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A Collins

Publications and source records attributed to A Collins.

At least 37 records · Page 2Linked to original sources
PubMed2001

PIRA PCR designer for restriction analysis of single nucleotide polymorphisms.

UNLABELLED: Primer-introduced restriction analysis (PIRA-PCR) is widely used to detect Single Nucleotide Polymorphisms (SNPs). To create artificial Restriction Fragment Length Polymorphism (RFLP), a mismatch is usually introduced near the end of the primer that is close to the mutation of interest. We describe in this report a www-based computer program that screens for the suitable mismatches, designs the primers, lists the appropriate restriction enzymes and other related information. AVAILABILITY: The computer program, with related descriptions, is available at http://cedar.genetics.soton.ac.uk/public_html/primer2.html.

Base Pair Mismatch↗
PubMed2001

A sequence-based integrated map of chromosome 22.

The near-completion of the sequence for chromosome 22q revolutionizes map integration. We describe a sequence-based integrated map containing 968 loci including 516 known or predicted gene sequences, 317 STSs not included in these sequences, and 135 nonexpressed multinucleotide polymorphisms. The published sequence spans 34.6 Mb, inclusive of gaps estimated to total 1.1 Mb, compared with a top-down estimate of 43 Mb. This discrepancy is discussed, but will not be resolved until more of the genome is analyzed. The radiation hybrid map has 5% error in order and 34% error in location exceeding 1 Mb. The utility of a composite location based on evidence other than sequence is limited to regions not yet sequenced. A genetic map conditional on sequence order was constructed from pairwise lods. Its length of 74.8 cM in males and 80.2 cM in females is slightly less than the previous estimate not constrained by sequence order. Five recombination hot spots are detected, with differences in location between the sexes. Male recombination correlates with repetitive DNA, whereas female recombination does not. It remains to be seen whether this is true for other human chromosomes. An algorithm to improve the fit of cytogenetic bands sequence location reduces the discrepancies in cytogenetic assignment from 61 to 38. This sequence-based integrated map is represented in the genetic location database (LDB2000), which is available at http://cedar.genetics.soton.ac.uk/public_html/LDB2000.html.

Base Sequence↗
PubMed2001

Combination of linkage evidence in complex inheritance.

The central problem of complex inheritance is to combine evidence from data that typically differ in markers, phenotypes, ascertainment, and other factors, without sacrificing the reliability that lods have given to linkage mapping for major loci. Here we evaluate 5 possible solutions on 200 replicates simulated in Genetic Analysis Workshop 10. Two methods differ from less efficient ones by distinguishing the tails of a normal distribution. Maximum likelihood scores (currently implemented only for the BETA model) and the approach of Self and Liang perform about as well as pooling samples, which is not feasible with heterogeneous data. With moderately heterogeneous data the Self and Liang method appears to be more efficient than maximum likelihood scores. Although improvements are being made in sample design and statistical analysis, the problem of combining linkage evidence from multiple data sets appears to have been solved. Allelic association presents different problems not yet addressed.

Alleles↗
PubMed2001

A tournament of linkage tests in complex inheritance.

The performance of some weakly parametric linkage tests in common use was compared on 200 replicates of oligogenic inheritance from Genetic Analysis Workshop 10. Each random sample for the quantitative trait was dichotomized at different thresholds and also selected through 2 affected sibs, generating 8 combinations of sample and variable. The variance component program SOLAR performed best with a continuous trait, even in selected samples, when the population mean was used. The sib-pair program SIBPAL2 was best in most other cases when the phenotype product, population mean, and empirical estimates of pair correlations were used. The BETA program that introduced phenotype products was slightly more powerful than maximum likelihood scores under the null hypothesis and approached but did not exceed SIBPAL2 under its optimal conditions. Type I errors generally exceeded expectations from a chi(2) test, but were conservative with respect to bounds on lods. All methods can be improved by use of the population mean, empirical correlations, logistic representation for affection status, and correct lods for samples that favour the null hypothesis. It remains uncertain whether all information can be extracted by weakly parametric methods and whether correction for ascertainment bias demands a strongly parametric model. Performance on a standard set of simulated data is indispensable for recognising optimal methods.

Algorithms↗
PubMed2001

Experimental prostate epithelial morphogenesis in response to stroma and three-dimensional matrigel culture.

