H Butler
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Publication
Journal: Nature Genetics
June/11/2000
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Publication
Journal: Science
March/29/2000
Abstract
The fly Drosophila melanogaster is one of the most intensively studied organisms in biology and serves as a model system for the investigation of many developmental and cellular processes common to higher eukaryotes, including humans. We have determined the nucleotide sequence of nearly all of the approximately 120-megabase euchromatic portion of the Drosophila genome using a whole-genome shotgun sequencing strategy supported by extensive clone-based sequence and a high-quality bacterial artificial chromosome physical map. Efforts are under way to close the remaining gaps; however, the sequence is of sufficient accuracy and contiguity to be declared substantially complete and to support an initial analysis of genome structure and preliminary gene annotation and interpretation. The genome encodes approximately 13,600 genes, somewhat fewer than the smaller Caenorhabditis elegans genome, but with comparable functional diversity.
Publication
Journal: Molecular Psychiatry
December/27/2010
Abstract
Autism spectrum disorders are a group of highly heritable neurodevelopmental disorders with a complex genetic etiology. The International Molecular Genetic Study of Autism Consortium previously identified linkage loci on chromosomes 7 and 2, termed AUTS1 and AUTS5, respectively. In this study, we performed a high-density association analysis in AUTS1 and AUTS5, testing more than 3000 single nucleotide polymorphisms (SNPs) in all known genes in each region, as well as SNPs in non-genic highly conserved sequences. SNP genotype data were also used to investigate copy number variation within these regions. The study sample consisted of 127 and 126 families, showing linkage to the AUTS1 and AUTS5 regions, respectively, and 188 gender-matched controls. Further investigation of the strongest association results was conducted in an independent European family sample containing 390 affected individuals. Association and copy number variant analysis highlighted several genes that warrant further investigation, including IMMP2L and DOCK4 on chromosome 7. Evidence for the involvement of DOCK4 in autism susceptibility was supported by independent replication of association at rs2217262 and the finding of a deletion segregating in a sib-pair family.
Publication
Journal: Thorax
February/14/2004
Authors
Publication
Journal: Australian and New Zealand Journal of Psychiatry
December/21/2000
Abstract
OBJECTIVE
The objective of this paper is to outline the conceptual background and strategy of intervention for a systematic and sustainable approach to mental health promotion in secondary schools.
METHODS
The conceptual origins of the Gatehouse Project are described in terms of the epidemiology of adolescent mental health problems, attachment theory, education reform research and health promotional theory and practice. The elements of health promotional work are described in terms of structural change and priority setting; implementation at multiple levels within the participating schools is described.
RESULTS
The conceptual framework of the Gatehouse Project emphasises healthy attachments with peers and teachers through the promotion of a sense of security and trust, effective communication and a sense of positive self-regard based on participation in varied aspects of school and community life. A school social climate profile is derived from a questionnaire survey of students. An adolescent health team uses this information to set priorities for change within the school. Interventions may focus on the promotion of a positive social climate of the whole school or in the classroom. Curriculum-based health education is also used and based on materials that are relevant to the normal developmental experiences of teenagers. These are integrated into the mainstream curriculum and incorporate a strong component of teacher professional development. Lastly, the intervention promotes linkage between the school and broader community with a particular emphasis on the needs of young people at high risk of school drop-out.
CONCLUSIONS
Educational environments are complex systems undergoing continuous and simultaneous changes. The Gatehouse Project will provide unique information on the relationship between the social environment and the emotional wellbeing of young people. More importantly it outlines a sustainable process for building the capacity of schools to promote the social and emotional development of young people.
Publication
Journal: Health Education and Behavior
October/17/2001
Abstract
The Gatehouse Project is an innovative, comprehensive approach to mental health promotion in secondary schools. It sets out to promote student engagement and school connectedness as the way to improve emotional well-being and learning outcomes. The key elements of the whole-school intervention are the establishment and support of a school-based adolescent health team; the identification of risk and protective factors in each school's social and leaning environment from student surveys; and, through the use of these data, the identification and implementation of effective strategies to address these issues. The project evaluation used a cluster-randomized controlled trial design involving 26 schools with initial results demonstrating considerable success in reducing smoking rates among Year 8 children. This article describes and accounts for how system-level changes have been made in schools through a process of capacity building. This encourages teachers, parents, and students to view the core business of education differently.
