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B Roe

Publications and source records attributed to B Roe.

At least 19 recordsLinked to original sources
PubMed1998

Characterization of the human class Mu glutathione S-transferase gene cluster and the GSTM1 deletion.

A partial physical map has been constructed of the human class Mu glutathione S-transferase genes on chromosome 1p13.3. The glutathione S-transferase genes in this cluster are spaced about 20 kilobase pairs (kb) apart, and arranged as 5'-GSTM4-GSTM2-GSTM1-GSTM5-3'. This map has been used to localize the end points of the polymorphic GSTM1 deletion. The left repeated region is 5 kb downstream from the 3'-end of the GSTM2 gene and 5 kb upstream from the beginning of the GSTM1 gene; the right repeated region is 5 kb downstream from the 3'-end of the GSTM1 and 10 kb upstream from the 5'-end of the GSTM5 gene. The GSTM1-0 deletion produces a novel 7.4-kb HindIII fragment with the loss of 10.3- and 11.4-kb HindIII fragments. The same novel fragment was seen in 13 unrelated individuals (20 null alleles), suggesting that most GSTM1-0 deletions involve recombinations between the same two regions. We have cloned and sequenced the deletion junction that is produced at the GSTM1-null locus; the 5'- and 3'-flanking regions are more than 99% identical to each other and to the deletion junction sequence over 2.3 kb. Because of the high sequence identity between the left repeat, right repeat, and deletion junction regions, the crossing over cannot be localized within the 2.3-kb region. The 2.3-kb repeated region contains a reverse class IV Alu repetitive element near one end of the repeat.

Base Sequence↗
PubMed1998

Genetic and physical mapping of the Lps locus: identification of the toll-4 receptor as a candidate gene in the critical region.

On the basis of 2093 meioses analyzed in two separate intraspecific backcrosses, the location of the mouse Lpsd mutation was circumscribed to a genetic interval 0.9 cM in size. A total of 19 genetic markers that lie in close proximity to the mutation were examined in mapping. Most of these were previously unpublished polymorphic microsatellites, identified by fragmentation of YAC and BAC clones spanning the region of interest. Lpsd was found to be inseparable from the microsatellite marker D4MIT178, and from three novel polymorphic microsatellites identified near D4MIT178. The mutation was confined between two novel microsatellite markers, herein designated "B" and "83.3." B lies centromeric to the mutation, and was separated by four crossovers in a panel of 1600 mice; 83.3 lies distal to the mutation and was separated by three crossovers in a panel of 493 mice. 66 BAC clones and one YAC clone were assembled to cover > 95% of the critical region. Estimates based on pulsed field gel electrophoresis and fluorescence in situ hybridization indicate that the The B-->83.3 interval is about 3.2 Mb in length. A minimal area of zero recombinational distance from Lpsd was also assigned, and found to occupy approximately 1.2 Mb of physical size. To identify gene candidates, nearly 40,000 sequencing runs were performed across the critical region. Selective hybridization and exon trapping were also employed to identify genes throughout the "zero" region. Only a single intact gene was identified within the entire critical region. This gene encodes the Toll-4 receptor, a member of the IL-1 receptor family.

Animals↗
PubMed1998

The SOX10/Sox10 gene from human and mouse: sequence, expression, and transactivation by the encoded HMG domain transcription factor.

The SOX genes form a gene family related by homology to the high-mobility group (HMG) box region of the testis-determining gene SRY. We have cloned and sequenced the SOX10 and Sox10 genes from human and mouse, respectively. Both genes encode proteins of 466 amino acids with 98% sequence identity. Significant expression of the 2.9-kb human SOX10 mRNA is observed in fetal brain and in adult brain, heart, small intestine and colon. Strong expression of Sox10 occurs throughout the peripheral nervous system during mouse embryonic development. SOX10 shows an overall amino acid sequence identity of 59% to SOX9. Like SOX9, SOX10 has a potent transcription activation domain at its C-terminus and is therefore likely to function as a transcription factor. Whereas SOX9 maps to 17q, a SOX10 cosmid has previously been mapped by us to the region 22q13.1. Mutations in SOX10 have recently been identified as one cause of Waardenburg-Hirschsprung disease in humans, while a Sox10 mutation underlies the mouse mutant Dom, a murine Hirschsprung model.

