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Biomedical subjects

B Roe

Publications and source records attributed to B Roe.

At least 19 recordsLinked to original sources
PubMed2001

A novel member of the WD-repeat gene family, WDR11, maps to the 10q26 region and is disrupted by a chromosome translocation in human glioblastoma cells.

Allelic deletions of 10q25-26 and 19q13.3-13.4 are the most common genetic alterations in glial tumors. We have identified a balanced t(10;19) reciprocal translocation in the A172 glioblastoma cell line which involves both critical regions on chromosomes 10 and 19. In addition, loss of an entire copy of chromosome 10 has occurred in this cell line suggesting that the translocation event may provide a highly specific critical inactivating event in a gene responsible for tumorigenesis. Positional cloning of this translocation breakpoint resulted in the identification of a novel chromosome 10 gene, WDR11, which is a member of the WD-repeat gene family. The WDR11 gene is ubiquitously expressed, including normal brain and glial tumors. WDR11 is composed of 29 exons distributed over 58 kilobases and oriented towards the telomere. The translocation resulted in deletion of exon 5 and consequently fusion of intron 4 of WDR11 to the 3' untranslated region of a novel member, ZNF320, of the Krüppel-like zinc finger gene family. Since ZNF320 is oriented toward the centromere of chromosome 19, both genes appeared on the same derivative chromosome der(10). The chimeric transcript encodes the WDR11 polypeptide, which is truncated after the second of six WD-repeats. ZNF320 is also expressed in A172 cells, although it is not clear if the translocation affects the expression of the altered gene because of the presence of another unrearranged gene on chromosome 19. We suggest that, because of its localization in a region frequently showing LOH and the observation of inactivation of this gene in glioblastoma cells, WDR11 is a candidate gene for the frequently proposed tumor suppressor gene in 10q25-26 which is involved in tumorigenesis of glial and other tumors showing frequent alterations in the distal 10q region.

Alleles↗
PubMed2001

Public awareness and health education: findings from an evaluation of health services for incontinence in England.

Improving the health and well being of local populations is a feature of international and national health policy and initiatives. Promotion of health has been attempted traditionally via health education and public awareness campaigns. More recently, attention has been drawn to inter-agency collaboration and alliances in formalised health improvement programmes. This study has evaluated health services for incontinence in two health authorities in England in relation to health education and public awareness. One health authority had an established continence service and the other did not. A convenience sample of self selecting respondents from an earlier postal survey were interviewed via the telephone (n=376). Significantly, more people in the health authority with a continence service than the one without received information on incontinence from within formal health services (p<0.001) and read about services in health centres and clinics (p<0.001), whereas people in the health authority without a continence service were more likely to obtain information on incontinence from local newspapers (p<0.01) and local chemist shops (p<0.01). People in the health authority without a continence service were significantly more likely to feel that services could be improved than those where there was a service (p<0.0001). Only a minority of people with incontinence had received information about their condition or related health care and services. The availability of a continence service significantly influenced the information received. More information on incontinence had been obtained from informal sources than formal health sources. Local initiatives on the availability of services and how to access them, as well as health education information on incontinence may be more effective in raising public awareness and should supplement national campaigns.

Adult↗
PubMed2001

A SNP resource for human chromosome 22: extracting dense clusters of SNPs from the genomic sequence.

The recent publication of the complete sequence of human chromosome 22 provides a platform from which to investigate genomic sequence variation. We report the identification and characterization of 12,267 potential variants (SNPs and other small insertions/deletions) of human chromosome 22, discovered in the overlaps of 460 clones used for the chromosome sequencing. We found, on average, 1 potential variant every 1.07 kb and approximately 18% of the potential variants involve insertions/deletions. The SNPs have been positioned both relative to each other, and to genes, predicted genes, repeat sequences, other genetic markers, and the 2730 SNPs previously identified on the chromosome. A subset of the SNPs were verified experimentally using either PCR-RFLP or genomic Invader assays. These experiments confirmed 92% of the potential variants in a panel of 92 individuals. [Details of the SNPs and RFLP assays can be found at http://www.sanger.ac.uk and in dbSNP.]