To reproduce the structural and functional differentiation of human prostatic acini in vivo, prostatic epithelial and stromal cells derived from human primary cultures were cocultured in Matrigel. In the absence of stroma and serum, epithelial spheroids composed of solid masses of stratified and cuboidal cells formed. Outer cells of the spheroid expressed cytokeratins 1, 5, 10, and 14, whereas the inner cells expressed cytokeratin 18. The addition of 2% serum induced formation of a lumen surrounded by a layer of one or two cuboidal and columnar epithelial cells. The further addition of stromal cultures, dihydrotestosterone, and estrogen induced polarization of the epithelium and increased spheroid-forming efficiency. Epithelium expressed either cytokeratin 18 alone or additionally cytokeratins 1, 5, 14, and 10. All spheroid epithelium expressed prostate-specific antigen and prostate-specific membrane antigen. Androgen receptor was only detected in the presence of stroma, serum, and hormones. Thus, development of a functional and morphologically correct prostate gland in vitro is dependent on extracellular matrix, steroid hormones, and factors from stromal cells and serum.

Animals↗
PubMed2000

Allelic association in the FRAX region.

The sex chromosomes enable direct determination of haplotypes, and the analysis of 8 microsatellite markers from the FRAX region on Xq27-q28 contributes 7219 independent haplotypes from our study in Wessex. Allelic association increases with frequency of alleles, and is less for trinucleotide than dinucleotide repeats. The estimate of epsilon, the exponential decline of association with distance in kb, is 0.0023. The swept radius 1/epsilon estimates the distance at which disequilibrium falls to e(-1) approximately .37 of its initial value. The current study estimates the swept radius of association to be 433 kb, which is surprisingly close to estimates for SNPs, and suggests that a marker density of 1/100 kb should be powerful in regions such as FRAX. An explanation for these results is offered, and some speculations made about what will be found when SNPs are subjected to an equally intensive study in multiple regions.

Alleles↗
PubMed2000

The influence of stress and state anxiety on the outcome of IVF-treatment: psychological and endocrinological assessment of Swedish women entering IVF-treatment.

BACKGROUND: Comparing stress levels in women entering IVF treatment with those of fertile controls as well as relating these levels to the outcome of IVF. METHODS: State anxiety and personality profiles as well as stress hormones were studied in 22 normally menstruating women entering IVF treatment for tubal infertility. Their personality profiles as well as state anxiety scores measured before entering IVF treatment were related to the outcome of treatment. Twenty-two fertile women served as controls. Stress markers were serum prolactin and cortisol. These were estimated by radioimmunoassay. The psychological evaluation included the Karolinska Scales of Personality (KSP) and state anxiety as measured by the STAI questionnaire. Basal FSH on cycle day 3 and E2 and P4 AUC during the luteal phase were evaluated as hormonal predictors for the outcome of IVF treatment. RESULTS: Comparison of the personality profiles of the two groups, showed that infertile women had significantly higher scores of suspicion (p>0.05), guilt (p>0.05), and hostility (p>0.01), but lower somatic anxiety (0.05) and indirect aggression (0.05) than fertile controls. The infertile women also had significantly higher levels of prolactin and cortisol throughout the menstrual cycle. Serum cortisol, prolactin and FSH levels on cycle day 3 did not differ between the women who conceived after IVF treatment and those who did not conceive. However, significant differences were found in E2 and P4 AUC (p>0.01) in the luteal phase between those women who became pregnant and those who failed. There was a trend (p<0.06) toward higher state anxiety levels among the women who did not succeed in becoming pregnant after IVF treatment. CONCLUSIONS: The main findings suggest that infertile women have a different personality profile in terms of more suspicion, guilt and hostility as compared to the fertile controls, perhaps as a response to their infertility. Their stress levels in terms of circulating prolactin and cortisol levels were elevated compared to the fertile controls. Psychological stress may affect the outcome of IVF treatment since state anxiety levels among those who did not achieve pregnancy were slightly higher than among those who became pregnant.

Adult↗
PubMed2000

Combined segregation and linkage analysis of 59 Hodgkin's disease families indicates the role of HLA determinants.

