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Biomedical subjects

G E Davies

Publications and source records attributed to G E Davies.

At least 19 recordsLinked to original sources

Military perspective on the civilian response to the London bombings July 2005.

With the break up of the Warsaw Pact and changing global relations, current military deployments are becoming smaller and more expeditionary (e.g. Afghanistan, East Timor and Sierra Leone). During the Cold War, the use of weapons of mass effect was highly likely to have been seen on the battlefield. Ironically, the proliferation of CBRN agents and the knowledge of their application, as well as the manufacture of improvised explosive devices, have lead to the targeting of civilian populations by extremist groups. One of the benefits of military clinicians embedded in NHS hospital trusts, as well as a strong reservist cadre, is a greater understanding of the implications and management of asymmetric attacks against the U.K. The experience and skills of military clinicians may be of benefit to NHS trusts while this type of threat exists. Military clinicians are also likely to benefit from the experience that they get in certain NHS posts that provide skills that are readily transferable to military medicine. The events of 7th July highlighted the dynamic use of deployable medical resources and a rapid return to normal service provision. This type of 'Health Resilience' can only be achieved with a combination of effective emergency planning, on scene clinical risk management and clinical leadership.

Communication↗

London bombings July 2005: the immediate pre-hospital medical response.

On July 7th 2005 a series of terrorist bombs exploded in London. The transport system was targeted and at least 54 passengers were killed and around 700 injured. This paper describes the immediate pre-hospital medical response to the four scenes. From the perspective of the London Helicopter Emergency Medical Service the deployment, difficulties on scene and the initial lessons learned are discussed.

Blast Injuries↗

The ovine CCAAT-enhancer binding protein delta gene: cloning, characterization, and species-specific autoregulation.

Transcription factors belonging to the CCAAT-enhancer binding protein (C/EBP) family have been implicated in the regulation of gene expression during growth, differentiation, apoptosis, and inflammation. Autoregulation is relatively common in the modulation of C/EBP gene expression and, for the human and murine C/EBPalpha, it is known that species-specific autoregulatory mechanisms operate. It is therefore essential to investigate the autoregulation of additional C/EBP genes from a wider range of different species to gauge the degree of commonality, or otherwise, which exists. As an important step towards this goal, we report here the cloning and the characterisation of the ovine C/EBPdelta gene (ovC/EBPdelta) and analysis of its promoter region. Transient transfection assays reveal that ovC/EBPdelta acts as a transcriptional activator. Although several motifs that are characteristic of C/EBPdelta genes are conserved in the ovine sequence, including the basic region, leucine zipper, and activation domains, two regions have been identified that are specifically absent in the ovine and bovine homologues. The ovC/EBPdelta promoter is active in both the hepatoma Hep3B and the mammary epithelial HC11 cell lines, induced by the cytokine interleukin-6 and autoregulated by mechanisms that are potentially different from those described for the rat promoter. These results suggest that, in common with C/EBPalpha, the C/EBPdelta genes may also be subject to autoregulation by distinct species-specific mechanisms.

Amino Acid Sequence↗

Variation in alphoid DNA size and trisomy 21: a possible cause of nondisjunction.

The cause of nondisjunction of chromosome 21 remains largely unknown. In the present report, we investigate the hypothesis that variation in alphoid DNA size has a role in trisomy formation. Pulsed-field gel electrophoresis was used to examine the chromosome 21 alphoid DNA array lengths in 23 families (all of Northern European ancestry) with an affected child with trisomy 21 in whom the parental and meiotic origin of nondisjunction had been determined as maternal meiosis I, and in 38 controls. Initially, the combined alphoid size of both chromosome 21 homologues was assessed. This indicated an association between small combined alphoid size and maternal meiosis I nondisjunction. Moreover, in a subset of the families under study (n=12), it was possible to study the alpha21-I size of individual chromosome 21 homologues (simple alphoid size); this provided further evidence that the risk for nondisjunction is related to the size of the alphoid array of one of the two chromosome 21 homologues being small.

Adult↗

Heterotrisomy, a significant contributing factor to ventricular septal defect associated with Down syndrome?

