Biomedical subjects

A Collins

Publications and source records attributed to A Collins.

At least 19 recordsLinked to original sources

PubMed2006

Refined association mapping for a quantitative trait: weight in the H19-IGF2-INS-TH region.

Previous analyses have provided evidence for one or more loci affecting body weight in the H19-IGF2-INS-TH region on chromosome 11p15. To identify the location of a possible causal locus or loci we applied association analysis by composite likelihood to a large cohort under the Malecot model for body weight. A random sample of 2731 men in the UK were typed for eleven single nucleotide polymorphisms (SNPs) in IGF2, two SNPs in H19, one SNP in INS and one microsatellite marker in the TH genes. Using F tests appropriate to small marker sets, the superiority of regression over correlation was confirmed. All the evidence for association came from IGF2, with P= 0.007 for height-adjusted weight and P= 0.019 for weight additionally adjusted for smoking and alcohol drinking. Although the estimated point location for the suspected causal variant was close to IGF2 ApaI, the 95% confidence and support intervals covered most of IGF2 but none of the other loci. Identification of the causal SNP or SNPs within IGF2 will require typing of more variants in this region.

Body Mass Index↗

PubMed2006

Prevalence and transmission of honeybee viruses.

Transmission mechanisms of six honeybee viruses, including acute bee paralysis virus (ABPV), black queen cell virus (BQCV), chronic bee paralysis virus (CBPV), deformed wing virus (DWV), Kashmir bee virus (KBV), and sacbrood bee virus (SBV), in honey bee colonies were investigated by reverse transcription-PCR (RT-PCR) methods. The virus status of individual queens was evaluated by examining the presence of viruses in the queens' feces and tissues, including hemolymph, gut, ovaries, spermatheca, head, and eviscerated body. Except for head tissue, all five tissues as well as queen feces were found to be positive for virus infections. When queens in bee colonies were identified as positive for BQCV, DWV, CBPV, KBV, and SBV, the same viruses were detected in their offspring, including eggs, larvae, and adult workers. On the other hand, when queens were found positive for only two viruses, BQCV and DWV, only these two viruses were detected in their offspring. The presence of viruses in the tissue of ovaries and the detection of the same viruses in queens' eggs and young larvae suggest vertical transmission of viruses from queens to offspring. To our knowledge, this is the first evidence of vertical transmission of viruses in honeybee colonies.

Animals↗

PubMed2005

Regression of NMU-induced mammary tumors with the combination of melatonin and 9-cis-retinoic acid.

A significant increase in tumor regression was induced in N-nitroso-N-methylurea-induced mammary tumors in rats treated with the combination of melatonin and 9-cis-retinoic acid (9cRA). Treatment groups included: control (ethanolic saline), 9cRA (30 mg/kg chow/day), melatonin 500 microg/day, melatonin 1000 microg/day, melatonin 500 microg/day+9cRA and melatonin 1000 microg/day+9cRA. Rats treated with the lower dose of melatonin 500 microg+9cRA show the greatest degree of tumor regression (78%), with 54% undergoing complete regression and a significant increase in apoptotic cells observed by TUNEL Assay. Furthermore, tumor multiplicity and burden were significantly decreased by the combination of melatonin and 9cRA.

Alitretinoin↗

PubMed2005

A map of the human genome in linkage disequilibrium units.

Two genetic maps with additive distances contribute information about recombination patterns, recombinogenic sequences, and discovery of genes affecting a particular phenotype. Recombination is measured in morgans (w) over a single generation in a linkage map but may cover thousands of generations in a linkage disequilibrium (LD) map measured in LD units (LDU). We used a subset of single nucleotide polymorphisms from the HapMap Project to create a genome-wide map in LDU. Recombination accounts for 96.8% of the LDU variance in chromosome arms and 92.4% in their deciles. However, deeper analysis shows that LDU/w, an estimate of the effective bottleneck time (t), is significantly variable among chromosome arms because (i) the linkage map is approximated from the Haldane function, then adjusted toward the Kosambi function that is more accurate but still exaggerates w for all chromosomes, especially shorter ones; (ii) the non-pseudoautosomal region of the X chromosome is subject to hemizygous selection; and (iii) at resolution less than approximately 40,000 markers per w, there are indeterminacies (holes) in the LD map reflecting intervals of very high recombination. Selection and stochastic variation in small regions must have effects, which remain to be investigated by comparisons among populations. These considerations suggest an optimal strategy to eliminate holes quickly, greatly enhance the resolution of sex-specific linkage maps, and maximize the gain in association mapping by using LD maps.

