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Biomedical subjects

D Edgar

Publications and source records attributed to D Edgar.

At least 19 recordsLinked to original sources
PubMed2005

Maintaining physical therapy standards in an emergency situation: solutions after the Bali bombing disaster.

In a mass casualty event, treatment is traditionally provided in a 'best for the most' fashion. This paper examines the challenges encountered by physical therapists while providing rehabilitation to 28 survivors who suffered burns after the terrorist bombing in Bali, Indonesia. Individual patient input was achieved with routine outcome measures and workload statistics. Workforce expansion, maintenance of treatment quality, and other practical initiatives used in order to achieve this goal are discussed.

Blast Injuries↗
PubMed2003

Angioedema of the tongue due to acquired C1 esterase inhibitor deficiency.

We describe the management of an 83-year-old woman who presented with upper airway obstruction due to angioedema of the tongue. Following definitive airway management, investigation showed a diagnosis of acquired C1 esterase inhibitor deficiency (acquired angioedema) that was considered to be subsequent to haematological malignancy. Resolution of the macroglossia followed treatment with C1 esterase inhibitor concentrate, but the patient failed to wean from ventilatory support and died in the Intensive Care Unit. This case report highlights the potential for acquired angioedema to cause upper airway obstruction. The various treatment modalities for acquired C1 esterase inhibitor deficiency are summarized.

Aged↗
PubMed2002

Loader Lite: a new software tool for the ABI PRISM 3700 DNA sequencer.

Here we describe the development of a novel software tool entitled Loader Lite that generates plate records or sample sheetsfor the ABI PRISMs 3700 DNA sequencer. The major advantage of this program is that it enables the ongoing operation of sequencing instruments without reference to external network(s). The autonomous operation of sequencing instruments is critical if sample throughput is to be maintained during periods of network outage. Loader Lite employs a deliberate strategy of inputting anonymous tray barcodes at run time. After sequencing, the barcodes are reconciled with relevant project details by reference to a database. This software takes advantage of barcode scanning technology by creating plate records directly on the local computer, serving an individual sequencer, immediately before importing and linking. This real-time synthesis of the plate records at the point of loading all but eliminates loading errors. Loader Lite is user-friendly, fully configurable, and permits the running of partial or full 384-well sample trays, using any standard combinations of run modules, dye sets, mobility files, analysis modules, etc. The 96-well format is not supported; however, this capability will appear in subsequent versions that are currently under development. This application is designed as an added value, adjunct program to the regular ABI PRISM 3700 Data Collection software. We have successfully used Loader Lite over the past six months to load approximately 7 million sequencing reactions and believe its utility and functionality will prove to be attractive to the wider sequencing community.

Sequence Analysis, DNA↗
PubMed2001

Regulation of laminin and COUP-TF expression in extraembryonic endodermal cells.

Laminin expression and the subsequent deposition of a basement membrane by primitive endoderm cells is necessary for early mammalian development. We demonstrate that the transcription factors COUP-TF I and II are up-regulated in primitive endoderm cells faster than LAMB1 and LAMC1, and that either COUP-TF is sufficient to induce expression of these laminin genes.

Animals↗
PubMed2001

The regulation of embryonic stem cell differentiation by leukaemia inhibitory factor (LIF).

LIF (leukaemia inhibitory factor) is commonly used to maintain mouse embryonic stem cells in an undifferentiated state. These cells spontaneously differentiate when allowed to aggregate in the absence of LIF, forming embryoid bodies in which early embryonic cell lineages develop. Using embryoid bodies cultured in the presence and absence of LIF, we show that although LIF inhibited the development of visceral and parietal endodermal cells, it did not affect the differentiation of the primitive endodermal cell precursors of these extraembryonic cell lineages. Furthermore, deposition of the basement membrane produced by the primitive endodermal cells, which separates them from the remaining cells of the embryoid body, still occurred. The differentiation of primitive ectodermal cells and their progeny was inhibited by LIF, as evidenced by the lack of expression of FGF-5, muscle, and neuronal markers. However, cavitation of the embryoid body and maintenance of the cells in contact with the primitive endodermal basement membrane as an epiblast epithelium still occurred normally in the presence of LIF. These results indicate that cavitation and formation of the epiblast epithelium are regulated by mechanisms distinct from those controlling the differentiation of epiblast cell lineages. Furthermore, although epithelium formation and cavitation do not require the differentiation of visceral endodermal cells, the results are consistent with the hypothesis that the primitive endodermal basement membrane is sufficient to induce the epithelialization of undifferentiated embryonic stem cells necessary for cavitation.

