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Biomedical subjects

David Marshall

Publications and source records attributed to David Marshall.

13 recordsLinked to original sources

Characterisation and functional analysis of two barley caleosins expressed during barley caryopsis development.

Two full-length cDNA sequences homologous to caleosin, a seed-storage oil-body protein from sesame, were identified from a series of barley grain development cDNA libraries and further characterised. The cDNAs, subsequently termed HvClo1 and HvClo2, encode proteins of 34 kDa and 28 kDa, respectively. Real-time RT-PCR indicated that HvClo1 is expressed abundantly during the later stages of embryogenesis and is seed-specific, accumulating in the scutellum of mature embryos. HvClo2 is expressed mainly in the endosperm tissues of the developing grain. We show that HvClo1 and HvClo2 are paralogs that co-segregate on barley chromosome 2HL. Transient expression of HvClo1 in lipid storage and non-storage cells of barley using biolistic particle bombardment indicates that caleosins have different subcellular locations from the structural oil-body protein oleosin, and by inference participate in different sorting pathways. We observe that caleosin sorts via small vesicles, suggesting a likely association with lipid trafficking, membrane expansion and oil-body biogenesis.

Calcium-Binding Proteins↗

GERMINATE. a generic database for integrating genotypic and phenotypic information for plant genetic resource collections.

The extensive germplasm resource collections that are now available for major crop plants and their wild relatives will increasingly provide valuable biological and bioinformatics resources for plant physiologists and geneticists to dissect the molecular basis of key traits and to develop highly adapted plant material to sustain future breeding programs. A key to the efficient deployment of these resources is the development of information systems that will enable the collection and storage of biological information for these plant lines to be integrated with the molecular information that is now becoming available through the use of high-throughput genomics and post-genomics technologies. The GERMINATE database has been designed to hold a diverse variety of data types, ranging from molecular to phenotypic, and to allow querying between such data for any plant species. Data are stored in GERMINATE in a technology-independent manner, such that new technologies can be accommodated in the database as they emerge, without modification of the underlying schema. Users can access data in GERMINATE databases either via a lightweight Perl-CGI Web interface or by the more complex Genomic Diversity and Phenotype Connection software. GERMINATE is released under the GNU General Public License and is available at http://germinate.scri.sari.ac.uk/germinate/.

Computational Biology↗

Self-regulation and inhibition in comorbid ADHD children: an evaluation of executive functions.

The relationship between executive function and comorbid diagnoses in ADHD children is examined. One hundred six children between 7 and 15 years of age are assessed using the Tower of London (TOL), a test of executive function, and the Kiddie Schedule of Affective Disorders and Schizophrenia, Present and Lifetime Version, a diagnostic interview. All children met the diagnostic criteria for ADHD. A majority of the children had comorbid anxiety disorders, mood disorders, or oppositional defiant disorder. Measures on the TOL are total move score, total initiation time, and total rule violations. Age is predictive in all three measures of executive function as assessed by the TOL. Gender is predictive of total initiation time and total rule violations. Comorbid disorders are found to not have significance on executive function as measured by the TOL. This study concludes that comorbid disorders may not affect executive function.

Adolescent↗

Amiodarone-induced thyroid dysfunction.

BACKGROUND: Little is known about the frequency of thyroid dysfunction (TD) associated with amiodarone therapy in southern Africa. OBJECTIVES: To determine the incidence of TD in a cohort of patients initiated on amiodarone therapy at a cardiac clinic in Cape Town, South Africa, believed to be an iodine-replete area. PATIENTS: Pharmacy records were used to obtain the names of patients who received amiodarone between November 1999 and December 2002. RESULTS: The sample size was 194, but data analysis was limited to the 163 patients for whom there were complete data. The mean age +/- standard deviation (SD) was 59.0 +/- 15.0 years (range 22 - 89 years). There were 67 female and 96 male patients. The indications for amiodarone therapy were supraventricular tachycardias (N = 102, 62.6%), ventricular tachycardia (N = 55, 33.7%), and prophylaxis against tachycardias (N = 3, 1.8%). The indication was uncertain in 3 patients (1.8%). The median duration of amiodarone treatment was 679.0 days (quartile deviation (QD) 1172 days, range 3 - 6425 days) in the whole cohort. The median duration of amiodarone therapy until new TD was 943 days (QD 1185 days), significantly longer than in patients who remained euthyroid (547 days, QD 1135 days) (P = 0.05). There were 45 new TD cases (27.6%): 11 patients (6.7%) were thyrotoxic, 1 (0.6%) transient thyrotoxicosis, 1 (0.6%) subclinical hyperthyroidism, 13 (8.0%) had subclinical hypothyroidism, 12 (7.4%) hypothyroidism and 7 (4.3%) had minor changes in thyroid function. CONCLUSIONS: We found a high incidence of new-onset TD, similar to the highest rates reported internationally. Local factors responsible for this need to be investigated.

