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Biomedical subjects

J Copeland

Publications and source records attributed to J Copeland.

At least 19 recordsLinked to original sources
PubMed2003

E-MSD: the European Bioinformatics Institute Macromolecular Structure Database.

The E-MSD macromolecular structure relational database (http://www.ebi.ac.uk/msd) is designed to be a single access point for protein and nucleic acid structures and related information. The database is derived from Protein Data Bank (PDB) entries. Relational database technologies are used in a comprehensive cleaning procedure to ensure data uniformity across the whole archive. The search database contains an extensive set of derived properties, goodness-of-fit indicators, and links to other EBI databases including InterPro, GO, and SWISS-PROT, together with links to SCOP, CATH, PFAM and PROSITE. A generic search interface is available, coupled with a fast secondary structure domain search tool.

Animals↗
PubMed2001

Safety, tolerability, and efficacy of cyclosporine microemulsion in heart transplant recipients: a randomized, multicenter, double-blind comparison with the oil-based formulation of cyclosporine--results at 24 months after transplantation.

BACKGROUND: The widespread use of cyclosporine has improved the survival of cardiac transplant patients as a result of reduced morbidity and mortality from rejection and infection. The original oil-based form of cyclosporine demonstrated unpredictable absorption resulting in an increased frequency of acute and chronic rejection in patients with poor bioavailability. The primary end. points of the present, prospective, randomized multicenter, double-blind trial were to compare the efficacy of the micro-emulsion form of cycolsporine (CsA-NL) with the oil-based formulation as determined by cardiac allograft and recipient survival and the incidence and severity of the acute rejection episodes and to determine the safety and tolerability of CsA-NL compared with Sandimmune CsA-(SM) in the study population. The 6-month analysis of the study showed reduced number of CsA-NL patients requiring antilymphocyte antibody therapy for rejection, fewer International Society of Heart and Lung Transplantation grade > or =3A rejections in female patients and fewer infections. Our report represents the final analysis of the results 24 months after transplantation. METHODS: A total of 380 patients undergoing de novo cardiac transplants at 24 centers in the United States, Canada, and Europe were enrolled in this double-blind, randomized trial evaluating the efficacy and safety of CsA-NL versus CsA-SM. Acute allograft rejection was diagnosed by endomyocardial biopsy and graded according to the International Society of Heart and Lung Transplantation nomenclature. Kaplan-Meier analysis and Fisher's exact test were used for comparisons between groups. RESULTS: After 24 months, allograft and recipient survival were identical in both groups. There were fewer CsA-NL patients (6.9%) requiring antilymphocyte antibody therapy for rejection than in the CsA-SM-treated patient group (17.7%, P=0.002). There were fewer discontinuations of study drug for treatment failures in the CsA-NL groups (7; 3.7%) compared with the CsA-SM group (18; 9.4%, P=0.037). The average corticosteroid dose was lower in the CsA-NL group (0.37 mg/kg/day) compared with the CsA-SM group (0.48 mg/kg/day, P=0.034) over the 24-month study period. Overall, there was no difference in blood pressure or creatinine between the two study groups. CONCLUSIONS: The final results of this multi-center, randomized study of two forms of cyclosporine confirmed that there were fewer episodes of rejection requiring antilymphocyte antibodies and fewer study discontinuations for treatment failures in CsA-NL-treated patients compared to those treated with CsA-SM. The use of CsA-NL did not predispose these patients to a higher risk of adverse events.

Adolescent↗
PubMed2001

Persecutory symptoms and perceptual disturbance in a community sample of older people: the Islington study.

BACKGROUND: While there are extensive studies of paranoid symptoms and perceptual disturbance (PPD) in younger adults, relatively little is known about older adults with similar symptoms. METHOD: This study took place in Islington, an inner London borough. Enumeration Districts were randomised to provide a sampling frame. Residents aged 65 or over were interviewed at home. The Short-CARE was used to elicit psychiatric symptoms and diagnosis. Sociodemographic particulars were elicited using the Client Sociodemographic and Service Receipt Inventory. Questions were asked regarding sight and hearing. We used subsections of the geriatric mental scale to identify people who had PPD symptoms. Medications taken were recorded. We asked 'Do you have any health problems?' as a screening question for subjective health problems. RESULTS: We interviewed 720 people. Twenty-eight (3.9%) participants scored positively on the PPD sub-scales of the GMS. A forward logistic regression analysis for independent predictors of PPD found the significant independent predictors were dementia (p = 0.0000; odds ratio 6.8), drinking alcohol in last 6 months (p < 0.03; odds ratio 0.3), drinking alcohol to help sleep (p < 0.005; odds ratio 9.6), subjective memory loss (p < 0.007; odds ratio 3.3) and uncorrected visual impairment (p < 0.02; odds ratio 2.8). CONCLUSION: There is a relatively high prevalence of PPD in older people living in the community. This is not associated with higher use of services despite the increased needs. Further studies should consider interventions to meet this unmet need.

