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James Moore

Publications and source records attributed to James Moore.

15 recordsLinked to original sources
PubMed2006

The GermOnline cross-species systems browser provides comprehensive information on genes and gene products relevant for sexual reproduction.

We report a novel release of the GermOnline knowledgebase covering genes relevant for the cell cycle, gametogenesis and fertility. GermOnline was extended into a cross-species systems browser including information on DNA sequence annotation, gene expression and the function of gene products. The database covers eight model organisms and Homo sapiens, for which complete genome annotation data are available. The database is now built around a sophisticated genome browser (Ensembl), our own microarray information management and annotation system (MIMAS) used to extensively describe experimental data obtained with high-density oligonucleotide microarrays (GeneChips) and a comprehensive system for online editing of database entries (MediaWiki). The RNA data include results from classical microarrays as well as tiling arrays that yield information on RNA expression levels, transcript start sites and lengths as well as exon composition. Members of the research community are solicited to help GermOnline curators keep database entries on genes and gene products complete and accurate. The database is accessible at http://www.germonline.org/.

Animals↗
PubMed2006

APC gene methylation is inversely correlated with features of the CpG island methylator phenotype in colorectal cancer.

The notion of a CpG island methylator phenotype (CIMP) was proposed to describe a subset of colorectal cancers (CRC) displaying frequent and concordant methylation of CpG islands located within gene promoter regions. Some workers have failed to observe associations between CIMP and specific clinicopathological features of CRC, possibly because of the choice of genes used to define this phenotype. The aim of the current study was to determine whether the aberrant methylation of 6 genes implicated in CRC development was associated with the same phenotypic features of this tumour type. The MethyLight assay was used to provide quantitative estimates of MLH1, P16, TIMP3, P14, DAPK and APC methylation levels in 199 unselected colorectal tumours. The methylation of MLH1, P16, TIMP3 and P14 was highly concordant (p < 0.0001 for each pair) but that of DAPK and APC was not. An inverse association was observed between the methylation of APC and TIMP3 (p = 0.004). Methylation of the MLH1, P16, TIMP3 and P14 genes was associated with tumour infiltrating lymphocytes (p < 0.05), microsatellite instability (p < 0.001), BRAF mutation (p < 0.0001) and elevated concentrations of the methyl group carriers tetrahydrofolate (THF) and 5,10-methylene THF (p < 0.05). In contrast, APC methylation was associated with wildtype BRAF (p = 0.003) and with lower concentrations of methyl group carriers (p < 0.05). These findings highlight the importance of gene selection in studies that aim to characterize the biological features and clinical behaviour of CIMP+ tumours.

Adaptor Proteins, Signal Transducing↗
PubMed2006

Student debt amongst junior doctors in New Zealand; part 1: quantity, distribution, and psychosocial impact.

AIMS: To quantify student debt owed by first-year house officers at graduation, and to describe the effects of student debt on their lives. METHODS: A questionnaire was sent was to all 296 New Zealand-graduate first-year house officers practicing in New Zealand. The survey included questions on demographics, level of debt, student support received, repayment since graduation, psychosocial and financial impact of debt, and career intentions. RESULTS: The response rate was 53%. Ninety-two percent of respondents had some form of student debt, with 85% having a government student loan. The average total debt from all sources (excluding mortgages) at graduation was NZ65,206 dollars. Seventy-five percent of respondents owed more than 50,000 dollars and 13% had owed more than 100,000 dollars. Eighty-eight percent of respondents reported increased levels of stress as a result of their student loan, with 31% reporting that they worried about their student loan 'often' or 'always'. Eighty-three percent reported that their student loan had made it more difficult to save for their future, such as for a house deposit or for their retirement, and 42% stated that their student loan debt had influenced their decision whether to have children (or more children). CONCLUSION: Student debt has a major negative impact on the lives of house officers in New Zealand. These data provide a baseline for studying how changes in medical education affect junior doctors.

Education, Medical, Undergraduate↗
PubMed2006

Student debt amongst junior doctors in New Zealand; part 2: effects on intentions and workforce.

AIMS: To assess the effects of student debt on the intentions of first-year house officers in relation to location of practice and vocation, and to evaluate the relative importance of incentives to remain practising in New Zealand (NZ). METHODS: A questionnaire sent to all 296 New Zealand-graduate first-year house officers practicing in New Zealand. RESULTS: The response rate was 53%. Eighty percent of respondents intended to practice in New Zealand for the bulk of their careers; however, 65% of respondents intended to leave New Zealand within 3 years of graduating. The most important factors influencing the decision to leave NZ were overseas travel, financial opportunities, and job/training opportunities. Fifty-five percent of respondents had considered leaving the country, specifically because of the student loan debt. The most important factors influencing vocational intentions were interest, lifestyle, and intellectual challenge. Forty-three percent of respondents stated that their student debt had influenced their intended specialty, and only 9% of respondents indicated their intention to pursue a career in general practice. The highest rated incentives for staying in New Zealand were increased salaries, employer contributions towards student loans, and training opportunities within New Zealand. CONCLUSION: Student debt influences both emigration and specialty choice intentions of junior doctors in New Zealand. This effect is an unintended but important consequence of our current tertiary education system in New Zealand. These results paint a worrying picture for the junior doctor and general practitioner workforce in New Zealand's future.

