Biomedical subjects
Publications and source records attributed to D Hughes.
In summary, non-menstrual TSS is potentially lethal if overlooked. Postoperative TSS can be particularly difficult to diagnose because patients often present with mild nonspecific, "flu like" symptoms and usually do not have evidence of local wound infection. It is therefore important to have a high suspicion index of occult wound infection complicated by TSS in postoperative patients with fever, rash, gastrointestinal symptoms or hypotension.
Each of the two genes encoding EF-Tu in Salmonella typhimurium has been inactivated using a mini-Mu MudJ insertion. Eleven independently isolated insertions are described, six in tufA and five in tufB. Transduction analysis shows that the inserted MudJ is 100% linked to the appropriate tuf gene. A mutant strain with electrophoretically distinguishable EF-TuA and EF-TuB was used to show, on two-dimensional gels, that the MudJ insertions result in the loss of the appropriate EF-Tu protein. Southern blotting, using cloned Escherichia coli tuf sequences as probes, shows that each MudJ insertion results in the physical breakage of the appropriate tuf gene. The degree of growth-rate impairment associated with each tuf inactivation is independent of which tuf gene is inactivated. The viability of S. typhimurium strains with either tuf gene inactive contrasts strongly with data suggesting that in the closely related bacterium E. coli, an active tufA gene is essential for growth. Finally the strains described here facilitate the analysis of phenotypes associated with individual mutant or wild-type Tus both in vivo and in vitro.
The two EF-Tu encoding genes, tufA and tufB, of Salmonella typhimurium have been sequenced. Nearly all the differences from their Escherichia coli counterparts are third position changes which do not alter the encoded amino acids. Unexpectedly, most of the changes in one Salmonella tuf gene are paralleled by changes in the other tuf gene perhaps due to gene repair despite the distance separating the genes. Three mutants which cause mis-framing, have their substitutions at codon 375. Explanations for mutants which cause mis-framing are considered and the mechanism of normal reading frame maintenance discussed.
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A case is presented in which the Nd:YAG laser obviated the need for a major thoracic procedure. A 7-year-old boy presented with an 18-month history of persistent nonproductive cough, preceded by a choking spell while eating pistachio nuts. High-grade left mainstem bronchial obstruction was caused by friable granulation tissue secondary to an underlying foreign body. By advancing a laser fiber through the working channel of a 5-mm Storz ventilating bronchoscope, the granulation tissue was vaporized, showing an irregular piece of pistachio nut shell embedded within the bronchial wall. After retrieval of the foreign body, bronchial patency was restored. Recovery was complete and uneventful. The bronchoscopic laser permits the delivery of precise and effective treatment to lesions within confined areas, and has a useful role in the management of some central airway lesions in children.
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The value of combining morphine with bupivacaine for caudal analgesia was investigated. Thirty children, undergoing orchidopexy, received a caudal block of 0.125% bupivacaine with or without morphine 0.05 mg kg-1. Analgesia, side-effects, ventilatory frequency and oxygen saturation (SaO2) were recorded after operation. None of the 15 patients receiving the bupivacaine-morphine mixture required post-operative opioids, whereas eight of 15 patients receiving bupivacaine alone needed additional opioid analgesia. The incidence of side effects after surgery was similar for the two groups and there was no detectable difference in ventilatory frequency or SaO2.
The apparent digestibility of a molassed, chaffed grass hay/straw mixture was determined using four mature horses (mean weight 606 kg). Animals were stalled individually and kept on rubber mats. A preliminary feeding period of 18 days was followed by a 10 day collection period. Chromium-mordanted hay was given before the first feed at 08.00 h and subsequent meals were at 12.00, 16.00 and 20.00 h. On Days 3 and 10 of the collection, all faeces were sampled over a 24 h period. In addition, throughout the 10 day collection, faecal material was sampled at 10.00 and 16.00 h. The mean (+/- se) chromium recovery was 96.5 per cent +/- 0.76 and the hay/straw mixture contained 7 MJDE/kg dry matter and 15.1 g DCP/kg dry matter. There was no significant difference between the methods used to estimate apparent digestibility although chromium measurements consistently underestimated whilst acid-insoluble ash consistently overestimated digestibility values. There was a large variation in faecal chromium concentration for each horse over a 24 h period compared to acid-insoluble ash concentrations and, consequently, indirect estimates of apparent digestibility of nutrients in the equine are prone to large errors if chromium is used as a marker. If total faecal collection is impractical, acid-insoluble ash is the preferred indirect marker for the estimation of apparent digestibility coefficients for nutrients in horses.
