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PubMedDate not supplied

A method for rapid acquisition of data from dispersed individuals.

We have developed a data-collection system that we believe has wide applicability in dispersed organizations that have different local information systems infrastructures. A questionnaire was developed using commonly available software tools and was implemented several times across a dispersed network of individuals to rapidly collect, organize, and analyze information with a minimum of secretarial time and administrative cost. A common e-mail database was created identifying all of the medical directors and care management directors in the Blue Cross Blue Shield system. Initial polling of these individuals yielded specific questions of interest, and a final questionnaire was developed. The focus of the project centered on the evaluation of disease state management initiatives within each of the plans and on the ongoing use and future potential for various medical management initiatives. A questionnaire was developed using a Microsoft Excel spreadsheet with the ultimate development of a database in mind. All of the questions, whether single or multiple answers, were mapped from question response sections to a hidden specified range created to import the flat file answer block into a database. Individual cells containing answers to questions were each mapped to a hidden area of the spreadsheet arrayed as a series of rows. As each questionnaire was returned to the central site, data was imported from the hidden range name into a Microsoft Access database. The process of collecting extensive information on a questionnaire-by-questionnaire basis took approximately 20 seconds of time per questionnaire. A final report was ultimately created composed of some 24 pages of detailed information on managed care across the participants, representing some 90% of the member organizations. Secretarial costs were needed only for final transcription of the report.

Access to Information↗
PubMed2017

Drug target ontology to classify and integrate drug discovery data.

BACKGROUND: One of the most successful approaches to develop new small molecule therapeutics has been to start from a validated druggable protein target. However, only a small subset of potentially druggable targets has attracted significant research and development resources. The Illuminating the Druggable Genome (IDG) project develops resources to catalyze the development of likely targetable, yet currently understudied prospective drug targets. A central component of the IDG program is a comprehensive knowledge resource of the druggable genome. RESULTS: As part of that effort, we have developed a framework to integrate, navigate, and analyze drug discovery data based on formalized and standardized classifications and annotations of druggable protein targets, the Drug Target Ontology (DTO). DTO was constructed by extensive curation and consolidation of various resources. DTO classifies the four major drug target protein families, GPCRs, kinases, ion channels and nuclear receptors, based on phylogenecity, function, target development level, disease association, tissue expression, chemical ligand and substrate characteristics, and target-family specific characteristics. The formal ontology was built using a new software tool to auto-generate most axioms from a database while supporting manual knowledge acquisition. A modular, hierarchical implementation facilitate ontology development and maintenance and makes use of various external ontologies, thus integrating the DTO into the ecosystem of biomedical ontologies. As a formal OWL-DL ontology, DTO contains asserted and inferred axioms. Modeling data from the Library of Integrated Network-based Cellular Signatures (LINCS) program illustrates the potential of DTO for contextual data integration and nuanced definition of important drug target characteristics. DTO has been implemented in the IDG user interface Portal, Pharos and the TIN-X explorer of protein target disease relationships. CONCLUSIONS: DTO was built based on the need for a formal semantic model for druggable targets including various related information such as protein, gene, protein domain, protein structure, binding site, small molecule drug, mechanism of action, protein tissue localization, disease association, and many other types of information. DTO will further facilitate the otherwise challenging integration and formal linking to biological assays, phenotypes, disease models, drug poly-pharmacology, binding kinetics and many other processes, functions and qualities that are at the core of drug discovery. The first version of DTO is publically available via the website http://drugtargetontology.org/ , Github ( http://github.com/DrugTargetOntology/DTO ), and the NCBO Bioportal ( http://bioportal.bioontology.org/ontologies/DTO ). The long-term goal of DTO is to provide such an integrative framework and to populate the ontology with this information as a community resource.

Biological Ontologies↗
PubMed2003

Reliability of a quantification imaging system using magnetic resonance images to measure cartilage thickness and volume in human normal and osteoarthritic knees.

