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D J Sharp

Publications and source records attributed to D J Sharp.

At least 19 recordsLinked to original sources
PubMed2006

Model of chromosome motility in Drosophila embryos: adaptation of a general mechanism for rapid mitosis.

During mitosis, ensembles of dynamic MTs and motors exert forces that coordinate chromosome segregation. Typically, chromosomes align at the metaphase spindle equator where they oscillate along the pole-pole axis before disjoining and moving poleward during anaphase A, but spindles in different cell types display differences in MT dynamicity, in the amplitude of chromosome oscillations and in rates of chromatid-to-pole motion. Drosophila embryonic mitotic spindles, for example, display remarkably dynamic MTs, barely detectable metaphase chromosome oscillations, and a rapid rate of "flux-pacman-dependent" anaphase chromatid-to-pole motility. Here we develop a force-balance model that describes Drosophila embryo chromosome motility in terms of a balance of forces acting on kinetochores and kMTs that is generated by multiple polymer ratchets and mitotic motors coupled to tension-dependent kMT dynamics. The model shows that i), multiple MTs displaying high dynamic instability can drive steady and rapid chromosome motion; ii), chromosome motility during metaphase and anaphase A can be described by a single mechanism; iii), high kinetochore dynein activity is deployed to dampen metaphase oscillations, to augment the basic flux-pacman mechanism, and to drive rapid anaphase A; iv), modulation of the MT rescue frequency by the kinetochore-associated kinesin-13 depolymerase promotes metaphase chromosome oscillations; and v), this basic mechanism can be adapted to a broad range of spindles.

Anaphase↗
PubMed2002

Do patients who self-harm consult their general practitioner soon after hospital discharge? A cohort study.

BACKGROUND: Deliberate self-harm (DSH, attempted suicide) is one of the most common reasons for emergency hospital admission in Great Britain. Approximately 20 % of patients repeat self-harm in the 12 months after admission. The GP's role in DSH aftercare and the prevention of repeat episodes is unclear. METHODS: The data were obtained from a 12-month follow-up of a series of 968 consecutive patients from 49 practices who attended an accident and emergency (A&E) department in Bristol or Bath, UK, following an episode of self-harm between 26(th) May 1997 and 1(st) March 1999. RESULTS: Information on consultation patterns were available for 681 (70 %) of the patients. Two hundred and fourteen (31 %) of these consulted their GP in the week following the episode, 360 (53 %) within 4 weeks. Of the subjects, 44 % were discharged directly from A & E; these patients were more likely to consult their GP in the 4 weeks after the episode. Over the 12-month follow-up, 117 (17 %) attended hospital for a repeat episode of DSH; 9 % of these repeats occurred within 1 week and 28 % within 4 weeks of the index event. Although few (2 out of 11 patients--18 %) of those repeating in the first week after the index episode consulted their GP prior to repeating, 50 % (11/22) of those who repeated in the 1-4 weeks after an episode did so. CONCLUSIONS: Consultation patterns indicate that most people who deliberately self-harm consult their GP soon after the episode. This consultation may provide an opportunity for preventing repeat DSH and suicide.

Adolescent↗
PubMed2002

Cigarette acquisition and proof of age among US high school students who smoke.

OBJECTIVE: To determine how US high school students who are under 18 years of age and who smoke obtain their cigarettes and whether they are asked for proof of age. DESIGN AND SETTING: Data from the Centers for Disease Control and Prevention's 1995, 1997, and 1999 national Youth Risk Behavior Surveys which employed national probability samples of students in grades 9-12 (ages 14-18 years). MAIN OUTCOME MEASURES: Associations of usual source of cigarettes and request for proof of age with variables such as sex, race/ethnicity, grade, and frequency of smoking. RESULTS: In 1999, among current smokers under age 18 years, 23.5% (95% confidence interval (CI), -4.5% to +4.5%) usually purchased their cigarettes in a store; among these students, 69.6% (95% CI -5.7% to +5.7%) were not asked to show proof of age. As days of past month smoking increased, reliance on buying cigarettes in a store (p < 0.001) and giving someone else money to buy cigarettes (p < 0.001) increased, and usually borrowing cigarettes decreased (p < 0.001). From 1995 to 1999, relying on store purchases significantly decreased (from 38.7% (95% CI -4.6% to + 4.6%) to 23.5% (95% CI -4.5% to +4.5%)); usually giving someone else money to buy cigarettes significantly increased (from 15.8% (95% CI -3.6% to +3.6%) to 29.9% (95% CI -4.5% to + 4.5%)). CONCLUSIONS: Stricter enforcement of tobacco access laws is needed to support other community and school efforts to reduce tobacco use among youth. Furthermore, effective interventions to reduce non-commercial sources of tobacco, including social, need to be developed and implemented.