Activities of Daily Living↗
PubMed2001

Perflubron emulsion reduces inflammation during extracorporeal circulation.

The recovery from cardiac surgery and cardiopulmonary bypass can be complicated by an acute inflammatory response. Circulating blood through an extracorporeal circuit (ECC) contributes to this complication. Perfluorocarbon-based blood substitutes (PFCs) are under investigation for use as a component of the ECC "prime" solution, because PFCs increase the oxygen-carrying capacity of the diluted blood. Some PFCs may provide the additional benefit of attenuating the ECC-induced inflammatory response. Earlier, we reported that perflubron emulsion (PFE, Alliance Pharmaceutical Corp.) reduced neutrophil (PMN) activation in vivo. However, the potential of PFE to reduce ECC-induced PMN activation has not been investigated. In this study, we used a small-scale ECC model to quantify the extent of PMN activation during circulation and to examine if PFE treatment attenuated PMN activation. ECC circuits were filled with a mixture of blood and Plasmalyte. Two groups were studied: an untreated group containing blood plus PlasmaLyte and a treated group in which some of the Plasmalyte was substituted with PFE (4.5 g/100 ml). Hematology and measures of whole blood PMN activation were made from blood samples taken periodically throughout the 120-min ECC circulation period. We found, for the untreated group, a significant decrease in the number of circulating PMNs and an increase in PMN activation with time. PMN activation was demonstrated as a significant increase in the expression of the PMN adhesion protein CD11b (P < 0.05) and an increase in PMN oxygen free radical production (reactive oxygen species (ROS)). After 120 min of circulation, the PMNs remained capable of a significant response to a second inflammatory stimulus, but PFE treatment significantly attenuated the fMLP-induced increase in PMN ROS at t = 120 min (P < 0.05). These results suggest that PFE may have dual utility in cardiac surgery, to increase oxygen delivery and to serve as an antiinflammatory agent.

Animals↗
PubMed2001

Clinical profile of participants in a brief intervention program for cannabis use disorder.

The increasing demand for cannabis dependence treatment has led to the identification of significant gaps in the knowledge of effective interventions. A randomized controlled trial of brief cognitive-behavioral interventions (CBT) for cannabis dependence was undertaken to address this issue. A total of 229 participants were assessed and allocated to either a 6-session CBT program, a single-session brief intervention, or a delayed-treatment control group. This paper demonstrates that individuals with cannabis use disorder will present for a brief intervention program. While they report similar patterns of cannabis use to nontreatment samples, they report a range of serious health and psychosocial consequences. While they appear relatively socially stable, they typically demonstrated severe cannabis dependence and significantly elevated levels of psychological distress, with the most commonly cited reason for cannabis use being stress relief. There were clinically relevant gender differences among the sample. This study provides more evidence of the demand for, and nature of issues relevant to, interventions for cannabis use disorders, and supports the need for further research into how best to assist individuals with these disorders.

Adolescent↗
PubMed2001

A randomized controlled trial of brief cognitive-behavioral interventions for cannabis use disorder.

The increasing demand for treatment for cannabis dependence in Australia and internationally has led to the identification of significant gaps in knowledge of effective interventions. A randomized controlled trial of brief cognitive-behavioral interventions (CBT) for cannabis dependence was undertaken to address this issue. A total of 229 participants were assessed and randomly assigned to either a six-session CBT program (6CBT), a single-session CBT intervention (1CBT), or a delayed-treatment control (DTC) group. Participants were assisted in acquiring skills to promote cannabis cessation and maintenance of abstinence. Participants were followed-up a median of 237 days after last attendance. Participants in the treatment groups reported better treatment outcomes than the DTC group. They were more likely to report abstinence, were significantly less concerned about their control over cannabis use, and reported significantly fewer cannabis-related problems than those in the DTC group. Those in the 6CBT group also reported more significantly reduced levels of cannabis consumption than the DTC group. While the therapist variable had no effect on any outcome, a secondary analysis of the 6CBT and 1CBT groups showed that treatment compliance was significantly associated with decreased dependence and cannabis-related problems. This study supports the attractiveness and effectiveness of individual CBT interventions for cannabis use disorders and the need for multisite replication trials.