Career Choice↗
PubMed2006

BRAF mutations are associated with distinctive clinical, pathological and molecular features of colorectal cancer independently of microsatellite instability status.

BACKGROUND: BRAF is a member of RAF family of serine/threonine kinases and mediates cellular responses to growth signals through the RAS-RAF-MAP kinase pathway. Activating mutations in BRAF have recently been found in about 10% of colorectal cancers, with the vast majority being a V600E hotspot mutation. The aim of the present study was to evaluate the clinical, pathological and molecular phenotype of colorectal tumors with BRAF mutations. RESULTS: Mutations in BRAF were identified in 8% (23/275) of colorectal cancers. They were 5-10-fold more frequent in tumors with infiltrating lymphocytes, location in the proximal colon, poor histological grade and mucinous appearance (P < 0.002 for each). Tumors with BRAF mutation were also 10-fold more likely to show microsatellite instability and frequent DNA methylation (P < 0.0001) compared to tumors without this mutation. The characteristic morphological features of tumors with BRAF mutation (infiltrating lymphocytes, poor grade, mucinous) remained after stratification according to microsatellite instability and methylator phenotypes. Mutations in BRAF were mutually exclusive with mutations in KRAS but showed no clear association with the presence of TP53 mutation. CONCLUSION: BRAF mutation identifies a colorectal cancer subgroup with distinctive phenotypic properties independent of microsatellite instability status and thus could be a valuable marker for studies into the clinical properties of these tumors.

Adaptor Proteins, Signal Transducing↗
PubMed2005

Standardized infection surveillance in long-term care: interfacility comparisons from a regional cohort of facilities.

OBJECTIVES: To measure infection rates in a regional cohort of long-term-care facilities (LTCFs) using standard surveillance methods and to analyze different methods for interfacility comparisons. SETTING: Seventeen LTCFs in Idaho. DESIGN: Prospective, active surveillance for LTCF-acquired infections using standard definitions and case-finding methods was conducted from July 2001 to June 2002. All surveillance data were combined and individual facility performance was compared with the aggregate employing a variety of statistical and graphic methods. RESULTS: The surveillance data set consisted of 472,019 resident-days of care with 1717 total infections for a pooled mean rate of 3.64 infections per 1000 resident-days. Specific infections included respiratory (828; rate, 1.75), skin and soft tissue (520; rate, 1.10), urinary tract (282; rate, 0.60), gastrointestinal (77; rate, 0.16), unexplained febrile illnesses (6; rate, 0.01), and bloodstream (4; rate, 0.01). Initially, methods adopted from the National Nosocomial Infections Surveillance System were used comparing individual rates with pooled means and percentiles of distribution. A more sensitive method appeared to be detecting statistically significant deviations (based on chi-square analysis) of the individual facility rates from the aggregate of all other facilities. One promising method employed statistical process control charts (U charts) adjusted to compare individual rates with aggregate monthly rates, providing simultaneous visual and statistical comparisons. Small multiples graphs were useful in providing images valid for rapid concurrent comparison of all facilities. CONCLUSION: Interfacility comparisons have been demonstrated to be valuable for hospital infection control programs, but have not been studied extensively in LTCFs.

Cohort Studies↗
PubMed2004

Dissection of floral pollination syndromes in Petunia.

Animal-mediated pollination is essential in the reproductive biology of many flowering plants and tends to be associated with pollination syndromes, sets of floral traits that are adapted to particular groups of pollinators. The complexity and functional convergence of various traits within pollination syndromes are outstanding examples of biological adaptation, raising questions about their mechanisms and origins. In the genus Petunia, complex pollination syndromes are found for nocturnal hawkmoths (P. axillaris) and diurnal bees (P. integrifolia), with characteristic differences in petal color, corolla shape, reproductive organ morphology, nectar quantity, nectar quality, and fragrance. We dissected the Petunia syndromes into their most important phenotypic and genetic components. They appear to include several distinct differences, such as cell-growth and cell-division patterns in the basal third of the petals, elongation of the ventral stamens, nectar secretion and nectar sugar metabolism, and enzymatic differentiation in the phenylpropanoid pathway. In backcross-inbred lines of species-derived chromosome segments in a transposon tagging strain of P. hybrida, one to five quantitative trait loci were identified for each syndrome component. Two loci for stamen elongation and nectar volume were confirmed in introgression lines and showed large allelic differences. The combined data provide a framework for a detailed understanding of floral syndromes from their developmental and molecular basis to their impact on animal behavior. With its molecular genetic tools, this Petunia system provides a novel venue for a pattern of adaptive radiation that is among the most characteristic of flowering plants.