Adolescent↗
PubMed2001

Mitosis, microtubules, and the matrix.

The mechanical events of mitosis depend on the action of microtubules and mitotic motors, but whether these spindle components act alone or in concert with a spindle matrix is an important question.

Animals↗
PubMed2001

Reviews of evidence regarding interventions to reduce tobacco use and exposure to environmental tobacco smoke.

This report presents the results of systematic reviews of effectiveness, applicability, other effects, economic evaluations, and barriers to use of selected population-based interventions intended to reduce tobacco use and exposure to environmental tobacco smoke. The related systematic reviews are linked by a common conceptual approach. These reviews form the basis of recommendations by the Task Force on Community Preventive Services (TFCPS) regarding the use of these selected interventions. The TFCPS recommendations are presented on page 67 of this supplement.

Adolescent↗
PubMed2001

What do people with MS want and expect from health-care services?

OBJECTIVE: To determine the health-care preferences of people with Multiple Sclerosis (MS). DESIGN: Cross-sectional survey using a postal questionnaire comprising standardized measures of health related quality of life (SF-36) and of depression (BDI) and original questions about issues linked to health-care, prioritized by people with MS during an earlier qualitative phase. PARTICIPANTS: A stratified sample of 318 people with MS in Scotland and England. RESULTS: Questionnaires were sent to 471 people with multiple sclerosis. The 318 respondents (68%) reported a wide variation in quality of life, but on average scored significantly lower than normative values in all dimensions of the SF-36. The most commonly used home treatment during the previous year was evening primrose oil, taken by almost half of the sample (47%). Use of cannabis was acknowledged by 8%. There was evidence that many preferences concerning health services were not satisfied. For instance lack of advice about at least one MS related issue was reported lacking for three-quarters of the sample and 17% lacked advice in at least five areas. Advice about exercise was the single most requested area. The most frequently consulted health professional was the GP (78%) followed by the hospital consultant (50%). The professional that respondents most commonly said they would like to have seen was a specialist MS nurse (30%). Forty-three percent of the sample said they had attended a special meeting for people with MS or disabilities. They were equally divided between those who did and who did not find their last attendance helpful. CONCLUSIONS: People with MS display a wide variation in their preference for services and unmet needs. Information about management (both conventional and unconventional), relevant tailored advice and access to appropriately skilled professionals should be feasible components of high quality care. This work has highlighted the value of involving people with MS in the identification of their preferences; further research is needed to show how these might be provided most effectively.

Adult↗
PubMed2001

Cluster randomised controlled trial comparing the effectiveness and cost-effectiveness of two primary care interventions aimed at improving attendance for breast screening.

OBJECTIVES: To examine the effectiveness and cost-effectiveness of two interventions based in primary care aimed at increasing uptake of breast screening. SETTING: 24 General practices with low uptake in the second round of screening (below 60%) in north west London and the West Midlands, UK. Participants were all women registered with these practices and eligible for screening in the third round. METHODS: Pragmatic factorial cluster randomised controlled trial, with practices randomised to a systematic intervention (general practitioner letter), an opportunistic intervention (flag in women's notes prompting discussion by health professionals), neither intervention, or both. Outcome measures were attendance for screening 6 months after the practices had been screened and cost-effectiveness of the interventions. RESULTS: 6,133 Women were included: 1,721 control; 1,818 letter; 1,232 flag; 1,362 both interventions. Attendance data were obtained for 5,732 (93%) women. The two interventions independently increased breast screening uptake in a logistic regression model adjusted for clustering, with the flag (odds ratio (OR) 1.43, 95% confidence interval (95% CI) 1.14 to 1.79; p=0.0019) marginally more effective than the letter (OR 1.31, 95% CI 1.05 to 1.64; p=0.015). Health service costs per additional attendance were 26 pounds (letter) and 41 pounds (flag). CONCLUSIONS: Although both interventions increased attendance for breast screening, the letter was the more cost-effective. Any decision to implement both interventions rather than just the letter will depend on whether the additional (41 pounds) costs are judged worthwhile in terms of the gains in breast screening uptake.

