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At least 937 records · Page 52Linked to original sources
PubMed2004

Dissecting tBHQ induced ARE-driven gene expression through long and short oligonucleotide arrays.

This paper compares the gene expression profiles identified by short (Affymetrix U95AV2) or long (Agilent Hu1A) oligonucleotide arrays on a model for upregulation of a cluster of antioxidant responsive element-driven genes by treatment with tert-butylhydroquinone. MAS 5.0, dCHIP, and RMA were applied to normalize the Affymetrix data, and Lowess regression was considered for Agilent data. SAM was used to identify the differential gene expression. A set of biological markers and housekeeping genes were chosen to evaluate the performance of multiple normalization approaches. Both arrays illustrated a definite set of overlapping genes between the data sets regardless of data mining tools used. However, unique gene expression profiles based on the platform used were also revealed and confirmed by quantitative RT-PCR. Further analysis of the data revealed by alternative approaches suggested that alternative splicing, multiple vs. single probe(s) measurement, and use or nonuse of mismatch probes may account for the discrepant data. Therefore, these two microarray technologies offer relatively reliable data. Integration of the gene expression profiles from different array platforms may not only help for cross-validation but also provide a more complete view of the transcriptional scenario.

Alternative Splicing↗
PubMed2004

Quality assurance system using statistical process control: an implementation for image cytometry.

AIMS: Optical technologies have shown some promise for improving the care of cervical neoplasia. We are currently evaluating fluorescence and reflectance spectroscopy and quantitative cyto-histopathology for cervical neoplasia screening and diagnosis. Here we describe the establishment and application of a quality assurance (QA) system for detecting system malfunctions and assessing the comparability of four image cytometers used in a multicenter clinical trial. METHODS: Our QA system involves three levels of evaluation based on the periodicity and complexity of the measurements. We implemented our QA system at three image cytometers at the British Columbia Cancer Agency and one at M.D. Anderson Cancer Center. The measurements or tasks were performed daily, monthly, and semi-annually. The current and voltage of the lamp, the calibration image characteristics, and the room temperature were checked daily. Long-term stability over time, short-term variability over time, and spatial response field uniformity were evaluated monthly. Camera linearity was measured semi-annually. Control charts based on statistical process control techniques were used to detect when the system did not perform optimally. RESULTS: Daily measurements have shown good consistency in room temperature, lamp and calibration behaviour. Monthly measurements have shown small coefficients of variation between and within the four devices. There have been greater differences between sessions than within sessions. Comparability among the four systems is reasonably good. Semi-annual measurements have shown stable camera linearity. QA events were detected using the QA system. Multiple examples of event detection leading to correction of system malfunction are described in this report. CONCLUSIONS: QA programs are critical for ensuring data integrity and therefore for the conduct of multicenter clinical trials.

Female↗
PubMed2005

Expression of HOXB2, a retinoic acid signaling target in pancreatic cancer and pancreatic intraepithelial neoplasia.

PURPOSE: Despite significant progress in understanding the molecular pathology of pancreatic cancer and its precursor lesion: pancreatic intraepithelial neoplasia (PanIN), there remain no molecules with proven clinical utility as prognostic or therapeutic markers. Here, we used oligonucleotide microarrays to interrogate mRNA expression of pancreatic cancer tissue and normal pancreas to identify novel molecular pathways dysregulated in the development and progression of pancreatic cancer. EXPERIMENTAL DESIGN: RNA was hybridized to Affymetrix Genechip HG-U133 oligonucleotide microarrays. A relational database integrating data from publicly available resources was created to identify candidate genes potentially relevant to pancreatic cancer. The protein expression of one candidate, homeobox B2 (HOXB2), in PanIN and pancreatic cancer was assessed using immunohistochemistry. RESULTS: We identified aberrant expression of several components of the retinoic acid (RA) signaling pathway (RARalpha, MUC4, Id-1, MMP9, uPAR, HB-EGF, HOXB6, and HOXB2), many of which are known to be aberrantly expressed in pancreatic cancer and PanIN. HOXB2, a downstream target of RA, was up-regulated 6.7-fold in pancreatic cancer compared with normal pancreas. Immunohistochemistry revealed ectopic expression of HOXB2 in 15% of early PanIN lesions and 48 of 128 (38%) pancreatic cancer specimens. Expression of HOXB2 was associated with nonresectable tumors and was an independent predictor of poor survival in resected tumors. CONCLUSIONS: We identified aberrant expression of RA signaling components in pancreatic cancer, including HOXB2, which was expressed in a proportion of PanIN lesions. Ectopic expression of HOXB2 was associated with a poor prognosis for all patients with pancreatic cancer and was an independent predictor of survival in patients who underwent resection.