Chromosome Mapping↗
PubMed2003

The folate pool in colorectal cancers is associated with DNA hypermethylation and with a polymorphism in methylenetetrahydrofolate reductase.

PURPOSE: Aberrant DNA methylation occurs in a subset of colorectal cancers and is characterized by regional areas of hypermethylation at CpG islands. The aims of this study were firstly to evaluate the levels of folate intermediates (FIs) in tumors with aberrant DNA methylation and secondly to determine whether these levels are affected by polymorphisms in key genes involved in folate metabolism. EXPERIMENTAL DESIGN: The concentrations of two major intracellular FIs, 5,10-methylenetetrahydrofolate and tetrahydrofolate (FH4), were measured in 103 surgically resected colorectal cancers. DNA hypermethylation at seven different CpG islands was measured using the MethylLight assay. Genotyping for polymorphisms in the thymidylate synthase, cystathionine beta-synthase, methionine synthase, and methylenetetrahydrofolate reductase (MTHFR) genes was carried out using PCR and PCR-RFLP. RESULTS: Significantly higher levels of FH4 were found in tumors from the proximal colon compared with those originating in the distal colon and rectum. Tumors with aberrant DNA methylation of CpG islands within promoter regions of the hMLH1, TIMP3, and ARF genes also contained higher levels of both 5,10-methylenetetrahydrofolate and FH4. In contrast, patients who were homozygous for the C667T polymorphism of the MTHFR gene had significantly lower concentrations of both these FIs in their tumor tissue. CONCLUSIONS: The concentrations of FIs in colorectal tumors are directly related to the presence of frequent DNA hypermethylation and inversely related to the presence of a common polymorphism in the MTHFR gene. FIs could serve as biochemical markers for the risk of developing this disease, as well as for the prediction of toxicity and efficacy of fluorouracil-based treatments.

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗
PubMed2003

Regulation of peripheral inflammation by spinal adenosine: role of somatic afferent fibers.

Spinal administration of adenosine inhibits neutrophil accumulation in skin. The neural pathways mediating this action are unknown. We investigated individually the roles of capsaicin sensitive primary afferent fibers, sympathetic efferent fibers, and dorsal roots in this regulation. One week after implantation of intrathecal (IT) catheters into rats, the adenosine receptor agonist cyclohexyladenosine (CHA) or vehicle was injected intrathecally. Inflammatory skin lesions were induced by intradermal carrageenan. Three hours later, skin was harvested and assayed for neutrophils by measuring myeloperoxidase (MPO) activity. Intrathecal CHA (5 microg/kg) decreased neutrophil infiltration into skin lesions. Nociceptive peptides were largely depleted from central terminals of primary afferents by IT capsaicin pretreatment. This depletion had no effect on either basal neutrophil infiltration or CHA-mediated modulation. Sympathetic fibers were largely destroyed by systemic 6-hydoxydopamine (6-OHDA) pretreatment; sympathectomy did not affect basal neutrophil infiltration or block its suppression by IT CHA. Thus, spinal adenosine effects on skin neutrophil trafficking appear to be independent of sympathetic nerves and primary afferent peptides, although incomplete lesions by chemical pretreatments may have confounded our results. Sensory fibers were interrupted by prior unilateral dorsal rhizotomies. This procedure had no effect on neutrophil accumulation in control rats. However, rhizotomy blocked the CHA effect, with MPO levels 45 +/- 18% greater in denervated than control skin in IT CHA-treated animals (P < 0.05). It is clear that the spinal adenosine effect requires intact somatic connectivity. Information on pain and inflammation in the periphery is transmitted to the nervous system, where increased spinal adenosine levels can suppress peripheral inflammation.

Adenosine↗
PubMed2002

Fish tissue quality in near-coastal areas of the Gulf of Mexico receiving point source discharges.