Chromosome Mapping↗

PubMed2005

Assessment of feto-placental well-being in the mare from mid-gestation to term: transrectal and transabdominal ultrasonographic features.

Ultrasound assessment of feto-placental well-being has found its application in the equine field, as a valid diagnostic tool. Most reports on equine fetal parameters focus on advanced to late gestation. The aim of the present study was to further validate the technique of ultrasound evaluation of the equine fetal environment, by extending its application to earlier stages of pregnancy. Fetal parameters were collected (on 150 pregnancies) over a 3-year period. Data included in the study were selected according to the clinical behaviour of the mare, the neonate/fetus and fetal membranes at the termination of gestation. Validation of the ultrasound technique was also undertaken on a number of specimens collected at an abbatoir. At the completion of the study, a substantial number of measurements and observations were collected. No fetal parameters associated in previous reports with a negative outcome were observed at any of the examinations during this study. Therefore, data collected during the present study should be of value in feto-placental assessment of well-being, in mid- to late-gestation.

Animals↗

PubMed2005

Vitamin D intake and status in Irish postmenopausal women.

OBJECTIVE: The objective of this study was to assess vitamin D status during late-summer and late-winter/early-spring in postmenopausal Irish women, and whether it was influenced by vitamin D-containing supplement use. DESIGN: A longitudinal observational study. SETTING: Cork City, Ireland (51 degrees north). SUBJECTS: A total of 59 apparently healthy, free-living, postmenopausal women aged between 51 and 69 y were sampled during February/March 2002. Of these, 48 and 47 returned during August/September 2002 and February/March 2003, respectively. None of the women were suffering from any medical condition likely to affect vitamin D status. Fasting serums were collected and analysed for 25-hydroxyvitamin D (25 (OH) D) and parathyroid hormone (PTH) by enzyme immunoassays. RESULTS: Mean daily intake of vitamin D was 3.2 microg from food sources alone and 5.8 microg when vitamin D-containing supplements were included (P<0.01). Serum 25 (OH) D was significantly lower (P<0.001) during February/March 2002 than both August/September 2002 and February/March 2003. Serum 25 (OH) D was also significantly higher (P < or = 0.05) in women who were vitamin D-containing supplement users than nonusers during all three sampling points. Between 17 and 36% of women had inadequate vitamin D status (defined as serum 25 (OH) D <40 nmol/l) during late-winter, but only 4% had inadequate vitamin D status during late-summer. Serum 25 (OH) D was inversely related to serum PTH (r = -0.33; P = 0.028). CONCLUSION: Suboptimal vitamin D status is common in postmenopausal Irish women during winter. Vitamin D supplementation is associated with improved vitamin D status, even during summertime.

Aged↗

PubMed2005

Linkage disequilibrium analysis of case-control data: an application to generalized aggressive periodontitis.

Several studies have shown a role for the involvement of interleukin (IL)-1 gene cluster polymorphisms in the risk of periodontal diseases. In the present study, we tested polymorphisms, derived from genes of the IL-1 cluster, for association with generalized aggressive periodontitis (GAP) through both allelic association and by constructing a linkage disequilibrium (LD) map of the 2q13-14 disease candidate region. The IL-1RN (VNTR) genotype distribution observed was significantly different in GAP and control subjects (P=0.019). We also observed some evidence for an association between GAP and the IL-1B(+3953) polymorphism (P=0.039). The pattern of association in the region, represented as an LD map, identifies a recombination hot area between the IL-1B(+3953) and IL-1B(-511) polymorphisms. Multilocus modelling of association with disease gives a location for the peak association at the IL-1B(+3953) marker, although support for the peak is not significant. Haplotype analysis identifies a IL-1B(+3953)-IL-1B(-511) haplotype as having the lowest P-value in the region. Recognition of the presence of a recombination hot area between the IL-1B(+3953) and IL-1B(-511) polymorphisms will have an important bearing on future efforts to develop higher resolution SNP analysis in this region for both this and other diseases for which this cluster is implicated.