Mutant forms of elongation factor Tu encoded by tufA8 and tufB103 in Salmonella typhimurium cause suppression of some but not all frameshift mutations. All of the suppressed mutations in S. typhimurium have frameshift windows ending in the termination codon UGA. Because both tufA8 and tufB103 are moderately efficient UGA suppressors, we asked whether the efficiency of frameshifting is influenced by the level of misreading at UGA. We introduced plasmids synthesizing either one of the release factors into strains in which the tuf mutations suppress a test frameshift mutation. We found that overproduction of release factor 2 (which catalyzes release at UGA and UAA) reduced frameshifting promoted by the tuf mutations at all sites tested. However, at one of these sites, trpE91, overproduction of release factor 1 also reduced suppression. The spontaneous level of frameshift "leakiness" at three sites in trpE, each terminating in UGA, was reduced in strains carrying the release factor 2 plasmid. We conclude that both spontaneous and suppressor-enhanced reading-frame shifts are influenced by the activity of peptide chain release factors. However, the data suggest that the effect of release factor on frameshifting does not necessarily depend on the presence of the normal triplet termination signal.
The malignant histiocytosis sarcoma virus (MHSV), in contrast to other viruses with the ras oncogene, induces acute histiocytosis in newborn and adult mice. Molecular structure and function studies were initiated to determine the basis of its unique macrophage-transforming potential. Characterization of the genomic structure showed that the virus evolved by recombination of the Harvey murine sarcoma virus (Ha-MuSV) and a virus of the Friend-mink cell focus-forming virus family. Structural analysis of MHSV showed two regions of the genome that are basically different from the Ha-MuSV: (i) the ras gene, which is altered by a point mutation in codon 181 leading to a Cys----Ser substitution of the p21 protein, and (ii) the U3 region of the long terminal repeat, which is largely derived from F-MCFV and contains a deletion of one direct repeat as well as a duplication of an altered enhancer-like region. Biological studies of Ha-MuSV, MHSV, and recombinants between the two viruses show that the U3 region of the MHSV long terminal repeat is essential for the malignancy and specificity of the disease. A contributing role of the ras point mutation in determining macrophage specificity, however, cannot be excluded.
Human osteoblast cultures derived as out-growths from trabecular bone released tumor necrosis factor (TNF alpha) upon stimulation of the cells with human recombinant interleukin 1 (IL1; 10(-13)-10(-11) M), human recombinant granulocyte-macrophage colony-stimulating factor (100-1000 U/ml), and bacterial lipopolysaccharide (5-500 ng/ml). The osteotropic hormones 1,25-dihydroxyvitamin D3, PTH, and calcitonin had no effect on TNF production. The TNF released by the osteoblasts was identified as TNF alpha, using a specific anti-TNF alpha monoclonal antibody to neutralize its activity. Immunohistochemical staining of the cells using the same antibody revealed that all of the cells in the cultures were capable of producing TNF alpha, including those that also expressed alkaline phosphatase activity. Immunoreactive protein could be detected in the perinuclear region when cells were cultured in the presence of monensin, suggesting accumulation of newly synthesised protein in the Golgi apparatus. These results suggest that human osteoblasts, which have been shown previously to respond to TNF alpha, can synthesize and release TNF in response to IL1 and granulocyte-macrophage colony-stimulating factor. TNF may, therefore, not only have a pathological role in conditions of chronic inflammation, but also may act as a local paracrine or autocrine regulator of osteoblast function.
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Buspirone is an anxiolytic drug with an unknown mechanism of action. We have addressed the proposal that its therapeutic effect is due to a metabolite, 1-(2-pyrimidinyl)-piperazine (1-PP), increasing the open probability of gamma-aminobutyric acid (GABA)-activated channels. By making whole-cell recordings from cultured spinal neurones we demonstrated that 1-PP, in contrast to flurazepam, actually antagonizes GABA- and glycine-activated currents. These observations are inconsistent with this proposed mechanism of action for buspirone.