Through a literature search, we identified a total of 59 nuclear families with Hodgkin's disease (HD). The affected individuals in these families were HLA haplotyped. To evaluate the role of HLA-linked determinants of HD and investigate the mode of inheritance of familial HD, a combined segregation and linkage analysis was performed, together with a semi-parametric analysis of sib pairs. Amongst single locus models, a general single locus model showed no improvement over an additive model. However, a two locus additive model gave the best overall fit and a lod score of 3.55. We conclude that HD is most likely to be determined by both an HLA-associated major gene and other non-HLA genetic factors together with environmental effects.

HLA Antigens↗
PubMed2000

Combined segregation and linkage analysis of inflammatory bowel disease in the IBD1 region using severity to characterise Crohn's disease and ulcerative colitis. On behalf of the GISC.

Inflammatory bowel disease (IBD) is a chronic relapsing disorder affecting the gastro-intestinal tract and is subdivided into two main subtypes: Crohn's disease (CD) and ulcerative colitis (UC). Although the aetiology of IBD is unknown, a strong genetic susceptibility is suggested and different candidate regions have been identified for both CD and UC. The IBD1 region on chromosome 16 has been confirmed to be important for susceptibility to CD, whereas conflicting evidence has been obtained for UC. We performed a combined linkage and segregation analysis in the identified IBD1 region on a sample of 82 extended families with IBD using a parametric method implemented in the computer program COMDS. This approach allows simultaneous evaluation of linkage while estimating the mode of inheritance and to include severity of the trait to characterise the CD and UC phenotypes. Our results are consistent with the presence of a major gene in the IBD1 region close to D16S408 involved in both UC and CD. Furthermore, our data support evidence that a single mutation in the gene leads more frequently to UC, whereas inheritance of two mutant alleles results in the more severe CD. In our study the IBD1 locus was found to have a major role in IBD predisposition in the Italian population.

Adult↗
PubMed2000

Psychosocial factors, attitude to menopause and symptoms in Swedish perimenopausal women.

OBJECTIVES: To analyze attitude to menopause from women's own accounts and to examine whether psychosocial factors and attitude are associated with symptom reporting. METHODS: The data form part of a population-based longitudinal study of a cohort of women who have been followed annually for 5 years using psychological interviews and rating scales, health screening and hormonal characterization. The data reported here were collected at the fourth follow-up when the women (n = 148) were 53 years old. RESULTS: Women were classified as perimenopausal (27%), postmenopausal (15%), hormone replacement therapy (HRT) users (52%) and hysterectomized (6%), based on self-reports. More than half the women (51%) had a positive attitude to menopause, 24% had a negative attitude and 25% had a neutral attitude. Menopausal status was not associated with attitude to menopause. Factor analysis of symptom ratings yielded ten independent factors comprising negative mood, vasomotor symptoms, decreased sexual desire, memory problems, sleep-related symptoms, vaginal dryness, urogenital problems, joint pain, vitality and increased sexual desire. Only vasomotor symptoms and joint pain were associated with menopausal status. The other symptoms were more strongly related to psychosocial factors, life-style and attitude to menopause. CONCLUSIONS: The results support the view of the menopause as a developmental phase associated with an increased self-awareness and a stronger personal identity. More than half the women held a positive view of the menopause, whereas the remaining proportion of women had either a negative or a neutral attitude. Only vasomotor symptoms and joint pain were associated with postmenopausal status. Other symptoms were significantly related to psychosocial factors, life-style and attitude to menopause.

Affect↗
PubMed2000

Linkage disequilibrium mapping using single nucleotide polymorphisms--which population?

There is considerable interest in the potential of single nucleotide polymorphisms (SNPs) for mapping complex traits which are determined by genes of small individual effect (oligogenes). It is thought likely that many oligogenes are themselves common polymorphisms, perhaps biallelic, for which there is effectively neutral selection reflected in late age of onset. The extent of detectable linkage disequilibrium between SNP x SNP pairs and SNP x oligogene pairs is of considerable interest, particularly in the context of identifying 'favourable' populations. Unfortunately data are sparse and few populations have been extensively sampled. Polymorphisms with the appropriate characteristics that have been studied are blood groups in the Rhesus and MNS systems for which there are extensive data on four pairs of biallelics. These might be regarded as surrogates for SNP-SNP or SNP-oligogene pairs. By developing and applying an approach, previously used for major genes, to evaluate association (rho) in SNP haplotypes, it is evident that, with some exceptions, there is little difference between isolates and large populations. Furthermore it is apparent that there is useful linkage disequilibrium even for the MN-Ss locus pair (0.195 cM apart), in both large populations and isolates. This is somewhat more favourable to linkage disequilibrium mapping than a recent simulation suggests.