Case-Control Studies↗

PubMed2005

Antioxidant supplementation reduces inter-individual variation in markers of oxidative damage.

The aim of this study was to examine the effect of antioxidant supplementation on oxidative damage and chromosome stability in middle-aged men, smokers and non-smokers. A total of 124 men aged 48+/-6 years from Bratislava and from the rural population near Bratislava were investigated; 64 men (22 smokers and 42 non-smokers) were supplemented for 12 weeks with antioxidants, while 60 (25 smokers and 35 non-smokers) were given placebo. The daily antioxidant supplementation consisted of vitamin C (100 mg), vitamin E (100 mg), ss-carotene (6 mg), and selenium (50 microg). Samples of blood were taken on two occasions: At the beginning and at the end of the supplementation trial. Concentrations of dietary antioxidants, ferric reducing ability, malondialdehyde as an indicator of lipid peroxidation in plasma, micronuclei and chromosome aberrations in lymphocytes were measured. Antioxidant supplementation significantly increased the levels of vitamin C, ss-carotene, a-tocopherol and selenium in plasma. The overall antioxidant status of plasma measured as ferric reducing ability of plasma (FRAP) increased significantly (p<0.001) after antioxidant supplementation as well. The increase in antioxidant parameters after supplementation were consistently more pronounced in non-smokers than in smokers. There was a significant decrease of malondialdehyde concentration in the non-smokers, while in smokers the decrease of malondialdehyde concentration was not significant. Antioxidant supplementation did not affect the proportion of lymphocytes with micronuclei or the total number of micronuclei; however, there was a significant positive correlation (p<0.001) between the malondialdehyde concentration at the beginning of the supplementation trial and the difference in number of cells with micronuclei before and after the supplementation. The percent of cells with chromosome aberrations decreased significantly after antioxidant supplementation in smokers. These results indicate that a combined antioxidant supplementation (a) is effective even at very moderate doses; (b) significantly diminishes oxidative damage to lipids when it is high initially; and (c) is effective in decreasing chromosomal instability in lymphocytes of middle-aged men.

Antioxidants↗

PubMed2005

Multiple mechanisms are implicated in the generation of 5q35 microdeletions in Sotos syndrome.

BACKGROUND: Sotos syndrome is characterised by learning difficulties, overgrowth, and a typical facial appearance. Microdeletions at 5q35.3, encompassing NSD1, are responsible for approximately 10% of non-Japanese cases of Sotos. In contrast, a recurrent approximately 2 Mb microdeletion has been reported as responsible for approximately 50% of Japanese cases of Sotos. METHODS: We screened 471 cases for NSD1 mutations and deletions and identified 23 with 5q35 microdeletions. We investigated the deletion size, parent of origin, and mechanism of generation in these and a further 10 cases identified from published reports. We used "in silico" analyses to investigate whether repetitive elements that could generate microdeletions flank NSD1. RESULTS: Three repetitive elements flanking NSD1, designated REPcen, REPmid, and REPtel, were identified. Up to 18 cases may have the same sized deletion, but at least eight unique deletion sizes were identified, ranging from 0.4 to 5 Mb. In most instances, the microdeletion arose through interchromosomal rearrangements of the paternally inherited chromosome. CONCLUSIONS: Frequency, size, and mechanism of generation of 5q35 microdeletions differ between Japanese and non-Japanese cases of Sotos. Our microdeletions were identified from a large case series with a broad range of phenotypes, suggesting that sample selection variability is unlikely as a sole explanation for these differences and that variation in genomic architecture might be a contributory factor. Non-allelic homologous recombination between REPcen and REPtel may have generated up to 18 microdeletion cases in our series. However, at least 15 cannot be mediated by these repeats, including at least seven deletions of different sizes, implicating multiple mechanisms in the generation of 5q35 microdeletions.

