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Biomedical subjects

A Davies

Publications and source records attributed to A Davies.

At least 109 records · Page 6Linked to original sources
PubMed1997

Protection of sensitive patient-connected medical devices from the subversive use of mobile telecommunication equipment.

The UK Department of Health has recently advised caution with respect to the uncontrolled use of private mobile telecommunication equipment in designated sensitive hospital areas. This advice, which has clear implications for patient safety and well being, was issued following reports of the interference of automatic drug delivery devices, infusion pumps and other sensitive systems. The difficulty of monitoring relatives, visitors and, occasionally, staff who use such mobile telephones in the sensitive areas has led to an initiative by The Princess Margaret Hospital to automatically and continuously monitor the frequencies used by the mobile telephones and to initiate an alarm should such phones be used within a designated area. This paper describes a protocol for the use of these monitors developed in the Princess Margaret Hospital which is designed to minimize the number of monitoring units while providing optimum departmental cover.

Artifacts↗
PubMed1997

Cloning of a human nucleoside transporter implicated in the cellular uptake of adenosine and chemotherapeutic drugs.

In most mammalian cells nucleoside uptake occurs primarily via broad-specificity, es (e, equilibrative; 5, sensitive to NBMPR inhibition) transporters that are potently inhibited by nitrobenzylthioinosine (NBMPR). These transporters are essential for nucleotide synthesis by salvage pathways in hemopoietic and other cells that lack de novo pathways and are the route of cellular uptake for many cytotoxic nucleosides used in cancer and viral chemotherapy. They play an important role in adenosine-mediated regulation of many physiological processes, including neurotransmission and platelet aggregation, and are a target for coronary vasodilator drugs. We have previously reported the purification of the prototypic es transporter from human erythrocytes and have shown that this glycoprotein of apparent M, 55,000 is immunologically related to nucleoside transporters from several other species and tissues, including human placenta. Here we report the isolation of a human placental cDNA encoding a 456-residue glycoprotein with functional characteristics typical of an es-type transporter. It is predicted to possess 11 membrane-spanning regions and is homologous to several proteins of unknown function in yeast, nematodes, plants and mammals. Because of its central role in the uptake both of adenosine and of chemotherapeutic nucleosides, study of this protein should not only provide insights into the physiological roles of nucleoside transport but also open the way to improved therapies.

Adenosine↗
PubMed1997

Clastogenic and aneugenic effects of tamoxifen and some of its analogues in hepatocytes from dosed rats and in human lymphoblastoid cells transfected with human P450 cDNAs (MCL-5 cells).

Tamoxifen and its analogues 4-hydroxytamoxifen, toremifene, 4-hydroxytoremifene, clomifene and droloxifene were tested for clastogenic effects in a human lymphoblastoid cell line (MCL-5) expressing elevated native CYP1A1 and containing transfected CYP1A2, CYP2A6, CYP2E1 and CYP3A4 and epoxide hydrolase and in a cell line containing only the viral vector (Ho1). MCL-5 or Ho1 cells were incubated with 4-hydroxytamoxifen, 4-hydroxytoremifene, clomifene or droloxifene and the incidence of micronuclei estimated. With MCL-5 cells there was an increase in micronuclei with 4-hydroxytamoxifen, 4-hydroxytoremifene and clomifene but not with droloxifene. With Ho1 cells only 4-hydroxytamoxifen and 4-hydroxytoremifene caused an increase in micronuclei. MCL-5 cells were incubated with tamoxifen, 4-hydroxytamoxifen, toremifene, droloxifene, clomifene or diethylstilbestrol (0.25-10 microg/ml) for 48 h and subjected to 3 h treatment with vinblastine (0.25 microg/ml) to arrest cells in metaphase. The incidence of cells with chromosomal numerical aberrations (aneuploidy) was increased in cells treated with tamoxifen, 4-hydroxytamoxifen, toremifene, clomifene and diethylstilbestrol but not droloxifene. The frequency of cells with structural abnormalities (excluding gaps) was increased in cells treated with tamoxifen and toremifene but not 4-hydroxytamoxifen, clomifene, droloxifene or diethylstilbestrol. The clastogenic activities of tamoxifen (35 mg/kg), toremifene (36.3 mg/kg), droloxifene (35.2 mg/kg) and diethylstilbestrol (25 mg/kg) were compared in groups of four female Wistar rats. Each chemical was dissolved in glycerol formal, administered as a single dose by gavage and hepatocytes isolated by collagenase perfusion 24 h later. The cells were cultured in the presence of epidermal growth factor (40 ng/ml) for 48 h, colchicine (10 microg/ml) being added for the final 3 h of incubation. At least 100 chromosomal spreads were examined from each animal for the presence of numerical and structural abnormalities. The incidences of aneuploidy following treatment were: tamoxifen 81%, toremifene 46%, droloxifene 9.6%, diethylstilbestrol 45.7%, vehicle control 5.3%. The incidences of chromosomal structural abnormalities excluding gaps were: tamoxifen 4.3%, toremifene 0.8%, droloxifene 0.5%, diethylstilbestrol 0.8%, control 0.5%. The incidence of chromosomal structural aberrations excluding gaps in the treated animals was not statistically significantly different from controls except in the tamoxifen-treated group. Tamoxifen (35 mg/kg per os) and toremifene (36.3 mg/kg per os) were dosed to rats for 4 weeks and chromosomal spreads made from hepatocytes. The incidences of aneuploidy were: tamoxifen 94%, toremifene 57%, control 6.5%. The incidences of chromosomal aberrations excluding gaps were: tamoxifen 12%, toremifene 1%, control 0.5%. The incidence of tamoxifen-induced chromosomal structural abnormalities was significantly elevated compared with control levels. The results demonstrate that tamoxifen and toremifene are the only two drugs tested in the study that cause chromosomal structural and numerical aberrations in vitro and tamoxifen is the only drug that induces both these effects in rat liver cells stimulated to divide in culture following oral dosing. Since chromosomal mutations require cell division for their manifestation and tamoxifen is the only compound of those tested that causes hyperplasia in the rat liver, chromosomal aberrations and aneuploidy in the rat liver would only be expected to occur following treatment with tamoxifen alone, although aneuploidy could be induced by toremifene in conjunction with a promoter such as phenobarbitone.