OBJECTIVE: The aim of this study was to evaluate the reliability of a software tool that assesses knee cartilage volumes using magnetic resonance (MR) images. The objectives were to assess measurement reliability by: (1) determining the differences between readings of the same image made by the same reader 2 weeks apart (test-retest reliability), (2) determining the differences between the readings of the same image made by different readers (between-reader agreement), and (3) determining the differences between the cartilage volume readings obtained from two MR images of the same knee image acquired a few hours apart (patient positioning reliability). METHODS: Forty-eight MR examinations of the knee from normal subjects, patients with different stages of symptomatic knee osteoarthritis (OA), and a subset of duplicate images were independently and blindly quantified by three readers using the imaging system. The following cartilage areas were analyzed to compute volumes: global cartilage, medial and lateral compartments, and medial and lateral femoral condyles. RESULTS: Between-reader agreement of measurements was excellent, as shown by intra-class correlation (ICC) coefficients ranging from 0.958 to 0.997 for global cartilage (P<0.0001), 0.974 to 0.998 for the compartments (P<0.0001), and 0.943 to 0.999 for the condyles(P<0.0001). Test-retest reliability of within-reader data was also excellent, with Pearson correlation coefficients ranging from 0.978 to 0.999 (P<0.0001). Patient positioning reliability was also excellent, with Pearson correlation coefficients ranging from 0.978 to 0.999 (P<0.0001). CONCLUSIONS: The results of this study establish the reliability of this MR imaging system. Test-retest reliability, between-reader agreement, and patient positioning reliability were all extremely high. This study represents a first step in the overall validation of an imaging system designed to follow progression of human knee OA.

Adult↗
PubMed2000

Prediction of genetic structure in eukaryotic DNA using reference point logistic regression and sequence alignment.

MOTIVATION: Current software tools are moderately effective in predicting genetic structure (exons, introns, intergenic regions, and complete genes) from raw DNA sequence data. Improvements in accuracy and speed are needed to deal with the increasing volume of data from large scale sequencing projects. RESULTS: We present a two-stage computer program to predict genetic structure in eukaryotic DNA. The first stage makes use of a novel statistical technique, called reference point logistic (RPL) regression, to calculate scores for potential functional sites. These site scores are combined with interval content, length, and state scores, via a Generalized Hidden Markov Model, to determine a combined score for each possible parse of a given DNA sequence into exons, introns, and intergenic regions. An optimal parse is found using a dynamic programming algorithm. In the second stage, protein sequence alignment methods are applied to improve the accuracy of the initial parse. Computation in the first stage of the program is very fast (1 s on a 360 MHz CPU for a 16 kb sequence) and its predictive accuracy typically matches or exceeds the best results reported for other methods (Sensitivity = 0.93 and Specificity = 0.93 for the Burset/Guigótest set). Computation in the second stage is slower, but the final predictions are more accurate (Sn = 0.97, Sp = 0.97). The program (called GRPL) can handle partial, single, and multi-gene sequences. The program is also capable of predicting the genetic structure of vertebrate, invertebrate, and plant DNA with nearly equal accuracy. Statistical techniques have also been introduced to model the effects of varying C+G content in a continuous manner and to control overfitting of parameters for smaller training sets. AVAILABILITY: An academic implementation of GRPL, compiled for SUN workstations, is available by anonymous ftp from snipe.pharmacy. ualberta.ca/pub. The training and test sets used in this work, together with supplementary material, can be found at the same location. A commercial implementation is available as a component of GeneTool (BioTools Inc., http://biotools.com).

Algorithms↗
PubMed2003

Automatic registration of the prostate for computed-tomography-guided radiotherapy.