Abnormalities, Multiple↗

PubMed2004

The optimal measure of linkage disequilibrium reduces error in association mapping of affection status.

We have developed a simple yet powerful approach for disease gene association mapping by linkage disequilibrium (LD). This method is unique because it applies a model with evolutionary theory that incorporates a parameter for the location of the causal polymorphism. The method exploits LD maps, which assign a location in LD units (LDU) for each marker. This approach is based on single marker tests within a composite likelihood framework, which avoids the heavy Bonferroni correction through multiple testing. As a proof of principle, we tested an 890 kb region flanking the CYP2D6 gene associated with poor drug-metabolizing activity in order to refine the localization of a causal mutation. Previous LD mapping studies using single markers and haplotypes have identified a 390 kb significant region associated with the poor drug-metabolizing phenotype on chromosome 22. None of the 27 Single nucleotide polymorphisms was within the gene. Using a metric LDU map, the commonest functional polymorphism within the gene was located at 14.9 kb from its true location, surrounded within a 95% confidence interval of 172 kb. The kb map had a relative efficiency of 33% compared with the LDU map. Our findings indicate that the support interval and location error are smaller than any published results. Despite the low resolution and the strong LD in the region, our results provide evidence of the substantial utility of LDU maps for disease gene association mapping. These tests are robust to large numbers of markers and are applicable to haplotypes, diplotypes, whole-genome association or candidate region studies.

Chromosomes, Human, Pair 22↗

PubMed2004

Folate levels determine effect of antioxidant supplementation on micronuclei in subjects with cardiovascular risk.

We have investigated the effect of modest supplementation with alpha-tocopherol (100 mg/day), beta-carotene (6 mg/day), vitamin C (100 mg/day) and selenium (50 microg/day) on oxidative stress and chromosomal damage, and the influence of methylenetetrahydrofolate reductase (MTHFR) genotype on these end-points. Subjects were two groups of middle-aged men differing in cardiovascular risk; 46 survivors of myocardial infarction before age 50 and 60 healthy controls. They were randomly divided into equal groups to receive antioxidants or placebo for 12 weeks. Twenty-eight patients and 58 controls completed the intervention. Micronucleus levels in peripheral lymphocytes and changes seen after intervention were studied in relation to the MTHFR C677T genotype, basal homocysteine and plasma folate levels. Ferric reducing ability of plasma and concentration of malondialdehyde were measured to assess the antioxidant effect of supplementation. There was no association of micronuclei with folate, homocysteine or malondialdehyde levels before supplementation. Micronucleus frequencies and plasma folate levels did not vary significantly with MTHFR genotype. Homocysteine levels in subjects with the TT variant genotype were significantly higher compared with CT or CC (P = 0.001), especially in subjects with low folate (P = 0.012). In the placebo control group an increase in micronuclei (P = 0.04) was detected at the end of the intervention period. This effect was not seen in the supplemented group. In antioxidant-supplemented myocardial infarction survivors we found an increase in the ferric reducing ability of plasma (P < 0.001) and a decrease in malondialdehyde (P = 0.001). Micronucleus frequency showed a decrease, strongest in subjects with normal folate levels (P = 0.015). In subjects with low folate levels, a high correlation was found between micronuclei after supplementation and homocysteine, both before (r = 0.979, P = 0.002) and after supplementation (r = 0.922, P = 0.009). Thus, folate deficiency may amplify the effect of other risk factors such as elevated homocysteine levels or variant MTHFR genotype, as well as influencing the ability of antioxidant supplementation to protect against genetic damage.

Antioxidants↗

PubMed2004

Lipid peroxidation in men after dietary supplementation with a mixture of antioxidant nutrients.