Animals↗
PubMed2001

Regulation of the differentiation and behaviour of extra-embryonic endodermal cells by basement membranes.

Both the extracellular matrix and parathyroid hormone-related peptide (PTHrP) have been implicated in the differentiation and migration of extra-embryonic endodermal cells in the pre-implantation mammalian blastocyst. In order to define the individual roles and interactions between these factors in endodermal differentiation, we have used embryoid bodies derived from Lamc1(-/-) embryonic stem cells that lack basement membranes. The results show that in the absence of basement membranes, increased numbers of both visceral and parietal endodermal cells differentiate, but they fail to form organised epithelia. Furthermore, although parietal endodermal cells only migrate away from control embryoid bodies in the presence of PTHrP, they readily migrate from Lamc1(-/-) embryoid bodies in the absence of PTHrP, and this migration is unaffected by PTHrP. Thus, the basement membrane between epiblast and extra-embryonic endoderm is required for the proper organisation of visceral and parietal endodermal cells and also restricts their differentiation to maintain the population of primitive endodermal stem cells. Moreover, this basement membrane inhibits migration of parietal endodermal cells, the role of PTHrP being to stimulate delamination of parietal endodermal cells from the basement membrane rather than promoting migration per se.

Animals↗
PubMed2000

Regulation of programmed cell death by basement membranes in embryonic development.

The formation of the proamniotic cavity in the mammalian embryo is the earliest of many instances throughout development in which programmed cell death and the formation of epithelia play fundamental roles (Coucouvanis, E., and G.R. Martin. 1995. Cell. 83:279-287). To determine the role of the basement membrane (BM) in cavitation, we use embryoid bodies derived from mouse embryonic stem cells in which the LAMC1 genes have been inactivated to prevent BM deposition (Smyth, N., H.S. Vatansever, P. Murray, M. Meyer, C. Frie, M. Paulsson, and D. Edgar. 1999. J. Cell Biol. 144:151-610). We demonstrate here that LAMC1-/- embryoid bodies are unable to cavitate, and do not form an epiblast epithelium in the absence of a BM, although both embryonic ectodermal cells and extraembryonic endodermal cells do differentiate, as evidenced by the expression of cell-specific markers. Acceleration or rescue of BM deposition by exogenous laminin in wild-type or LAMC1-/- embryoid bodies, respectively, results in cavitation that is temporally and spatially associated with restoration of epiblast epithelial development. We conclude that the BM not only directly regulates development of epiblast epithelial cells, but also indirectly regulates the programmed cell death necessary for cavity formation.

Animals↗
PubMed2000

Diagnosis of defects in the type 1 cytokine pathway.

Patients with inherited defects in the interleukin-12 (IL-12)-dependent, 'high-output' interferon-gamma (IFN-gamma) pathway exhibit selective susceptibility to poorly pathogenic mycobacterial and salmonella infections. This review summarises the extended clinical spectrum seen in this group of patients and indicates a strategy for the identification of putative defects in the type 1 cytokine pathway.

Adult↗
PubMed2000

The measurement of impedance to assess myocardial contractility and rhythm stability.

By introducing an alternating current through the ventricular cavity via a multipolar catheter the potential difference measured between adjacent electrodes can be used to assess ventricular volume. This is possible by the measurement of intracardiac impedance. The data obtained can be used to construct pressure-volume loops allowing the continuous real-time assessment of myocardial contractility. Clinical applications of this research tool are now becoming apparent. Further derivations of impedance measurement have been incorporated into commercially available permanent pacing systems, allowing effective heart rate modulation.

Electric Impedance↗
PubMed2000

Polymicrobial tenosynovitis with Pasteurella multocida and other gram negative bacilli after a Siberian tiger bite.

Mammalian bites present a considerable clinical problem because they are often associated with bacterial infections. Pasteurella multocida is a microorganism that commonly infects both canine and small feline bites. Zoonotic infections developing after large feline bites have been recognised, although their reports are limited. We describe a 35 year old man who was bitten by a Siberian tiger and who developed infectious tenosynovitis secondary to P multocida, Bergeyella (Weeksella) zoohelcum, and Gram negative bacteria most like CDC group EF-4b and comamonas species. The latter three bacteria have not been isolated previously from large feline bite wounds.