Adult↗
PubMed2000

Anabolic-androgenic steroid use disorders among a sample of Australian competitive and recreational users.

Illicit anabolic-androgenic steroid (AAS) use, for body building and body image purposes, is increasing internationally. This study describes the prevalence and symptoms of AAS use disorders obtained using a semi-structured interview among a mixed-gender sample of 100 current Australian users, that were recruited from a variety of sources. The median age of the sample was 27 years and 94% were male. The full range of DSM IV symptoms of AAS abuse and dependence were reported and over three quarters (78%) of the sample exhibited at least one symptom of abuse or dependence on AAS. A total of 23% of the participants qualified for a diagnosis of AAS dependence using DSM IV criteria and a further 25% met criteria for AAS abuse. There were no gender differences in AAS abuse or dependence diagnoses. The only variable related to an AAS substance use disorder was reporting the experience of AAS-related aggression, which may be a useful clinical indicator of the disorder.

Adolescent↗
PubMed2000

One year follow-up of cannabis dependence among long-term users in Sydney, Australia.

Eighty one percent of a sample of long-term cannabis users was followed up at 1 year (162/200). Half (51%) were daily smokers, while 20% had substantially decreased or ceased use. More than half received a dependence diagnosis on each of three measures in the last year, with 44% dependent on all three. Remission was much more common than incidence of dependence. Nevertheless, use and dependence patterns were strongly related over time. Longitudinal analyses revealed that quantity of use and severity of dependence at baseline were the primary predictors of those same variables at follow-up. These data suggest that cannabis use and dependence are fairly stable among long-term users.

Adolescent↗
PubMed2000

Validation of the Hamilton Depression Rating Scale and Montgommery and Asberg Rating Scales in terms of AGECAT depression cases.

OBJECTIVE: To validate the Hamilton Depression (17) and Montgommery and Asberg Depression Scales as research instruments in older depressed community residents. DESIGN: External validation against GMS/AGECAT case level in the recruitment of older community residents for an antidepressant trial. ANALYSES: Receiver operator curves were generated for each rating scale, using GMS/AGECAT case level in external criterion. The sensitivity, specificity, positive and negative predictive values of both rating instruments were examined in the whole sample and age and gender subgroups. MADRS and HAM-D cut-off scores differentiating GMS/AGECAT cases from subcases were identified. RESULTS: HAM-D cut-off score of 16 and MADRS score of 21 were identified as differentiating case from sub-case. Diagnostic accuracy of both instruments was good, reflecting good sensitivity and specificity across both genders and sub-age groups. CONCLUSIONS: Both scales performed well in this population. These scores provide researchers with externally validated and clinically relevant cut-off scores in designing trials in the management of older depressed community residents.

Aged↗
PubMed2000

Pretreatment with cationic lipid-mediated transfer of the Na+K+-ATPase pump in a mouse model in vivo augments resolution of high permeability pulmonary oedema.

Resolution of pulmonary oedema is mediated by active absorption of liquid across the alveolar epithelium. A key component of this process is the sodium-potassium ATPase (Na+K+-ATPase) enzyme located on the basolateral surface of epithelial cells and up-regulated during oedema resolution. We hypothesised that lung liquid clearance could be further up-regulated by lipid-mediated transfer and expression of exogenous Na+K+-ATPase cDNA. We demonstrate proof of this principle in a model of high permeability pulmonary oedema induced by intraperitoneal injection of thiourea (2.5 mg/kg) in C57/BL6 mice. Pretreatment of mice (24 h before thiourea) by nasal sniffing of cationic liposome (lipid #67)-DNA complexes encoding the alpha and beta subunits of Na+K+-ATPase (160 microg per mouse), significantly (P<0.01) decreased the wet:dry weight ratios measured 2 h after thiourea injection compared with control animals, pretreated with an equivalent dose of an irrelevant gene. Whole lung Na+K+-ATPase activity was significantly (P<0.05) increased in mice pretreated with Na+K+-ATPase cDNA compared both with untreated control animals as well as animals pretreated with the irrelevant gene. Nested RT-PCR on whole lung homogenates confirmed gene transfer by detection of vector-specific mRNA in three of four mice studied 24 h after gene transfer. This demonstration of a significant reduction in pulmonary oedema following in vivo gene transfer raises the possibility of gene therapy as a novel, localised approach for pulmonary oedema in clinical settings such as ARDS and lung transplantation.

