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Biomedical subjects

D Hughes

Publications and source records attributed to D Hughes.

At least 217 records · Page 12Linked to original sources
PubMed1992

Primary choroid plexus papilloma of the cerebellopontine angle: magnetic resonance imaging, computed tomographic and angiographic appearances.

The computed tomographic, angiographic and magnetic resonance imaging (MRI) appearances of a benign primary choroid plexus papilloma of the cerebellopontine angle are reported. Although benign, this tumour showed local invasion of the petrous temporal bone and mastoid air cells. The differential diagnosis of cerebellopontine angle lesions is discussed. Papilloma is suggested by the presence of a vascular, calcified, enhancing extra-axial mass in or around the cerebellopontine angle. MRI may show evidence of high vascularity and internal haemorrhage. Differentiation from other cerebellopontine tumours, most particularly meningioma, may not be possible on radiological features.

Adult↗
PubMed1992

Alternative treatments for asthma: assessing the need.

Alternative treatments such as troleandomycin methotrexate, gold, and intravenous gamma globulin are sometimes considered for severe asthmatics to minimize the need for systemic corticosteroids and reduce adverse effects. These alternative therapies may also be associated with significant toxicity and expense. The ability to reduce corticosteroid use and the need for alternative treatment interventions in 125 pediatric patients at our institution were reviewed. Because corticosteroid requirements were reduced significantly, only 23 of 125 children evaluated were considered for treatment alternatives with only 10 receiving such therapy. This study emphasizes the importance of a thorough and comprehensive review of corticosteroid requirements and usage prior to initiating alternative approaches to treatment in moderate to severe asthmatics as well as in patients thought to be "steroid-dependent."

Administration, Inhalation↗
PubMed1991

Sequencing of exons 16 and 17 of the beta-amyloid precursor protein gene in 14 families with early onset Alzheimer's disease fails to reveal mutations in the beta-amyloid sequence.

A mutation within exon 17 at codon 717 of the beta-amyloid protein precursor (APP) gene is one cause of early onset familial Alzheimer's disease. Direct sequencing of exons 16 and 17 of the beta-amyloid precursor protein gene in 14 families with familial early onset Alzheimer's disease without the known pathogenic mutation (APP717) failed to reveal other mutations within the beta-amyloid sequence in this form of the disorder.

Adult↗
PubMed1991

Early-onset Alzheimer's disease caused by mutations at codon 717 of the beta-amyloid precursor protein gene.

A mutation at codon 717 of the beta-amyloid precursor protein gene has been found to cosegregate with familial Alzheimer's disease in a single family. This mutation has been reported in a further five out of approximately 100 families multiply affected by Alzheimer's disease. We have identified another family, F19, in which we have detected linkage between the beta-amyloid precursor protein gene and Alzheimer's disease. Direct sequencing of exon 17 in affected individuals from this family has revealed a base change producing a Val----Gly substitution, also at codon 717. The occurrence of a second allelic variant at codon 717 linked to the Alzheimer's phenotype supports the hypothesis that they are pathogenic mutations.

Alzheimer Disease↗
PubMed1991

The nucleotide sequence of rpsL and its flanking regions in Salmonella typhimurium.

The ribosomal protein (r-protein)-encoding gene, rpsL, and regions flanking it, from Salmonella typhimurium, have been sequenced directly from polymerase chain reaction-amplified chromosomal DNA. The deduced amino acid sequence is identical to that of the Escherichia coli rpsL encoded r-protein. At the nucleotide level, the similarity is 98%, suggesting a strong pressure for the conservation of this important protein. More surprisingly, the noncoding sequences surrounding the gene are also conserved at the 98% level, suggesting that they too are functionally important.

Amino Acid Sequence↗
PubMed1991

A question of judgement.

Ministerial accountability was one of the founding principles of the NHS, but the shift to the internal market raises legal questions. David Hughes asks whether the duty to provide comprehensive healthcare can now be enforced in the courts.

Comprehensive Health Care↗
PubMed1991

Crystal parameters and molecular replacement of an anticholera toxin peptide complex.