Adult↗
PubMed1998

Telephone or face-to-face interviews?: a decision made on the basis of a pilot study.

De Vaus (1991) highlights five main considerations that may be key factors in decisions about whether to use telephone or face-to-face interviews for survey work: response rates, ability to produce representative samples, effects on interview schedule design, quality of responses and implementation problems. De Vaus' discussion of these five issues is outlined at the start of this article. The five issues are then applied to the experiences of researchers conducting a study on continence care. Description and discussion of pilot interviews, which explored both interview modes, are followed by a similar examination of the main study which employed telephone interviews. Ideas in this discussion are supported and challenged by reference to other publications on the subject of telephone and face-to-face interviews. The success of the decision to use telephone interviews in the main study is evaluated and recommendations are made.

Humans↗
PubMed1998

Consensus guidelines for the promotion and management of continence by primary health care teams: development, implementation and evaluation. NHS Executive Nursing Directorate.

A project was undertaken as part of the NHS Executive Strategy for Major Clinical Guidelines, involving the development of national clinical guidelines for the promotion and management of continence by primary health care teams, through the process of managed consensus based on scientific review. The guidelines were then implemented at one urban general practice. This article outlines the development and implementation of the guidelines and describes the study undertaken to evaluate the impact of implementation on clinical outcomes. The study involved a pre-and post-implementation postal survey of a random sample of 17% of patients aged 18 years and over from the practice (n = 1503). The pre-implementation survey determined the period prevalence of incontinence, related biological data and data on the pre-implementation management of incontinence. Incontinence sufferers were invited to have their condition assessed or reviewed. All sufferers who agreed to be followed-up were sent the post-implementation survey, which identified those patients who had sought help, and ascertained reasons for not seeking help. Data on the management of incontinence post-implementation were also obtained. Clinical outcomes measured pre- and post-implementation were a validated severity index for urinary incontinence, (also adapted for faecal incontinence) and perception of the incontinence as a problem. A 3-month period was allowed between pre- and post-implementation surveys. The study confirmed previous research which showed that few incontinence sufferers respond to invitations to seek help, and that help-seeking behaviour was significantly related to severity of incontinence. The guidelines did not have any positive impact on the clinical outcomes measured, although slight improvements in approaches taken by the primary health care team to the promotion and management of continence were recorded. However, the study was limited by the small sample size and short time scale. Further evaluation of the impact of the guidelines on these outcomes is therefore recommended.

Female↗
PubMed1998

Interviewing older people by telephone following initial contact by postal survey.

Although the use of the telephone for interviewing has become a commonly used and largely accepted research method, the literature on this subject makes it clear that certain reservations remain. Some of these relate to problems encountered when interviewing older adults by telephone and others concern the use of the telephone in interviews where there has been no prior face-to-face contact. The conclusions of others who have studied these two sets of problems in combination are that special difficulties exist. These conclusions are examined with reference to researchers' experiences of conducting a study on continence care, in which a postal survey (as opposed to face-to-face contact) preceded telephone interviews. Interviews were conducted with adults of all ages, including a high proportion of older people. Researchers encountered few major difficulties and were satisfied with both response rate and response quality. Research to compare the effects of a variety of initial contact modes on telephone interviews with both younger and older adults is recommended.

Aged↗
PubMed1998

The effect of work status on initiation and duration of breast-feeding.

OBJECTIVES: In this study, longitudinal data are used to examine the effect of work status on breast-feeding initiation and duration. METHODS: Mothers from a mail panel completed questionnaires during late pregnancy and 10 times in the infant's first year. Mother's work status was categorized for initiation by hours she expected, before delivery, to work and for duration by hours she worked at month 3. Covariates were demographics; parity; medical, delivery, and hospital experiences; social support; embarrassment; and health promotion. RESULTS: Expecting to work part-time neither decreased nor increased the probability of breast-feeding relative to expecting not to work (odds ratios [ORs] = .83 and .89, P > .50), but expecting to work full-time decreased the probability of breast-feeding (OR = .47, P < .01). Working full-time at 3 months postpartum decreased breast-feeding duration by an average of 8.6 weeks (P < .001) relative to not working, but part-time work of 4 or fewer hours per day did not affect duration, and part-time work of more than 4 hours per day decreased duration less than full-time work. CONCLUSION: Part-time work is an effective strategy to help mothers combine breast-feeding and employment.

