Search PubMed⌕ Search

Biomedical subjects

J Copeland

Publications and source records attributed to J Copeland.

At least 37 records · Page 2Linked to original sources

Signal-regulated activation of serum response factor is mediated by changes in actin dynamics.

Serum response factor (SRF) regulates transcription of many serum-inducible and muscle-specific genes. Using a functional screen, we identified LIM kinase-1 as a potent activator of SRF. We show that SRF activation by LIM kinase-1 is dependent on its ability to regulate actin treadmilling. LIM kinase activity is not essential for SRF activation by serum, but signals depend on alterations in actin dynamics. Studies with actin-binding drugs, the actin-specific C2 toxin, and actin overexpression demonstrate that G-actin level controls SRF. Regulation of actin dynamics is necessary for serum induction of a subset of SRF target genes, including vinculin, cytoskeletal actin, and srf itself, and also suffices for their activation. Actin treadmilling provides a convergence point for both serum- and LIM kinase-1-induced signaling to SRF.

3T3 Cells↗

Retention of the BUB3 checkpoint protein on lagging chromosomes.

Accurate chromosome segregation at mitosis is ensured both by the intrinsic fidelity of the mitotic machinery and by the operation of checkpoints that monitor chromosome-microtubule attachment. When unattached kinetochores are present, anaphase is delayed and the time available for chromosome-microtubule capture increases. Genes required for this delay first were identified in budding yeast (the MAD and BUB genes), but it is not yet known how the checkpoint senses unattached chromosomes or how it signals cell-cycle arrest. We report the isolation and analysis of a murine homologue of BUB3, a gene whose deletion abolishes mitotic checkpoint function in Saccharomyces cerevisiae. mBub3 belongs to a small gene family that has been highly conserved through evolution. By expressing recombinant proteins in insect cells, we show that mBub3, like yeast Bub3p, binds to Bub1 to form a complex with protein kinase activity. During prophase and prometaphase, preceding kinetochore-microtubule attachment, Bub3 localizes to kinetochores. High levels of mBub3 remain associated with lagging chromosomes but not with correctly aligned chromosomes during metaphase, consistent with a role for Bub3 in sensing microtubule attachment. Intriguingly, the number of lagging chromosomes with high Bub3 staining increases dramatically in cells treated with low (and pharmacologically relevant) concentrations of the chemotherapeutic taxol and the microtubule poison nocodazole.

Amino Acid Sequence↗

Understanding and assessing the motivations of volunteers: a functional approach.

The authors applied functionalist theory to the question of the motivations underlying volunteerism, hypothesized 6 functions potentially served by volunteerism, and designed an instrument to assess these functions (Volunteer Functions Inventory; VFI). Exploratory and confirmatory factor analyses on diverse samples yielded factor solutions consistent with functionalist theorizing; each VFI motivation, loaded on a single factor, possessed substantial internal consistency and temporal stability and correlated only modestly with other VFI motivations (Studies 1, 2, and 3). Evidence for predictive validity is provided by a laboratory study in which VFI motivations predicted the persuasive appeal of messages better when message and motivation were matched than mismatched (Study 4), and by field studies in which the extent to which volunteers' experiences matched their motivations predicted satisfaction (Study 5) and future intentions (Study 6). Theoretical and practical implications are discussed.

Adult↗

Choosing a diagnostic cut-off for cannabis dependence.

AIM: While cannabis dependence has been increasingly recognized, there is little research on the measurement issues involved in operationalizing the dependence syndrome for this drug. This paper aimed to investigate the diagnostic utility and appropriate diagnostic cut-offs of three short dependence measures among long-term cannabis users. SETTING AND PARTICIPANTS: Two hundred long-term, regular cannabis users were recruited and interviewed in Sydney, Australia. MEASUREMENTS: Receiver Operating Characteristic analyses compared the diagnostic performance of the short University of Michigan CIDI, a measure of ICD-10 dependence and the Severity of Dependence Scale against the "gold standard" of moderate or more severe DSM-III-R cannabis dependence, as diagnosed by the Substance Abuse Module of the CIDI. FINDINGS: The measures were of equal utility in diagnosing at least moderate DSM-III-R cannabis dependence. While the optimal diagnostic cut-offs for the short University of Michigan CIDI and the ICD-10 dependence measure remained unchanged from those conventionally applied, a more liberal cut-off was optimal for the Severity of Dependence Scale. The amended prevalence of cannabis dependence was 77% using the short University of Michigan CIDI, 72% by the ICD-10 measure and 62% by the Severity of Dependence Scale. CONCLUSIONS: The three instruments were able to diagnose cannabis dependence at levels substantially better than chance. They were generally robust in terms of the optimal diagnostic cut-off in a population of long-term cannabis users. This paper provides guidelines for choosing optimal cut-offs within different contexts.

Adolescent↗

Exploring the nature of the relationship between child sexual abuse and substance use among women.

