Coding of pointers in the segregation analysis program POINTER.
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Bias↗
Biomedical subjects
A Collins
Publications and source records attributed to A Collins.
Integration of gene maps: chromosome X.
Omitting 1137 loci that are included in the location database but have only cytogenetic assignment, there are 605 loci in the integrated map that synthesizes physical and genetic data and subsumes a composite physical location, cytogenetic and regional assignments, mouse homology, rank, and references. With error filtration and allowance for interference the genetic length is 211 cM, to which the p arm contributes 100 cM. The physical length is 164 Mb, with 62 Mb in the p arm. Current problems in map integration are discussed and some solutions proposed.
Animals↗
Reproductive health, use of estrogen and experience of symptoms in perimenopausal women: a population-based study.
OBJECTIVE: The aim of the study was to examine reproductive health, use of estrogen, lifestyle, experience of menopausal symptoms and work-role related issues in a population-based sample of perimenopausal women. METHODS: All women aged 48 years and residing in the catchment area of the Karolinska Hospital were recruited through the Swedish population register. They received a questionnaire covering sociodemographic background, reproductive health and gynaecological characteristics, social and work role related issues as well as a symptom rating scale. RESULTS: Seventy percent of the women returned the questionnaire. Of these, 73% were premenopausal, 21% were postmenopausal and 6% were perimenopausal. Hormone replacement therapy was used by 7.5% of the respondents and the rate of hysterectomy was 8.6%. Regular exercise was reported by 44.4%. Factor analysis of the symptom ratings yielded four independent dimensions: Negative Moods, Vasomotor symptoms, Decreased Sexual Desire and Well-being. Multiple regression analyses showed that only vasomotor symptoms were significantly related to menopausal status. Negative Mood and Reduced Sexual Interest were better explained by the presence of vasomotor symptoms and by reproductive health and lifestyle variables such as current or previous PMS, dysmenorrhea, smoking and lack of exercise. CONCLUSIONS: Only vasomotor symptoms were significantly related to menopausal status. Psychosocial and lifestyle variables as well as past or current reproductive health are more important determinants of women's psychological well-being during transition to menopause than menopausal status.
Attitude to Health↗
Micronutrients and oxidative stress in the aetiology of cancer.
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Antioxidants↗
Genetic epidemiology of hereditary non-polyposis colorectal cancer syndromes in Modena, Italy: results of a complex segregation analysis.
Complex segregation analysis was conducted in a series of patients with hereditary non-polyposis colorectal cancer (HNPCC) ascertained through probands registered in the Cancer Registry of the Health Care District of Modena in Northern Italy. Altogether there were 71 nuclear families segregating for HNPCC in 28 pedigrees. The analysis favoured the two-loci model, in which the segregation at the major locus is compatible with codominant transmission with a frequency of 0.0044 for the high-risk allele for HNPCC and a lifetime penetrance of 0.728 for heterozygotes.
Adult↗
Genetic epidemiology of early onset breast cancer.
Risks for breast cancer when there is a family history of the disease are usually calculated using data from segregation analyses which favour a single dominant gene with high penetrance. There are, however, at least three loci known to be associated with familial breast cancer (p53, BRCA1, and an as yet unpublished locus) and the frequencies and penetrances of these genes are not likely to be the same. We have attempted to address the problem of which genetic parameters should be used to calculate risks for different patterns of familial breast cancer. Data from 384 nuclear families ascertained through a proband selected for early onset breast cancer were subjected to complex segregation analysis, correcting for ascertainment bias resulting from selection for severe phenotype. Age of onset of breast cancer, incorporated as severity, provides additional information to the segregation model over and above that given by assigning liability classes on the basis of age at observation. The use of this additional parameter in the analysis is described. There is fair agreement between estimates from this sample and previous predictions from consecutive probands and consultands. The differences suggest more than one rare dominant gene for susceptibility to breast cancer, with different penetrances. Although refinements of segregation analysis will help to delineate these different genes, perfect resolution will require identification of the mutant alleles. Methods to estimate genetic parameters under genotype specific mortality need to be developed. Meanwhile, we suggest that high and low estimates of penetrance be used in risk estimation for genetic counselling, and as a guide to candidates for entry into clinical trials of screening and chemoprevention in breast cancer.