Adult↗
PubMed1999

Absence of basement membranes after targeting the LAMC1 gene results in embryonic lethality due to failure of endoderm differentiation.

The LAMC1 gene coding for the laminin gamma1 subunit was targeted by homologous recombination in mouse embryonic stem cells. Mice heterozygous for the mutation had a normal phenotype and were fertile, whereas homozygous mutant embryos did not survive beyond day 5.5 post coitum. These embryos lacked basement membranes and although the blastocysts had expanded, primitive endoderm cells remained in the inner cell mass, and the parietal yolk sac did not develop. Cultured embryonic stem cells appeared normal after targeting both LAMC1 genes, but the embryoid bodies derived from them also lacked basement membranes, having disorganized extracellular deposits of the basement membrane proteins collagen IV and perlecan, and the cells failed to differentiate into stable myotubes. Secretion of the linking protein nidogen and a truncated laminin alpha1 subunit did occur, but these were not deposited in the extracellular matrix. These results show that the laminin gamma1 subunit is necessary for laminin assembly and that laminin is in turn essential for the organization of other basement membrane components in vivo and in vitro. Surprisingly, basement membranes are not necessary for the formation of the first epithelium to develop during embryogenesis, but first become required for extra embryonic endoderm differentiation.

Animals↗
PubMed1999

Effects of axotomy on the expression and ultrastructural localization of N-cadherin and neural cell adhesion molecule in the quail ciliary ganglion: an in vivo model of neuroplasticity.

Postganglionic nerve crush of the avian ciliary ganglion induces detachment of preganglionic terminals from the soma of the injured ciliary neurons, followed by reattachment at about the same time that the postganglionic axons regenerate to their targets. In order to determine the role played by cell adhesion molecules in this response, we have studied injury-induced changes in the amount and distribution of N-cadherin and neural cell adhesion molecule, together with modifications in the expression of their messenger RNAs. Both N-cadherin and neural cell adhesion molecule immunoreactivities associated with postsynaptic specializations decreased between one and three days following postganglionic nerve crush, preceding the detachment of the preganglionic boutons. Immunoreactivities subsequently increased between 13 and 20 days, in parallel with restoration of synaptic contacts on the ganglion cells and the progressive reinnervation of the peripheral targets. In contrast to the rapid decrease in immunoreactivity, the messenger RNA levels of N-cadherin and neural cell adhesion molecule both increased after crush, and remained elevated throughout the 20-day period of the experiment. These results are consistent with roles for N-cadherin and neural cell adhesion molecule in the maintenance of synaptic contacts. The rapid regulation of these proteins in injury-induced synaptic plasticity occurs at the post-transcriptional level, whereas longer term regulation associated with the re-establishment of synapses may be promoted by the increased levels of gene expression.

Animals↗
PubMed1999

A human IFNGR1 small deletion hotspot associated with dominant susceptibility to mycobacterial infection.

The immunogenetic basis of severe infections caused by bacille Calmette-Guérin vaccine and environmental mycobacteria in humans remains largely unknown. We describe 18 patients from several generations of 12 unrelated families who were heterozygous for 1 to 5 overlapping IFNGR1 frameshift small deletions and a wild-type IFNGR1 allele. There were 12 independent mutation events at a single mutation site, defining a small deletion hotspot. Neighbouring sequence analysis favours a small deletion model of slipped mispairing events during replication. The mutant alleles encode cell-surface IFNgamma receptors that lack the intra-cytoplasmic domain, which, through a combination of impaired recycling, abrogated signalling and normal binding to IFNgamma exert a dominant-negative effect. We thus report a hotspot for human IFNGR1 small deletions that confer dominant susceptibility to infections caused by poorly virulent mycobacteria.

Adolescent↗
PubMed1999

Calling for the absent male.

BACKGROUND: This is an edited version of a keynote address given by Dr Don Edgar at both the VicHealth Conference on 'Healthy Relationships in the Workplace' held in August 1998 and the Tasmanian Men's Health Conference held in Launceston in November 1998. DISCUSSION: Men's lack of communication skills and emotional intelligence has serious negative consequences for their own physical and mental health, the wellbeing of their families and for the quality of their performance in the workplace.

Adaptation, Psychological↗