Adult↗
PubMed2006

Identification of the sex-determining locus of Atlantic salmon (Salmo salar) on chromosome 2.

We have integrated data from linkage mapping, physical mapping and karyotyping to gain a better understanding of the sex-determining locus, SEX, in Atlantic salmon (Salmo salar). SEX has been mapped to Atlantic salmon linkage group 1 (ASL1) and is associated with several microsatellite markers. We have used probes designed from the flanking regions of these sex-linked microsatellite markers to screen a bacterial artificial chromosome (BAC) library, representing an 11.7x coverage of the Atlantic salmon genome, which has been HindIII fingerprinted and assembled into contigs. BACs containing sex-linked microsatellites and their related contigs have been identified and representative BACs have been placed on the Atlantic salmon chromosomes by fluorescent in situ hybridization (FISH). This identified chromosome 2, a large metacentric, as the sex chromosome. By positioning several BACs on this chromosome by FISH, it was possible to orient ASL1 with respect to chromosome 2. The region containing SEX appears to lie on the long arm between marker Ssa202DU and a region of heterochromatin identified by DAPI staining. BAC end-sequencing of clones within sex-linked contigs revealed five hitherto unmapped genes along the sex chromosome. We are using an in silico approach coupled with physical probing of the BAC library to extend the BAC contigs to provide a physical map of ASL1, with a view to sequencing chromosome 2 and, in the process, identifying the sex-determining gene.

Animals↗
PubMed1997

Contour-guided brain tumor surgery using a stereotactic navigating microscope.

OBJECTIVE: The benefit of intraoperative radiological data integration in approach planning and resection of brain tumors using a computer navigating microscope (MKM Zeiss) was investigated. METHODS: Since February 1995, out of 86 MKM-guided surgical procedures, 53 contour-guided tumor cases (24 females, 29 males, mean age 51.6) including 16 metastasis, 14 glioblastomas, 10 low-grade gliomas, 6 anaplastic gliomas, 3 meningiomas and 4 others were performed. The preoperative planning was based on CT in 42 cases and Magnetic Resonance Tomography (MRT) in 11 cases using skin markers (4-9, mean 6). Neuroradiologically defined tumor contours were transferred into the ocular of the microscope and projected into the operating field during the procedure. RESULTS: The advantages of the system were: (1) preoperative approach planning; (2) minimal, accurate skin incision and craniotomy; (3) intraoperative detection of deep seated lesions or lesion components; (4) determination of lesion boundaries; (5) minimized traumatization in/near eloquent areas. Mean registration accuracy improved from 5.3 mm for the first 10 cases up to 2 mm for the last 18 cases. In glioma surgery, the system provided exact definition of radiologically planned resection borders. In meningioma surgery, it allowed a tailored craniotomy, dura opening and resection, lowering the risk of recurrence. In metastasis surgery, it provided a safe approach to deep and eloquent located lesions. CONCLUSION: Contour-guided operation planning and resection guidance using the investigated navigating microscope provides additional security to avoid some potential risks in brain tumor surgery.

Adult↗
PubMedDate not supplied

Temporal quantification of Alzheimer's disease severity: 'time index' model.

A fundamental issue in the clinical and neuropathological assessment of Alzheimer's disease patients is quantification of dementia severity progression. Several methods have been advanced for the purpose of staging dementia with various sensitivities at different phases of the disease, but no mathematical function has been developed to link these measures to a physical continuum. Using a dynamic method for quantifying illness severity, change in severity over time was referenced to a cumulative temporal index, a physical dimension. Data from 33 patients with probable Alzheimer's disease with at least 2 successive assessments on three 50-point scales measuring cognitive, behavioral, and daily living skills were used to determine rate of change. 'Fuzzylogic' smoothing of the data, integration over time, and least-squares regression were used to derive a cubic polynomial function to calculate a severity measure in which 'days of illness' was estimated from the severity score. This method can be used to improve the comparability of performance across various mental status tests, and to link measures of very early phases of preclinical dementia and late profound dementia phases. This method also provides a description of an 'average' time course for any population from which the index is derived.