TE33 is an Fab fragment of a monoclonal antibody raised against a 15-residue long peptide (CTP3), corresponding in sequence to residues 50-64 of the cholera toxin B subunit. Crystals of the complex between TE33 and CTP3 have been grown from 20% (w/v) polyethylene glycol-8000 at pH 4.0. The crystals are orthorhombic, space group P2(1)2(1)2, with unit cell dimensions a = 104.15, b = 110.61, and c = 40.68 A. X-Ray data have been collected to a resolution of 2.3 A. The asymmetric unit contains one molecule of Fab and one molecule of CTP3. The presence of CTP3 has been demonstrated by fluorescence quenching of the dissolved crystal after X-ray data collection. A molecular replacement solution was found based on the coordinates of DB3, an antiprogesterone Fab fragment.

Antibodies, Monoclonal↗
PubMed1991

Missense substitutions lethal to essential functions of EF-Tu.

We have used a simple selection and screening method to isolate function defective mutants of EF-Tu. From 28 mutants tested, 12 different missense substitutions, individually lethal to some essential function of EF-Tu, were identified by sequencing. In addition we found a new non-lethal missense mutation. The frequency of isolation of unique mutations suggests that this method can be used to easily isolate many more. The lethal mutations occur in all three structural domains of EF-Tu, but most are in domain II. We aim to use these mutants to define functional domains on EF-Tu.

Base Sequence↗
PubMed1991

Post-traumatic stress disorder in the community: an epidemiological study.

Post-traumatic stress disorder (PTSD) was studied in the Piedmont region of North Carolina. Among 2985 subjects, the lifetime and six month prevalence figures for PTSD were 1.30 and 0.44% respectively. In comparison to non-PTSD subjects, those with PTSD had significantly greater job instability, family history of psychiatric illness, parental poverty, child abuse, and separation or divorce of parents prior to age 10. PTSD was associated with greater psychiatric comorbidity and attempted suicide, increased frequency of bronchial asthma, hypertension, peptic ulcer and with impaired social support. Differences were noted between chronic and acute PTSD on a number of measures, with chronic PTSD being accompanied by more frequent social phobia, reduced social support and greater avoidance symptoms.

Adolescent↗
PubMed1991

Investigation of children with suspected spinal dysraphism by magnetic resonance imaging.

Findings on Magnetic Resonance Imaging (MRI) of 52 children with suspected spinal dysraphism have been reviewed. In 24, no significant spinal abnormality was demonstrated. Seven patients had scoliosis or vertebral segmentation anomalies without demonstrable abnormality of the underlying soft tissues and one had an isolated subcutaneous haemangioma. In 20 children with spinal dysraphism, a low tethered cord was the most frequent finding, occurring in 80%. Other manifestations included myelo- or meningocoele (60%), syringomyelia (30%), lipoma (25%), congenital tumour (20%), diastematomyelia (15%) and thickened filum terminale (5%). The relationship between the clinical reason for requesting MRI and the scan results are discussed.

Adolescent↗
PubMed1991

Costing consultations in general practice: towards a standardized method.

The cost of a consultation with a general practitioner forms an integral part of many economic evaluations. If resources are to be allocated efficiently it is necessary to provide accurate costings. Despite this, the research literature lacks any established method for costing consultations. This paper reviews some of the approaches used in previous studies, considers some of the issues involved in costing consultations, and provides some guidelines to follow when costing general practitioner consultations.

Costs and Cost Analysis↗
PubMed1991

Error-prone EF-Tu reduces in vivo enzyme activity and cellular growth rate.

Mutations in Salmonella typhimurium encoding error-prone EF-Tu (tufA8, tufB103) enhance translational error levels and also cause a reduced growth rate. The relative changes in error level and growth rate are inversely related and dependent on the status of the two tuf genes. Possible causes of the reduced growth rate were investigated. Several important parameters with the potential to alter growth rate (the EF-Tu-ribosome interaction, the in vivo elongation rate and the processivity of translation), are all relatively unaffected by the tuf mutations. The small reduction in processivity observed in some strains is not quantitatively related to the growth rate reduction. Instead, the error-enhancing mutations are associated with a large reduction in the specific activity of a test protein, beta-galactosidase, suggesting by inference that the reduced growth rate is a consequence of the synthesis of error-containing proteins.

