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Biomedical subjects

D Heffernan

Publications and source records attributed to D Heffernan.

5 recordsLinked to original sources
PubMed1998

The age-associated decrease in the amount of amplifiable full-length mitochondrial DNA in human skeletal muscle.

There has been a continuous evolution in our concept [1] that mtDNA undergoes a range of mutations with age and that such alterations lead to a decline in mitochondrial bioenergy capacity. Here we report that a wide range of deletion mutations accumulate with age and the amount of full-length mtDNA (FLmtDNA) amplifiable by extra-long PCR (XL-PCR) markedly decreases with age. An analysis of single human quadriceps muscle fibres reveals a close correlation between the decrease in FLmtDNA and the decline in cytochrome c oxidase activity, an exemplifier of mitochondrial bioenergy. However, Southern blotting analysis of unamplified genomic DNA shows that there is little decrease in FLmtDNA in aged quadriceps. The results are interpreted to indicate that while there is little change in the total mtDNA with age, nonetheless a significant proportion of this mtDNA is extensively damaged such that it cannot be amplified by XL-PCR. The amplifiable FLmtDNA, which putatively represents the functional component of the mtDNA, decreases markedly with age.

Adolescent↗
PubMed1997

Expression and analysis of heparin-binding regions of the amyloid precursor protein of Alzheimer's disease.

Deletion mutagenesis studies have suggested that there are two domains within APP which bind heparan sulphate. These domains have been cloned and expressed in the yeast Pichia pastoris. Both recombinant proteins bound to heparin. One domain (APP316-447) was further characterised by binding studies with peptides encompassing this region. Peptides homologous to APP316-346 and APP416-447 were found to bind heparin. Circular dichroism studies show that APP416-447 shifted towards an alpha-helical conformation in the presence of heparin. This study suggests that heparin-binding domains may lie within regions high in alpha-helical structure.

Alzheimer Disease↗
PubMed1997

Identification of heparin-binding domains in the amyloid precursor protein of Alzheimer's disease by deletion mutagenesis and peptide mapping.

Recent studies have shown that the binding of the amyloid protein precursor (APP) of Alzheimer's disease to heparan sulfate proteoglycans (HSPGs) can modulate a neurite outgrowth-promoting function associated with APP. We used three different approaches to identify heparin-binding domains in APP. First, as heparin-binding domains are likely to be within highly folded regions of proteins, we analyzed the secondary structure of APP using several predictive algorithms. This analysis showed that two regions of APP695 contain a high degree of secondary structure, and clusters of basic residues, considered mandatory for heparin binding, were found, principally within these regions. To determine which domains of APP bind heparin, deletion mutants of APP695 were prepared and analyzed for binding to a heparin affinity column. The results suggested that there must be at least two distinct heparin-binding regions in APP. To identify novel heparin-binding regions, peptides homologous to candidate heparin-binding domains were analyzed for their ability to bind heparin. These experiments suggested that APP contains at least four heparin-binding domains. The presence of more than one heparin-binding domain on APP suggests the possibility that APP may interact with more than one type of glycosaminoglycan.

Alzheimer Disease↗
PubMedDate not supplied

ResusSim 98--a PC advanced life support trainer.

Advanced life support (ALS) requires several different skills and the recall of complex information. The personal computer is an ideal tool for the teaching of factual information. We have developed a computer programme that simulates a variety of cardiac arrest scenarios. Its aim is to communicate specialist knowledge to junior staff in a challenging and entertaining way. Each scenario has a real time ECG, clinical signs of the simulated patient, blood pressure, oxygen saturation and temperature. Arterial blood samples can be analysed and the medical record can be reviewed. Interventions available include defibrillation, intubation, fluid and drug therapy. Built-in variation means that repeating a scenario may lead to different patient behaviour. An important part of the programme is the intelligent debriefing of the user after each patient. Each action elicits a comment that is based upon the current European Resuscitation Council guidelines. This is then hyperlinked to an extensive help file that includes the text of the guidelines, diagrams, pictures and algorithms that aid the user in the learning of ALS skills in association with existing teaching programmes. ResusSim 98 runs under Windows 3.1, Windows 95/98 and Windows NT 4.0.

Computer Simulation↗