Activities of Daily Living↗
PubMed2001

Electroanatomic mapping of entrained and exit zones in patients with repaired congenital heart disease and intra-atrial reentrant tachycardia.

BACKGROUND: Characterization of reentrant circuits and targeting ablation sites remains difficult for intra-atrial reentrant tachycardias (IART) in congenital heart disease (CHD). METHODS AND RESULTS: Electroanatomic mapping and entrainment pacing were performed before successful ablation of 18 IART circuits in 15 patients with CHD. Principal features of IART circuits were atrial septal defect (4 patients), atriotomy (3 patients), other atrial scar (3 patients), crista terminalis (3 patients), and right atrioventricular valve (5 patients). A median of 176 sites (range, 96 to 317 sites) was mapped for activation and 13 sites (range, 9 to 28 sites) for entrainment response. Postpacing intervals within 20 ms of tachycardia cycle length and stimulus-to-P-wave intervals of 0 to 90 ms (exit zones) were mapped to atrial surfaces generated by electroanatomic mapping. Criteria for entrainment were met over a median of 21 cm2 of atrial surface (range, 2 to 75 cm2), 19% (range, 1% to 81%) of total area tested. Using integrated data, relations between activation sequence and protected corridor of conduction could be inferred for 16 of 17 LARTs. Successful ablation was achieved at a site distant from the putative protected corridor in 9 of 18 (50%) circuits. CONCLUSIONS: The right atrium in CHD supports a variety of IART mechanisms. Fusion of activation and entrainment data provided insight into specific IART mechanisms relevant to ablation.

Adolescent↗
PubMed2025

New Genetic Loci Implicated in Cardiac Morphology and Function Using Three-Dimensional Population Phenotyping.

BACKGROUND: Cardiac remodeling occurs in the mature heart and is a cascade of adaptations in response to stress, which are primed in early life. A key question remains as to the processes that regulate the geometry and motion of the heart and how it adapts to stress. METHODS: We performed spatially resolved phenotyping using machine learning-based analysis of cardiac magnetic resonance imaging in 47 549 UK Biobank participants. We analyzed 16 left ventricular spatial phenotypes, including regional myocardial wall thickness and systolic strain in both circumferential and radial directions. In up to 40 058 participants, genetic associations across the allele frequency spectrum were assessed using genome-wide association studies with imputed genotype participants, and exome-wide association studies and gene-based burden tests using whole-exome sequencing data. We integrated transcriptomic data from the GTEx project and used pathway enrichment analyses to further interpret the biological relevance of identified loci. To investigate causal relationships, we conducted Mendelian randomization analyses to evaluate the effects of blood pressure on regional cardiac traits and the effects of these traits on cardiomyopathy risk. RESULTS: We found 42 loci associated with cardiac structure and contractility, many of which reveal patterns of spatial organization in the heart. Whole-exome sequencing revealed 3 additional variants not captured by the genome-wide association study, including a missense variant in CSRP3 (minor allele frequency 0.5%). The majority of newly discovered loci are found in cardiomyopathy-associated genes, suggesting that they regulate spatially distinct patterns of remodeling in the left ventricle in an adult population. Our causal analysis also found regional modulation of blood pressure on cardiac wall thickness and strain. CONCLUSIONS: These findings provide a comprehensive description of the pathways that orchestrate heart development and cardiac remodeling. These data highlight the role that cardiomyopathy-associated genes have on the regulation of spatial adaptations in those without known disease.

Humans↗
PubMed2025

Perirenal Adipose Tissue and Hypertension: Observational and Genetic Analyses.