Cell Division↗
PubMed1991

Mutant ribosomes can generate dominant kirromycin resistance.

Mutations in the two genes for EF-Tu in Salmonella typhimurium and Escherichia coli, tufA and tufB, can confer resistance to the antibiotic kirromycin. Kirromycin resistance is a recessive phenotype expressed when both tuf genes are mutant. We describe a new kirromycin-resistant phenotype dominant to the effect of wild-type EF-Tu. Strains carrying a single kirromycin-resistant tuf mutation and an error-restrictive, streptomycin-resistant rpsL mutation are resistant to high levels of kirromycin, even when the other tuf gene is wild type. This phenotype is dependent on error-restrictive mutations and is not expressed with nonrestrictive streptomycin-resistant mutations. Kirromycin resistance is also expressed at a low level in the absence of any mutant EF-Tu. These novel phenotypes exist as a result of differences in the interactions of mutant and wild-type EF-Tu with the mutant ribosomes. The restrictive ribosomes have a relatively poor interaction with wild-type EF-Tu and are thus more easily saturated with mutant kirromycin-resistant EF-Tu. In addition, the mutant ribosomes are inherently kirromycin resistant and support a significantly faster EF-Tu cycle time in the presence of the antibiotic than do wild-type ribosomes. A second phenotype associated with combinations of rpsL and error-prone tuf mutations is a reduction in the level of resistance to streptomycin.

Base Sequence↗
PubMed1991

Combined morphine-bupivacaine caudals for reconstructive penile surgery in children: systemic absorption of morphine and postoperative analgesia.

We wished to determine if the addition of a small dose of morphine (0.05 mg.kg-1) to a caudal solution of 0.25% bupivacaine could extend the duration of analgesia after major reconstructive penile surgery and also to measure the systemic absorption of morphine after caudal injection. Thirty children undergoing reconstructive penile surgery received a caudal injection of 0.25% bupivacaine 0.75 ml.kg-1 with or without morphine 0.05 mg.kg-1. All patients awoke pain-free, but eight of the fifteen patients receiving bupivacaine alone required supplementary injections of opioid postoperatively, whereas none of the patients receiving the bupivacaine-morphine mixture required additional opioids. The incidence of side-effects was similar for the two groups. Morphine was absorbed rapidly after caudal injection to reach a peak plasma level of 21.2 (+/- 4.8) ng.ml-1 at ten minutes and then fell to 10.1 (+/- 3.8) ng.ml-1 at one hour and 4.1 (+/- 2.6) ng.ml-1 at three hours. These levels are low compared with plasma levels associated with systemic analgesia. We conclude that the extended duration of analgesia from morphine 0.05 mg/kg given caudally is due at least in part to specific spinal analgesia.

Analgesia, Epidural↗
PubMed1991

The MEL gene: a new member of the RAB/YPT class of RAS-related genes.

The MEL gene was identified following transfection of NIH3T3 mouse fibroblasts with DNA from a human melanoma cell line. The human MEL gene has been localized to 19cen-p13.2, a region in which translocation breakpoints occur in a number of malignancies. We have identified and sequenced human and mouse MEL cDNA clones which show homology of 92% and 96% at the nucleotide and amino acid levels respectively. The predicted human MEL protein shows only six amino acid differences between it and the recently described dog RAB8 protein. All of these changes occur in the 30 amino acids at the C-terminal of these proteins. MEL is similar to the RAB/YPT proteins in the region corresponding to the putative effector domain, suggesting that they may interact with the same cellular substrates. However, MEL contains a C-terminal CAAX motif in common with the majority of the RAS superfamily, unlike YPT1 and the majority of the RAB proteins.

Amino Acid Sequence↗