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Biomedical subjects

D A Simpson

Publications and source records attributed to D A Simpson.

17 recordsLinked to original sources
PubMed1992

Genetic analysis of Pseudomonas aeruginosa adherence: distinct genetic loci control attachment to epithelial cells and mucins.

Infection of mucosal tissues by the opportunistic pathogen Pseudomonas aeruginosa is initiated by attachment of the bacterium to host tissues. To gain a better understanding of this interaction, we used two methods to isolate mutants of P. aeruginosa with altered adherence to cultured A549 cells and to mucins. First, from a population of nonpiliated mutants of P. aeruginosa mutagenized with transposon Tn5G, we have isolated variants that are defective in binding to both A549 cells and respiratory mucins. Using a cloned transposon plus flanking DNA from one such mutant as a DNA probe, we have isolated plasmids from a cosmid bank, which, upon reintroduction to the original mutants, restored adhesion to both A549 cells and mucin. The second strategy to identify genes involved in adhesion used mutagenesis of P. aeruginosa N1G, an rpoN mutant which is unable to bind to either A549 cells or mucin, with transposon Tn5 containing an outward-directed promoter. From this bank of mutagenized P. aeruginosa N1G, two classes of adhesion variants were isolated; one class attached to A549 cells and to mucin, and the other class restored binding of the rpoN mutant to mucin but not to A549 cells. These findings suggest that P. aeruginosa can express at least two adhesins distinct from pili, one recognizing receptors shared by epithelial cells and mucins and the other recognizing mucins alone.

Bacterial Adhesion↗
PubMed1992

Alterations to influenza virus hemagglutinin cytoplasmic tail modulate virus infectivity.

The influenza virus hemagglutinin (HA) contains a cytoplasmic domain that consists of 10 to 11 amino acids, of which five residues have sequence identity for 10 of 13 HA subtypes. To investigate properties of these conserved residues, oligonucleotide-directed mutagenesis was performed, using an HA cDNA of influenza virus A/Udorn/72 (H3N2) to substitute the conserved cysteine residues with other residues, to delete the three C-terminal conserved residues, or to remove the entire cytoplasmic domain. The altered HAs were expressed in eukaryotic cells, and the rates of intracellular transport were examined. It was found that substitution of either conserved cysteine residue within the cytoplasmic domain did not affect the rate of intracellular transport, whereas deletion of residues within the C-terminal domain resulted in delayed cell surface expression. All the altered HAs were biologically active in hemadsorption and fusion assays. To investigate whether the wild-type HA and HAs with altered cytoplasmic tails could complement the influenza virus temperature-sensitive transport-defective HA mutant A/WSN/33 ts61S, the HA cDNAs were expressed by using a transient expression system and released virus was assayed by plaque analysis. The wild-type HA expression resulted in a release of approximately 10(3) PFU of virus per ml. Antibody neutralization of complemented virus indicated that the infectivity was due to incorporation of wild-type H3 HA into ts61S virions. Sucrose density gradient analysis of released virions showed that each of the HA cytoplasmic domain mutants was incorporated into virus particles. Virions containing HAs with substitution of the cysteine residues in the cytoplasmic domain were found to be infectious. However, no infectivity could be detected from virions containing HAs that had deletions in their cytoplasmic domains. Possible roles of the HA cytoplasmic domain in forming protein-protein interactions in virions and their involvement in the initiation of the infection process in cells are discussed.

Amino Acid Sequence↗
PubMed1992

Usefulness of beta 2-transferrin assay in the detection of cerebrospinal fluid leaks following head injury.

The clinical value of analyzing various fluids and exudates for beta 2-transferrin (beta 2-Tfn) to detect cerebrospinal fluid (CSF) leakage following head trauma was reviewed in a series of 11 cases. Qualitative detection of beta 2-Tfn was performed by agarose gel electrophoresis of tears, ear and nose exudates, cerebral cyst fluid, and wound discharge fluid in different cases. In each instance the presence of beta 2-Tfn in the analyzed fluid supported the diagnosis of a CSF leak. Equally, the demonstration of the absence of beta 2-Tfn in the fluid excluded the diagnosis of such a leak. Neither false-positive nor false-negative results were found, as indicated by separate radiological investigations and/or subsequent clinical assessment of patients. The detection of beta 2-Tfn in suspect fluids thus provides a highly sensitive and selective, rapid, and noninvasive test for the detection of CSF leakage in cases of head trauma.

Adolescent↗
PubMed1991

Pseudomonas aeruginosa exoenzyme S is an adhesion.

Exoenzyme S from Pseudomonas aeruginosa has been studied as an adhesion for glycosphingolipids and buccal cells. Binding of exoenzyme S to gangliotriosylceramide (GalNAc beta 1-4Gal beta 1-4Glc beta 1-1Cer), gangliotetraosylceramide (Gal beta 1-3 GalNAcT beta 1-4 Gal beta 1-4Glc beta 1-1Cer), and lactosylceramide (Gal beta 1-4Glc beta 1-1Cer) separated on thin-layer chromatograms was observed. Binding curves for exoenzyme S with dilutions of gangliotetraosylceramide immobilized on plastic plates were similar to previously reported results for the intact bacteria. Binding of exoenzyme S to sialylated counterparts of these glycosphingolipids was not seen, indicating that the addition of a sialic acid residue interferes with binding. Exoenzyme S and monoclonal antibody to exoenzyme S inhibit the binding of P. aeruginosa to buccal cells. The presence of exoenzyme S on the surface of P. aeruginosa was detected by immunogold labeling of bacteria with antibodies to exoenzyme S. Results of these studies led us to conclude that exoenzyme S is an important adhesion of P. aeruginosa.