The objective of this study was to determine inorganic and organic contaminant concentrations in edible tissue of fish collected from eight coastal areas receiving wastewater discharges and from two reference locations. Trace metal residues were statistically similar regardless of the collection site. Zinc (100% detection in all samples), total mercury (100%), total arsenic (92%), copper (92%), and selenium (88%) were the more commonly detected trace metals. Mercury concentrations exceeded the Florida health-based standard of 0.5 microg/g for limited fish consumption in 30% of the total samples and averaged 0.40 (+/- 1 S.D. = 0.22, range < or = 0.08 to 0.85) microg/g wet weight. The average total PAH concentrations were 1.79 (+/- 1.60) ng/g (reference areas) and 2.17 (+/- 3.29) ng/g (wastewater-impacted areas). Pyrene was detected most frequently (63% of the total samples) and averaged 0.74 (+/- 0.35) ng/g wet wt. The average total PCB concentrations were 4.8 (+/- 7.1) ng/g (reference areas) and 31.6 (+/- 31.3) ng/g (wastewater-impacted areas) Concentrations of dieldrin and cis-chlordane were approximately eight times greater, respectively, in fish collected from wastewater receiving waters, whereas total DDT and total pesticide concentrations were not elevated in the same areas. Concentrations of total PCBs and all chlorinated pesticides were below US health-based standards. The lack of a published reference data base for fish tissue quality in near-coastal areas of the Gulf of Mexico restricts an assessment of the environmental significance of results from this and similar studies investigating the fate of point source contaminants.

Animals↗
PubMed2002

Spinal adenosine receptor activation inhibits inflammation and joint destruction in rat adjuvant-induced arthritis.

OBJECTIVE: To examine the effect of spinal cord adenosine (Ado) receptor stimulation on rat adjuvant-induced arthritis (AIA). METHODS: Long-term intrathecal (IT) catheters were implanted into rats to provide spinal access for drug delivery. Animals were immunized with complete Freund's adjuvant at the tail base. Eight days later and every other day thereafter until day 20, rats were treated IT with the selective Ado A1 receptor agonist cyclohexyladenosine (CHA) or vehicle. In some experiments, animals received an additional daily intraperitoneal injection of the nonselective Ado antagonist theophylline. Paw swelling was measured by water displacement plethysmometry. The effect of IT CHA on the activation of activator protein 1 (AP-1) was determined by electromobility shift assay. Spinal cord c-Fos expression was determined by immunohistochemistry. RESULTS: Spinal CHA significantly inhibited inflammation in AIA, with a mean +/- SEM 20.9 +/- 16.9% increase in paw swelling in the IT CHA group compared with 81.3 +/- 10.6% in the saline group. The antiinflammatory effect of CHA was mediated through Ado receptors since the effect was reversed by coadministration of systemic theophylline. In addition, radiographs showed significantly less bone and cartilage destruction in the CHA-treated animals. Synovial expression of AP-1, which is a key regulator of metalloproteinase expression, was lower in IT CHA-treated animals. C-Fos expression was localized to spinal laminae I-VI, with a modest decrease observed in the superficial laminae in IT CHA-treated rats. CONCLUSION: These data demonstrate that the spinal cord can regulate peripheral inflammation. Therapeutic strategies that target the central nervous system might be useful in arthritis.

Adenosine↗
PubMed2002

Correlation of mismatch repair genes immunohistochemistry and microsatellite instability status in HNPCC-associated tumours.

AIM: The aim of this study was to assess the performance of immunohistochemistry using antibodies for MLH1, MSH2, MSH6 and PMS2 mismatch repair gene proteins against microsatellite instability (MSI) testing. METHODS: Tumour samples included in this study were derived from referred patients for screening for hereditary non-polyposis colorectal cancer (HNPCC) and patients who had resections for colorectal cancer that were examined at our institution. MSI was assessed at nine loci (BAT25, BAT26, BAT40, D2S123, D10S197, D17S579, D18S34, D5S346 and D17S250) in all cases. Immunohistochemistry for MLH1 and MSH2 was performed in all cases. Staining for MSH6 and PMS2 was performed in selected cases only. RESULTS: There were 742 tumours including 661 colorectal lesions and 81 extracolonic tumours of the HNPCC spectrum. Among the 555 MSI-negative tumours, 554 showed an intact protein expression. Amongst the 187 MSI-positive tumours, 126 showed abnormal expression of MLH1 gene protein, 41 showed abnormal expression of MSH2 gene, three showed abnormal expression of MSH6 only, one showed abnormal expression of PMS2 gene protein only and one case showed abnormal expression of all four proteins. CONCLUSION: Immunohistochemistry offers an alternative method for assessment of MSI status which is fast and relatively inexpensive compared with MSI testing. We achieved a sensitivity rate of 92% and specificity of 99.8% for immunohistochemistry testing assessed against the MSI testing. It has to be accepted that a small fraction of MSI-positive cases will be missed by testing with immunohistochemistry alone.

Adaptor Proteins, Signal Transducing↗