Down syndrome (DS; trisomy 21) is associated with a wide range of variable clinical features, one of the most common being congenital heart defects (CHD). We used molecular genetic techniques to study the inheritance of genes on chromosome 21 in children with DS and CHD. Polymorphic markers on the long arm of chromosome 21 were analysed in 99 families who had a child with DS. Of these, 60 children had a CHD and 39 children had no CHD. Heterotrisomy describes the inheritance of an allele from each of three different grandparents. In some cases heterotrisomy will involve the inheritance of three different alleles. Heterotrisomic regions were defined as those showing retention of non-disjoining parental heterozygosity at polymorphic loci in the non-disjoined chromosomes of children with DS. Using polymorphic non-coding markers, we identified a consistent 9.6-cM minimum region (D21S167-HMG14) of heterotrisomy in children with DS and ventricular septal defect (VSD). Comparing individuals with DS and VSD to all others with DS (those either with no CHD or with any other CHD combined) shows the individuals with DS and VSD to have significantly more non-reduction or heterotrisomy in this region (P=0.006, Fisher's exact test, two-tailed). We postulate that heterotrisomy for a gene or genes in this region is a contributing factor to the pathogenesis of VSD in trisomy 21 either through the presence of three different specific alleles or through the presence of specific combinations of alleles.

Adult↗

Novel methodology for the detection of chromosome 21-specific alpha-satellite DNA sequences.

We present a novel method, based on the hybridization of allele-specific oligonucleotide probes, that allows the specific detection of chromosome 21 alpha-satellite sequences. Absence of informative polymorphic markers from the centromeric region of chromosome 21 has constituted one of the difficulties in studying the centromere of this chromosome. The alpha-satellite subfamilies from chromosomes 21 and 13 are almost identical in sequence and thus cannot be distinguished using conventional hybridization techniques. Analysis using nuclear families showed that the centromeric polymorphism, detected using our specific probe and pulsed-field gel restriction analysis, segregates in a Mendelian fashion and exhibits a high degree of polymorphism among unrelated individuals. The alphoid DNA of chromosome 21 is highly polymorphic, useful not only as a definitive anchor for the genetic map, but also for studies of chromosome 21 nondisjunction, including the unequivocal assignment of meiotic origin.

Base Sequence↗

Expression of the genes encoding CCAAT-enhancer binding protein isoforms in the mouse mammary gland during lactation and involution.

Transcription factors belonging to the CCAAT-enhancer binding protein (C/EBP) family have been implicated in the activation of gene expression in the mammary gland during lactation. We have therefore investigated the detailed expression profile of the C/EBP family during lactation and involution of the mouse mammary gland. The expression of C/EBPbeta and C/EBPdelta mRNA was low during lactation, increased dramatically at the beginning of involution and remained constant thereafter. In contrast, C/EBPalpha mRNA expression was relatively high during the early stages of lactation, declined to low levels during the late stages of lactation and at the start of involution, and increased again during involution. Electrophoretic mobility-shift assays showed a close correlation between the expression of the C/EBP genes and the functional C/EBP DNA-binding activity and, additionally, demonstrated the participation of heterodimers, formed from among the three proteins, in DNA-protein interactions. The DNA-binding activity of the activator protein 1 (AP1) family of transcription factors was also induced during involution. These results therefore point to potentially important regulatory roles for both the C/EBP and the AP1 family during lactation and involution of the mammary gland.

Animals↗

Allelic variability in D21S11, but not in APP or APOE, is associated with cognitive decline in Down syndrome.

Genetic variation in the APOE gene and variation in chromosome 21 genotypes, including the APP locus, may influence age-associated cognitive decline in adults with Down syndrome. Molecular genetic and longitudinal neuropsychological analysis was performed for 41 unrelated Caucasian individuals (mean age 48.1 +/- 1.1 years (s.c.m.)) with free trisomy 21. Allele frequencies and genotype distributions were compared among subgroups with or without evidence of cognitive decline. Genetic variability at APOE and APP was not significantly associated with evidence of cognitive decline. However, aged individuals with Down syndrome, without evidence of cognitive decline, demonstrated unusual allelic variability at D21S11. These findings are discussed in the context of current hypotheses of Alzheimer-type dementia in Down syndrome and in the general population.