Adult↗

A practical method for monitoring general practice mortality in the UK: findings from a pilot study in a health board of Northern Ireland.

BACKGROUND: The Baker report into Dr Harold Shipman's murders recommended monitoring mortality in general practice, but there is currently no practical method available to implement this. AIM: To monitor mortality rates in response to the Baker report and to use the data to improve quality of care. DESIGN OF STUDY: Prospective mortality monitoring study. SETTING: Eastern Health and Social Services Board, Northern Ireland. METHOD: Linked quarterly mortality data from 1994-2001 were compiled for 114 general practices in Eastern Health and Social Services Board in Northern Ireland. Cross-sectional control charts compared crude and adjusted mortality rates across all the practices. Longitudinal control charts analysed quarterly mortality rates over 28 quarters within each practice. Practices were sent their own control charts and invited to feedback workshops. Special cause variation in mortality was investigated as follows: checks on data, case-mix, practice structures, processes of care and finally individual carers. RESULTS: Age, sex and deprivation adjusted cross-sectional control charts identified 18 practices as showing special cause variation in their mortality (11 high and 7 low). Assignable causes were found for all high special cause practices: large numbers of nursing home patients (six practices), very high levels of deprivation and high morbidity not captured by our case-mix adjustment (five practices). For three of seven low special cause practices, case-mix adjustment underestimated affluence and overestimated morbidity levels. Feedback indicated widespread support for the principle of monitoring, but concerns about the public disclosure of mortality data. CONCLUSIONS: We have successfully developed and piloted a general practice mortality monitoring system with the support and participation of local stakeholders. This used control charts for analysis and followed a scientific strategy for investigating special cause variation.

Epidemiologic Methods↗

Relocalization of nuclear ALY proteins to the cytoplasm by the tomato bushy stunt virus P19 pathogenicity protein.

The P19 protein of tomato bushy stunt virus (TBSV) is a multifunctional pathogenicity determinant involved in suppression of posttranscriptional gene silencing, virus movement, and symptom induction. Here, we report that P19 interacts with the conserved RNA-binding domain of an as yet uncharacterized family of plant ALY proteins that, in animals, are involved in export of RNAs from the nucleus and transcriptional coactivation. We show that the four ALY proteins encoded by the Arabidopsis genome and two ALY proteins from Nicotiana benthamiana are localized to the nucleus. Moreover, and in contrast to animal ALY, all but one of the proteins are also in the nucleolus, with distinct subnuclear localizations. Infection of plants by TBSV or expression of P19 from Agrobacterium results in relocation of three of the six ALY proteins from the nucleus to the cytoplasm demonstrating specific targeting of the ALY proteins by P19. The differential effects on subcellular localization indicate that, in plants, the various ALY proteins may have different functions. Interaction with and relocalization of ALY is prevented by mutation of P19 at residues previously shown to be important for P19 function in plants. Down-regulation of expression of two N. benthamiana ALY genes by virus-induced gene silencing did not interfere with posttranscriptional gene silencing. Targeting of ALY proteins during TBSV infection may therefore be related to functions of P19 in addition to its silencing suppression activity.

Amino Acid Sequence↗

Changes in gene expression during meristem activation processes in Solanum tuberosum with a focus on the regulation of an auxin response factor gene.