Aneuploidy↗
PubMed1997

Complement and immunity to viruses.

Complement is one of the first lines of host defence to be faced and countered by viruses as they struggle to establish an infection. As an important arm of the humoral immune response, the complement system is immediately ready to target and eliminate virus particles and to interact with the surface of virus-infected cells to mark them for destruction by other branches of the immune response. Nevertheless, some viruses are still very successful human pathogens. This article will discuss the role of complement in antiviral immunity, the mechanisms by which complement may be activated by viruses or virus-infected cells, and explore some of the strategies which viruses have evolved to subvert the immune response, including mechanisms by which complement activation may be prevented or aborted.

Animals↗
PubMed1997

Permanent cardiac pacing in elderly patients with recurrent falls, dizziness and syncope, and a hypersensitive cardioinhibitory reflex.

The study was designed to assess the outcome of treatment with permanent dual-chamber pacing of elderly patients with falls, dizziness and syncope associated with the demonstration of a hypersensitive cardioinhibitory reflex. Questionnaires were sent to patients (and their general practitioners) who had been referred to a regional pacing centre with recurrent falls, dizziness or syncope diagnosed as likely to be secondary to cardioinhibitory carotid sinus syndrome or predominantly cardioinhibitory vasovagal syndrome. After pacemaker insertion, 84% of patients had no further syncope over a mean follow-up period of 10 (range 1.5 to 30) months. Minor symptoms persisted in only 40% of all patients. Symptoms were unchanged in 22%. It was concluded that permanent dual-chamber pacing is an effective treatment for elderly patients with recurrent falls, dizziness and syncope in whom a hypersensitive cardioinhibitory reflex is found. Good results were obtained in this group with a simple diagnostic work-up.

Aged↗
PubMed1997

Dissection of the 5.5 Mbp region directly telomeric of HLA-B including a long range restriction map, YAC and PAC contigs.

A large number of diseases are associated with the human major histocompatibility (HLA) complex located in 6p21.3. The underlying defect of most of these has not yet been determined even after detailed analysis of the HLA region. Due to the extended haplotypes found in this area, several of the HLA-linked disease genes may be located also telomeric of the class I region. In order to analyse the area covering the 4 megabases directly telomeric of HLA-F in close detail, we have generated 50 new markers. These and other markers have been used to establish a SalI restriction map from 46 YACs. A subset of 42 markers was applied to construct a genomic long range restriction map from an HLA-A2/B13 haplotype. Both maps have been compared revealing the presence of additional 150 kb in the HLA-A2 haplotype close to the RFP locus. Additionally, 47 PACs have been selected mapping to this region and grouped into 7 contigs. Sequencing of these PAC contigs has already been initiated.

Chromosomes, Artificial, Yeast↗
PubMed1997

Feline fits.

Explore the source record for details and available documents.

Animals↗
PubMed1996

Genetic analysis of the epidermal differentiation complex (EDC) on human chromosome 1q21: chromosomal orientation, new markers, and a 6-Mb YAC contig.

The epidermal differentiation complex (EDC) unites a remarkable number of structurally, functionally, and evolutionarily related genes that play an important role in terminal differentiation of the human epidermis. It is localized within 2.05 Mb of region q21 on human chromosome 1. We have identified and characterized 24 yeast artificial chromosome (YAC) clones by mapping individual EDC genes, sequence-tagged site (STS) markers (D1S305, D1S442, D1S498, D1S1664), and 10 new region-specific probes (D1S3619-D1S3628). Here we present a contig that covers about 6 Mb of 1q21 including the entire EDC. Fluorescence in situ hybridization on metaphase chromosomes with two YACs flanking the EDC determined its chromosomal orientation and established, in conjunction with physical mapping results, the following order of genes and STSs: 1cen-D1S442-D1S498-S100A10-THH-FLG- D1S1664-IVL-SPRR3-SPRR1-SPRR2-LOR- S100A9-S100A8-S100A7-S100A6-S100A5-S100 A4- S100A3-S100A2-S100A1-D1S305-1qtel. These integrated physical, cytogenetic, and genetic mapping data will be useful for linkage analyses of diseases associated with region 1q21 and for the identification of novel genes and regulatory elements in the EDC.