BACKGROUND: Perirenal adipose tissue (PRAT) consists of white and brown adipocytes with good vascularization and dense innervation, which could influence the blood pressure. We aim to investigate the association of PRAT thickness with risks of overall and specific forms of hypertension. METHODS: We measured PRAT thickness in the UK Biobank and CONPASS (Chongqing Primary Aldosteronism Study). We prospectively examined the correlation between PRAT thickness and incident hypertension in the UK Biobank. We cross-sectionally explored associations between PRAT thickness and common forms of hypertension in CONPASS. Integrating data from GWAS (Genome-Wide Association Study), we investigated the potential causal relationship between PRAT and hypertension forms by 2-sample Mendelian randomization analyses. RESULTS: In the prospective analysis of the UK Biobank, participants whose PRAT thickness was &#x2265;46.1 mm showed a higher risk of developing hypertension than participants whose PRAT thickness was <16.4 mm (hazard ratio, 2.91 [95% CI, 1.97-4.32]). In the cross-sectional analysis of CONPASS, a 1 SD increment in PRAT thickness was associated with a 2.77-fold higher adjusted odds of low-renin essential hypertension and a 3.89-fold higher adjusted odds of idiopathic hyperaldosteronism. PRAT thickness was not significantly associated with other forms of hypertension, such as aldosterone-producing adenoma and obstructive sleep apnea. In 2-sample Mendelian randomization analyses, PRAT thickness was only significantly associated with a higher risk of idiopathic hyperaldosteronism (inverse variance weighted odds ratio, 1.33 [95% CI, 1.09-1.62]), with no evidence of significant heterogeneity or substantial directional pleiotropy. CONCLUSIONS: PRAT is causally associated with idiopathic hyperaldosteronism rather than essential hypertension and other forms of secondary hypertension.

Humans↗
PubMed1983

Alexithymia: examining the development of a psychological concept.

Alexithymia is a clinically derived concept that refers to difficulty patients have with verbal expression of emotions and with fantasy elaborations. Since its recent introduction into the literature, it has been discussed in various contexts and has been considered by some to be a useful concept in integrating data from a variety of disciplines. The authors contend that many of the speculations about alexithymia are based on an inadequately researched data base and that its application in some areas is premature. They recommend careful investigation of any newly introduced psychological concept to avoid either its premature rejection or its reification.

Affective Symptoms↗
PubMed1998

Factual sources of psychiatric patients' perceptions of coercion in the hospital admission process.

OBJECTIVE: The purpose of this study was to determine what predicts patients' perceptions of coercion surrounding admission to a psychiatric hospital. METHOD: For 171 cases, the authors integrated data from interviews with patients, admitting clinicians, and other individuals involved in the patients' psychiatric admissions with data from the medical records. Using a structured set of procedures, coders determined whether or not nine coercion-related behaviors occurred around the time of admission. Correlation and regression analyses were used to describe the predictors of patients' scores on the MacArthur Perceived Coercion Scale. RESULTS: The use of legal force, being given orders, threats, and "a show of force" were all strongly correlated with perceived coercion. A least squares regression accounted for 43.3% of the variance in perceived coercion. The evidence also suggested that force is typically only used in conjunction with less coercive pressures. CONCLUSIONS: Force and negative symbolic pressures, such as threats and giving orders about admission decisions, induce perceptions of coercion in persons with mental illness. Positive symbolic pressures, such as persuasion, do not induce perceptions of coercion. Such positive pressures should be tried in order to encourage admission before force or negative pressures are used.

Adult↗
PubMed2003

The New York-New York housing initiative and use of public shelters by persons with severe mental illness.

OBJECTIVE: The study examined changes in the use of shelters in New York City by mentally ill persons with a history of homelessness who received housing placements through the New York-New York (NY/NY) housing initiative between 1990 and 1999 and the impact of the initiative on the overall demand for shelter beds in the city. METHODS: Computerized service records on housing, shelter use, and health care services were linked to create an integrated data set for 3,167 persons who received NY/NY housing placements, which provided mental health services, and for a matched control group of persons with mental illness who used shelters but did not receive housing placements. Regression analyses were used to assess the relationships between shelter use and receipt of a placement. Differences in postplacement shelter use between NY/NY housing recipients and the matched control group were then examined at an individual level and a population level. RESULTS: Heavy users of the shelter system were more likely to be placed in NY/NY housing. In the two-year postplacement period, persons who received a NY/NY housing placement used, on average, 128.2 fewer shelter days than those in the control group. In 1996, the NY/NY housing initiative reduced the average nightly census in New York City shelters by an estimated 4.6 percent. CONCLUSIONS: Providing housing combined with mental health services is an effective approach to reducing shelter use among mentally ill persons who have a history of homelessness.