Breast Neoplasms↗
PubMed2001

Improving attendance for breast screening among recent non-attenders: a randomised controlled trial of two interventions in primary care.

OBJECTIVES: To examine the effectiveness and cost-effectiveness of two primary care based interventions aimed at increasing breast screening uptake for women who had recently failed to attend. SETTING: 13 General practices with low uptake in the second round of breast screening (below 60%) in north west London and the West Midlands, United Kingdom. Participants were women in these practices who were recent non-attenders for breast screening in the third round. METHODS: Pragmatic factorial randomised controlled trial, with people randomised to a systematic intervention (general practitioner letter), an opportunistic intervention (flag in women's notes prompting discussion by health professionals), neither intervention, or both. Outcome measures were attendance for screening 6 months after randomisation and cost-effectiveness of the interventions. RESULTS: 1,158 Women were individually randomised as follows: 289 control; 291 letter; 290 flag; 288 both interventions. Attendance was ascertained for 1,148 (99%) of the 1,158 women. Logistic regression adjusting for the other intervention and practice produced an odds ratio (OR) for attendance of 1.51 (95% confidence interval (95% CI 1.02 to 2.26; p=0.04) for the letter, and 1.39 (95% CI 0.93 to 2.07; p=0.10) for the flag. Health service costs/ additional attendance were 35 pounds (letter) and 65 pounds (flag). CONCLUSIONS: Among recent non-attenders, the letter was effective in increasing breast screening attendance. The flag was of equivocal effectiveness and was considerably less cost-effective than the letter.

Adult↗
PubMed2001

The distress and risk assessment method (DRAM).

Our aim was to judge the influence of preoperative psychological disturbance on the outcome of lumbar discectomy. We evaluated 66 patients, before and after operation, using a self-administered questionnaire. Disability was assessed using the Oswestry disability index and psychological disturbance the Distress and Risk Assessment Method (DRAM) score. Patients were classified as normal, at risk or distressed, and the outcome of surgery in the three groups was compared at a follow-up of six months. The mean self-reported preoperative disability was significantly higher in those with psychological disturbance. A total of 54 patients (82%) returned completed postoperative questionnaires. Postoperative disability scores at six months were not significantly different in the three risk groups. Psychological disturbance improved after surgery. Our study suggests that the early outcome of lumbar discectomy is not affected by preoperative psychological disturbance. We conclude that a patient with a symptomatic prolapsed intervertebral disc should not be denied surgery on the basis of preoperative psychological assessment.

Adult↗
PubMed2000

Roles of two homotetrameric kinesins in sea urchin embryonic cell division.

To improve our understanding of the roles of microtubule cross-linking motors in mitosis, we analyzed two sea urchin embryonic kinesin-related proteins. It is striking to note that both of these proteins behave as homotetramers, but one behaves as a more compact molecule than the other. These observations suggest that these two presumptive motors could cross-link microtubules into bundles with different spacing. Both motors localize to mitotic spindles, and antibody microinjection experiments suggest that they have mitotic functions. Thus, one of these kinesin-related proteins may cross-link spindle microtubules into loose bundles that are "tightened" by the other.

Amino Acid Sequence↗
PubMed2000

Microtubule motors in mitosis.

The mitotic spindle uses microtubule-based motor proteins to assemble itself and to segregate sister chromatids. It is becoming clear that motors invoke several distinct mechanisms to generate the forces that drive mitosis. Moreover, in carrying out its function, the spindle appears to pass through a series of transient steady-state structures, each established by a delicate balance of forces generated by multiple complementary and antagonistic motors. Transitions from one steady state to the next can occur when a change in the activity of a subset of mitotic motors tips the balance.