The recent development of integrated computed tomography (CT)/linear accelerator (LINAC) combinations, where the CT scanner and the LINAC use the same patient couch, and of kilovoltage cone-beam CT systems attached to the LINAC gantry, means that suitable hardware is now available for CT-guided localization of the prostate. Clinical implementation is, however, currently impeded by the lack of robust and accurate software tools to compare the position of the prostate in the CT images used for the treatment plan with its position in the daily CT images. Manual registration of the planning CT images with the daily CT images can be slow and can introduce significant inter-user variations. We have developed an automatic registration technique that is not adversely influenced by changes in prostate shape, size or orientation, presence of rectal gas, or bladder filling. The cost function used in the registration is the mean absolute difference in CT numbers voxel-by-voxel between the daily CT image and the planning CT image for a volume extracted from the planning CT images using the original physician-drawn gross tumor volume contours. To enhance soft tissue contrast in the prostate region and to reduce the impact of rectal gas calcifications and bone on the registration, voxels with CT numbers that represent gas or bone are filtered out from the calculation. The results of the automatic registration agreed with the mean results of seven human observers, with standard deviations of 0.5 mm, 0.5 mm, and 1.0 mm in the left/right (RL), anterior/posterior (AP), and superior/inferior (SI) directions, respectively, for a patient that was relatively easy to localize. Agreement (one standard deviation) for a patient that was difficult to localize was 0.6 mm, 1.4 mm, and 1.9 mm in the RL, AP, and SI directions, respectively. These results are better than the interuser uncertainties reported for a manual alignment technique and are close to the reported intrauser uncertainties. The results are independent of the shape of contours in the original treatment plan, reducing the impact of interobserver variations in contouring the prostate. The algorithm is fast and reliable, allowing the entire CT localization process to take place in 5-9 minutes. In 120 CT image sets from seven patients, the failure rate was found to be less than 1%. The use of this algorithm will facilitate the clinical implementation of CT-guided localization of the prostate.

Algorithms↗
PubMed2004

Interactively optimizing signal-to-noise ratios in expression profiling: project-specific algorithm selection and detection p-value weighting in Affymetrix microarrays.

MOTIVATION: The most commonly utilized microarrays for mRNA profiling (Affymetrix) include 'probe sets' of a series of perfect match and mismatch probes (typically 22 oligonucleotides per probe set). There are an increasing number of reported 'probe set algorithms' that differ in their interpretation of a probe set to derive a single normalized 'signal' representative of expression of each mRNA. These algorithms are known to differ in accuracy and sensitivity, and optimization has been done using a small set of standardized control microarray data. We hypothesized that different mRNA profiling projects have varying sources and degrees of confounding noise, and that these should alter the choice of a specific probe set algorithm. Also, we hypothesized that use of the Microarray Suite (MAS) 5.0 probe set detection p-value as a weighting function would improve the performance of all probe set algorithms. RESULTS: We built an interactive visual analysis software tool (HCE2W) to test and define parameters in Affymetrix analyses that optimize the ratio of signal (desired biological variable) versus noise (confounding uncontrolled variables). Five probe set algorithms were studied with and without statistical weighting of probe sets using the MAS 5.0 probe set detection p-values. The signal-to-noise ratio optimization method was tested in two large novel microarray datasets with different levels of confounding noise, a 105 sample U133A human muscle biopsy dataset (11 groups: mutation-defined, extensive noise), and a 40 sample U74A inbred mouse lung dataset (8 groups: little noise). Performance was measured by the ability of the specific probe set algorithm, with and without detection p-value weighting, to cluster samples into the appropriate biological groups (unsupervised agglomerative clustering with F-measure values). Of the total random sampling analyses, 50% showed a highly statistically significant difference between probe set algorithms by ANOVA [F(4,10) > 14, p < 0.0001], with weighting by MAS 5.0 detection p-value showing significance in the mouse data by ANOVA [F(1,10) > 9, p < 0.013] and paired t-test [t(9) = -3.675, p = 0.005]. Probe set detection p-value weighting had the greatest positive effect on performance of dChip difference model, ProbeProfiler and RMA algorithms. Importantly, probe set algorithms did indeed perform differently depending on the specific project, most probably due to the degree of confounding noise. Our data indicate that significantly improved data analysis of mRNA profile projects can be achieved by optimizing the choice of probe set algorithm with the noise levels intrinsic to a project, with dChip difference model with MAS 5.0 detection p-value continuous weighting showing the best overall performance in both projects. Furthermore, both existing and newly developed probe set algorithms should incorporate a detection p-value weighting to improve performance. AVAILABILITY: The Hierarchical Clustering Explorer 2.0 is available at http://www.cs.umd.edu/hcil/hce/ Murine arrays (40 samples) are publicly available at the PEPR resource (http://microarray.cnmcresearch.org/pgadatatable.asp http://pepr.cnmcresearch.org Chen et al., 2004).