Adolescent↗
PubMed1998

High-Dose Chemotherapy in the Adjuvant Treatment of Breast Cancer: Benefit/Risk Analysis.

BACKGROUND: High-dose chemotherapy (HDRx) may improve the prognosis of patients with high-risk breast cancer but at the expense of increased toxicity. However, no randomized, controlled trials have been published that clearly demonstrate the superiority of HDRx over conventional adjuvant chemotherapy. METHODS: We developed a simple model to compare benefits and risks of HDRx with conventional adjuvant chemotherapy (SDRx). The model integrates data on efficacy and risks of two competing treatment strategies into a single decision rule. RESULTS AND CONCLUSIONS: Using data from phase II studies, we show that if a disease-free survival is considered to be the most important outcome, HDRx should be administered when the probability of breast cancer relapse at five years exceeds 54% to 71% for patients with 4 to 9 positive nodes and exceeds 29% to 40% for patients with >9 positive nodes. If the endpoint of interest is five-year overall survival, then the treatment should be administered when the probability of relapse exceeds 77% to 83% for patients with 4 to 9 nodes involved and 22% to 31% for those with >9 lymph nodes involved. While awaiting results of randomized, controlled trials to definitively establish the efficacy rate of HDRx, we also found that HDRx could be considered in the management of high-risk breast cancer if its efficacy rate is at least 54% to 60% superior to SDRx in reducing relapse risk in breast cancer patients with 4 to 9 nodes and at least 31% to 38% for >9 positive nodes. If survival data are used instead of disease-free survival outcomes, HDRx efficacy should be at least 47% to 48% superior to SDRx in reducing death risk in breast cancer patients with 4 to 9 nodes and at least 27% to 30% superior for >9 positive nodes to consider its use in the adjuvant setting.

Journal Article↗
PubMed2004

Information management for entomology screening.

The successful introduction of genetically modified (GM) crops has created a revolutionary transformation of the agricultural industry with GM crops currently planted on some 130 million acres. Historically, agricultural companies were involved in the discovery of conventional insecticide chemistries in processes that were very similar to those in the pharmaceutical industry. With the introduction of GM technologies, the process has radically changed. The new process is best described as the pharmaceutical equivalent of a very large-scale limited clinical trial conducted at the discovery stage. For example, unlike pharmaceutical screens, GM crop discovery screens frequently involve live insects challenged with complex protein containing soups. Furthermore, the nature of the potential avenues for discovery mandates that assay models also support protein engineering, proteomics, and genomics efforts. The range in sample demand ranges from ultra-low to high throughput. Finally, regulatory and good business stewardship demands that data integrity and tractability is in place, from discovery through varietal introduction, to manage the information generated in support of a commercialized GM plant variety. The authors describe their discovery workflow and detail how they have customized a commercially available database software package to achieve an optimum configuration for entomology screening.

Animals↗
PubMed2003

Promotion and advocacy for improved complementary feeding: can we apply the lessons learned from breastfeeding?

Although many successes have been achieved in promoting breastfeeding, this has not been the case for complementary feeding. Some successes in promoting complementary feeding at the community level have been documented, but few of these efforts have expanded to a larger scale and become sustained. To discover the reasons for this difference, the key factors for the successful promotion of breastfeeding on a large scale were examined and compared with the efforts made in complementary feeding. These factors include definition and rationale, policy support, funding, advocacy, private-sector involvement, availability and use of monitoring data, integration of research into action, and the existence of a well-articulated series of steps for successful implementation. The lessons learned from the promotion of breastfeeding should be applied to complementary feeding, and the new Global Strategy for Infant and Young Child Feeding provides an excellent first step in this process.

Breast Feeding↗
PubMed2004

mlstdbNet - distributed multi-locus sequence typing (MLST) databases.

BACKGROUND: Multi-locus sequence typing (MLST) is a method of typing that facilitates the discrimination of microbial isolates by comparing the sequences of housekeeping gene fragments. The mlstdbNet software enables the implementation of distributed web-accessible MLST databases that can be linked widely over the Internet. RESULTS: The software enables multiple isolate databases to query a single profiles database that contains allelic profile and sequence definitions. This separation enables isolate databases to be established by individual laboratories, each customized to the needs of the particular project and with appropriate access restrictions, while maintaining the benefits of a single definitive source of profile and sequence information. Databases are described by an XML file that is parsed by a Perl CGI script. The software offers a large number of ways to query the databases and to further break down and export the results generated. Additional features can be enabled by installing third-party (freely available) tools. CONCLUSION: Development of a distributed structure for MLST databases offers scalability and flexibility, allowing participating centres to maintain ownership of their own data, without introducing duplication and data integrity issues.

