Biomedical subjects
Publications and source records attributed to D Hodgson.
Through a multidisciplinary team approach, a competency-based tool has been developed to help to assess and identify training and development needs for staff working within the cancer field. The tool assists both individuals and organisations to gain a micro and macro picture of staff's existing skills and their development needs.
Collaborative education and training is the only way forward for the cancer care work force. The Calman-Hine report has become the benchmark on which to build practice since its launch in 1995. A forward looking group--the Cancer Care Alliance of Teesside, South Durham and North Yorkshire Education Group and the University of Teesside--adopted its principles from the Calman-Hine Report and developed some strategic projects to address and achieve them. A needs assessment of cancer education influenced the agenda within the Cancer Care Alliance. The education portfolio that was developed had a multiprofessional focus, incorporating both academic and non-academic study.
Cases of acute epiglottitis in children have become very uncommon in recent years. This study set out to find whether the introduction of the Haemophilus influenzae b (Hib) vaccine in the UK in October 1992 has influenced the incidence of acute epiglottitis in the Sheffield region, and whether the pathogenesis has altered. A 10-year retrospective case note review was undertaken. A total of 30 children were treated for acute epiglottitis in Sheffield Children's Hospital over that time period. A sharp decline in the number of cases was found after the vaccine was introduced. Most children presenting with the disease after October 1992 had not been vaccinated. In addition, the pathogens isolated in those children who had received the vaccine were all Streptococci. This is the first study in the UK to examine the influence of the Hib vaccine on acute paediatric epiglottitis.
We wish to identify genes associated with disease. To do so, we look for novel genes whose expression patterns mimic those of known disease-associated genes, using a method we call Guilt-by-Association (GBA), on the basis of a combinatoric measure of association. Using GBA, we have examined the expression of 40,000 human genes in 522 cDNA libraries, and have discovered several hundred previously unidentified genes associated with cancer, inflammation, steroid-synthesis, insulin-synthesis, neurotransmitter processing, matrix remodeling, and other disease processes. The majority of the genes thus discovered show no sequence similarity to known genes, and thus could not have been identified by homology searches. We present here an example of the discovery of eight genes associated with prostate cancer. Of the 40,000 most-abundant human genes, these 8 are the most closely linked to the known diagnostic genes, and thus are prime targets for pharmaceutical research.
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A software system for transforming fragments from four-color fluorescence-based gel electrophoresis experiments into assembled sequence is described. It has been developed for large-scale processing of all trace data, including shotgun and finishing reads, regardless of clone origin. Design considerations are discussed in detail, as are programming implementation and graphic tools. The importance of input validation, record tracking, and use of base quality values is emphasized. Several quality analysis metrics are proposed and applied to sample results from recently sequenced clones. Such quantities prove to be a valuable aid in evaluating modifications of sequencing protocol. The system is in full production use at both the Genome Sequencing Center and the Sanger Centre, for which combined weekly production is approximately 100, 000 sequencing reads per week.
DNA computation is a novel and exciting recent development at the interface of computer science and molecular biology. We describe the current activity in this field following the seminal work of Adleman, who recently showed how techniques of molecular biology may be applied to the solution of a computationally intractable problem.
Current ablative techniques for treating menorrhagia are unsatisfactory. We tried microwave energy, delivered by an 8 mm diameter probe in the uterine cavity, to treat 23 patients with functional menorrhagia. The mean treatment time was 2 min 12 s (range 50-310 s). 6 months after treatment the success rate is 83%, 13 patients (57%) are amenorrhoeic, and six (26%) are experiencing light menstruation. Three initial failures have been successfully retreated. The technique is safe, and is easier and quicker to perform than current alternatives.
The reaction of the bismethylenedioxy derivative of cortisol (cortisol-BMD) with heptafluorobutyric anhydride to give the corresponding 3,5-dienol heptafluorobutyrate (cortisol-BMD-HFB) has been shown to proceed with dehydration. Acid-promoted dehydration of either cortisol-BMD or cortisol-BMD-HFB, or concurrent dehydration of both, is the proposed reaction mechanism leading to a trienol heptafluorobutyrate, whose chromatographic properties and mass spectral data are consistent with the additional double bond in the C9-C11 position. Forming the 3,5-dienol heptafluorobutyrate of cortisol-BMD in benzene rather than acetone gave a compound whose chromatographic properties and mass spectral data were different to that of the 3,5,9(11)-trienol heptafluorobutyrate but consistent with that of a cortisol-BMD-HFB. The mass fragmentometry of this new cortisol derivative was found to be more suited to the technique of isotope dilution mass spectrometry than the 3,5,9(11)-trienol heptafluorobutyrate, and thus was applied to our intended goal of measuring urinary free cortisol by gas chromatography-mass spectrometry. An efficient and convenient solid-phase extraction technique is employed in our assay to isolate cortisol from 5 ml of urine.
We have constructed an expression vector to produce, in Escherichia coli, a fusion protein containing successively two IgG binding domains from staphyloccocal protein A, a nine-amino-acid linker peptide terminating in a methionine residue and the phospholipase A2 notechis 11'2L, an isoform of notexin of Notechis scutatus scutatus venom. Notechis 11'2L is a mutant of the naturally occurring notechis 11'2 [Bouchier, C., Boyot, P., Tesson, F., Trémeau, O., Bouet, F., Hodgson, D., Boulain, J. C. & Ménez, A. (1991) Eur. J. Biochem. 202, 493-500] in which Met8 has been replaced by Leu. The fusion protein was recovered in the periplasmic extract with a yield of 0.25 mg/l culture. It was hydrolyzed with cyanogen bromide, yielding a protein having the molecular mass, amino acid composition and N-terminal sequence of notechis 11'2L. Notechis 11'2L and the wild notechis 11'2 displayed identical circular dichroic spectra and shared similar enzymatic, myotoxic and antigenic properties, suggesting that the recombinant notechis 11'2L was directly generated in a correctly folded form.
