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Biomedical subjects

C McConville

Publications and source records attributed to C McConville.

17 recordsLinked to original sources

Positive and negative mood in the elderly: the ZENITH study.

OBJECTIVE: To assess the quality of positive and negative affect (mood) in an ageing European sample. BACKGROUND: Mood quality has important implications for both physical and mental wellbeing. Poor quality moods are associated with deficits in the diverse areas of cognitive function, health, and social relationships. The ageing process presents a number of potential challenges to successful mood regulation that could have wider implications. DESIGN AND PARTICIPANTS: The current study examines the quality of positive and negative affect in 387 healthy participants from three European countries. Moods were measured four times a day for 4-7 d with the Positive and Negative Affect Schedule (PANAS) mood scales. Measures of zinc (Zn) status were taken also. SETTING: Two centres concentrated on 55-70 yr olds (Coleraine, N.Ireland, n = 93 and Clermont-Ferrand, France, n = 95), and two centres concentrated on 70-87 yr olds (Rome, Italy, n = 108, and Grenoble, France, n = 91). RESULTS: Positive affect scores for the centre in Rome were significantly (P < 0.01) lower than for the other three centres, and the Grenoble centre had significantly (P < 0.05) higher scores on negative affect than the other three centres. Mood was not related to measures of zinc status (all Ps > 0.05). CONCLUSIONS: The two centres with the oldest participants showed deficits in mood quality that may have implications for broader well-being.

Affect↗

Cognitive function in healthy older European adults: the ZENITH study.

OBJECTIVE: Baseline data are reported from a study of the effects of zinc supplementation on cognitive function in older adults as assessed by the CANTAB computerised test battery. DESIGN: This is a multicentre prospective intervention study employing a randomised double-blind design. SETTING: European community-based study. PARTICIPANTS: There are 387 healthy adults aged 55-87 y from centres in France, Italy and Northern Ireland. INTERVENTIONS: Measures of visual memory, working memory and attention were obtained at baseline (prior to supplementation). RESULTS: Younger adults (<70 y) performed significantly better than older adults (>70 y) on all tests, with minimal differences between centres. In addition, men outperformed women on tests of spatial span, pattern recognition memory and reaction times, although these gender differences varied somewhat between centres. CONCLUSIONS: The results are generally consistent with previous age- and gender-related effects on cognitive functioning.

Age Factors↗

Exclusion of candidate genes and chromosomal regions in familial neuroblastoma.

Two families with recurrence of neuroblastoma one Italian and one British with three and two affected children respectively were genotyped using polymorphic markers on chromosome 1 spanning the p32-p36 region frequently deleted in neuroblastoma tumor cells. Linkage to this region was excluded by haplotype inspection and negative lod scores. Furthermore, the exclusion of genes involved in neurocristopathies sometimes associated with neuroblastoma was carried out by typing the Italian family with polymorphic markers located in or near the corresponding genes. Finally, linkage analysis in the two families showed negative lod scores for markers spanning the 16p12-13 chromosomal region where a locus for familial neuroblastoma has been recently mapped. Our findings indicate that different genes are involved in the pathogenesis of familial neuroblastoma.

Chromosome Mapping↗

Direct equilibration of soil water for delta(18)O analysis and its application to tracer studies.

Current methods for stable oxygen isotopic (delta (18)O) analysis of soil water rely on separation of water from the soil matrix before analysis. These separation procedures are not only time consuming and require relatively large samples of soil, but also have been shown to introduce a large potential source of error. Current research at Queen's University Belfast is focused on using direct equilibration of CO(2) with the pore water to eliminate this extraction step using the automated Multiprep system and a Micromass Prism III isotope ratio mass spectrometer (IRMS). The findings of this research indicate the method is less time consuming, more reliable, and reproducible to within accepted limits (+/-0.1% per thousand delta (18)O). In this study the direct equilibration method is used to analyse delta (18)O tracer profiles in the unsaturated zone of field soils, concurrently with chloride tracer profiles, which can be used to assess infiltration rates and mechanisms through the unsaturated zone. Copyright 1999 John Wiley & Sons, Ltd.

Journal Article↗

Physical mapping of 38 highly informative genetic markers to 10 intervals of chromosome 11q: integration of the physical and genetic maps.

A large number of highly polymorphic microsatellite markers particularly suitable for genetic linkage analysis have recently been developed. In order to facilitate integration of the genetic maps of chromosome 11q generated using these types of markers with the physical maps of 11q currently being assembled, we have regionally assigned the Genethon markers and the 11q designated index plus other commonly used polymorphic markers to ten physical intervals of 11q. These intervals are defined by translocation breakpoints immortalized in somatic cell hybrid lines and can therefore serve as readily accessible and stable landmarks for detailed map integration and facilitate the derivation and placement of new markers and cloned contigs.