Cluster Analysis↗
PubMed2000

Computer-aided assessment of bony nasal pyramid dimensions.

OBJECTIVE: To develop a computer-enabled paradigm for assessment of bony nasal pyramid dimensions. DESIGN: Retrospective review of archived computed tomographic data. SETTING: Tertiary level academic center. PATIENTS: Patients who had undergone computed tomographic scans for computer-aided transsphenoidal hypophysectomy were included. Previous nasal surgery, inflammatory sinus disease, and documented maxillofacial trauma were exclusion criteria. INTERVENTION: Archived computed tomographic scan images were reviewed using the software tools on a computer-aided surgical (CAS) system (StealthStation; Sofamor Danek, Memphis, Tenn). Standardized methods for the measurement of nasal bone thickness and bony nasal pyramid projection were established. MAIN OUTCOME MEASUREMENTS: Bony nasal pyramid projection and nasal bone thickness were determined. RESULTS: Computed tomographic scans from 8 patients were reviewed. Nasal bone thickness at the level of lateral osteotomy was 2.39 +/- 0.68 (mean + SD) mm, while nasal bone thickness at the level of intermediate osteotomy was 1.18 + 0.30 mm. Nasal projection from the nasomaxillary suture to the rhinion in the axial plane was 19.20 + 3. 10 (mean + SD) mm, while the corresponding nasal projection at the nasion was 20.61 + 3.52 mm. CONCLUSIONS: This brief report presents a new paradigm for the assessment of the bony nasal pyramid. Additional normative data are necessary. This information has important implications for rhinoplasty instrument design, surgical planning, and aesthetic assessment. It is likely that computer-enabled review of archived computed tomographic images for maxillofacial assessment will become increasingly accepted. Of course, further modifications of computer technology and its specific applications are expected.

Adult↗
PubMed1998

Transcriptional profiling on all open reading frames of Saccharomyces cerevisiae.

Open reading frames (6116) of the budding yeast Saccharomyces cerevisiae were PCR-amplified from genomic DNA using 12,232 primers specific to the ends of the coding sequences; the success rate of amplification was 97%. PCR-products were made accessible to hybridization by being arrayed at very high density on solid support media using various robotic devices. Probes made from total RNA preparations were hybridized for the analysis of the transcriptional activity of yeast under various growth conditions and of different strains. Experimental factors that proved critical to the performance, such as different RNA isolation procedures and the assessment of hybridization results, for example, were investigated in detail. Various software tools were developed that permit convenient handling and sound analysis of the large data quantities obtained from transcriptional profiling studies. Comprehensive arrays are being distributed within the European Yeast Functional Analysis Network (EUROFAN) and beyond.

Blotting, Western↗
PubMedDate not supplied

National health accounts in developing countries: appropriate methods and recent applications.