Base Composition↗
PubMed2000

A transcription map of the minimally deleted region from 13q14 in B-cell chronic lymphocytic leukemia as defined by large scale sequencing of the 650 kb critical region.

Extensive analysis of tumors has demonstrated homozygous and heterozygous deletions in chromosome region 13q14.3 in B-cell chronic lymphocytic leukemia (B-CLL), suggesting the site of a tumor suppressor gene. Since previous searches for this gene have not yielded any viable candidates, we now present the sequence of the BACs which span the minimally deleted approximately 650 kb region between markers D13S319 and D13S25. This sequence has allowed us to create the definitive transcription map for the region which reveals 93 ESTs and 12 Unigene clusters in this region. Using gene prediction programs, a further 19 potential genes are also identified. The genes show an asymmetrical distribution throughout the region with most of them clustering at the extreme ends. This sequencing effort provides for the definitive structure of the B-CLL deletion region and the identification of the vast majority of the potential candidate genes. Of all the genes identified, only three have homologies to known genes: two L1 repeat genes and rabbit epididymal protein 52. This 13q14.3 sequence provides the final substrate from which to characterize the B-CLL tumor suppressor gene.

Chromosomes, Artificial, Bacterial↗
PubMed2000

An approach for obtaining perfect hybridization probes for unknown polyketide synthase genes: a search for the epothilone gene cluster.

An approach is described for obtaining 'perfect probes' for type I modular polyketide synthase (PKS) gene clusters that in turn enables the identification of all such gene clusters in a genome. The approach involves sequencing small fragments of a random genomic DNA library containing one or more modular PKS gene clusters, and identifying which fragments emanate from PKS genes. Knowing the approximate sizes of the genome and the target gene cluster, one can predict the the frequency that a PKS gene fragment will be present in the library sequenced. Computer simulations of the approach were applied to the known PKS and non-ribosomal peptide synthetase (NRPS) gene clusters in the Bacillus subtilus genome. The approach was then used to identify PKS gene fragments in a strain of Sorangium cellulosum that produces epothilone. In addition to identifying fragments of the epothilone gene cluster, we obtained 11 unique fragments from other PKS gene clusters; the results suggest that there may be six to eight PKS gene clusters in this organism. In addition, we identified four unique fragments of NRPS genes, demonstrating that the approach is also applicable for identification of these modular gene clusters.

Antineoplastic Agents↗
PubMed2000

Comparative sequence analysis of 634 kb of the mouse chromosome 16 region of conserved synteny with the human velocardiofacial syndrome region on chromosome 22q11.2.

Mouse genomic DNA sequence extending 634 kb on proximal mouse chromosome 16 was compared to the corresponding human sequence from chromosome 22q11.2. Haploinsufficiency for this region results in velocardiofacial syndrome (VCFS) in humans. The mouse region is rearranged into three conserved blocks relative to human, but gene content and position are highly conserved within these blocks. Examination of the boundaries of one of these blocks suggested that the evolutionary chromosomal rearrangement occurred in the mouse lineage, resulting in inactivation of the mouse orthologue of ZNF74. Sequence analysis identified 21 genes and 15 ESTs. These include 2 novel genes, Srec2 and Cals2, and previously undescribed splice variants of several other genes. Exon discovery was carried out using GRAIL2, MZEF, or comparative analysis across 491 kb of conserved mouse and human sequence. Sequence comparison was highly effective, identifying every gene and nearly every exon without the high frequency of false-positive predictions seen when algorithmic methods were used alone. In combination, these procedures identified every gene with no false-positive predictions. Comparative sequence analysis also revealed regions of extensive conservation among noncoding sequences, accounting for 6% of the sequence. A library of such sequences has been established to form a resource for generalized studies of regulatory and structural elements.

