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Biomedical subjects

K Davies

Publications and source records attributed to K Davies.

At least 73 records · Page 4Linked to original sources
PubMed1995

Dystroglycan mRNA expression during normal and mdx mouse embryogenesis: a comparison with utrophin and the apo-dystrophins.

Alpha dystroglycan (156 kDa DAG) and beta dystroglycan (43 kDa DAG) are encoded by the same gene and are components of the dystrophin-associated membrane glycoprotein complex. The dystroglycans together with dystrophin form a link between the extracellular matrix and the intracellular cytoskeleton of the muscle fibre. Using in situ hybridisation to mRNA in embryo sections we have examined the expression of the mouse dystroglycan gene. Dystroglycan transcripts are ubiquitously expressed throughout development but are most abundant in cardiac, skeletal and smooth muscle and in ependymal cells lining the developing neural tube and brain. The expression patterns of dystroglycan and dystrophin overlap in major muscle systems during development, suggesting that the dystrophin-dystroglycan complex plays an important role during myogenesis. In contrast, the major sites of utrophin expression do not co-localize with those of dystroglycan suggesting that utrophin may interact with a distinct membrane-associated complex in these non-muscle sites. In mdx embryos the pattern of distribution of dystroglycan mRNA remains unchanged, as do those of utrophin and apo-dystrophin mRNAs. This observation implies that the observed changes in the relative abundance of DAGs and utrophin in dystrophin-deficient muscle occur post-transcriptionally.

Animals↗
PubMed1995

The effect of glucocorticoids on the accumulation of utrophin by cultured normal and dystrophic human skeletal muscle satellite cells.

Human muscle cultures undergo a long-term loss of myotubes and a decline in dystrophin content, which can be prevented by glucocorticoid treatment of the cultures. We confirmed these findings and extended them to show that the utrophin content of control and dexamethasone-treated normal myotube cultures is not significantly different. In contrast to normal cultures, the utrophin content of long-term dexamethasone-treated DMD myotube cultures was significantly greater than that of the corresponding untreated cultures. Utrophin mRNA transcript levels normalized to total poly (A) were unaffected by dexamethasone treatment of either normal or DMD myotube cultures, suggesting the effect of dexamethasone on utrophin accumulation by DMD cultures is mediated post-transcriptionally. A combination of an increase in myotube numbers and lack of competition with dystrophin for membrane-binding sites in DMD myotubes may explain the distinct effects of dexamethasone on utrophin levels in normal and DMD cultures.

Cells, Cultured↗
PubMed1995

An autosomal genetic linkage map of the sheep genome.

We report the first extensive ovine genetic linkage map covering 2070 cM of the sheep genome. The map was generated from the linkage analysis of 246 polymorphic markers, in nine three-generation full-sib pedigrees, which make up the AgResearch International Mapping Flock. We have exploited many markers from cattle so that valuable comparisons between these two ruminant linkage maps can be made. The markers, used in the segregation analyses, comprised 86 anonymous microsatellite markers derived from the sheep genome, 126 anonymous microsatellites from cattle, one from deer, and 33 polymorphic markers of various types associated with known genes. The maximum number of informative meioses within the mapping flock was 222. The average number of informative meioses per marker was 140 (range 18-209). Linkage groups have been assigned to all 26 sheep autosomes.

Animals↗
PubMed1995

Identifying nursing research priorities: general and neuroscience specific at an acute care hospital.

As a result of economic and health care changes the role of the nurse continues to expand and research-based practice is changing its focus. Limited resources and staff shortages have revealed new areas for research study. Clinical nurses have valuable questions to share that can form the basis of future nursing research. The purposes of the study were to: (a) Determine the priorities for nursing research within a single acute care teaching hospital; (b) Promote nurses' awareness of the importance of research-based practice; (c) Facilitate the development of future nursing research. It was assumed that nurses who carry out direct and indirect patient care roles are "experts" and therefore, are in a position to identify what they see as important questions and in need of further investigation. Three hundred and sixty-six nurses (24%) responded to round #1 of the open ended survey and submitted a total of 912 clinical practice issues. Initially, issues were broadly categorized into clinical and indirect clinical themes in a series of subcategories. Round #2 was conducted to identify nurses' ratings of the priority of the final 123 research issues for future clinical research and practice improvement efforts. Results of the two rounds will be presented, including issues identified by neuroscience nurses. This information will provide a valuable source for additional neuroscience research at either the local or international level.

Acute Disease↗
PubMed1995

Two new cases of FMR1 deletion associated with mental impairment.