Adult↗

Genetic variation in the COL6A1 region is associated with congenital heart defects in trisomy 21 (Down's syndrome).

Genetic variation in the COL6A1-COL6A2 gene cluster on chromosome 21 was studied in 113 controls and 58 European families (including control and family subgroups of British/Irish origin) having a child with trisomy 21. There were statistically significant differences among subgroups of trisomic children with and without congenital heart defects (CHD) in distributions of definitive, 3-RFLP haplotype classes received from their nondisjoining and disjoining parents. Haplotypes received by trisomic children with CHD from their disjoining parents were not a random sample of controls' haplotypes. Analysis of parental single-RFLP genotypes and linkage disequilibrium patterns confirmed this parent subgroup differed from a random sample of controls. There were no significant differences in parent subgroup genotype distribution at any of nine control loci distributed along chromosome 21q. This sample showed an association between genetic variation in the COL6A1 gene region and congenital heart defects in trisomy 21.

Adolescent↗

Unusual genotypes in the COL6A1 gene in parents of children with trisomy 21 and major congenital heart defects.

Collagen type VI is a candidate for a role in the pathogenesis of congenital heart defects (CHD) in Down's syndrome. Three restriction fragment length polymorphisms of the COL6A1 gene were used to determine COL6A1 genotypes in 50 families of affected children with trisomy 21 (29 with congenital heart defects and 21 without) and 37 unrelated volunteers. We found seven unusual genotypes in the parents of affected children with Down's syndrome, five being unique to the parents of children with trisomy 21 and CHD. There were no unusual genotypes associated with other chromosome 21 loci. No single COL6A1 genotype was associated with CHD. Thus, the unusual genotypes unique to parents of affected children suggest that genetic variation in the COL6A1 gene region contributes to the pathogenesis of CHD in Down's syndrome.

Child↗

Giant cell arteritis presenting as oculomotor nerve palsy with pupillary dilatation.

Acute complete oculomotor palsy with headache is a classical presentation of an extrinsic compression most commonly due to a posterior communicating artery aneurysm. We present a patient with such a presentation but with histologically proven giant cell arteritis. This possibility should be considered especially in the elderly to avoid complications and the need for angiography.

Aged↗

Polymorphisms and linkage disequilibrium in the COL6A1 and COL6A2 gene cluster: novel DNA polymorphisms in the region of a candidate gene for congenital heart defects in Down's syndrome.

The COL6A1 and COL6A2 (collagen VI) gene cluster on chromosome 21 is a candidate region for defects leading to congenital heart anomalies in Down's syndrome. We report a variable number of tandem repeats (VNTR) and a restriction fragment length polymorphism (RFLP) in this gene region, detected using a COL6A1 cDNA probe. Linkage disequilibrium relationships were studied among the RFLPs of this gene cluster. The RFLP reported here shows no significant linkage disequilibrium with any others in the region. It has a polymorphism information content value of 0.27, raising the informativity of the locus.

Chi-Square Distribution↗

Meiotic crossing-over in nondisjoined chromosomes of children with trisomy 21 and a congenital heart defect.

We have used DNA polymorphisms to study meiotic crossovers of chromosome 21q in 27 nuclear families. Each family had a child with Down syndrome and a congenital heart defect. Twenty DNA polymorphisms on chromosome 21 were used to determine parental and meiotic origin of nondisjunction and to identify crossovers. Twenty-four cases were of maternal origin, and three were of paternal origin. Twenty-two unequivocal crossover events were identified. Sixteen crossovers were observed in 22 chromosome pairs nondisjoining at the second meiotic division. Fifty percent of crossover events in MI nondisjunction are detectable by molecular genetic means. Thus, the results suggest that, in this sample, each nondisjoined chromosome 21 pair has been involved in at least one crossover event.

Adolescent↗

Iliac aneurysms.

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Aged↗