ADP Ribose Transferases↗
PubMed1990

Extradural haemorrhage in infancy and childhood. A review of 35 years' experience in South Australia.

One hundred and two paediatric cases of extradural haemorrhage (EDH) were treated in Adelaide, South Australia, during the period 1954-1988; 10 were infants (0-2 years) and 92 were children (2-14 years). There were 9 deaths (mortality 8.8%). Long-term disabilities severe enough to interfere with school and/or employment were seen in 8 (7.8%) survivors. This relatively low number of adverse outcomes is partly an expression of a low incidence (5.9%) of associated intradural haematomas and few high-velocity impacts due to vehicular accidents. There is reason to believe that the results of treatment have improved in the decade 1977-1988. We attribute this in part to early diagnosis by computed tomography (CT), but a contributory factor may be earlier referrals from country centres to a paediatric trauma centre and rapid transfer, by air or road, by medical retrieval teams.

Adolescent↗
PubMed1979

Functional consequences of the transcallosal removal of intraventricular tumours.

Colloid cysts and other benign tumours of the third and lateral ventricles may be exposed through a small incision in the body of the corpus callosum. This approach is practicable even when ventricular dilatation is slight, and is theoretically less likely to cause epilepsy than the more usual transcortical approach. Disturbances of memory have been noted soon after such operations, but do not cause serious long-term disability. Three patients who underwent transcallosal removal of cysts or tumours some years earlier have been tested by procedures designed to demonstrate interhemispheric transfer of information: they were all found to have defects in transfer of tactile data, but not of information obtained visually. They were not aware of this inability, and do not appear to be inconvenienced by it. The transcallosal route is convenient. The operation sacrifices a functionally significant part of the corpus callosum, but the neurological sequelae have seemed acceptable. However, especially in the elderly, stereoventriculoscopic aspiration may be considered as the initial method of treatment.

Adolescent↗
PubMed1978

Planning for better standards in the care of the neurological sequelae of trauma.

Injuries of the nervous system are common, and cause many deaths and much permanent disability. They inflict an enormous financial burden on the national economy; in Australia, adequate data are at present lacking, but a simple extrapolation from Canadian statistic suggests an estimate of more than $500,000,000 annually for the injuries resulting from road traffic accidents alone; if other causes of injury are included, the figure may reach one billion dollars. The neurosurgeon is specifically trained to undertake the management of all forms of neurological trauma; however, in Australia, and in many other countries, only a small minority of such injuries receive neurosurgical care. This is chiefly because the number of neurosurgeons at present available is small in relation to the tasks. Many cases must therefore be in the care of general or orthopaedic surgeons, especially in country centres, and it is important that these surgeons should have some basic neurosurgical training. The Neurosurgical Society of Australasia wishes to formulate a programme to ensure that opportunities for such training are available throughout Australia. This programme should also embody a national plan for research into the treatment and prevention of neurological trauma.

Accidents, Traffic↗
PubMed1977

Orthopaedic aspects of spinal tumors in children.

A retrospective survey has been made of forty children with spinal tumours. Difficulties in establishing the correct diagnosis are mentioned and the value of radiological and cerebrospinal fluid investigations discussed. The major orthopaedic disabilities are spinal deformity or instability, and paraplegia. The main factor in the development of the former is the site of laminectomy: the higher the level the greater is the likelihood of deformity or instability developing. Measures to prevent this distressing complication are discussed. The role of the orthopaedic surgeon in the management of these children is emphasised.

Adolescent↗
PubMed1975

Premature craniosynostosis-a complication of thyroid replacement therapy.

Three hypothyroid children with premature craniosynostosis are presented, who have been treated intensively with 1-thyroxine from early infancy. It is postulated that the craniosynostosis is the result of iatrogenic hyperthyroidism during a critical period of skull growth. Various regimens of treatment for hypothyroidism are discussed with recommendations for avoiding this potentially hazardous complication of therapy.

Child↗
PubMed1975

Dandy-Walker syndrome associated with congenital heart defects: report of three cases.

Three cases of Dandy-Walker syndrome associated with congenital heart defects are reported, and their management is described. The various theories concerning the aetiology of the Dandy-Walker syndrome are discussed and it is suggested that the theory of primary developmental atresia of the foramina of Magendie and Luschka is still acceptable. If the child with Dandy-Walker syndrome requires treatment by extracranial CSF drainage it is proposed that a ventriculo-peritoneal shunt is preferable when there is any suspicion of cardiac anomaly. The proximal catheter should be placed in the posterior fossa cyst (dilated fourth ventricle) rather than in the lateral ventricle.

Brain↗
PubMedDate not supplied

Head injuries in infants and children: measures to reduce mortality and morbidity in road accidents.

In the 6-year period from 1983 to 1988, 12 infants (less than 24 months of age) and 103 children (2 to 14 years of age) were killed in road crashes in South Australia. This represents an annual incidence of 6.4 deaths per 100,000 children at risk. At least 4 other children were killed in off-road vehicle-related accidents. Of these deaths, approximately half were car passengers, one third pedestrians, and one sixth pedal cyclists. Most of these infants and children died at the accident site or soon after, but 26 of them survived long enough to be admitted to hospitals with neurosurgical units and an audit of these patients suggests that there were at least 3 preventable deaths. However, autopsies of 78 patients show that the great majority of these deaths resulted from devastating brain and/or trunk visceral injuries. Better emergency care and the use of neurosurgical retrieval teams may save some lives. But more lives might be saved by the use of appropriate restraints for infants and children in cars, by reducing the exposure of child pedestrians and cyclists to road traffic, and by mandatory use of helmets by child cyclists. Off-road vehicular accidents are not as a rule included in road crash statistics; the practice of giving small motorcycles to young children has created a new category of vehicular accidents sometimes causing severe head injury.

Accidents, Traffic↗