Bacterial Typing Techniques↗
PubMed2006

Text mining of full-text journal articles combined with gene expression analysis reveals a relationship between sphingosine-1-phosphate and invasiveness of a glioblastoma cell line.

BACKGROUND: Sphingosine 1-phosphate (S1P), a lysophospholipid, is involved in various cellular processes such as migration, proliferation, and survival. To date, the impact of S1P on human glioblastoma is not fully understood. Particularly, the concerted role played by matrix metalloproteinases (MMP) and S1P in aggressive tumor behavior and angiogenesis remains to be elucidated. RESULTS: To gain new insights in the effect of S1P on angiogenesis and invasion of this type of malignant tumor, we used microarrays to investigate the gene expression in glioblastoma as a response to S1P administration in vitro. We compared the expression profiles for the same cell lines under the influence of epidermal growth factor (EGF), an important growth factor. We found a set of 72 genes that are significantly differentially expressed as a unique response to S1P. Based on the result of mining full-text articles from 20 scientific journals in the field of cancer research published over a period of five years, we inferred gene-gene interaction networks for these 72 differentially expressed genes. Among the generated networks, we identified a particularly interesting one. It describes a cascading event, triggered by S1P, leading to the transactivation of MMP-9 via neuregulin-1 (NRG-1), vascular endothelial growth factor (VEGF), and the urokinase-type plasminogen activator (uPA). This interaction network has the potential to shed new light on our understanding of the role played by MMP-9 in invasive glioblastomas. CONCLUSION: Automated extraction of information from biological literature promises to play an increasingly important role in biological knowledge discovery. This is particularly true for high-throughput approaches, such as microarrays, and for combining and integrating data from different sources. Text mining may hold the key to unraveling previously unknown relationships between biological entities and could develop into an indispensable instrument in the process of formulating novel and potentially promising hypotheses.

Cell Line, Tumor↗
PubMed2006

methBLAST and methPrimerDB: web-tools for PCR based methylation analysis.

BACKGROUND: DNA methylation plays an important role in development and tumorigenesis by epigenetic modification and silencing of critical genes. The development of PCR-based methylation assays on bisulphite modified DNA heralded a breakthrough in speed and sensitivity for gene methylation analysis. Despite this technological advancement, these approaches require a cumbersome gene by gene primer design and experimental validation. Bisulphite DNA modification results in sequence alterations (all unmethylated cytosines are converted into uracils) and a general sequence complexity reduction as cytosines become underrepresented. Consequently, standard BLAST sequence homology searches cannot be applied to search for specific methylation primers. RESULTS: To address this problem we developed methBLAST, a sequence similarity search program, based on the original BLAST algorithm but querying in silico bisulphite modified genome sequences to evaluate oligonucleotide sequence similarities. Apart from the primer specificity analysis tool, we have also developed a public database termed methPrimerDB for the storage and retrieval of validated PCR based methylation assays. The web interface allows free public access to perform methBLAST searches or database queries and to submit user based information. Database records can be searched by gene symbol, nucleotide sequence, analytical method used, Entrez Gene or methPrimerDB identifier, and submitter's name. Each record contains a link to Entrez Gene and PubMed to retrieve additional information on the gene, its genomic context and the article in which the methylation assay was described. To assure and maintain data integrity and accuracy, the database is linked to other reference databases. Currently, the database contains primer records for the most popular PCR-based methylation analysis methods to study human, mouse and rat epigenetic modifications. methPrimerDB and methBLAST are available at http://medgen.ugent.be/methprimerdb and http://medgen.ugent.be/methblast. CONCLUSION: We have developed two integrated and freely available web-tools for PCR based methylation analysis. methBLAST allows in silico assessment of primer specificity in PCR based methylation assays that can be stored in the methPrimerDB database, which provides a search portal for validated methylation assays.

Algorithms↗