Better information on the financing of the health sector is an essential basis for wise policy change in the area of health sector reform. Analysis of health care financing should begin with sound estimates of national health expenditure--total spending, the contributions to spending from different sources and the claims on spending by different uses of the funds. The member countries of the OECD have successfully established such comparative health expenditure accounts in terms of standardized definitions of the uses of funds and breakdowns by public and private sector sources. This has resulted in important research on health system differences which could explain variations in the level and composition of financing. The United States has developed a more detailed approach called National Health Accounts, which expands the OECD method into a more disaggregated 'sources and uses' matrix. In the developing countries, analysis of health expenditures has been much less systematic, despite several decades of calls by international researchers for more attention. This paper reviews previous work done in developing countries and proposes renewed attention to national health expenditures, adapting the recent experience of the United States. Because most developing countries have more pluralistic health financing structures than are found in most industrialized countries, an enhanced and adapted version of the 'sources and uses' matrix method is proposed. This method should be modified to address the relevant categories of expenditures prevalent in the developing countries. Examples of recent applications of such 'national health accounts' from the Philippines, Egypt, India, Mexico, Colombia and Zambia are presented. Experience to date suggests that development of sound estimates using this method in low and middle income countries is feasible and affordable. National health accounts estimates can significantly influence policy. They provide decision makers with a holistic picture of the health sector, showing the actual emphasis of spending and the roles of different payers. They also provide a consistent framework for modelling reforms and for monitoring the effects of changes in financing and provision. An easy to use software tool has been developed for training and data management. Regional networks of collaborating national groups are proposed as a first step in expanding use of the method and to gain both national and cross-national comparative benefits.

Accounting↗
PubMed2000

Website review: UK CropNet.

This review explores the UK CropNet site. The project is aimed at aiding the comparative mapping of cereal and other crop genomes. The site provides software tools for use by those working on genome mapping, and access to an array of databases that will be of interest to all members of the plant genomics research community, using several ACeDB interfaces. All screen views from the website are reproduced with the kind permission of Dr Sean May, Director, Nottingham Arabidopsis Stock Centre (NASC).

Crops, Agricultural↗
PubMed2000

Familial associations of lipid profiles: a generalized estimating equations approach.

Elevated plasma levels of apolipoproteins A1 (apoA1) and B (apoB) are important protective factors and risk factors, respectively, for atherosclerosis and coronary heart disease. It is well known that both apoA1 and apoB reveal strong familial aggregation. Our goal was to investigate whether exogenous variables influence these associations. We used marginal regression models for the mean and association structure (generalized estimating equations 2; GEE2) to analyse data from 1435 family members within 469 families of different sizes included in the Donolo-Tel Aviv Three-Generation Offspring Study. The usual robust variance matrix was approximated by extensions of jack-knife estimators of variance to GEE2 models. Estimation of standard errors in models with quite complex correlation structures was possible using this approach. All analyses were easily carried out using a menu-driven stand-alone software tool for marginal regression modelling. We demonstrate that a variety of hypotheses can be tested using Wald statistics by modelling regression matrices for the association structure. We show that correlation for apoB between parent-offspring pairs increased with decreasing age difference and that pairs with individuals of the same gender had more similar apoA1 levels than individuals of different gender. Associations between different relative pairs did not all agree with those expected from differences in kinship coefficients. The analysis using GEE2 models revealed structures that would not have been detected by other models and should therefore be used in addition to traditional approaches of analysing family data. GEE2 should be considered a standard method for the investigation of familial aggregation.

Apolipoproteins A↗
PubMed2005

Quantification and functional analysis of chemotaxis by laser scanning cytometry.

BACKGROUND: Evaluation of chemotaxis assays traditionally relies on cumbersome and at times inaccurate visual counting. Moreover, many physiologic parameters that could be evaluated in conjunction with chemotactic migration, aside from morphologic changes, usually are not assessed due to the lack of a simultaneous method of analysis. We tested the suitability of laser scanning cytometry (LSC) as a convenient platform for counting migrated cells and for concurrent analysis of some features associated with their physiologic status. METHODS: We induced migration of THP-1 monocytes across Nuclepore filters with monocyte chemotactic protein-1 or vascular endothelial growth factor, alone or in combination. Filters were collected, and cells were fixed on filters and stained with the nuclear stain propidium iodide. Chemotactic indices were obtained by counting representative microscopic fields and by scanning the filters in LSC mode. RESULTS: We found an excellent correlation between direct counting and LSC. In addition, the software tools embodied in the LSC instrument allowed the observation of changes in nuclear compactness (increase in propidium iodide brightness) and morphology (increase in nuclear area and perimeter) that occurred in transmigrated cells. Monocyte chemotactic protein-1 and vascular endothelial growth factor acted as additive stimuli on these parameters. CONCLUSIONS: LSC analysis of cells undergoing chemotaxis provides a reliable and comprehensive assessment of the numbers and distribution of migrated cells and some of their nuclear parameters. The method can be easily extended to include the assessment of coincident molecular changes in cells due to chemotactic stimulation.