Adult↗
Lean body mass estimation by creatinine kinetics.
A new technique for estimating lean body mass (LBM) from creatinine kinetics has been developed. It is based on the principle that creatinine production is proportional to LBM and that, in the steady state, creatinine production is equal to the sum of creatinine excretion (urinary and dialytic) and metabolic degradation. This technique was applied to 17 normal subjects, 26 stable, chronic hemodialysis (HD) patients, and 71 stable, chronic peritoneal dialysis (PD) patients. In the HD group, LBM was also determined by bioimpedance in 11 patients and calculated from total body water, measured as the volume of urea distribution of a sterile urea infusion, in 15 patients. In normal subjects and in the PD group, LBM was assessed by creatinine kinetics as well as by bioimpedance, near infrared, and anthropometric techniques. In the HD patients, LBM by creatinine kinetics correlated significantly with LBM from total body water and the bioimpedance technique. There was no statistical difference between the total body water and creatinine kinetics techniques, but the bioimpedance values were systematically higher than those obtained by the kinetic technique. In the PD group and in normal volunteers, LBM values by creatinine kinetics correlated significantly with the other methods but were lower. Forty-seven percent of the HD patients and 66% of the PD patients had significantly lower LBM by creatinine kinetics than expected for their sex and age. Estimation of LBM by creatinine kinetics is proposed as a simple and convenient technique for the routine nutritional assessment of dialysis patients.
Anthropometry↗
Medico-legal aspects of antidepressant prescribing: a comment.
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Antidepressive Agents, Tricyclic↗
Segregation analysis of complex phenotypes: an application to schizophrenia and auditory P300 latency.
Traditional models of the genetic transmission of human diseases have often assumed that the phenotype is a simple dichotomous trait, which is unrealistic for many psychiatric conditions, and may result in loss of valuable information. We describe a new model for complex phenotypes, implemented in the program COMDS, which subclassifies normal and affected individuals into polychotomies correlated with the underlying genetic liability to the disorder. The model is applied to 18 Scottish pedigrees ascertained for schizophrenia, in which auditory P300 latency had been measured as a possible correlate of the genetic predisposition to schizophrenia. The results suggest that there may be a major locus for schizophrenia, but that there are also other familial determinants, possibly a second modifier locus. In addition, the results indicate that auditory P300 latency may be a useful measure of the genetic predisposition to schizophrenia among asymptomatic relatives, although the relationship between P300 latency and the degree of genetic predisposition in clinical cases was not significant, presumably because other factors are operating on P300 latency. Because of the possible selection biases in this sample, there is a need to replicate these findings in systematically ascertained pedigrees.
Discriminant Analysis↗
Combined segregation and linkage analysis of Graves disease with a thyroid autoantibody diathesis.
Combined segregation and linkage analysis is a powerful technique for modeling linkage to diseases whose etiology is more complex than the effect of a well-described single genetic locus and for investigating the influence of single genes on various aspects of the disease phenotype. Graves disease is familial and is associated with human leukocyte antigen (HLA) allele DR3. Probands with Graves disease, as well as close relatives, have raised levels of thyroid autoantibodies. This phenotypic information additional to affection status may be considered by the computer program COMDS for combined segregation and linkage analysis, when normals are classified into diathesis classes of increasing thyroid autoantibody titer. The ordinal model considers the cumulative odds of lying in successive classes, and a single additional parameter is introduced for each gene modeled. Distributional assumptions are avoided by providing estimates of the population frequencies of each class. Evidence for linkage was increased by considering the thyroid autoantibody diathesis and by testing two-locus models. The analysis revealed evidence for linkage to HLA-DR when the strong coupling of the linked locus to allele DR3 was considered (lod score of 6.6). Linkage analysis of the residual variation revealed no evidence of linkage to Gm, but a suggestion of linkage to Km.
Adolescent↗
Integration of gene maps: chromosome 21.