A suppression subtractive hybridization approach (SSH) was used to generate a cDNA library enriched in clones representing genes that are up-regulated in the potato tuber apical bud on dormancy release. The sequences of cDNAs representing 385 different genes were determined. This study focuses on the characterization of one of these cDNAs. On the basis of sequence similarity, the cDNA was identified as encoding a member of the auxin response factor family (ARF6). The expression pattern of potato ARF6 was determined by in situ hybridization. In apical tuber buds in the early stages of sprouting, relatively high levels of ARF6-specific transcripts were detected, especially in the peripheral zones of the tunica and corpus of the apical meristems. Expression was also detected in procambial and early vascular tissues, both subtending the meristem and in adjacent leaf primordia. By contrast, in dormant buds no expression of ARF6 could be detected. The expression pattern was also determined during the tuberization process; steady-state expression levels decreased c. 10-fold in the apical region as tuberization proceeded. In non-growing buds, exhibiting correlative inhibition, ARF6-specific transcript levels were relatively low, but rapidly increased when apical dominance was removed by excision of the apical bud. The effects of gibberellin and auxin on axillary bud growth and ARF6 expression are described.

Amino Acid Sequence↗

Obesity in people with intellectual disabilities: the impact of nurse-led health screenings and health promotion activities.

BACKGROUND: Obesity appears to be more common among people with intellectual disabilities, with few studies focusing on achieving weight reduction. AIM: Firstly, to follow-up people identified as overweight and obese following special health screening clinics and to determine the actions taken. Secondly, to evaluate the impact of health promotion classes on participants' weight loss. METHODS: A clinic led by two learning disability nurses was held for all people aged 10 years and over (n = 464) who attended special services within the area of one Health and Social Services Trust in Northern Ireland. In a second study, the nurses organized health promotion classes for 20 people over a 6- or 8-week period. FINDINGS: The health screen identified 64% of adults and 26% of 10-19-year olds as being overweight or obese. Moreover, those aged 40-49 years who were obese had significantly higher levels of blood pressure. However, information obtained from a follow-up questionnaire sent after 3 months suggested that of the 122 people identified for weight reduction, action had been taken for only 34% of them and only three were reported to have lost weight. The health promotion classes, however, led to a significant reduction in weight and body mass index scores. CONCLUSIONS: Health screening per se has limited impact on reducing obesity levels in this client group. Rather, health personnel such as general practitioners, nurses and health promotion staff need to work in partnership with service staff, carers and people with intellectual disabilities to create more active lifestyles.

Adolescent↗

Self-defense and martial arts evaluation for college women: preliminary validation of perceptions of dangerous situations scale.

Martial arts and self-defense programs train fearful people, especially women, to be more competent and confident to defend themselves in dangerous situations. However, there are no validated instruments to evaluate the effectiveness of programs purporting to teach self-protection. The Perceptions of Dangerous Situations Scale (PDSS), composed of fear, likelihood and confidence subscales, was developed and validated for university women. Participants were 368 university women, ages 17 to 45 years (M age = 20.7 years). Content validity of the PDSS was established through an expert panel, and construct validity was established through principal components analysis and determination of instructional sensitivity. Reliability was established through alpha coefficients. The PDSS, when used with university women, offers promising measurement opportunities in self-defense and martial arts settings.

Adolescent↗

Adrenocortical carcinoma: clinical, morphologic, and molecular characterization.