Animals↗
PubMed2000

Cannabis use among Australian adolescents: findings of the 1998 National Drug Strategy Household Survey.

OBJECTIVE: To describe the prevalence, context and recent trends in cannabis use among Australian adolescents. METHOD: Data was collected from 1,581 adolescents aged 14-19 years as part of the 1998 National Drug Strategy Household Survey, and comparisons were made with data from 350 adolescents who participated in the 1995 survey. RESULTS: Among 14-19 year olds, 47.8% have had the opportunity to use cannabis in the past year and 45.2% have used cannabis at least once in their lifetime. Substantial increases have occurred since 1995 in the prevalence of use among young females. While most cannabis use was fairly infrequent, a minority of 14-19 year olds (9.4%) used cannabis at least weekly. Cannabis use was associated with regular tobacco and alcohol use, and other illicit drug use. Regular cannabis users had lower levels of health on the general health and vitality dimensions of the SF-36. IMPLICATIONS: These results show that cannabis availability and use is common among Australian adolescents, and confirm that there has been an increase in use between 1995 and 1998, although only among young females. Future research is required to understand why this recent increase has occurred, and trends in cannabis uptake and use patterns among this group should be carefully monitored. Interventions may need to be developed and made available to the group of young people who are using cannabis heavily.

Adolescent↗
PubMed1999

Safety, tolerability and efficacy of cyclosporine microemulsion in heart transplant recipients: a randomized, multicenter, double-blind comparison with the oil based formulation of cyclosporine--results at six months after transplantation.

BACKGROUND: The introduction of cyclosporine has resulted in significant improvement in the survival of cardiac allograft recipients due to decreased mortality from infection and rejection. The original oil-based cyclosporine formulation exhibits variable and unpredictable bioavailability that correlates with an increased incidence of acute and chronic rejection in those patients in whom this is most pronounced. The primary objectives of this prospective, multicenter, randomized, double-blind study in cardiac transplant patients were: to compare the efficacy of cyclosporine microemulsion (CsA-NL) with oil-based cyclosporine (CsA-SM) as measured by cardiac allograft and recipient survival and the incidence and severity of acute rejection episodes; and to assess the safety and tolerability of CsA-NL compared with CsA-SM in this population. This report represents the analysis of results 6 months after transplantation. METHODS: A total of 380 patients undergoing their first cardiac transplant at 24 centers in the United States, Canada, and Europe were enrolled in this double-blind, randomized trial examining the safety and efficacy of CsA-NL versus CsA-SM. Rejection was diagnosed using endomyocardial biopsy and were graded according to standardized criteria of the International Society of Heart and Lung Transplantation (ISHLT). Clinical parameters were monitored during the study. Survival and freedom from were used for analysis as was Fisher's exact test for comparisons between groups. RESULTS: At 6 months after transplantation, allograft and patient survival were the same for both groups. The frequency of ISHLT grade 3A or greater episodes in the two groups was identical. Fewer CsA-NL patients (5.9%) required antilymphocyte antibody (ATG or OKT-3) therapy for rejection compared with the CsA-SM-treated patients (14.1%, P=0.01). Females with ISHLT rejection grade > or = 3A treated with CsA-NL had a 46% lower incidence of rejection compared with the CsA-SM-treated group (31.3% vs. 57.6%, P=0.032). Fewer infections were seen in the CsA-NL. With the exception of baseline and 1 week posttransplant creatinines which were higher in the CsA-NL group, the overall creatinine was not significantly different between the two groups. CONCLUSIONS: This multicenter, randomized study of cardiac transplant recipients documented less severe rejection (in particular those requiring antibody therapy) and a lower incidence of infection in CsA-NL-treated patients. Results from the female subgroup analysis suggest that the improved bioavailability of CsA-NL might reduce the frequency of rejection episodes in female patients. The use of CsA-NL was not associated with an increased risk of adverse events.

Adolescent↗
PubMed1999

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↗
PubMed1999

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↗