Chromosome Mapping↗

Genetic haplotyping of ataxia-telangiectasia families localizes the major gene to an approximately 850 kb region on chromosome 11q23.1.

The genotyping data given localize the major A-T gene to an approximately 850 kb region. They also localize the group A A-T gene (ATA) to a region that contains the approximately 850 kb region. They are compatible with linking A-TFresno to 11q22-23. NBS-V2 does not link to this region. Four non-linking families contain only single affecteds, suggesting that these may be spontaneous mutations rather than evidence for an A-T gene outside the 11q22-23 region. Finally, two other non-linking families contain recombinant haplotypes that are compatible with a second A-T gene at 11q22-23, slightly distal to the approximately 850 kb region. However, convincing evidence for a second gene is still lacking.

Adult↗

Solution conformation of endothelin, a potent vaso-constricting bicyclic peptide. A combined use of 1H NMR spectroscopy and distance geometry calculations.

The solution structure of endothelin-1, a newly discovered potent bicyclic peptide vaso-constrictor agent, has been investigated using 1H NMR conformational constraints and distance geometry calculations. The conformation is constrained by two disulphide bridges between Cys1-Cys15 and Cys3-Cys11 but the NMR data and computed conformers show additional helical structure between residues Leu6 and Cys11. Our results are compared with previous conflicting reports on the solution conformation of this peptide.

Amino Acid Sequence↗

Localization of an ataxia-telangiectasia locus to a 3-cM interval on chromosome 11q23: linkage analysis of 111 families by an international consortium.

Linkage of at least two complementation groups of ataxia-telangiectasia (AT) to the chromosomal region 11q23 is now well established. We provide here an 18-point map of the surrounding genomic region, derived from linkage analysis of 40 CEPH families. On the basis of this map, 111 AT families from Turkey, Israel, England, Italy, and the United States were analyzed, localizing the AT gene(s) to an 8-cM sex-averaged interval between the markers STMY and D11S132/NCAM. A new Monte Carlo method for computing approximate location scores estimates this location as being at least 10(8) times more likely than the next most likely interval, with a support interval midway between STMY and D11S132 that is either 5.2 cM (sex-averaged and conservatively based on 3 lod scores from the maximum-location score) or 2.8 cM (male specific, based on a 2.72:1 interval-specific female-to-male distance ratio.

Ataxia Telangiectasia↗

Interpreting mood scores: clinical implications of individual differences in mood variability.

Mood variability is shown to be a stable characteristic of individuals, such individual differences accounting for some 25 per cent of the total variability of mood scores over time. This large effect is shown to have three major consequences: it is impossible to use tables of norms to assess the severity of a given mood for an individual; the whole logic of using norms for the interpretation of moods is flawed; and correlations between moods and traits have been underestimated in the literature. Various techniques are discussed for minimizing the effects of bias caused by individual differences in mood variability.

Affect↗

Rearrangement of the same chromosome regions in different SV40 transformed human skin keratinocyte lines is associated with tumourigenicity.

Twelve different human keratinocyte strains were transformed with recombinant plasmid pSV6-1 which contained an origin defective SV40 genome. When injected into athymic nude mice lines produced either squamous cell carcinomas (SCC) in all animals, SCC in some animals and epidermal cysts in others, or epidermal cysts only in all the animals. The tumourigenic capacity of the lines could be correlated with the chromosomal changes present initially in the transformed cells. Lines which produced SCC in all the animals within a short period of time all showed simultaneous loss of part of chromosomes 3p, 8p and 11p in one homologue. Lines which were not tumourigenic did not show these simultaneously appearing rearrangements. These specific rearrangements are acquired in vitro and the time taken for a recognisable tumour to appear is related to the proportion of such cells in the line. The rearrangement of the same chromosome regions in different tumourigenic cell lines suggests that genes in these regions are important in the development of squamous cell carcinoma, possibly by loss of heterozygosity, at particular loci.

Animals↗

Increased radiosensitivity and the basic defect in ataxia telangiectasia.