PURPOSE: To define multimolecular phenotypes of adrenocortical carcinoma (ACC) and to correlate outcome with morphologic and molecular parameters. PATIENTS AND METHODS: Clinical data were analyzed for 124 patients, histopathologic slides for 67 primary tumors, and tissue specimens for 74 patients (38 primary and 36 metastatic tumors) with ACC and for 38 normal adrenal tissue samples. Molecular expression profiles were investigated by immunohistochemistry. The prognostic significance of 12 gross and histologic parameters in 67 primary ACCs was evaluated. Morphologic and protein expression patterns were correlated with disease-specific survival (DSS). Univariate influence of prognostic factors on DSS was analyzed by log-rank test and multivariate analysis by Cox regression. RESULTS: The median follow-up period was 4.7 years. Significant predictors of DSS included distant metastasis at time of initial presentation; venous, capsular, and adjacent organ invasion; tumor necrosis, mitotic rate, atypical mitosis, and mdm-2 overexpression. Five-year DSS by number (one to six) of adverse histologic parameters was as follows: one to two, 84%; three to four, 37%; more than four, 9% (P =.005). The phenotype Ki-67(-)p53(-)mdm-2(+)cyclinD1(-)Bcl-2(-)p21(-)p27(+) was observed in 83% of normal and 3% of malignant adrenal tissue (P =.01). Molecular phenotypic expression was more heterogeneous in malignant than in normal (10 v five phenotypes) adrenal tissue. CONCLUSION: Meticulous morphologic evaluation, mitotic count, and tumor stage are essential in determining prognosis for patients with ACC. Multimolecular phenotyping demonstrates that the molecular complexity and heterogeneity of these neoplasms are such that targeted therapy needs to be patient specific.

Adolescent↗

The effect of contaminated surgical margins revisited.

The current study was done to assess the oncologic outcomes after inadvertent intraoperative contamination in the treatment of musculoskeletal sarcomas, to determine the prognostic significance of these events. Forty-three patients with malignant lesions and either positive margins or intraoperative tumor penetration are included in the study. There were 12 bone lesions and 31 soft tissue lesions. The final margin was intracapsular in 11 patients, contaminated marginal in 13 patients, and contaminated wide in 19 patients. Thirty-two patients received radiation therapy with doses from 4560 to 7000 cGy. The mean followup was 69 months (range, 24-179 months). In patients in whom the surgical margin was contaminated, additional tissue was removed with the goal being to obtain tumor-free surgical margins. Local recurrence occurred in four of 32 patients (12.5%) with no gross residual tumor. There was a significant difference in the recurrence rate between a wide (0 of 19) versus a marginal or intracapsular margin (nine of 24) based on the final surgical margin. High-grade lesions were more likely to recur than low-grade lesions, and soft tissue lesions were more likely to recur than bone lesions. Similar to previous reports, treatment of inadvertent contamination with reexcision and irrigation of the wound results in a similar recurrence rate to cases without contamination. Efforts should be made to achieve a wide final margin. Adjuvant therapies should be used whenever feasible.

Adolescent↗

Purpose-in-life and breast health behavior in Hispanic and Anglo women.

Hispanic and Anglo women differ in their practice of breast health behavior. A likely factor is differences in purpose-in-life (PIL) that influence motivation to achieve goals. To determine the relationship between PIL and breast health behavior, the PIL Test was modified and translated into Spanish, and the Breast Health Behavior Questionnaire (BHBQ) was generated. Both Spanish and English versions of the PIL Test and the BHBQ were measured in 40 Spanish and 40 Anglo women ages 20 to 49. Cronbach's alpha for the PIL Test were .86 for the English version and .72 for the Spanish; Cronbach's alpha for the BHBQ were .78 for the English and .70 for the Spanish version. There was a significant relationship between PIL and breast health behaviors in Anglo women but not in Hispanic women. Findings suggest further study of PIL in Hispanic women and may indicate a need for teaching the benefits of self-regulation to maintain health.

Adult↗

Providing a healthcare input to children in special schools.

The education of children with special educational needs is often accompanied by a requirement for medical or healthcare provision. If this cannot be done safely then the child's access to education is limited. No standardized template for the delivery of a healthcare input to children in special schools is apparent. This study sought to explore, through the use of an indepth needs assessment exercise and focus group interviews, what the most appropriate healthcare role was for delivering health care in a special school catering for children with a broad range of severe learning disabilities. While an overwhelming viewpoint of participants in focus groups perceived that a nurse was the only suitable person to undertake the role, the evidence gathered prompted the research steering group to suggest to the contrary, i.e. that the role of a healthcare worker with a national vocational qualification (NVQ) level 3 in care was the more appropriate person to maximize both the role of the nurse and the quality of care provided to these children.

Child↗