Cell Differentiation↗
PubMed1996

Near-infrared spectroscopy and spectral mapping of Jupiter and the Galilean satellites: results from Galileo's initial orbit.

The Near Infrared Mapping Spectrometer performed spectral studies of Jupiter and the Galilean satellites during the June 1996 perijove pass of the Galileo spacecraft. Spectra for a 5-micrometer hot spot on Jupiter are consistent with the absence of a significant water cloud above 8 bars and with a depletion of water compared to that predicted for solar composition, corroborating results from the Galileo probe. Great Red Spot (GRS) spectral images show that parts of this feature extend upward to 240 millibars, although considerable altitude-dependent structure is found within it. A ring of dense clouds surrounds the GRS and is lower than it by 3 to 7 kilometers. Spectra of Callisto and Ganymede reveal a feature at 4. 25 micrometers, attributed to the presence of hydrated minerals or possibly carbon dioxide on their surfaces. Spectra of Europa's high latitudes imply that fine-grained water frost overlies larger grains. Several active volcanic regions were found on Io, with temperatures of 420 to 620 kelvin and projected areas of 5 to 70 square kilometers.

Ammonia↗
PubMed1996

An outbreak of Salmonella typhimurium DT104 food poisoning associated with eating beef.

An outbreak of Salmonella typhimurium DT104 infection in Shropshire in May 1995 was identified when four isolates were noted to be from members or supporters of a local football team that had held several social functions in the same week. The subsequent investigation identified 16 people with gastrointestinal symptoms and 12 with microbiologically confirmed infection. The outbreak was complex, associated with several social functions on different days, but infection was associated with eating beef at a public house. A number of errors were detected in the cooking, storage, and handling of the implicated food. The investigation identified beef as the vehicle of infection in this outbreak but was unable to show whether it was the original source of infection or whether cross or manual contamination occurred in the kitchen.

Animals↗
PubMed1996

Effect of lactic acid isomers on keratinocyte ceramide synthesis, stratum corneum lipid levels and stratum corneum barrier function.

Alpha-hydroxy acids are effective agents for the treatment of skin xerosis and it is known that, following treatment with lotions containing D,L-lactic acid, the stratum corneum prevents xerosis more effectively. To date, the relative efficacy of the different isomers of lactic acid has not been evaluated and the mode of action of lactic acid in improving stratum corneum resilience is not known. The objective of the present studies was to determine the effects of lactic acid isomers on keratinocyte ceramide biosynthesis, stratum corneum barrier function and the resistance of the stratum corneum to the appearance of skin xerosis. In vitro, lactic acid enhanced the production of ceramides by keratinocytes. L-Lactic acid was more effective than the D isomer (300% increase vs 100% increase). Carbon label from lactic acid was incorporated into all keratinocyte lipid species and a greater incorporation of label into ceramides was achieved with L-lactate than with D-lactate. In vivo, lactic acid increased the levels of stratum corneum ceramides. Whereas, lotions containing L-lactic acid resulted in the greatest increase (48% increase) followed by D,L-lactic acid (25% increase), D-lactic acid had no effect on stratum corneum ceramide levels. The increases in stratum corneum ceramide levels following lactic acid treatment also led to improvements in stratum corneum barrier function, measured by transepidermal water loss following a challenge to the skin with SLS and in the regression phase of a moisturization efficacy study. Significant improvements in barrier function and resistance to the appearance of skin xerosis were observed following L-lactic acid and D,L-lactic acid, but not following D-lactic acid treatment. From these results we believe that lactic acid, particularly the L isomer, stimulates ceramide biosynthesis leading to increased stratum corneum ceramide levels which results in superior lipid barrier and a more effective resistance against xerosis.

Adult↗
PubMed1996

A pericentric inversion of chromosome six in a patient with Peutz-Jeghers' syndrome and the use of FISH to localise the breakpoints on a genetic map.

Karyotypic analysis in a patient with Peutz-Jeghers' syndrome demonstrated a pericentric inversion on chromosome 6. Further investigation was undertaken using fluorescence in situ hybridisation (FISH) with yeast artificial chromosome clones selected to contain genetic markers from chromosome 6, and a probe for the centromeric alphoid repeat array. This analysis located one inversion breakpoint within the alphoid array, in a 1-cM interval between D6S257 and D6S402, and the other in a 4-cM interval between D6S403 and D6S311. The oestrogen receptor gene locus (ESR) is excluded from the latter interval.

Adult↗