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Previously, we deduced the amino acid sequence of a novel phospholipase-A2-like protein (PLA2) from the nucleotide sequence of a cDNA isolated from a library prepared from the venom gland of the Australian elapid Notechis scutatus scutatus. The corresponding protein has now been identified, purified from the venom and named Notechis 11'2. Its complete amino acid sequence has been determined by automated Edman degradation of both the whole protein and peptides generated by Staphylococcus aureus protease digestion and chemical cleavage at a tryptophan residue. As predicted from its sequence which contains all the residues putatively required for PLA2 activity, Notechis 11'2 exhibits an esterase activity, preferentially against neutral phospholipids. However, despite its sequence homology with other highly toxic PLA2 present in the venom of Notechis scutatus scutatus, notechis 11'2 has no lethal activity. This observation further supports the view that the lethal activity of PLA2 from Notechis scutatus scutatus is not due to the esterasic activity only.
Fifty-eight foals were divided into two groups for study of aspects of the clinical anesthetic management of foals and to characterize effects of halothane (n = 30) and isoflurane (n = 28) in foals. There were no significant differences (P greater than 0.05) in the demographics of the two groups. Results of hemograms and biochemical analysis of venous blood samples before and after anesthesia were either not influenced or only mildly (clinically unimportant) affected by either agent. Like adult horses, foals have an increased PaCO2 when anesthetized with inhaled anesthetics. We could detect no difference in the magnitude of increase in PaCO2 with either anesthetic. Anesthetic induction and recovery was most rapid with isoflurane. The quality of induction and recovery was similarly acceptable with either agent. Heart rate during isoflurane was not significantly different from conscious conditions but during halothane, heart rate was significantly less than control except at 91-120 min when statistical significance was not detected. These results support the clinical impression that foals can be safely and reliably anesthetized with either agent.
Of 30 agoraphobic married women undertaking home-based behaviour therapy, 15 each had a female friend as co-therapist and 15 had their own husband as co-therapist. At 12 months follow-up, women spent a mean of approximately 40 minutes a day more outside the home alone than at baseline. Women assisted by female friends made somewhat more behavioural gains than those assisted by husbands. Women in both groups whose husbands had been more depressed 2 months after the beginning of therapy did less well at 6 months. Husbands who become more depressed may retard their wives' progress in therapy, but the effect was small, and was outweighed by other considerations.
A fatty acid auxotroph of Caulobacter crescentus, AE6001, which displays a strict requirement for unsaturated fatty acids to grow on glucose as the carbon source has been isolated. Starvation of AE6001 for unsaturated fatty acids resulted in a block in the cell cycle. Starved cultures accumulated at the predivisional cell stage after a round of DNA replication had been completed and after a flagellum had been assembled at the pole of the cell. Cell division and cell growth failed to occur probably because the mutant was unable to synthesize a membrane. An analysis of double mutants containing the fatB503 allele and other mutations in membrane biogenesis demonstrated that the cell cycle of AE6001 blocked at a homeostatic state. The addition of oleic acid to starved cultures permitted cell division and the initiation of a new round of DNA replication. The coincident block in both the initiation of DNA replication and membrane assembly, exhibited by starved cultures of this mutant, suggests that the fatB503 gene product may be involved in the coordination of these events.
A mutant of Caulobacter crescentus has been isolated which has an auxotrophic requirement for unsaturated fatty acids or biotin for growth on medium containing glucose as the carbon source. This mutant exhibits a pleiotropic phenotype which includes (i) the auxotrophic requirement, (ii) cell death in cultures attempting to grow on glucose in the absence of fatty acids or biotin, and (iii) a major change in the outer membrane protein composition before cell death. This genetic lesion did not appear to affect directly a fatty acid biosynthetic reaction because fatty acid and phospholipid syntheses were found to continue in the absence of supplement. Oleic acid repressed fatty acid biosynthesis and induced fatty acid degradation in the wild-type parent, AE5000 . The mutant strain, AE6000 , was altered in both of these regulatory functions. The AE6000 mutant also showed specific inhibition of the synthesis of outer membrane and flagellar proteins. Total phospholipid, DNA, RNA, and protein syntheses were unaffected. The multiple phenotypes of the AE6000 mutant were found to cosegregate and to map between hclA and lacA on the C. crescentus chromosome. The defect in this mutant appears to be associated with a regulatory function in membrane biogenesis and provides evidence for a direct coordination of membrane protein synthesis and lipid metabolism in C. crescentus.
Problems encountered during halothane anesthesia in 3 horses included increasing rectal temperature, muscle rigidity or movement during anesthesia, irregular breathing patterns, and difficulty in stabilizing blood pressure. One horse had prolonged muscle fasciculations and failure to relax after administration of succinylcholine in addition to halothane. That horse developed severe, bilateral myositis of the triceps, lumbar, and gluteal muscles. Problems encountered were similar to those caused by the disease known as malignant hyperthermia.