Publication
Journal: FEMS Microbiology Reviews
October/22/1997
Abstract
Eukaryotic microorganisms (protists) are a very important component of microbial communities inhabiting groundwater aquifers. This is not unexpected when one considers that many protists feed heterotrophically, by means of either phagotrophy (bacterivory) or osmotrophy. Protistan numbers are usually low (< 10(2) per g dw of aquifer material) in pristine, uncontaminated aquifers but may increase by several orders of magnitude in aquifers subject to organic pollution. Small flagellates (typically 2-3(5) microns in size in situ) are by far the dominant protists in aquifers, although amoebae and occasionally ciliates may also be present in much lower numbers. Although a wealth of new taxonomic information is waiting to be brought to light, interest in the identity of aquifer protists is not exclusively academic. If verified, the following hypotheses may prove to be important towards our understanding of the functioning of microbial communities in aquifers: (1) Differences in swimming behavior between species of flagellates lead to feeding heterogeneity and niche differentiation, implying that bacterivorous flagellates graze on different subsets of the bacterial community, and therefore play different roles in controlling bacterial densities. (2) Bacterivorous flagellates grazing on bacteria capable of degrading organic compounds have an indirect effect on the overall rates of biodegradation.
Publication
Journal: European Journal of Clinical Investigation
January/21/2003
Abstract
BACKGROUND
Metabolic acidaemia stimulates protein catabolism in skeletal muscle cells, leading to muscle wasting. As this occurs without decreasing cytosolic pH, the initial signal is unclear. A possible explanation is that extracellular pH acts on solute transporters at the cell surface, inhibiting nutrient influx.
METHODS
Influx through glucose and Pi transporters and System A amino acid transporters into L6 skeletal muscle cells was assessed using 3H-2-deoxyglucose (2-DG), 33Pi and 14C-methylaminoisobutyrate (MeAIB), respectively. Protein degradation (PD) was assessed from 14C efflux from cells prelabelled with 14C-Phe. Branched-chain amino acids and Phe were assayed by selective fluorimetric assays.
RESULTS
While acid (pH 7.1) had little immediate effect on 2-DG or 33Pi influx, exposure to pH 7.1 rapidly inhibited MeAIB influx. To determine whether System A inhibition was sufficient to trigger PD, it was blocked at pH 7.5 by a saturating dose (10 mmol L(-1)) of nonmetabolisable substrate (MeAIB). Like acid, this increased PD and decreased total protein. It also mimicked the decreases in protein synthesis, DNA synthesis, glucose transport and glycolysis, and depletion of branched-chain amino acids and Phe, which are induced in L6 by acid. The onset of inhibition of PD by an extracellular Gln load was retarded at pH 7.1, and stimulation of PD by acid was negligible if PD had already been stimulated by Gln depletion. The stimulatory effect of MeAIB on PD was selectively blunted by an excess of Gln, whereas the inhibitory effect of Gln on PD was blocked by excess MeAIB.
CONCLUSIONS
The similarity of changes in response to MeAIB and acid implies that these share a common intracellular signalling pathway triggered by inhibition of System A. Even though System A is only a minor contributor to total Gln influx in L6 cells, it is suggested that blockade of System A with acid or MeAIB induces a catabolic state by denying Gln access to a key intracellular regulatory site.
Publication
Journal: Journal of Anatomy
June/30/2000
Authors
Publication
Journal: Journal of Anatomy
October/31/1998
Publication
Journal: Journal of Anatomy
June/28/2010
Authors
Publication
Journal: Annals of Surgery
October/23/1968
Publication
Journal: Veterinary Microbiology
June/1/2014
Abstract
Fatal exudative dermatitis (FED) is a recently described condition affecting red squirrels (Sciurus vulgaris) on the Isle of Wight and Jersey (Simpson et al., 2010a). Staphylococcus aureus strains isolated from skin lesions in cases of FED were characterised by molecular and phenotypic approaches. The strains were found to belong to a single MLST clonal complex (CC49) representing either ST49 or a novel single locus variant thereof (ST1957), were closely related by other molecular typing approaches, and all possessed the leukotoxin M encoding gene (lukM). In contrast S. aureus was either not isolated from none-FED cases or belonged to distinct and diverse molecular types that, with one exception, did not encode lukM. All isolates from FED cases were susceptible to all antimicrobials tested, including penicillin, and all proved negative for mecA and mecC as well as 14 other staphylococcal toxin genes. As all squirrels affected by FED were infected with S. aureus of the same lineage and encoded the lukM gene, it is possible that strains of this lineage may be involved in the pathogenesis of the dermatitis.
