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Biomedical subjects

V Webb

Publications and source records attributed to V Webb.

16 recordsLinked to original sources

Linkage disequilibrium mapping provides further evidence of a gene for reading disability on chromosome 6p21.3-22.

Linkage disequilibrium (LD) mapping was used to follow up reports of linkage between reading disability (RD) and an 18 cM region of chromosome 6p21.3-22. Using a two-stage approach, we tested for association between RD and 22 microsatellite markers in two independent samples of 101 (Stage 1) and 77 (Stage 2) parent/proband trios in which RD was rigorously defined. The most significant replicated associations were observed between combinations of markers D6S109/422/1665 (Stage 1, P=0.002 (adjusted for multiple testing); Stage 2, P=0.0001) and D6S506/1029/1660 (Stage 1, P=0.02 (adjusted), Stage 2, P=0.0001). The only two-marker association observed in both samples was with D6S422/1665 (P=0.01, 0.04). No single marker showed replicated association but D6S506 produced values of P=0.01 and 0.08 which were significant when combined (P=0.02). We observed weaker and less consistent evidence of association in a region of confirmed linkage to RD in previous studies. The most consistently significant haplotypic association D6S109/422/1665, showed association with single-word reading, spelling, phonological awareness, phonological decoding, orthographic accuracy and random automised naming, but not with vocabulary or Attention Deficit Hyperactivity Disorder. Our findings strongly support the presence of a gene contributing to RD in a region of chromosome 6 between markers D6S109 and D6S1260, but do not rule out the presence of a gene between D6S1556 and MOG.

Adolescent↗

Family-based association mapping provides evidence for a gene for reading disability on chromosome 15q.

Family-based association mapping was used to follow up reports of linkage between reading disability (RD) and a genomic region on chromosome 15q. Using a two-stage approach, we ascertained 101 (stage 1) and 77 (stage 2) parent-proband trios, in which RD was characterized rigorously. In stage 1, a set of eight microsatellite markers spanning the region of putative linkage was used and a highly significant association was detected between RD and a three-marker haplotype (D15S994/D15S214/D15S146: P and empirical P < 0.001). A significant association with the same three-marker haplotype was also observed in the second-stage sample (P = 0.009, empirical P = 0.006). Our data therefore provide strong evidence for one or more genes contributing to RD being located in the vicinity of the region including D15S146 and D15S994. In addition, our results provide support for association analysis being a useful method to map susceptibility loci for complex disorders.

Chromosome Mapping↗

A systematic review of treatments for settling problems and night waking in young children.

OBJECTIVES: To assess the efficacy of treatments for settling problems and night waking in young children. DESIGN: A systematic review of randomised controlled trials of interventions for settling problems and night waking in young children. SETTING: Electronic bibliographic databases and references on identified papers, hand searches, and personal contact with specialists. SUBJECTS: Children aged 5 years or less who had established settling problems or night waking. INTERVENTIONS: Interventions had to be described and a placebo, waiting list, or another intervention needed to have been used as a comparison. Interventions comprised drug trials or non-drug trials. MAIN OUTCOME MEASURES: Number of wakes at night, time to settle, or number of nights in which these problems occurred. RESULTS: Drugs seemed to be effective in treating night waking in the short term, but long term efficacy was questionable. In contrast, specific behavioural interventions showed both short term efficacy and possible longer term effects for dealing with settling problems and night waking. CONCLUSIONS: Given the prevalence and persistence of childhood sleep problems and the effects they can have on children and families, treatments that offer long lasting benefits are appealing and these are likely to be behavioural interventions.

Behavior Therapy↗

Urological cancers: do early detection strategies exist?

OBJECTIVE: To determine the perceptions of healthcare professionals and the general public about the symptoms, diagnosis and available treatment of urological cancers, and thus the perceived value of screening for their early detection. SUBJECTS AND METHODS: Two questionnaires were developed, based on semi-structured interviews, and distributed to 288 healthcare professionals, comprising 182 general practitioners (GPs), 56 practice nurses and 50 urology nurses, and to 250 members of the general public in three different socio-economic groups. The questionnaires asked about the symptoms, diagnosis and treatment of prostate, bladder and testicular cancer, and whether the respondents considered that screening for these cancers would be useful in ameliorating morbidity or death from these diseases. RESULTS: The response rate was very poor (13 of the GPs, 7%; 34 of the nurses, 32%; and 58 members of the general public, 23%). This severely limited the interpretation of the results, but the responses highlighted areas which need addressing. Obvious symptoms were well understood by all the groups but less well-known symptoms could be missed. No GP supported screening for prostate cancer and only seven of the GPs believed in teaching testicular self-examination, but practice nurses were considerably more active in all aspects of patient education. The general public felt that they needed more information to make decisions about urological cancers, although there was a general feeling that 'screening saved lives'. CONCLUSION: This survey showed that no healthcare professional seems to have a clearly defined role in informing potential patients about screening. The general public, who seem to perceive from the media that early detection is beneficial, are confused by the lack of clarity about policies for urological cancers.