Animals↗
PubMed2000

A kinesin-related protein, KRP(180), positions prometaphase spindle poles during early sea urchin embryonic cell division.

We have investigated the intracellular roles of an Xklp2-related kinesin motor, KRP(180), in positioning spindle poles during early sea urchin embryonic cell division using quantitative, real-time analysis. Immunolocalization reveals that KRP(180) concentrates on microtubules in the central spindle, but is absent from centrosomes. Microinjection of inhibitory antibodies and dominant negative constructs suggest that KRP(180) is not required for the initial separation of spindle poles, but instead functions to transiently position spindle poles specifically during prometaphase.

Amino Acid Sequence↗
PubMed2000

Roles of motor proteins in building microtubule-based structures: a basic principle of cellular design.

Eukaryotic cells must build a complex infrastructure of microtubules (MTs) and associated proteins to carry out a variety of functions. A growing body of evidence indicates that a major function of MT-associated motor proteins is to assemble and maintain this infrastructure. In this context, we examine the mechanisms utilized by motors to construct the arrays of MTs and associated proteins contained within the mitotic spindle, neuronal processes, and ciliary axonemes. We focus on the capacity of motors to drive the 'sliding filament mechanism' that is involved in the construction and maintenance of spindles, axons and dendrites, and on a type of particle transport called 'intraflagellar transport' which contributes to the assembly and maintenance of axonemes.

Animals↗
PubMed2000

Evaluation of computer based clinical decision support system and risk chart for management of hypertension in primary care: randomised controlled trial.

OBJECTIVES: To investigate the effect of a computer based clinical decision support system and a risk chart on absolute cardiovascular risk, blood pressure, and prescribing of cardiovascular drugs in hypertensive patients. DESIGN: Cluster randomised controlled trial. SETTING: 27 general practices in Avon. PARTICIPANTS: 614 patients aged between 60 and 79 years with high blood pressure. INTERVENTIONS: Patients were randomised to computer based clinical decision support system plus cardiovascular risk chart; cardiovascular risk chart alone; or usual care. MAIN OUTCOME MEASURES: Percentage of patients in each group with a five year cardiovascular risk >/=10%, systolic blood pressure, diastolic blood pressure, prescribing of cardiovascular drugs. RESULTS: Patients in the computer based clinical decision support system and chart only groups were no more likely to have cardiovascular risk reduced to below 10% than patients receiving usual care. Patients in the computer based clinical decision support group were more likely to have a cardiovascular risk >/=10% than chart only patients, odds ratio 2.3 (95% confidence interval 1.1 to 4.8). The chart only group had significantly lower systolic blood pressure compared with the usual care group (difference in means -4.6 mm Hg (95% confidence interval -8.4 to -0.8)). Reduction of diastolic blood pressure did not differ between the three groups. The chart only group were twice as likely to be prescribed two classes of cardiovascular drugs and over three times as likely to be prescribed three or more classes of drugs compared with the other groups. CONCLUSIONS: The computer based clinical decision support system did not confer any benefit in absolute risk reduction or blood pressure control and requires further development and evaluation before use in clinical care can be recommended. Use of chart guidelines are associated with a potentially important reduction in systolic blood pressure.

Aged↗
PubMed2000

Cytoplasmic dynein is required for poleward chromosome movement during mitosis in Drosophila embryos.

The movement of chromosomes during mitosis occurs on a bipolar, microtubule-based protein machine, the mitotic spindle. It has long been proposed that poleward chromosome movements that occur during prometaphase and anaphase A are driven by the microtubule motor cytoplasmic dynein, which binds to kinetochores and transports them toward the minus ends of spindle microtubules. Here we evaluate this hypothesis using time-lapse confocal microscopy to visualize, in real time, kinetochore and chromatid movements in living Drosophila embryos in the presence and absence of specific inhibitors of cytoplasmic dynein. Our results show that dynein inhibitors disrupt the alignment of kinetochores on the metaphase spindle equator and also interfere with kinetochore- and chromatid-to-pole movements during anaphase A. Thus, dynein is essential for poleward chromosome motility throughout mitosis in Drosophila embryos.

Anaphase↗