Abnormalities, Multiple↗
PubMed2000

Sequence, structure, and evolution of a complete human olfactory receptor gene cluster.

The olfactory receptor (OR) gene cluster on human chromosome 17p13.3 was subjected to mixed shotgun automated DNA sequencing. The resulting 412 kb of genomic sequence include 17 OR coding regions, 6 of which are pseudogenes. Six of the coding regions were discovered only upon genomic sequencing, while the others were previously reported as partial sequences. A comparison of DNA sequences in the vicinity of the OR coding regions revealed a common gene structure with an intronless coding region and at least one upstream noncoding exon. Potential gene control regions including specific pyrimidine:purine tracts and Olf-1 sites have been identified. One of the pseudogenes apparently has evolved into a CpG island. Four extensive CpG islands can be discerned within the cluster, not coupled to specific OR genes. The cluster is flanked at its telomeric end by an unidentified open reading frame (C17orf2) with no significant similarity to any known protein. A high proportion of the cluster sequence (about 60%) belongs to various families of interspersed repetitive elements, with a clear predominance of LINE repeats. The OR genes in the cluster belong to two families and seven subfamilies, which show a relatively high degree of intermixing along the cluster, in seemingly random orientations. This genomic organization may be best accounted for by a complex series of evolutionary events.

Base Sequence↗
PubMed2000

Bladder training for urinary incontinence in adults.

BACKGROUND: Bladder training is widely used for the treatment of urinary incontinence. It is generally used for the treatment of people with urge incontinence or detrusor instability, although it is also thought that it might be of use for people with mixed incontinence or stress incontinence. OBJECTIVES: To assess the effects of bladder training for the treatment of urinary incontinence. SEARCH STRATEGY: We searched the Cochrane Incontinence Group trials register up to July 1999. Date of the most recent search: July 1999. SELECTION CRITERIA: Randomised or quasi-randomised trials of bladder training for the treatment of incontinence. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data that were then cross-checked by the third reviewer. All three reviewers assessed trial quality. MAIN RESULTS: We found seven eligible trials with a total of 259 predominantly female patients with urinary urge incontinence. The quality of trials was variable. Three trials involving 92 women compared bladder training with no bladder training. These tended to favour bladder training but data were available for only a limited number of pre-specified outcomes that varied across the three trials. No data describing long term follow up are available. One trial compared bladder training with drug therapy, but was inconclusive. Another trial compared bladder training with an electronic prompt device. The trial was small and included only 20 women. Data were not presented in a form suitable for quantitative analysis. Two further trials compared bladder training supplemented by drug therapy with bladder training alone. Again, the limited data provided insufficient evidence on which to draw conclusions. REVIEWER'S CONCLUSIONS: Bladder training may be helpful for the treatment of urinary urge incontinence, but this conclusion can only be tentative, based on the evidence available. There was not enough evidence to show whether drug therapy was better than bladder training or useful as a supplement to it.

Adult↗
PubMed2000

Prompted voiding for the management of urinary incontinence in adults.

BACKGROUND: Prompted voiding is a behavioural therapy used mainly in North American nursing homes. It aims to improve bladder control for people with or without dementia using verbal prompts and positive reinforcement. OBJECTIVES: To assess the effects of prompted voiding for the management of urinary incontinence in adults. SEARCH STRATEGY: We searched the Cochrane Incontinence Group trials register (to February 2000) and reference lists of relevant articles. We contacted investigators in the field to locate extra studies. Date of the most recent searches: February 2000. SELECTION CRITERIA: All randomised or quasi-randomised trials which addressed prompted voiding for the management of urinary incontinence. The trials included adult men and women, with or without cognitive impairment, diagnosed as having urinary incontinence as identified by the trialists, either by symptom classification or by urodynamic investigation. DATA COLLECTION AND ANALYSIS: The identified reports were assessed for eligibility. Two reviewers independently reviewed the selected studies for methodological quality. Data describing six pre-specified outcomes were extracted independently by each reviewer and consensus reached when there was disagreement. Trial investigators were consulted when clarification or further detail was required. A third reviewer was recruited to proof read the review at different stages. MAIN RESULTS: Five trials were included in the review. These involved 355 elderly people, most of whom were women. One other trial was excluded because no relevant outcome data were reported, and one trial is awaiting assessment. Prompted voiding was compared with no prompted voiding in four trials. The limited evidence suggested that prompted voiding increased self-initiated voiding and decreased incontinent episodes in the short-term. There was no evidence about long-term effects. A single small trial suggested that adding the muscle relaxant, Oxybutinin, reduced the number of incontinent episodes in the short-term: This study used a cross-over design and so did not address long-term effects. REVIEWER'S CONCLUSIONS: There was insufficient evidence to reach firm conclusions for practice. There was suggestive, although inconclusive, evidence of short-term benefit from prompted voiding and from adding the muscle relaxant, Oxybutinin to prompted voiding.