Breast Feeding↗
PubMed1997

Molecular characterization of a serine/threonine kinase in the DiGeorge minimal critical region.

The majority of patients with DiGeorge, velocardiofacial or conotruncal anomaly facial syndromes share a common genetic etiology, deletion of chromosomal region 22q11.2. This report describes a computational approach toward the identification and molecular characterization of a newly identified serine/threonine kinase from the minimal critical deleted region (MDGCR). A cosmid contig of the minimal critical region has been assembled and sequenced in its entirety. Database searches and computer analysis of one cosmid (111f11) for coding sequences identified two regions with high similarity to the mouse serine/threonine kinase, Tsk1. Our investigations demonstrate that one of these regions contains a testis-specific gene that undergoes differential splicing, while the other region is most likely a pseudogene. Northern blot analysis and cDNA cloning demonstrate that there is alternate processing of the 3'UTR without altering the conserved kinase domains within the open reading frame. Serine/threonine kinases can play a regulatory role and have been found to be expressed during early embryogenesis. Based on its position in the MDGCR and possible function, the gene reported here is a candidate for the features seen in the 22q11 deletion syndrome.

Alternative Splicing↗
PubMed1997

Isolation and characterization of a gene from the DiGeorge chromosomal region homologous to the mouse Tbx1 gene.

DiGeorge syndrome, velocardiofacial syndrome, conotruncal anomaly face syndrome, and isolated and familial forms of conotruncal cardiac defects have been associated with deletions of chromosomal region 22q11.2. This report describes the identification, cloning, and characterization of the human TBX1 gene, which maps to the center of the DiGeorge chromosomal region. Further, we have extended the mouse cDNA sequence to permit comparisons between human and mouse Tbx1. TBX1 is a member of a phylogenetically conserved family of genes that share a common DNA-binding domain, the T-box. T-box genes are transcription factors involved in the regulation of developmental processes. There is 98% amino acid identity between human and mouse TBX1 proteins overall, and within the T-box domain, the proteins are identical except for two amino acids. Expression of human TBX1 in adult and fetal tissues, as determined by Northern blot analysis, is similar to that found in the mouse. Additionally, using 3 'RACE, we obtained a differentially spliced message in adult skeletal muscle. Mouse Tbx1 has been previously shown to be expressed during early embryogenesis in the pharyngeal arches, pouches, and otic vesicle. Later in development, expression is seen in the vertebral column and tooth bud. Thus, human TBX1 is a candidate for some of the features seen in the 22q11 deletion syndrome.

Adult↗
PubMed1997

Transcript mapping in a 46-kb sequenced region at the core of 12q13.3 amplification in human cancers.

We used a combination of sequence analysis and exon trapping in an effort to determine the complete transcript map for a cosmid (6E5) derived from 12q13.3, a region of DNA sequence amplification in human cancers. This cosmid, previously known to contain three genes (CDK4, SAS, and OS9), was sequenced, and that information was used for computer-assisted analysis. In addition, 6E5 was subjected to both internal and 3'-terminal exon-trapping protocols, and the results of these studies were used to guide cDNA cloning experiments. These studies demonstrate that this cosmid is derived from a remarkably gene-dense region and add two new transcripts (KIAA0167 and 6E5.2) to the list of sequences that are expressed in tumors bearing amplification of this region.

Amino Acid Sequence↗
PubMed1997

Disseminating research evidence. A controlled trial in continence care.

The dissemination of research evidence from which clinical practice should be based poses many well-documented problems for nurses. This study set out to overcome some of the common barriers to dissemination by providing a research-based clinical handbook for continence care. The impact of the handbook on nurses' knowledge of both urinary and faecal incontinence was tested using an experimental and control group. The experimental group received the handbook while the control group did not. Both groups completed an assessment questionnaire at week 1, prior to the intervention in the experimental group, followed by a second assessment at week 7 after the intervention in the experimental group. Data were collected using semi-structured questionnaires. Statistically significant improvements in knowledge were found for those nurses who received a copy of the handbook, and nurses reported that they found the handbook useful and acceptable as a form of clinical updating. The dissemination of research findings is essential if evidence-based nursing is to become a reality, and this study clearly demonstrates one method by which this can be successfully achieved.