Antioxidants and antioxidant enzymes protect living organisms against the attack of reactive oxygen species. An adequate daily intake of the individual antioxidants is therefore important to prevent the cells against oxidative damage. We investigated the effect of a modest dietary supplementation with a mixture of antioxidant nutrients (100 mg vitamin E, 100 mg vitamin C,6 mg beta-carotene and 50 microg of selenium per day) for 3 months on the plasma antioxidant capacity and indices of oxidative stress. Two groups of middle-age men were selected: group 1 with survivors of myocardial infarction (MI), and group 2 with clinically normal controls. The values of total antioxidant capacity of plasma (FRAP) significantly increased after supplementation with antioxidants in the both groups. Markers of in vivo lipid peroxidation, plasma malondialdehyde (MDA) and conjugated diene (CD) levels significantly decreased in the both supplemented groups. MDA and CD values were significantly higher at baseline in the group of survivors of myocardial infarction when compared with the group of healthy men. The results demonstrate that short-term and modest supplementation with a mixture of antioxidant nutrients improves antioxidative capacity and reduces products of lipid peroxidation in plasma. Since a more pronounced effect was observed within the group of survivors of myocardial infarction, a recommendation of antioxidant supplements seems appropriate for patients with a history of cardiovascular disease. (Fig. 1, Ref. 19.)

Antioxidants↗

PubMed2003

Overexpression of the MT1 melatonin receptor in MCF-7 human breast cancer cells inhibits mammary tumor formation in nude mice.

Overexpression of the MT1 melatonin receptor in MCF-7 human breast cancer cells significantly enhances the response of these cells to the growth-inhibitory actions of melatonin. Athymic nude mice implanted with MT1-overexpressing MCF-7 cells developed significantly fewer palpable tumors (60% reduction) compared to mice receiving vector-transfected MCF-7 cells (vt-MCF-7). In response to exogenous melatonin, tumor incidence in the mice receiving the MT1-overexpressing MCF-7 cells was decreased by 80% compared to mice receiving vt-MCF-7 cells. Interestingly, daily melatonin administration did not decrease tumor incidence in mice receiving vt-MCF-7 cells, but rather stimulated overall tumor formation.

Animals↗

PubMed2003

CpG islands in human X-inactivation.

Sequence comparison analyses have been carried out for 19 genes escaping X-inactivation versus 73 genes subject to X-inactivation, and 100 randomly chosen X chromosome genes versus 100 randomly chosen autosomal genes. The coding sequence of the genes and their upstream and downstream flanking sequences were investigated using a series of windows (1 kb, 2 kb, 5 kb, 10 kb and 100 kb). No significant difference in number of LINE-L1 elements was observed in genes escaping X-inactivation compared to genes subject to X-inactivation. This result, therefore, does not support the suggestion that lack of LINE repeat elements is a key factor for genes escaping X-inactivation. However, significantly reduced numbers of CpG islands and SINE MIR elements were found to be associated with genes escaping X-inactivation. Compared to genes known to be inactivated, genes escaping X-inactivation were observed to have fewer CpG islands, particularly within the 2 kb upstream flanking sequence close to the coding region. The results suggest that CpG islands may play a role in the process of X-inactivation by providing sufficient DNA methylation targets for the maintenance of X-inactivation. Lack of CpG islands may be a major reason for genes escaping X-inactivation regulation.

CpG Islands↗

PubMed2003

A metric linkage disequilibrium map of a human chromosome.

We used LDMAP (Maniatis et al. 2002) to analyse SNP data spanning chromosome 22 (Dawson et al. 2002), to obtain a whole-chromosome metric LD map. The LD map, with map distances analogous to the centiMorgan scale of linkage maps, identifies regions of high LD as plateaus ('blocks') and characterises steps which define the relationship between these regions. From this map we estimate that block regions comprise between 32% and 55% of the euchromatic portion of chromosome 22 and that increasing marker density within steps may increase block coverage. Steps are regions of low LD which correspond to areas of variable recombination intensity. The intensity of recombination is related to the height of the step and thus intense recombination hot-spots can be distinguished from more randomly distributed historical events. The LD maps are more closely related to the high-resolution linkage map (Kong et al. 2002) than average measures of rho with recombination accounting for between 34% and 52% of the variance in patterns of LD (r=0.58 - 0.71, p=0.0001). Step regions are closely correlated with a range of sequence motifs including GT/CA repeats. The LD map identifies holes in which greater marker density is required and defines the optimal SNP spacing for positional cloning, which suggests that some multiple of around 50,000 SNPs will be required to efficiently screen Caucasian genomes. Further analyses which investigate selection of informative SNPs and the effect of SNP allele frequency and marker density will refine this estimate.