Adult↗
PubMed2000

Prevalence of urinary incontinence and its relationship with health status.

A postal survey of two random samples of adult populations within two health authorities in the UK was undertaken during 1994. One health authority had an established continence advisory service (HA1) and the other one did not have a continence advisory service (HA2). A total of 12,529 patients (HA1, 6319; HA2, 6210) were mailed a structured questionnaire and 53% (n = 6139) returned completed questionnaires. A point prevalence of current urinary incontinence of 9% (n = 519, 95% CI, or confidence interval, from 7.9% to 9.3%) was found. A large number of people within the populations had experienced urinary incontinence at some time during their adult years (23%, n = 1427, 95% CI from 22.2% to 24.3%). People who were incontinent had a significantly lower health status than people who were continent (mean scores across all eight domains of the Short Form 36, SF36, P < 0.0001), indicative of greater health and social care needs. The prevalence of urinary incontinence in the adult populations of two communities indicates that it is a sizeable public health and primary healthcare issue.

Activities of Daily Living↗
PubMed2000

VI. Genome structure and cognitive map of Williams syndrome.

Williams syndrome (WMS) is a most compelling model of human cognition, of human genome organization, and of evolution. Due to a deletion in chromosome band 7q11.23, subjects have cardiovascular, connective tissue, and neurodevelopmental deficits. Given the striking peaks and valleys in neurocognition including deficits in visual-spatial and global processing, preserved language and face processing, hypersociability, and heightened affect, the goal of this work has been to identify the genes that are responsible, the cause of the deletion, and its origin in primate evolution. To do this, we have generated an integrated physical, genetic, and transcriptional map of the WMS and flanking regions using multicolor metaphase and interphase fluorescence in situ hybridization (FISH) of bacterial artificial chromosomes (BACs) and P1 artificial chromosomes (PACs), BAC end sequencing, PCR gene marker and microsatellite, large-scale sequencing, cDNA library, and database analyses. The results indicate the genomic organization of the WMS region as two nested duplicated regions flanking a largely single-copy region. There are at least two common deletion breakpoints, one in the centromeric and at least two in the telomeric repeated regions. Clones anchoring the unique to the repeated regions are defined along with three new pseudogene families. Primate studies indicate an evolutionary hot spot for chromosomal inversion in the WMS region. A cognitive phenotypic map of WMS is presented, which combines previous data with five further WMS subjects and three atypical WMS subjects with deletions; two larger (deleted for D7S489L) and one smaller, deleted for genes telomeric to FZD9, through LIMK1, but not WSCR1 or telomeric. The results establish regions and consequent gene candidates for WMS features including mental retardation, hypersociability, and facial features. The approach provides the basis for defining pathways linking genetic underpinnings with the neuroanatomical, functional, and behavioral consequences that result in human cognition.