Publication
Journal: Nature
August/31/2005
Publication
Journal: Pediatric Cardiology
May/14/2008
Abstract
With improvements in technology and surgical technique, pediatric cardiologists are challenging surgeons to close symptomatic ventricular septal defects (VSDs) in ever smaller patients. Although delaying surgery may facilitate operative repair, early intervention decreases the period of time these patients require therapy to prevent heart failure, maintains growth, and minimizes exposure to increased pulmonary pressures. To evaluate early intervention, we compare the outcomes of VSD closure in different-sized children. From December 2002 to July 2005, 225 patients underwent closure of a VSD. These patients were divided into four weight-based groups: <4 kg (group 1, n = 28), 4 to 6 kg (group 2, n = 93), 6 to 10 kg (group 3, n = 47), and >10 kg (group 4, n = 57). We reviewed operative and postoperative data, and comparisons were made between the groups. Median weights and ages at the time of surgery were 3.5 kg and 77 days (group 1), 4.9 kg and 128 days (group 2), 7.1 kg and 309 days (group 3), and 18.2 kg and 190 days (group 4). Operative data included cardiopulmonary bypass (CPB), aortic cross-clamp, and procedure times. CPB (p = 0.064), cross-clamp (p = 0.665), and procedure (p = 0.187) times were not significantly affected by decreasing weight. Postoperative continuous data included duration of ventilation and length of intensive care unit (ICU) and hospital stay. Ventilation (p = 0.667) and ICU (p = 0.976) times and length of hospital stay (p = 0.905) were also unaffected by decreasing weight. Postoperative catagoric data included complications and presence of a residual VSD. There was no significant difference in complications (p = 0.763) or residual VSD (p = 0.696) between groups. There was no mortality and no persistent heart block requiring placement of a permanent pacemaker. With improvements in technology and surgical technique, safe and effective VSD closure can be performed in increasingly smaller children. Earlier repair decreases the period of time these patients require aggressive medical therapy to prevent heart failure and maintain growth. It also decreases the period of time for which they are exposed to increased pulmonary pressures and are at risk for infectious respiratory complications. It does not appear to affect operative or postoperative outcomes.
Publication
Journal: Thorax
April/30/2003
Authors
Publication
Journal: Journal of Anatomy
February/14/2004
Authors
Publication
Journal: Thorax
February/14/2004
Authors
Publication
Journal: Archives of internal medicine
June/27/1978
Abstract
A 60-year-old patient with cyclic hemoptysis for 30 years was found to have bronchiectasis that was not present when hemoptysis began. Thoracic endometriosis and its possible relationship to bronchiectasis are discussed.
Publication
Journal: American Journal of Roentgenology
December/17/1984
Abstract
Twenty-three women with 27 instances of pelvic pathology were evaluated by magnetic resonance imaging (MRI). Different pulse sequences were used, which varied the dependence of the images on T1 and T2. Sonography was performed on 22 of the 23 patients. Five patients had CT examinations, including the patient who did not have sonography. MRI was also done in four normal volunteers. The spatial resolution of the MRI scans with short TR and TE intervals approached that of CT. There was overlap of MRI signal characteristics between various pathologic entities and also within the same entity (e.g., cystadenomas and endometriomas).
Publication
Journal: Contributions to primatology
February/17/1975
Authors
Publication
Journal: Archives of Disease in Childhood
April/30/2003
Authors
Publication
Journal: Pediatric Cardiology
September/24/2006
Publication
Journal: Journal of Asthma
November/3/2003
Abstract
A study involving eight children with moderate persistent asthma was undertaken to determine whether standard swimming lessons improved symptoms and pulmonary function tests (PFTs) in asthmatic children. Five children ages 7-12 years old with moderate persistent asthma were randomized to a swimming lesson group (5- to 6-week session) and three to a control group. Both groups completed pre- and poststudy period PFTs and symptom questionnaires. Swimming lessons did not produce a significant change in asthma symptoms or PFTs. Review of previous literature found that swimming has been shown to have definite benefits in improving cardiorespiratory fitness in asthmatic children. Swimming has been shown to be less asthmogenic than other forms of exercise. Some studies have also shown improvement in asthma symptoms in children participating in exercise programs.
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