Adolescent↗

A systematic review of treatment of settling problems and night waking in young children

OBJECTIVE: To assess the efficacy of treatment of settling problems and night waking in young children. DESIGN: A systematic review of randomized controlled trials of interventions. SETTING: Electronic bibliographic databases and references on identified papers, hand searches, and personal contact with specialists. SUBJECTS: Children aged 5 years or younger who had established settling problems or night waking. INTERVENTIONS: Interventions had to be described and a placebo, waiting list, or another intervention needed to have been used as a comparison. Interventions comprised drug trials or nondrug trials. Main outcome measures Number of wakes at night, time to settle, or number of nights in which these problems occurred. RESULTS: Drugs seemed to be effective in treating night waking in the short term, but long-term efficacy was questionable. In contrast, specific behavioral interventions showed both short-term efficacy and possible longer term effects for dealing with settling problems and night walking. CONCLUSIONS: Given the prevalence and persistence of childhood sleep problems and the effects they can have no children and families, treatments that offer long-lasting benefits are more appealing, and these are likely to be behavioral interventions.

Journal Article↗

Antibiotic preparations contain DNA: a source of drug resistance genes?

Fluorescence measurements and polymerase chain reaction amplification of streptomycete 16S ribosomal DNA sequences were used to show that a number of antibiotic preparations employed for human and animal use are contaminated with chromosomal DNA of the antibiotic-producing organism. The DNA contains identifiable antibiotic resistance gene sequences; the uptake of this DNA by bacteria and its functional incorporation into bacterial replicons would lead to the generation of antibiotic resistance determinants. We propose that the presence of DNA encoding drug resistance in antibiotic preparations has been a factor in the rapid development of multiple antibiotic resistance in bacteria.

Anti-Bacterial Agents↗

The SpoOA protein of Bacillus subtilis is a repressor of the abrB gene.

The spoOA gene of Bacillus subtilis is critical for the initial stages in the developmental cycle leading to the formation of an endospore. We show that one function of the SpoOA protein is to negatively regulate another regulatory locus, abrB, which controls the expression of many genes associated with the onset of sporulation. Purified SpoOA protein binds to a specific region of the abrB promoter and functions as a repressor of transcription in an in vitro assay. The binding of the SpoOA protein is independent of the binding of the AbrB protein, which is known to autoregulate its expression. This independence mirrors the temporal sequence of events in abrB control.

Bacillus subtilis↗

The cardiovascular actions of centrally administered neuropeptide Y.

The cardiovascular actions of intracerebroventricular (i.c.v.) administration of neuropeptide Y (NPY) were examined in conscious, unrestrained rats. A prolonged decrease in heart rate (HR) and a fall in mean arterial pressure (MAP) were obtained following i.c.v. administration of NPY (1 and 10 micrograms). Passive immunization with an antiserum directed against NPY confirmed that the slowing of HR following i.c.v. administration of NPY was mediated via a central nervous mechanism and not from leakage of NPY out of the brain. Administration of NPY into different brain parenchymal regions identified a putative site of action in the rostral region of the solitary tract. The mechanism of the decrease in HR caused by centrally administered NPY was investigated by i.c.v. administration of NPY to animals that were pretreated with agents that altered autonomic tone. Administration of NPY to atropine-treated animals produced a reversal of the atropine-induced tachycardia, suggesting that the NPY-induced decrease in HR was not due to augmented vagal tone. However, administration of NPY to animals pretreated with propranolol did not significantly lower HR below that obtained with propranolol alone. These data suggest that i.c.v. administration of NPY may cause a decrease in cardiac sympathetic outflow. The effects of centrally administered NPY on baroreflex function were studied. The changes in HR caused by NPY did not significantly alter baroreflex set-point or gain. These studies provide evidence that NPY acted within a brainstem region to decrease sympathetic nervous outflow, resulting in a decrease in HR and MAP.

Animals↗

Corticotropin-releasing factor: a physiologic regulator of adrenal epinephrine secretion.

Pituitary adrenocorticotropic hormone (ACTH) secretion following stress is mediated primarily by the release of corticotropin-releasing factor (CRF) from the brain. We have hypothesized that stress-induced alterations of autonomic nervous system activity also may be dependent on CRF release within the brain because administration of CRF into the brain produces changes in autonomic nervous system function that are similar to those observed following exposure to various types of stress. We now report confirmation of this hypothesis with studies using a CRF receptor antagonist. The CRF receptor antagonist, alpha-helical CRF9-41, placed into the brains of rats suppressed stress-induced elevations of plasma epinephrine levels. Thus, CRF appears to be physiologically involved in coordinating the pituitary and autonomic nervous system responses to stress.

Adrenal Medulla↗

Older man's burden.

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Aged↗