Chromosome Mapping↗

PubMed2003

A corneal model for slit-scanning elevation topography.

Computerised videokeratography is increasing in sophistication and accuracy. The Orbscan II Videokeratographer combines the advantages of Placido derived and slit-scanning derived topography, to acquire shape information on the posterior surface of the cornea. The purpose of this paper is to construct a model of slit-scanning elevation topography and highlight potential sources of variation in this methodology. Ray tracing calculations were performed on a defined, theoretical, spherical model to obtain a pachymetric measurement. These calculations were tested by comparing the pachymetry measurement derived from the model, over a refractive index shift from 1.376 to 1.400 with the pachymetry measurement obtained by Orbscan II, of a human eye, with an identical alteration in refractive index. The two methods of measurement differed by only 0.157 microm, suggesting that the model is a good representation of slit-scanning elevation topography, and that refractive index variations have only a minimal effect on Orbscan II pachymetry measurement.

Corneal Diseases↗

PubMed2003

Recommendations for conducting the in vivo alkaline Comet assay. 4th International Comet Assay Workshop.

The in vivo alkaline single cell gel electrophoresis assay, hereafter the Comet assay, can be used to investigate the genotoxicity of industrial chemicals, biocides, agrochemicals and pharmaceuticals. The major advantages of this assay include the relative ease of application to any tissue of interest, the detection of multiple classes of DNA damage and the generation of data at the level of the single cell. These features give the Comet assay potential advantages over other in vivo test methods, which are limited largely to proliferating cells and/or a single tissue. The Comet assay has demonstrated its reliability in many testing circumstances and is, in general, considered to be acceptable for regulatory purposes. However, despite the considerable data published on the in vivo Comet assay and the general agreement within the international scientific community over many protocol-related issues, it was felt that a document giving detailed practical guidance on the protocol required for regulatory acceptance of the assay was required. In a recent meeting held in conjunction with the 4th International Comet Assay Workshop (Ulm, Germany, 22-25 July 2001) an expert panel reviewed existing data and recent developments of the Comet assay with a view to developing such a document. This paper is intended to act as an update to the more general guidelines which were published as a result of the International Workshop on Genotoxicity Test Procedures. The recommendations are also seen as a major step towards gaining more formal regulatory acceptance of the Comet assay.

Animals↗

PubMed2003

Patterns of emotional responses to pregnancy, experience of pregnancy and attitudes to parenthood among IVF couples: a longitudinal study.

The aim of this longitudinal study was to compare couples who had conceived by in-vitro fertilization (IVF) with couples who had conceived naturally, regarding patterns of emotional response to different stages of pregnancy and to compare their expectations of and attitudes to pregnancy, parenthood and children. Fifty-seven IVF women and 55 of their male partners, and a control group of 43 pregnant women and 39 of their male partners participated. They completed scales measuring emotional responses to pregnancy, attitudes to pregnancy, parenthood and children. The IVF couples were interviewed about their experience of pregnancy. The overall anxiety about losing the pregnancy was higher among the IVF couples from early to late pregnancy. The IVF women experienced the pregnancy in a more positive way and they were less concerned about the child's gender and loss of freedom in their future lives as parents compared to controls. The IVF men were more anxious about the baby being injured during birth. The interviews with the IVF couples confirmed the self-ratings. In conclusion, the results suggest that it is important for healthcare providers to pay attention to an elevated anxiety among IVF couples and to give them extra time to discuss emotions during pregnancy and their future life as parents.

Affect↗