Aged↗
PubMed1997

Structural and mutational analysis of a conserved gene (DGSI) from the minimal DiGeorge syndrome critical region.

The majority of patients with DiGeorge syndrome (DGS), velocardiofacial syndrome (VCFS), conotruncal anomaly face syndrome (CTAFS) and some individuals with familial or sporadic conotruncal cardiac defects have hemizygous deletions of chromosome 22. Most patients with these disorders share a common large deletion, spanning > 1.5 Mb within 22q11.21-q11.23. Recently, the smallest region of deletion overlap has been narrowed to a 250 kb area, the minimal DGS critical region (MDGCR), which includes the locus D22S75 (N25). We have isolated and characterized a novel, highly conserved gene, DGSI, within the MDGCR. DGSI has 10 exons and nine introns encompassing 1702 bp of cDNA sequence and 11 kb of genomic DNA. The encoded protein has 476 amino acids with a predicted mol. wt of 52.6 kDa. The intron-exon boundaries have been analyzed and conform to the consensus GT/AG motif. The corresponding murine Dgsi has been isolated and localized to proximal mouse chromosome 16. The mouse gene contains the same number of exons and introns, and the predicted protein has 479 amino acids with 93.2% identity to that of the human DGSI gene. By database searching, both genes have significant homology to a Caenorhabditis elegans hypothetical protein, F42H10.7. Further, mutation analysis has been performed in 16 patients, who have no detectable 22q11.2 deletion and some of the characteristic clinical features of DGS/VCFS. We have detected eight sequence variants in DGSI. These occurred in the 5'-untranslated region, the coding region and the intronic regions adjacent to the intron-exon boundaries of the gene. Seven of the eight variants were also present in normal controls or unaffected family members, suggesting they may not be of etiologic significance.

Amino Acid Sequence↗
PubMed1997

Disruption of the clathrin heavy chain-like gene (CLTCL) associated with features of DGS/VCFS: a balanced (21;22)(p12;q11) translocation.

The smallest region of deletion overlap in the patients we have studied defines a DIGeorge syndrome/velocardiofacial syndrome (DGS/VCFS) minimal critical region (MDGCR) of approximately 250 kb within 22q11. A de novo constitutional balanced translocation has been identified within the MDGCR. The patient has some features which have been reported in individuals with DGS/VCFS, including: facial dysmorphia, mental retardation, long slender digits and genital anomalies. We have cloned the breakpoint of his translocation and shown that it interrupts the clathrin heavy chain-like gene (CLTCL) within the MDGCR. The breakpoint of the translocation partner is in a repeated region telomeric to the rDNA cluster on chromosome 21p. Therefore, it is unlikely that the patient's findings are caused by interruption of sequences on 21p. The chromosome 22 breakpoint disrupts the 3' coding region of the CLTCL gene and leads to a truncated transcript, strongly suggesting a role for this gene in the features found in this patient. Further, the patient's partial DGS/VCFS phenotype suggests that additional features of DGS/VCFS may be attributed to other genes in the MDGCR. Thus, haploinsufficiency for more than one gene in the MDGCR may be etiologic for DGS/VCFS.

Abnormalities, Multiple↗
PubMed1997

Using research for practice: a UK experience of the BARRIERS Scale.

It is generally recognized that the majority of health care has been largely based upon opinion rather than research evidence of clinical effectiveness. Attempts to rectify this have been initiated by increasing emphasis on the dissemination of findings. For example, in the UK this had been supported via the Cochran Collaboration and the Centre for Dissemination and Reviews. Dissemination does not, however, guarantee implementation. The complex nature of research utilization has been studied and obstacles identified that can influence the uptake of research by practising nurses. Sandra Funk and colleagues developed the BARRIERS Scale using this research and literature on research utilization. The scale may be helpful for identifying and measuring the barriers to research utilization perceived by nurses working within the UK and has formed the basis of the present study. A convenience sample of 316 comprising a broad spectrum of nurses working in the UK provided the data. Comparison is made with North American nurses from the studies used in the scale's development. The results suggest there ware items which are consistently perceived as either strong or negligible barriers by both groups of nurses. Differences, however, did emerge between nurses from the UK and North America on several items. These included the confidence in evaluating research and the perception of the nurse's authority to change patient procedures. Psychometric evaluation was also done. These findings are presented and discussed.