Physical, cytogenetic, and genetic data including microsatellite markers and a covering sequence-tagged site (STS) map have been entered into a location database and integrated into a summary map that subsumes a composite physical location, sex-specific genetic locations, cytogenetic and regional assignments, mouse homology, rank, and references. With the omission of 52 loci whose location is known only from cytogenetic assignment to an interval greater than 10 megabases, there are 198 loci in the covering STS map and an additional 145 loci. The physical length is consistent with 11 megabases for 21p and 39 megabases for 21q. With error filtration and allowance for high interference, the genetic length in males corresponds to the chiasma map (54.7 centimorgans), and the genetic length in females is 76.5 centimorgans. The relation between map integration and the STS paradigm is illustrated and discussed.
Chromosome Mapping↗
Kinship bioassay on hypervariable loci in blacks and Caucasians.
Four hypervariable loci were examined in DNA samples of American Blacks and Caucasians. Genetic diversity, measured by mean kinship within race, is 0.004 for a sliding window equal to twice the radius of coalescence of the autoradiographic bands. Kinship increases with the width of a window or bin, but it is an order of magnitude less than for blood groups and isozymes. This must reflect the greater mutability of hypervariable loci and absence of divergent selection. Low kinship implies that matching probabilities do not depend critically on race. Complete matching between pairs of loci shows deviations from independence, presumably because of inadvertent inclusion of replicated samples or related individuals. Multilocus matching probabilities were corrected for this (possibly spurious) dependence; the correction is negligible. When the complexities of coalescence, kinship, and dependent matching are allowed for, the probability calculations used in forensic identification are reliable. Recent counterarguments without theoretical basis or empirical support are discussed.
Black People↗
Achilles tendon healing: a correlation between functional and mechanical performance in the rat.
The pathogenesis and treatment of rupture of the Achilles tendon remain a source of controversy. This study presents the results of a biomechanical, functional, and morphological evaluation of a group of rats that had division and repair of the Achilles tendon. A total of 46 rats were used: 18 for biomechanical testing, 18 for functional evaluation, and 10 for histology. Morphological examination revealed an early inflammatory response with loose connective tissue formation that was replaced gradually by fibroblasts and a collagenous matrix. The functional evaluation (Achilles functional index [AFI]) was made from measurements of the hind pawprints of walking rats. Division and repair of the Achilles tendon produced a significant functional impairment (mean [+/- SEM] AFI = -87 +/- 8; p < 0.001), which gradually improved with healing time. The load to failure for the repaired tendons consistently improved with healing time, in a manner similar to the functional recovery. The average deformation (repair/control) varied considerably and was not related to healing time. The stiffness of the repaired tendons increased with healing time and was 60% of the corresponding control side by day 15. The major finding of this study was a strong correlation between the AFI and the failure load of the healing tendon-bone constructs (250-300 g group, r = 0.97, p < 0.001; 325-375 g group, r = 0.96, p < 0.001).
Achilles Tendon↗
A novel method for direct application of phospholipids to giant excised membrane patches in the study of sodium-calcium exchange and sodium channel currents.
Effects of membrane phospholipids on Na(+)-Ca2+ exchange and Na+ channel currents were studied in giant excised cardiac sarcolemmal patches. Phospholipids were suspended in an inert vehicle of alpha-tocopherol acetate and hexane and were then directly applied to the side of patch electrodes at a short distance from the tip during current recording. Phosphatidylserine strongly stimulated outward Na(+)-Ca2+ exchange current and altered the kinetics of cytoplasmic Na(+)- and Ca(2+)-dependent secondary modulation. This effect was partially reversed by phosphatidylcholine. Prolonged treatment with phosphatidylserine eliminated the inactivation transient normally observed upon rapid application of cytoplasmic Na+ but left cytoplasmic Ca2+ dependence largely intact. In such cases, subsequent chymotrypsin treatment removed cytoplasmic Ca2+ dependence, but had no further stimulatory effect, indicating maximum alleviation of inactivation by phosphatidylserine. While these results indicate that phosphatidylserine acts on a cytoplasmic, protease-sensitive regulatory domain of the exchanger, phosphatidylserine also stimulated the exchange current after deregulation by chymotrypsin, indicating an effect on the exchange mechanism itself. As in other myocyte preparations, cardiac Na+ currents in giant patches undergo a time-dependent negative shift in the voltage dependence of steady-state inactivation. Loss of phosphatidylserine from the cytoplasmic leaflet (i.e. loss of transbilayer asymmetry of phosphatidylserine distribution) does not appear to be the underlying cause, since phosphatidylserine did not reverse this shift, despite stimulation of Na(+)-Ca2+ exchange current in the same patches.
