components responsible for functional differences between polymers. The importance of these distinctions and the relevance of pyrolysis information to exopolysaccharide function in aquatic bacteria is discussed.

Carbohydrates↗

A new measure of health status for clinical trials in inflammatory bowel disease.

We have developed a measure of subjective health status (quality of life) for patients with inflammatory bowel disease (IBD). Ninety-seven patients with IBD described problems they had experienced as a result of the disease; the 32 most frequent and important items were included in the Inflammatory Bowel Disease Questionnaire (IBDQ). Sixty-one IBD patients were evaluated twice. One month separated the evaluations, at which disease activity indices, the IBDQ, and a number of other questionnaires were administered. Reproducibility studies in 19 stable patients showed improvement in scores, but also a small within-person standard deviation. Responsiveness studies revealed large changes in scores in patients who had improved or deteriorated and suggested that the IBDQ was more responsive than a general health status measure. Responsiveness appeared greater in patients with ulcerative colitis than in those with Crohn's disease. Predicted and observed correlations between changes in IBDQ score and changes in other measures were similar. We conclude that although further testing is required, particularly in examining the relation between changes in the IBDQ and changes in the activity of Crohn's disease, the IBDQ shows promise as a measure of health status for clinical trials in IBD.

Attitude to Health↗

Quality of life in patients with inflammatory bowel disease.

To investigate the effect of inflammatory bowel disease (IBD) on the quality of life, we interviewed 43 patients with ulcerative colitis (UC) and 54 with Crohn's disease. Patients identified frequent and important problems in five areas. Primary bowel symptoms, systemic symptoms, and altered emotional function were common; functional and social impairment were less frequent. Systemic symptoms such as fatigue were more prevalent in patients with Crohn's disease. Apart from primary bowel complaints, patients seldom volunteered other facets of quality of life impairment; this was particularly true for impairment of emotional function. We conclude that despite troublesome intestinal and systemic symptoms, most patients with IBD avoid major disruption in work and personal lives. Physicians must inquire specifically about emotional problems relating to IBD; in particular, fear of surgery is important to address. Psychosocial interventions should be targeted to those patients with problems in this area.

Adult↗

Mast cells from the human intestinal lamina propria. Isolation, histochemical subtypes, and functional characterization.

With the use of a collagenase dispersion technique, cells were isolated from the lamina propria of the human small and large intestine. The cell suspensions contained 8% mast cells, which on average contained 1 to 2 pg of histamine/cell. With the use of histochemical procedures based upon fixative sensitivity and dye binding, which identify functionally distinct mast cell subtypes in the rat, dispersed human intestinal mast cells contained approximately equal proportions of two histochemical subtypes analogous to those in the rat. Whether these are functionally distinct as in the rat remains to be determined. The histochemically mixed mast cell populations from the human intestinal mucosa secreted histamine in a dose- and energy-dependent manner in response to anti-IgE and A23187, but not 48/80. Theophylline, doxantrazole, quercetin, and salbutamol all significantly inhibited anti-IgE-induced histamine secretion by human intestinal mast cells, but cromolyn sodium and the experimental antisecretory drugs, nedocromil sodium and FPL 52694, did not inhibit histamine secretion by the mast cell mixture to a statistically significant extent. Cromolyn sodium inhibited histamine secretion by 15 to 30%, and whether this reflected inhibition of one of the two histochemical mast cell subtypes to a greater extent than the other or all the cells to a minimal degree remains to be established. Control investigations of the intestinal cell isolation procedure indicated that these qualities did not reflect effects of the cell dispersal procedure. Further characterization and analysis of intestinal mast cells is essential to determine if functionally distinct mast cell subtypes exist in human tissues.

Antibodies, Anti-Idiotypic↗

Mast cell heterogeneity in man. I. Histologic studies of the intestine.

We have studied the distribution and abundance of histochemically distinct mast cell subpopulations in the normal small and large intestine of man. One subpopulation has histochemical properties similar to the functionally distinct intestinal mucosal mast cell (MMC) of the rat and the other has properties similar to the widely distributed mast cell found in connective tissues and the peritoneal cavity of many animals. Both subpopulations are present in intestinal epithelium, lamina propria, submucosa and muscularis mucosa, and muscle. However, the subpopulation histochemically similar to the rodent MMC is significantly more abundant than the other in all sites in the large intestine and also in the lamina propria and muscle of the small intestine. It is important to determine whether these histochemically distinct mast cell subpopulations in man differ in their responses to various secretagogues and antiallergic compounds as in the rat.

Cell Count↗

Factor V deficiency and its reversal with gluten restriction. In a patient with celiac disease.

Hemorrhagic manifestations in patients with celiac disease are uncommon and, when present, are usually due to a deficiency of the vitamin K-dependent clotting factors. A patient with celiac disease was seen with a severe bleeding diathesis associated with deficiencies of factor V. The deficiencies of vitamin K-dependent clotting factors were rapidly reversed with parenteral administration of phytonadione. Factor V levels returned to normal levels only after gluten restriction.

Adult↗

Unique functional characteristics of mucosal mast cells.

Mast cells have been isolated from the intestine (IMC) of rats previously infected with the nematode, Nippostrongylus brasiliensis. Functional studies on IMC have shown that they are responsive to antigen and possess surface IgE but, in contrast to peritoneal mast cells (PMC), IMC are unresponsive to the basic secretagogues, 48/80 and bee venom peptide 401, and hyporesponsive to ionophores. Furthermore, sodium cromoglycate, AH9679 and theophylline inhibited secretion by PMC but not IMC, whereas doxantrazole inhibited secretion by both cells. Histochemical investigations established that there is mast cell heterogeneity in the human intestine as well as in the rat. Since GALT and BALT are important in intestinal mastocytosis it is important to determine whether the distinct functional properties of IMC reflect a distinct precursor population, inducer cell, or other factors in GALT or BALT.

Animals↗