Screening of families clinically ascertained for the fragile X syndrome phenotype revealed two mentally impaired males who were cytogenetically negative for the fragile X chromosome. In both cases, screening for the FMR1 trinucleotide expansion mutation revealed a rearrangement within the FMR1 gene. In the first case, a 660-bp deletion is present in 40% of peripheral lymphocytes. PCR and sequence analysis revealed it to include the CpG island and the CGG trinucleotide repeat, thus removing the FMR1 promoter region and putative mRNA start site. In the second case, PCR analysis demonstrated that a deletion extended from a point proximal to FMR1 to 25 kb into the gene, removing all the region 5' to exon 11. The distal breakpoint was confirmed by Southern blot analysis and localized to a 600-bp region, and FMR1-mRNA analysis in a cell line established from this individual confirmed the lack of a transcript. These deletion patients provide further confirmatory evidence that loss of FMR1 gene expression is indeed responsible for mental retardation. Additionally, these cases highlight the need for the careful examination of the FMR1 gene, even in the absence of cytogenetic expression, particularly when several fragile X-like clinical features are present.

Adult↗
PubMed1995

Health and development in the Hudson Bay/James Bay region.

This paper reviews the literature on the health status of native people in the Hudson Bay/James Bay region of Canada, and explores the role of development in explaining discrepancies between observed and expected demographic and health trends. Relevant scientific literature was identified using computerised searches of bibliographic databases, as well as manual searches of selected journals and contact with experts. Although there was evidence that native people in Hudson Bay/James Bay have experienced significant improvements in health status, overall health status remains much worse than that of other Canadians. In many native communities, the prevalence and incidence of formerly infrequent chronic diseases have now surpassed those observed in non-native populations, and injuries, poisonings and violence are at epidemic levels. While these trends may be attributable to a variety of factors, environmental contamination and accompanying social, economic and cultural changes appear to play an important role.

Canada↗
PubMed1994

Operon of vacuolar-type Na(+)-ATPase of Enterococcus hirae.

The Gram-positive bacteria Enterococcus hirae expel sodium by two systems: a Na+/H(+)-antiporter and a vacuolar-type Na(+)-ATPase. We isolated a mutant, NalkA, defective in the Na(+)-ATPase. NalkA grew normally at neutral pH but was unable to grow in the presence of > 100 mM sodium at pH 9.5. By functional complementation at high pH, we cloned pES1, a plasmid from an E. hirae gene bank containing a 5.2-kilobase pair region of genomic DNA. The genomic DNA in pES1 contains five complete open reading frames, ntpM, -N, -O, -P, and -Q, encoding proteins of 75, 16, 23, 38, and 11 kDa. A sixth incomplete open reading frame, ntp 'L, precedes ntpM. The 3'-end of the cloned DNA overlaps with a previously published sequence encoding the ntpA and ntpB subunits of the E. hirae Na(+)-ATPase (Takase, K., Yamato, I., and Kakinuma, Y. 1993) J. Biol. Chem. 268, 11610-11616). The insert of pES1 therefore represents the upstream region of the ntp operon that encodes the E. hirae Na(+)-ATPase. Complementation analysis with various deletions derived from pES1 suggest that the original mutation is in the ntpM gene. Of the new genes described here, three exhibited significant sequence similarity to known proteins; ntpM shares 24% identical amino acid residues with the "116-kDa" subunits of eukaryotic vacuolar ATPases, ntpN exhibits 28% sequence identity with the 16-kDa proteolipid of human vacuolar ATPase, and ntpO has sequence homology to the 31-kDa subunit of the bovine kidney vacuolar ATPase. No known proteins with sequence similarity to ntp'L, -P, or -Q could be identified. Disruption of either ntpM, -N, or -O in wild-type cells by cassette mutagenesis resulted in mutants unable to effect ATP-driven sodium extrusion. NtpM, -N, and -O therefore represent three new gene products involved in sodium extrusion by the vacuolar-type Na(+)-ATPase of E. hirae, and three more gene products, NtpL, -P, and -Q, may also be constituents of this enzyme. The ntp operon thus contains at least eight genes.

Adenosine Triphosphatases↗
PubMed1994

Body image and dieting in pregnancy.

The present study evaluated body image, body satisfaction and dieting practices in pregnancy: a stage of life when social pressures for slimness might be expected to be relaxed. Pregnant women had lower scores on the Drive for Thinness subscale of the Eating Disorder Inventory, and when Body Mass Index was controlled for, had significantly lower Body Dissatisfaction Scale scores than non-pregnant women. They also rated themselves as less overweight in terms of body size. Dietary restraint was lower and current attempts to lose weight were less frequent in the pregnant group. However, there was no evidence that pregnancy was associated with any relaxation of body image ideals: pregnant women chose a similar size of figure to non-pregnant women as their ideal. These results suggest that the state of pregnancy can be associated with reduced weight concern despite an increased body size, but the effect appears to be state-dependent and is not mediated by shifts in body size ideals.

Adult↗
PubMed1994

Cloning the shared components of complex DNA resources.