Adolescent↗
PubMed2000

Molecular basis of variant pseudo-hurler polydystrophy (mucolipidosis IIIC)

Mucolipidosis IIIC, or variant pseudo-Hurler polydystrophy, is an autosomal recessive disease of lysosomal hydrolase trafficking. Unlike the related diseases, mucolipidosis II and IIIA, the enzyme affected in mucolipidosis IIIC (N-Acetylglucosamine-1-phosphotransferase [GlcNAc-phosphotransferase]) retains full transferase activity on synthetic substrates but lacks activity on lysosomal hydrolases. Bovine GlcNAc-phosphotransferase has recently been isolated as a multisubunit enzyme with the subunit structure alpha(2)beta(2)gamma(2). We cloned the cDNA for the human gamma-subunit and localized its gene to chromosome 16p. We also showed, in a large multiplex Druze family that exhibits this disorder, that MLIIIC also maps to this chromosomal region. Sequence analysis of the gamma-subunit cDNA in patients from 3 families identified a frameshift mutation, in codon 167 of the gamma subunit, that segregated with the disease, indicating MLIIIC results from mutations in the phosphotransferase gamma-subunit gene. This is to our knowledge the first description of the molecular basis for a human mucolipidosis and suggests that the gamma subunit functions in lysosomal hydrolase recognition.

Amino Acid Sequence↗
PubMed2000

Effective and ineffective management of incontinence: issues around illness trajectory and health care.

In this article, findings from a study that investigated the impact of incontinence on individuals and the impact of effective and ineffective health interventions for the management of incontinence on patient careers and health care are reported. Twenty-seven participants whose incontinence was judged by health professionals as being successfully managed or unsuccessfully managed were interviewed. The participants were 19 women and 8 men (mean age: 61 years). Twenty-two participants experienced urinary incontinence, 4 people experienced both urinary and fecal incontinence, and 1 woman experienced fecal constipation. The findings have been set in the context of the management of chronic conditions and provide illuminating evidence that may be useful when reviewing health care and health services. People who were actively involved with their care and who were involved with decision making felt that their incontinence was being effectively managed. Multiple referrals and the marshaling and targeting of health professionals and services also appeared to be associated with effective management of incontinence.

Adaptation, Psychological↗
PubMed1999

Sequence-ready physical map of the mouse chromosome 16 region with conserved synteny to the human velocardiofacial syndrome region on 22q11.2.

Proximal mouse Chromosome (Chr) 16 shows conserved synteny with human Chrs 16, 8, 22, and 3. The mouse Chr 16/human Chr 22 conserved synteny region includes the DiGeorge/Velocardiofacial syndrome region of human Chr 22q11.2. A physical map of the entire mouse Chr 16/human Chr 22 region of conserved synteny has been constructed to provide a substrate for gene discovery, genomic sequencing, and animal model development. A YAC contig was constructed that extends ca. 5.4 Mb from a region of conserved synteny with human Chr 8 at Prkdc through the region conserved with human Chr 3 at DVL3. Sixty-one markers including 37 genes are mapped with average marker spacing of 90 kb. Physical distance was determined across the 2.6-Mb region from D16Mit74 to Hira with YAC fragmentation. The central region from D16Jhu28 to Igl-C1 was converted into BAC and PAC clones, further refining the physical map and providing sequence-ready template. The gene content and borders of three blocks of conserved linkage between human Chr 22q11.2 mouse Chr 16 are refined.

Animals↗
PubMed1999

Help seeking behaviour and health and social services utilisation by people suffering from urinary incontinence.

It is estimated that urinary incontinence can effect up to 23% of the population at some time during their adult years, with 9% currently experiencing symptoms. This study found that the majority of sufferers had spoken to or had contacted their GP about their incontinence, and that people currently suffering from incontinence were significantly more likely to have seen their GP within the last month than those who were continent. Help seeking behaviour was also influenced by the severity of incontinence, with people suffering from severe incontinence significantly more likely to have sought help than those with light to moderate incontinence. Two thirds of sufferers who did not seek help were too embarrassed to do so. Significantly more people who were incontinent that did not seek help in a health authority without an established continence service did not know that health services were available, compared with those in a health authority having an established continence service. It is important for health care providers to ensure that the public knows what services are on offer and how to access them. Significantly more incontinence sufferers in the health authority with an established continence service chose not to seek help from a health professional compared with those in the health authority without service, which could indicate there was an element of informed choice in not accessing the services available. Significantly more people who were incontinent than continent required help with their activities of daily living and personal self care. They were also significantly more likely than those who were continent to require formal and informal contacts provided by health services, local authority, the church or voluntary sector. It is important that people suffering from incontinence have their health and social needs assessed so that services can be effectively targeted.