Cross-Cultural Comparison↗
PubMed1997

A study of the efficacy of dressings in preventing infections of continuous ambulatory peritoneal dialysis catheter exit sites.

This paper describes a preliminary investigation into the efficacy of dressings in preventing catheter exit site infections in patients undergoing continuous ambulatory peritoneal dialysis (CAPD). It has been carried out in the form of a pilot study. The background to the study is described and the literature is reviewed. This revealed that it is an important field of research. Exit site infections are the main cause of morbidity and treatment failure in CAPD patients. The rationale for carrying the study out, the findings and the implications for further study are reported and discussed. There is little guidance in current literature for clinicians on the prevention of catheter exit site infection. Patients are difficult to recruit to research studies. Practising nurses need training and careful management as data collectors.

Bandages↗
PubMed1997

The DiGeorge syndrome minimal critical region contains a goosecoid-like (GSCL) homeobox gene that is expressed early in human development.

The majority of patients with DiGeorge syndrome (DGS) and velocardiofacial syndrome (VCFS) have deletions of chromosomal region 22q11.2. The abnormalities observed in these patients include conotruncal cardiac defects, thymic hypoplasia or aplasia, hypocalcemia, and characteristic facial features. To understand the genetic basis of these disorders, we have characterized genes within the region that is most consistently deleted in patients with DGS/VCFS, the minimal DiGeorge critical region (MDGCR). In this report, we present the identification and characterization of a novel gene, GSCL, in the MDGCR, with homology to the homeodomain family of transcription factors. Further, we provide evidence that this gene is expressed in a limited number of adult tissues as well as in early human development. The identification of GSCL required a genomic sequence-based approach because of its restricted expression and high GC content. The early expression, together with the known role of homeobox-containing proteins in development, make GSCL an outstanding candidate for some of the abnormalities seen in DGS/VCFS.

Abnormalities, Multiple↗
PubMed1997

Identification of complex genomic breakpoint junctions in the t(9;11) MLL-AF9 fusion gene in acute leukemia.

The MLL gene at chromosome 11, band q23, is involved in translocations with as many as 40 different chromosomal bands. Virtually all breakpoints occur within an 8.3 kb BamHI fragment and result in 5' MLL fused to partner genes in a 5'-3' orientation. The translocation t(9;11)(p22;q23), which results in the fusion of MLL to AF9, is the most common of the 11q23 chromosomal abnormalities observed in de novo acute myeloid leukemia (AML), in therapy related leukemia (t-AML), and rarely in acute lymphoblastic leukemia (ALL). We have studied 24 patients with a t(9;11) and an MLL rearrangement, including 19 patients with AML, four with t-AML, and one with ALL. To understand the mechanisms of this illegitimate recombination, we cloned and sequenced the t(9;11) translocation breakpoint junctions on both derivative chromosomes from one AML patient and from the Mono Mac 6 (MM6) cell line, which was derived from a patient with AML. Two different complex junctions were noted. In the AML patient, both chromosome 11 and 9 breaks were staggered, occurred in Alu DNA sequences, and resulted in a 331 bp duplication. In the MM6 cell line, breaks in chromosomes 11 and 9 were also staggered, but, in contrast to the finding in the AML patient, the breaks did not involve Alu DNA sequences and resulted in a 664 bp deletion at the breakpoints. Using reverse transcriptase (RT-) PCR, we analyzed 11 patient samples, including the two just described, for MML-AF9 fusions. The fusion occurred in six of seven AML patients, two of two t-AML patients, one patient with ALL, and in the MM6 cell line. Interestingly, all of the breaks within the AF9 gene in AML patients occurred in the central AF9 exon, called Site A by others, whereas in the single ALL patient the breakpoint mapped to a more 3' region of the AF9 gene. Our data, when combined with those of others, suggest that the fusion point within the AF9 gene, and thus the amount of AF9 material included in the MLL-AF9 fusion gene product, may influence the phenotype of the resulting leukemia. This further supports the proposal that the MML translocation partner genes play a critical role in the leukemogenic process.

Acute Disease↗