The complex and repetitive nature of mammalian genomes limits the ability of conventional molecular techniques to recover sequences of interest. Here we describe a rapid and simple procedure for the direct cloning of sequences which are coincident between DNA mixtures of whole genome complexity. The system, called end ligation coincident sequence cloning (EL-CSC), can enrich coincident DNA by greater than 10(6)-fold and overcomes problems associated with repetitive elements. Applying EL-CSC to various paired DNA resources enables the facile cloning of both genomic markers and novel genes. To demonstrate the power of the method we have i) selectively purified single copy sequences from a complete genome, and ii) isolated gene fragments from 260 kb of cloned genomic DNA.

Base Sequence↗
PubMed1993

Gene therapy begins.

Explore the source record for details and available documents.

Clinical Trials as Topic↗
PubMed1993

Interleukin-3 expression by activated T cells involves an inducible, T-cell-specific factor and an octamer binding protein.

Interleukin-3 (IL-3) is exclusively expressed by activated T and natural killer cells, a function that is tightly controlled both in a lineage-specific and in a stimulation-dependent manner. We have investigated the protein binding characteristics and functional importance of the ACT-1-activating region of the IL-3 promoter. This region binds an inducible, T-cell-specific factor over its 5' end, a site that is necessary for the expression of IL-3 in the absence of other upstream elements. Over its 3' end, it binds a factor that is ubiquitously and constitutively expressed. This factor is Oct-1 or an immunologically related octamer-binding protein, and it plays a role in coordinating the activity of several regulatory elements. These characteristics make the ACT-1 site analogous to the activating ARRE-1 site in the IL-2 promoter. Furthermore, and despite a lack of sequence homology, the promoters of IL-3 and IL-2 share an organizational pattern of regulatory elements that is likely to be important for the T-cell-specific expression of these genes.

Animals↗
PubMed1993

Cloning the Menkes disease gene.

Three groups have successfully isolated the gene responsible for the X-linked Menkes disease, heralding great promise for our understanding of copper metabolism and for diagnosis of the disorder.

Cloning, Molecular↗
PubMed1993

Expression of the dystrophin-related protein (utrophin) gene during mouse embryogenesis.

The utrophin (UTRN) locus is the autosomal homologue of the DMD (Duchenne muscular dystrophy) gene and encodes a protein, utrophin which is thought to be upregulated in the absence of dystrophin. In this study the spatial and temporal expression of the UTRN gene has been examined during mouse embryogenesis and compared with that of the DMD gene. The patterns of expression of these two genes are very different. Whilst DMD is expressed largely in mesodermal derivatives such as cardiac and striated muscle, UTRN shows a more widespread distribution and is expressed in neural tube, tissues which originate from neural crest and a variety of other sites of non-neural origin. In early embryos UTRN transcripts initially accumulate in the mid-neural plate and thereafter in the caudal neural tube. UTRN mRNA then becomes abundant in a subset of neural crest cell derived tissues, in particular the spinal and facial ganglia and ossifying facial cartilages. UTRN is also expressed in a variety of other sites and organs such as the tendon primordia in the digits, the pituitary, thyroid and adrenal glands, cardiac muscle, kidney and lung, follicles of the vibrissae and the outflow tract of the heart. Several patterns of UTRN expression are apparent and we discuss the possibility that these can be ascribed to a family of mRNAs transcribed from the UTRN gene using alternative promoters.

Animals↗
PubMed1993

Outcome of resective surgery for intractable partial epilepsy guided by subdural electrode arrays.

The aim of this paper was to evaluate the outcome and the factors predictive for a good prognosis of resective surgery for intractable partial epilepsy guided by subdural electrode arrays (SEA's) and operative electrocorticography. Sixty-four patients, aged 8-52 years, were evaluated with chronic SEAs in order to record interictal and ictal activity and delineate speech and motor areas by functionally mapping. Resection were individualized to each patient's SEA recorded electrocorticogram and operative electrocorticogram and functional mapping results (tailored resection). The follow-up time was a minimum of one year. Good seizure outcome was defined as seizure free from complex partial and secondary generalized seizures. After one year 70% of the patients with a temporal ictal focus was seizure free compared to 55% of the patients with an extra-temporal focus. Complete resection of interictal or ictal fields as mapped with SEAs, gave better prognosis than partial resection. Patients with no postresection spikes had a better prognosis than patients with residual postresection spikes evaluated with operative electrocorticography. Sex, age, duration of epilepsy prior to surgery, extent of temporal lobe resection and structural abnormalities determined by MRI were not associated with a favorable seizure outcome after surgery. We conclude that complete resection of the interictal and ictal field mapped with SEA's and absence of postresection spikes on operative electrocorticography are associated with an excellent seizure outcome.

Adolescent↗