AIMS: This study investigated whether child abuse (CSA) was associated with earlier substance use and greater severity of substance dependence and what aspects of CSA might predict substance abuse. DESIGN: The study compared (a) drug and alcohol treatment clients with and without a history of CSA and (b) CSA survivors outside drug and alcohol treatment who did or did not have current substance abuse. SETTINGS: Semi-structured interviews took place at participants' homes, treatment agencies or the research centre. PARTICIPANTS: Volunteer participants included 100 women recruited from drug and alcohol treatment programmes and 80 CSA survivors recruited through CSA counseling services and medial advertising. MEASUREMENTS: The results focus on data from the Opiate Treatment Index, Severity of Alcohol Dependence Questionnaire, Substance Dependence Scale, Self-Esteem Inventory and self-reported histories of CSA. FINDINGS: There were no differences between CSA survivors and other drug and alcohol treatment clients in their severity of dependence. Women with a history of CSA more frequently identified stimulants as their main problem drug and reported an earlier age of first intoxication and earlier use of inhalants. Among abused CSA survivors outside drug and alcohol treatment, women with current substance abuse had typically been abused during adolescence by someone outside the family, whereas those without current substance abuse were typically abused by family members before adolescence. CONCLUSIONS: The results suggest that adolescence is a crucial time for the influence of CSA experiences on substance abuse.

Adolescent↗

Treatment needs of women with alcohol and other drug problems: experiences and views of Australian treatment personnel.

One hundred treatment personnel completed a structured interview as part of an Australian national study of the treatment needs of women with alcohol and other drug problems. The aim of the survey was to ascertain personnel's experiences of, and beliefs about providing services to women. Respondents had a broad range of qualifications and experience, and were generally supportive of provision of gender-sensitive services to women. The interview addressed a number of issues, including: barriers to treatment access, ability to provide gender-sensitive services, appropriateness of women-only services, and addressing sexual abuse issues. It is concluded that while many agencies attempted to provide appropriate services for women, many experienced difficulties, such as a lack of resources and funding. There is a continuing need for research into the best method of service delivery for women.

Journal Article↗

Characteristics of long-term cannabis users in Sydney, Australia.

Two hundred long-term cannabis users (58% male) were interviewed on their characteristics and experience of use. Respondents had been regularly using cannabis for an average of 11 years and more than half used daily (56%). The most common route of administration was in a waterpipe, and nearly all (93%) smoked the flowering heads ot the plant. One in 5 (21%) had a cannabis-related conviction. The benefits of use were perceived to be its relaxing, mood-enhancing effects, and its ability to alter consciousness. The most commonly cited negative aspects of use were cost, negative psychological effects and legal status. Polydrug use was common, with alcohol and tobacco almost universally used on a regular basis. More than half the drinkers in the sample were consuming alcohol at hazardous or harmful levels.

Adolescent↗

Exploring male fertility options after spinal cord injury: the role of the nurse clinician.

Male sexual function and fertility are important areas that need to be addressed for men undergoing spinal cord injury (SCI) rehabilitation. Rehabilitation nurses need to understand what fertility after SCI involves. Significant advances in the areas of sperm retrieval and advanced reproductive technologies have made biological parenthood for many men with SCI a viable option. This article reviews the various sperm retrieval techniques and advanced reproductive technologies available today. It also describes the unique role of a nurse clinician working in a fertility clinic designed specifically to address the fertility concerns of men and their partners after SCI.

Critical Pathways↗

Placebo-controlled treatment trial of depression in elderly physically ill patients.

OBJECTIVES: To determine the response of physically ill elderly depressed patients to treatment. DESIGN: Acute geriatric medical inpatients with depression, randomly assigned to an 8-week double-blind placebo-controlled trial of fluoxetine. MAIN OUTCOME MEASURE: Response rate as defined by the 17-item Hamilton Depression Rating Scale. RESULTS: Eighty-two patients entered the trial; 62 patients (all those who had completed at least 3 weeks of treatment) were included in the efficacy analysis. Forty-two completed the full 8 weeks (21 in each group) with response rates of 67% in the fluoxetine group and 38% in the placebo group. No significant difference was found between the responses of the two groups (p = 0.12). There was a trend for results in the fluoxetine group to continue to improve with time. On secondary analysis those patients with serious physical illness who completed 5 or more weeks (N = 37) showed a significant improvement in mood if treated with fluoxetine (p = 0.02). CONCLUSIONS: The main benefit of antidepressants is to approximately double the chances of recovery. This trial showed the response rate of the fluoxetine treated group was increased by a factor of 1.8 over the placebo group in an 8-week period. The presence of physical illness, often severe and/or multiple, did not reduce the effectiveness of the medication, which was well tolerated overall. Those with serious physical disease responded significantly better to drug treatment; this will require further work. Psychological support was also considered to be important.

Aged↗

The effect of flash duration and flash shape on entrainment in Pteroptyx malaccae, a synchronic Southeast Asian firefly.