Animals↗
The single cell gel electrophoresis assay (comet assay): a European review.
The single cell gel electrophoresis (SCGE) assay is a rapid, simple, visual and sensitive technique for measuring DNA breakage in individual mammalian cells. Here we review the development of the SCGE assay (with particular reference to the alkaline version), existing protocols for the detection and analysis of comets, the relevant underlying principles determining the behaviour of DNA, and the potential applications of the technique.
Animals↗
Categories and resemblance.
Many theories of concepts link categorizing to similarity. If a new instance is sufficiently similar to category members, then the instance is likely to be a member itself. However, judged similarity are judged category likelihood sometimes diverge. In these studies, we describe frequency distributions for categories that vary along a single dimension, and ask Ss to rate the similarity, typicality, or category likelihood of instances along this continuum. The average ratings exhibit distinct patterns, with category likelihood depending on the instance's frequency and with similarity depending on distance from the instance to the center of the distribution. Typicality ratings show effects of both frequency and distance. These differences occur for bimodal distributions (Experiments 1 and 2) and for unimodal ones (Experiment 3). They appear both when we present the distributions as histograms and when we imply them in descriptions. We argue that similarity-based models of categorizing are incomplete and may apply mainly to situations in which more definitive information is unavailable.
Decision Making↗
Achilles tendon injuries: a comparison of surgical repair versus no repair in a rat model.
Controversy exists regarding the treatment of Achilles tendon ruptures. The aim of this study was to determine whether surgical repair of the rat Achilles tendon offered any biomechanical, functional, or morphological advantage over no repair. Thirty-two male Sprague-Dawley rats were randomly allocated into four groups: (1) sham operated (skin incision only), (2) no repair (complete division of the Achilles tendon and plantaris tendon without repair), (3) internal splint (plantaris left intact), and (4) Achilles repair (with a modified Kessler-type suture). Functional performance was determined from the measurements of hindpaw prints utilizing the Achilles Functional Index. On day 15, the animals were killed, and biochemical and histological evaluations were performed on both the injured and uninjured Achilles tendon constructs. All groups subjected to Achilles tendon division had a significant initial functional impairment that gradually improved so that by day 15 there were no functional or failure load impairments in any group. The injured tendons in all three groups subjected to Achilles tendon division had a 13-fold increase in the cross-sectional area and were less stiff and more deformable than uninjured and sham-operated tendons on day 15 (P < .001). The magnitude of the biomechanical and morphological changes at postoperative day 15 and the initial impairment and rate of functional recovery were similar for no repair, internal splint, and Achilles repair groups. In summary, this study demonstrates that surgical repair of the Achilles tendon in the rat does not offer any advantage over nonoperative management.
Achilles Tendon↗
Hormonal and biochemical profiles of premenstrual syndrome. Treatment with essential fatty acids.
Women diagnosed as suffering from premenstrual syndrome and symptom free controls were compared on hormonal parameters, glucose tolerance, mineralocorticoids, cholesterols, triglycerides, apolipoprotein (a), magnesium and calcium in the follicular and luteal phases of the menstrual cycle. The effect of treatment with essential fatty acids on the biochemical variables was also evaluated in a randomized, double-blind crossover design. The results showed that the hormonal and biochemical profiles of women with PMS and symptom free controls were markedly similar, except for aldosterone which was lower in the follicular and luteal phases and cholesterol which was higher in the follicular phase in women with PMS. No effects of treatment with essential fatty acids were found for any of the biochemical variables studied.
Adult↗