Activities of Daily Living↗
PubMed1999

Lifestyle factors and continence status: comparison of self-report data from a postal survey in England.

OBJECTIVE: To compare health and lifestyle factors of people with and without urinary incontinence (UI). DESIGN: A postal survey was undertaken that represents the first of a 3-stage project designed to evaluate the health interventions of primary health care teams and continence advisory services on patient outcomes related to UI. SETTING AND SUBJECTS: Two random samples of adult populations (N = 12,529) were included, generated from the family physician patient registers within 2 health authorities in England. INSTRUMENTS: Data were collected using a structured questionnaire that queried demography, perceived health status, activities of daily living, self-care, and use of local health and social services. Information was also collected on past and present continence status. METHODS: Structured questionnaires and a cover letter were mailed to the target population. Two reminders were sent to nonresponders to maximize the response rate. MAIN OUTCOME MEASURES: The main measures relate to factors associated with UI: mobility, sleep, childbirth, smoking, diet, body mass index, and accommodation. RESULTS: Significantly more women than men had UI (P < .0001). Respondents with UI were older than those who were continent (P < .0001). Women with UI were significantly more likely to have a greater number of pregnancies (P < .0001), were more likely to have given birth to a baby weighing more than 9 lb (P < .01), and to have had more than 4 children (P = .01) compared with women who were continent. People with UI were less likely to be single and more likely to be widowed than those who were continent (P < .0001). People who lived alone and who had UI were also significantly less likely to have a relative or friend that they could depend on for help than those who were continent (P < .001). UI was also found to be significantly associated with impaired mobility (P < .0001) and sleeping difficulties (P < .0001). No meaningful differences were found between diet and UI, although significantly more people with UI had higher mean body mass index, were obese, or reported that they felt too heavy for their height when compared with people who were continent (P < .0001). No association was found in the present study with smoking or ethnicity and UI. CONCLUSIONS: Key health and lifestyle factors associated with UI included age, gender, childbirth, mobility, sleep patterns, obesity, living alone, and access to help. These factors should be assessed when planning and implementing health care for persons with UI. Attention to these associated factors may prove useful in identifying new cases or people at risk of developing UI when screening people as part of routine health checks. This, in turn, could assist with targeting effective and efficient health care but may also contribute to prevention for some people.

Activities of Daily Living↗
PubMed1999

Incontinence and sexuality: findings from a qualitative perspective.

Incontinence remains a taboo where myths and misconceptions abound. The objectives of this study were to explore the impact of incontinence on an individual's sexuality and to identify the impact of health interventions for the management of incontinence on sexuality. A quota sample of subjects whose incontinence was regarded as being either successfully managed (n = 14) or unsuccessfully managed (n = 12) by continence advisers, community nurses and health visitors from two National Health Service Trusts were interviewed. A further subject whose incontinence was not classified was also interviewed, bringing the total number of interviews to 27. One Trust had an established continence advisory service of some 19 years, while the other Trust did not have a specific continence advisory service and relied upon members of the primary health care team to meet the needs of individuals suffering from incontinence. The qualitative data from this study were analysed using the constant comparative technique and were grouped into themes relating to clothing and appearance, intimacy and caring, management techniques and relationships and life trajectory. This is the first study to have examined management techniques for incontinence and their relationship to an individual's sexuality and therefore has important implications for clinical practice. It has also set the findings of incontinence and sexuality in the context of chronic conditions and their related patient careers and life trajectory.

Adult↗