Cell Line↗
PubMedDate not supplied

Gene expression in the spermatogenically inactive "dark" and maturing "light" testicular tissues of the prepubertal colt.

In the testis of the 1.5-year-old horse, spermatogenesis initiates locally in grossly light, central areas that contrast with grossly dark, peripheral areas that are as yet inactive in spermatogenesis. Gene expression was compared between "light" and "dark" tissues of 1.5-year-old horse testes to identify mechanisms important to the initiation of spermatogenesis. Microarrays containing human cDNAs were used to assess expression levels of 9132 genes simultaneously in matched pairs of dark and light testis tissues from 3 prepubertal colts. In all 3 analyses, dysferlin (DYS), down-regulated in ovarian cancer 1 (DOC1), and Golgi apparatus protein 1 (GLG1) genes were preferentially expressed in dark tissues, while outer dense fiber of sperm tails (ODF2) and phosphodiesterase 3B (PDE3B) genes were more highly expressed in light testis tissue (>1.7 balanced difference value, Incyte GEM tools software). Expression levels of 88 additional genes appeared to be different between dark and light tissues in 2 of the 3 microarray analyses. The preferential expression of DYS, DOC1, ODF2, and PDE3B genes in dark or light testis tissues was confirmed on Northern blots and localized to cell types by in situ hybridization. Future studies to determine the role of genes regulated during the initiation of spermatogenesis may aid in elucidating molecular mechanisms during this critical time as well as in identifying new therapies for enhancing male fertility.

Animals↗
PubMed2001

Gene profiling techniques and their application in angiogenesis and vascular development.

The analysis of gene expression in specific tissues and physiological processes has evolved over the last 20 years from the painstaking identification of selected genes to the relatively efficient and open-ended surveying of potentially all genes expressed in a tissue. Current art for gene discovery includes the use of large-scale arrays of cDNA sequences or oligonucleotides, and molecular 'tagging' techniques such as GeneCalling and SAGE. Common to each of these techniques is a reliance on the increasingly comprehensive databases of human and mouse EST and full-length gene sequences. Early efforts to characterize candidate genes were limited by their narrow scope, while current efforts are confounded by the enormous volume of data returned. Sophisticated software tools are an integral part of the analysis, helping to organize information into coherent groups with temporal or functional similarity. These techniques, in conjunction with the continued analysis of human genetic syndromes, transgenic, and knockout mice, have driven genetic analysis of angiogenesis and vascular development from describing which individual genes are involved to defining the outlines of regulatory networks.

Animals↗
PubMed2006

Quantitative proteomic analysis of the budding yeast cell cycle using acid-cleavable isotope-coded affinity tag reagents.

Quantitative profiling of proteins, the direct effectors of nearly all biological functions, will undoubtedly complement technologies for the measurement of mRNA. Systematic proteomic measurement of the cell cycle is now possible by using stable isotopic labeling with isotope-coded affinity tag reagents and software tools for high-throughput analysis of LC-MS/MS data. We provide here the first such study achieving quantitative, global proteomic measurement of a time-course gene expression experiment in a model eukaryote, the budding yeast Saccharomyces cerevisiae, during the cell cycle. We sampled 48% of all predicted ORFs, and provide the data, including identifications, quantitations, and statistical measures of certainty, to the community in a sortable matrix. We do not detect significant concordance in the dynamics of the system over the time-course tested between our proteomic measurements and microarray measures collected from similarly treated yeast cultures. Our proteomic dataset therefore provides a necessary and complementary measure of eukaryotic gene expression, establishes a rich database for the functional analysis of S. cerevisiae proteins, and will enable further development of technologies for global proteomic analysis of higher eukaryotes.