Various cellular defects have been found in ataxia telangiectasia (A-T) cells including increased radiosensitivity, increased sensitivity to various chemical agents, a probable DNA repair defect and a defect in DNA synthesis. How these different features are related to each other is at present unknown. It has been suggested that there is a defect in A-T that acts in tissue differentiation as well as during growth and in the mature adult. This hypothesis is supported by the observations, for example, of an immature thymus present in patients, the production of alpha-fetoprotein, which results in a high serum level, and ovarian dysgenesis. A gene for A-T has recently been localized to chromosome region 11q22-23, a site involved in chromosomes translocations in some non-lymphoid leukaemias. At the chromosomal level the spontaneous abnormalities in A-T include, first, an increased frequency of cells showing chromosome translocations involving immune system genes that normally undergo rearrangement to form a functional product; secondly, the formation of telometric dicentrics in both lymphocytes and fibroblasts; and thirdly formation of long-lived chromosome damage following exposure to ionizing radiation and radiomimetic drugs. The gene defect underlying this disorder is unknown and distinguishing between primary and secondary effects of the mutant gene is difficult. We consider alternative models for retention of translocation T cells. First, it is possible that there is a defect in recognition of site-specific damage leading to retention of translocation cells that might otherwise be removed. Secondly, a feature common to the production of illegitimate T-cell receptor gene rearrangements and to formation of telomeric dicentric chromosomes in A-T cells is an increased period of time available for chromosome interchange, possibly due to a site-specific defect in strand break repair. It is possible that this defect may also prevent chromosome restitution following exposure of cells to ionizing radiation.

Ataxia Telangiectasia↗

Uncontrolled nuclear division in normal x transformed somatic cell hybrids.

Uncontrolled nuclear division (UND), as indicated by progressive multinucleation when cell division is inhibited by cytochalasin B, is a very characteristic property of transformed cells growing in vitro. In an attempt to determine the genetic basis for this transformation phenotype we have produced a series of somatic cell hybrids between different transformed and normal cells. In all hybrids there was suppression of UND but in some this was only transient. In hybrids between transformed human cells and mouse 3T3 cells, UND was only re-expressed when the human parental cell line had been transformed by SV40 virus. The results lend tentative support to the suggestion that cellular mechanisms involved in the induction and suppression of UND may not be the same in all cell lines.

Animals↗

Effect of cytochalasin B on somatic cell hybrids between normal and transformed cells.

Cytochalasin B (CB) prevents cytokinesis in animal cells. In normal cells nuclear division and DNA synthesis are also blocked and the cells, held in the G1 phase of the cell cycle, remain either mononucleate or binucleate. In transformed cell lines DNA synthesis and nuclear division continue and the cells become multinucleate. We have examined the response to CB in two sets of somatic cell hybrids made between cells that display multinucleation after CB treatment and cells that do not. In a cross between transformed mouse LMTK cells and normal rat embryo lung cells, very little multinucleation was observed after treatment with CB for 7 days. The ability of the LMTK cells to form clones in soft agar was also significantly reduced in these hybrids. Segregant sub-clones that re-expressed both of these transformation phenotypes were isolated. These had reduced chromosome numbers. A second cross was made between two variants of the BHK cell line, one of which displayed a high level of multinucleation in CB while the other did not. Again the hybrids showed a response similar to that of the non-multinucleating parent. From the results obtained with these two hybrids we conclude that the multinucleation induced in transformed cells by CB behaves as a recessive character in crosses with normal cells.

Animals↗

Pediatric oncology and hematology in Birmingham, England.

The hematology and oncology service at Birmingham Children's Hospital was established in the late 1960s and now is one of the largest in the United Kingdom. It provides comprehensive care for the entire range of childhood malignancies, coagulation disorders, and hemoglobinopathies and other hematological disorders, and undertakes bone marrow transplant and megatherapy/peripheral blood stem cell procedures. Research includes clinical trials of treatments of childhood cancers; molecular biology studies on leukemia, Hodgkin's disease, neuroblastoma, and sarconas; childhood cancer epidemiology, and geographical and racial incidence; and treatment of hemophilia and molecular investigation of coagulation disorders. These activities involve collaboration with local, national, and international research groups.

Child↗

Evaluation of recharge in a small temperate catchment using natural and applied delta 18O profiles in the unsaturated zone.

A water balance study was used for determining recharge rate and mechanisms in the Enler Catchment, Northern Ireland. Here spatially limited data for the water balance resulted in varied calculation of the annual and monthly net infiltration rate. This paper outlines a method whereby high-resolution soil profiles (1 to 2 cm) were obtained from field cores in the upper 2 m of the unsaturated zone using delta 18O of water. These profiles show changes in isotopic composition that range from individual rainfall events to annually integrated cycles of rainfall. Recharge rates were calculated from stable isotope profiles for each of the four main soil types in the study catchment and summed over each area resulting in an average recharge in the range 55 to 70 mm/a, which is comparable with previous findings. Applied isotopic tracer tests were also conducted to evaluate the extent of preferential flow through the two main soil types in the catchment. Rates of water movement found from these experiments show good agreement with natural isotopic profiles; however, evidence suggests that preferential flow is not the dominant process controlling water movement in this catchment. This type of data provides valuable information about recharge rates and mechanisms and may facilitate better prediction of contaminant transport pathways in the vadose zone.

Environmental Monitoring↗