Alleles↗
PubMed2000

Association between hematocrit level and mortality in hemodialysis patients. Case study of the anemic patient.

A large, 4-year, retrospective study of the HCFA end-stage renal disease (ESRD) claims database, Parts A and B, was conducted to determine the association between hematocrit (Hct) level and survival in patients on hemodialysis. Patients who survived the last 6 months of each year and had at least 4 Epoetin alfa claims qualified for the study. Cohort entry years were 1990 through 1993, with the relative risk (RR) of mortality evaluated during the following year. Patients were stratified into four groups on the basis of mean Hct levels in the 6-month entry period: < 27%, 27% to < 30%, 30% to < 33%, and 33% to 36%. Using the 30% to < 33% Hct group as reference (relative risk (RR) = 1), patients whose mean 6-month Hct was in the 33% to 36% range were associated with significantly lower RR of mortality, while patients whose mean 6-month Hct was below 30% were associated with significantly higher RR of mortality. This epidemiologic study highlighted an important association between higher hematocrits in hemodialysis patients and lower RR of mortal.

Anemia, Iron-Deficiency↗
PubMed2000

Undetected hyperglycaemia among hospital in-patients.

To assess the prevalence of previously undiagnosed hyperglycaemia consistent with a diagnosis of Diabetes Mellitus in a consecutive series of hospital in-patients. Retrospective case note review. University Teaching Hospital. 800 consecutive hospitalised patients aged over 50 years. The main outcome measures the prevalence of hyperglycaemia [corrected]. We searched the biochemistry laboratory computerised database for results of all biochemistry tests carried out during each patient's admission. The medical records of those with at least one plasma glucose value in the hyperglycaemic range (glucose > or =11.1 mmol/l and/or > or =7.0 mmol/l on casual and/or fasting measurements respectively) were reviewed by two observers using a standardised method and a check list for data collection.

Age Distribution↗
PubMed2000

The impact of transplantation on survival with kidney failure.

Although the growth in the incidence and prevalence of ESKD has slowed, there will nevertheless be a substantial increase in the number of patients over the next decade. Indeed, between 1998 and 2010 there will be a doubling in the number of patients in the United States treated with renal replacement therapy. There has also been an increase in the number of new transplants carried out every year. Much of the growth in the number of new transplants has been from the growth in living-unrelated donor transplants. Unfortunately, the rate of increase in the number of new transplants has not been enough to keep pace with the growing number of ESKD patients. As a result, the number of patients on the transplant waiting list continues to increase. The inability to offer more ESKD patients transplantation is unfortunate, since transplantation is associated with improved survival. Indeed, analyses of comparable patients who are placed on the transplant waiting list suggest that transplantation reduces the risk of death by roughly 50%. Thus, it is likely that the overall survival of patients with ESKD will improve if a greater proportion of patients receive transplants in a timely manner. Reducing allograft rejection and the need for repeat transplants may help reduce the demand for donor kidneys. However, this is unlikely to have a major effect on the organ shortage, since the number of repeat transplants has been relatively small (and constant) over the past decade. Thus, only if more cadaveric and living-donor kidneys are made available will more ESKD patients enjoy the improved survival of kidney transplantation.

Adolescent↗
PubMed2000

Experience with anti-angiogenic therapy of giant cell granuloma of the facial bones.

Interferon alfa-2a inhibits angiogenesis and was discovered through a series of laboratory experiments that began in 1980. It was first used in 1989 in the management of a child with pulmonary haemangiomatosis. Interferon alfa A was then subsequently use to treat life threatening haemangiomas and other vascular tumours in various organs. Kaban reported on anti-angiogenic therapy of a recurrent giant cell tumour of the mandible in a 5 year old girl with interferon alfa-2a reasoning that as it was a rapidly proliferating vascular lesion it could be treated as an haemangioma. This paper reviews the history and role of interferon alfa-2a as an angiogenesis inhibitor in the treatment of complex haemangiomas and presents its use in the successful management of a rapidly growing central giant cell granuloma in a 4 year old boy in Australia.

Angiogenesis Inhibitors↗