Carbon Isotopes↗
PubMed2004

Trefoil factor 3 overexpression in prostatic carcinoma: prognostic importance using tissue microarrays.

BACKGROUND: Human intestinal trefoil factor 3 (TFF3) is a member of a family of polypeptides encoded by a cluster of genes on chromosome 21. Through gene expression profiling studies TFF3 mRNA has been found to be overexpressed in prostate cancer. METHODS: We used immunochemistry on tissue microarrays and software tools, collectively referred to as TMAJ, for online assessment of staining to analyze samples from 294 primary tumors and 61 metastatic lesions. RESULTS: Applying a cutoff of 20% of cells staining as positive, the frequency of staining was 18.8% in normal (51 of 272) and 47.0% in primary tumors (126 of 268), P < 0.0001, Wilcoxon rank sum). Expression of TFF3 in metastatic prostate cancer was similar to that in primary tumors. TFF3 expression was not associated with time to biochemical recurrence, development of distant metastasis, or death due to prostate cancer. Scoring data derived from visual estimation of expression correlated highly with semi-automated image analysis using the Automated Cellular Imaging System (ACIS) from Chromavision, Inc. CONCLUSIONS: These studies validate that TFF3 is overexpressed at the protein level in a subset of primary and metastatic prostate cancers, show the first use of the TMAJ database, and demonstrate the ability to semi-automatically scan and score immunohistochemically stained tissue microarray slides.

Biomarkers, Tumor↗
PubMed2006

The molecular scanner in microscope mode.

The combination of microscope mode matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS) with protein identification methodology: the molecular scanner, was explored. The molecular scanner approach provides improvement of sensitivity of detection and identification of high-mass proteins in microscope mode IMS. The methodology was tested on protein distributions obtained after separation by sodium dodecyl sulfate/polyacrylamide gel electrophoresis (SDS-PAGE). High-quality, high-spatial-resolution ion images were recorded on a TRIFT-II ion microscope after gold coating of the MALDI sample preparation on the poly(vinylidenedifluoride) capture membranes. The sensitivity of the combined method is estimated to be 5 pmol. The minimum amount of sample consumed, needed for identification, was estimated to be better than 100 fmol. Software tools were developed to analyze the spectral data and to generate broad mass range and single molecular component microscope mode ion images and single mass-to-charge ratio microprobe mode images.

Animals↗
PubMed2001

Screening for anabolic steroids and related compounds in illegal cocktails by liquid chromatography/time-of-flight mass spectrometry and liquid chromatography/quadrupole time-of-flight tandem mass spectrometry with accurate mass measurement.

Findings of illegal hormone preparations such as syringes, bottles, cocktails, and so on, are an important information source for the nature of the current abuse of anabolic steroids and related compounds as growth-promoting agents in cattle. A new screening method for steroids in cocktails is presented based on liquid chromatography (LC) with diode-array UV-absorbance detection and electrospray ionization time-of-flight mass spectrometry (ESI-TOFMS). Accurate mass measurements were performed at a mass resolution of 4000 using continuous introduction of a lock mass through a second (electro)sprayer. Similar experiments were carried out using dual-sprayer quadrupole time-of-flight mass spectrometry (ESI-QTOFMS/MS) at a mass resolution of 10 000 with data-dependent MS/MS acquisition; i.e. beyond an intensity threshold for the [M + H](+) ions, MS/MS spectra were automatically acquired at three different collision energies. Elemental compositions were calculated for precursor and product ions and it is shown that the combined information from LC retention behavior, UV spectra, elemental compositions, and accurate mass MS/MS spectra yield a fast impression of the steroids present in the complex mixture. Using a new software tool for structure elucidation of MS/MS spectra, an additional non-steroidal additive was identified as well.

Anabolic Agents↗