Southeast Asian synchronic fireflies respond to stimulus flashes by phase-shifting their endogenous oscillator. This is called 'flash entrainment'. The releasers for entrainment were studied by changing stimulus flash shape and duration in Pteroptyx malaccae. Stimulus flash shapes and durations were synthesized digitally and delivered by a field-portable computer system. The computer also recorded male firefly flashes that were detected with a photometer. We found that the type of entrainment and its magnitude was influenced by the duration of the entrainment flash and by its shape.

Journal Article↗

Child sexual abuse as a predictor of psychiatric co-morbidity and its implications for drug and alcohol treatment.

A study of 180 women in and outside drug and alcohol treatment showed that CSA survivors had higher overall levels of psychological distress, compared with drug and alcohol treatment clients who had not experienced CSA. They reported elevated levels of anxiety, somatisation and dissociation but not depression. Higher rates of self-harm, eating disorders and sexual dysfunction were also reported by CSA survivors. Women with a history of both CSA and substance abuse were more likely to have attempted suicide than other women. The results highlight the need for improved liaison between substance abuse treatment programs and other health services.

Adolescent↗

Predictors of graft patency 3 years after coronary artery bypass graft surgery. Department of Veterans Affairs Cooperative Study Group No. 297.

OBJECTIVES: The purpose of this analysis was to define the factors that predict 3-year graft patency. BACKGROUND: The success of coronary artery bypass graft surgery (CABG) is dependent on vein graft patency after the operation. It has been well established by a series of Department of Veterans Affairs Cooperative Trials that aspirin (325 mg daily) improves saphenous vein graft patency early (7 to 10 days) and at 1 year, but not at 3 years after CABG. This analysis, based on one of these trials, defined factors that predict 3-year graft patency. METHODS: This analysis consisted of 266 patients, with 656 grafts that were patent 7 to 10 days after the operation, who underwent 3-year catheterization. To determine which patient-specific and/or graft-specific factors, or both, predict graft occlusion, a multivariate logistic regression analysis in terms of latent variables was used. It yielded a model that also took into account possible intraclass correlations. RESULTS: For a vein graft that was patent at 7 to 10 days after the operation, the positive predictors, according to univariate analysis, for that graft being patent at 3 years were cross-clamp time < or = 80 min (p < 0.001), vein preservation solution temperature < or = 5 degrees C (p = 0.009), bypass time < or = 2 h (p = 0.042), number of proximal anastomoses < or = 2 (p = 0.018), operation time < or = 5 h (p = 0.044) and continuous versus intermittent cross-clamp technique (p = 0.024). There was also a trend with regard to recipient artery diameter > 1.5 mm (p = 0.063), serum cholesterol < or = 225 mg/dl (p = 0.084) and single versus sequential or Y vein graft (p = 0.060). Factors not predictive of 3-year patency were age, race, smoking history, high density lipoprotein cholesterol, vein source (thigh vs. calf), coronary artery grafted and aspirin treatment. Of all the predictors obtained in the univariate analysis, the only variables that were sufficient to yield a good model within the multivariate analysis were solution temperature (p = 0.004), serum cholesterol (p = 0.024), number of proximal anastomoses (p = 0.032) and recipient artery diameter (p = 0.034). CONCLUSIONS: For a patient with patent vein grafts 7 to 10 days after the operation, predictors of 3-year graft patency are more closely related to operative techniques and underlying disease and not to aspirin treatment.

Coronary Artery Bypass↗

Treatment of depression in the elderly: effect of physical illness on response.

OBJECTIVES: To determine the response to treatment of different subgroups within a sample of physically ill elderly depressed patients. DESIGN: Acute geriatric medical inpatients with depression, randomly assigned to an 8-week double-blind placebo-controlled trial of fluoxetine. MAIN OUTCOME MEASURE: Response rate as defined by the 17-item Hamilton Depression Rating Scale. RESULTS: Data were analysed in subgroups according to diagnosed physical problems and concomitant medication. A logistic regression analysis was performed to identify subgroups valid for separate analysis. Those reaching at least 5 weeks of treatment showed a significant improvement compared with the placebo group if they had serious life-threatening disease, cerebrovascular disease, were not demented, or were either on no analgesics or on analgesics stronger than paracetamol. CONCLUSION: While the response to treatment in these subgroups was encouraging, general physicians must not be led to believe that the answer to depression lies only in pharmacological intervention, just as the belief that the risk-benefit ratio of such treatment where indicated is too high must be discouraged.

Aged↗

Treatment needs and experiences of Australian women with alcohol and other drug problems.

Two hundred and sixty-seven women were interviewed as part of a national survey examining the treatment needs and experiences of Australian women who had received assistance for their alcohol and other drug problems. The majority of women had previously received assistance for their substance use, and of these most had left alcohol and other drug treatment programs before completion. While the women cited a number of ways in which they were helped by such services, several areas were identified by the women as important and amenable to improvement. Among the service issues raised were access, models of service delivery, service structure and staffing, physical environment, physical and psychological safety and the handling of issues such as health status and sexual assault.

Adolescent↗