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PubMed1998

A multipurpose model of radiology appropriateness criteria.

RATIONALE AND OBJECTIVES: Appropriateness criteria and practice guidelines are being developed in attempts to improve the cost-effectiveness of medical care. The authors sought to make a set of radiology appropriateness criteria usable for education, computer-based decision support, and utilization review. MODEL DEVELOPMENT: Sixty clinical conditions from the American College of Radiology's appropriateness criteria were selected. To make the information more suitable for automation, the names of the imaging procedures were standardized. Indexing terms were assigned to identify clinical conditions and to distinguish between each condition's variants. Semantic relationships between terms were defined. Information about the clinical conditions and variants, radiologic procedures, indexing terms, and relationships was encoded into a standardized language for document interchange. IMPLEMENTATION: The 1,956 rows in the appropriateness criteria tables for the 60 clinical conditions and their 212 variants were mapped into references to 163 distinct imaging procedures. The system's knowledge base included 301 indexing terms and 569 additional terms. CONCLUSION: Radiology appropriateness criteria can be indexed and encoded into a form that facilitates their use and interchange. The use of open, internationally accepted standards is an important step to make such knowledge portable and suitable for integration with evolving computer-based patient record systems.

Computing Methodologies↗

PubMed2001

Modeling a medical environment: an ontology for integrated medical informatics design.

Modern medical environments have seen an increase in technological complexity and pressures of handling more patients with fewer resources, resulting in higher demands on medical practitioners. Medical informatics designers will have to focus on the problem of organizing medical information more effectively to enable practitioners to cope with these challenges. This article addresses this research problem for the particular area of medical problem solving in patient care. First, we describe a traditional modeling approach for medical reasoning used as a basis for developing some decision support systems. We argue these models may be faithful to what is known about biomedical knowledge, but they have limitations for human problem solving, especially in unanticipated situations. Second, we present an ontological framework, known as the abstraction hierarchy (Rasmussen, IEEE Trans. Man. Cybernetics 15 (1985) 234-243), for integrating patient representations that are faithful to existing biomedical knowledge and that are consistent with what is known about human problem solving. Through an example of a critical event in the operating room, we reveal how this framework can support medical problem solving in unanticipated situations. Third, we show how to use these representations as a frame of reference for mapping medical roles, responsibilities, sensors, and controls in an operating room context. Finally, we provide some insight for medical informatics designers in using this framework to design novel training programs and human-computer displays.

Decision Support Techniques↗

PubMed1987

Myosin isoforms in normal and dystrophic chickens.

The myosin isoform content in the affected fibers of chickens with inherited muscular dystrophy has been investigated with a new high-performance liquid chromatographic procedure for separation of the tryptic fragments of myosin subfragment 1 (S-1). The results indicate that dystrophic muscle contains substantial amounts of normal adult myosin, together with various myosin species present in normal 5-day posthatch chickens. Confirmation was obtained by comparative peptide mapping of the S-1 tryptic fragments and by N-terminal sequencing of 20-kDa species. Together with data on other contractile proteins and certain metabolic enzymes [Obinata, T., Takano-Ohmura, H., & Matsuda, R. (1980) FEBS Lett. 120, 195-198; Mikasa, T., Takeda, S., Shimizu, T., & Kitaura, T. (1981) J. Biochem. (Tokyo) 89, 1951-1962; Feit, H., & Domke, R. (1982) Cell Motil. 2, 309-315; Cosmos, E. (1966) Dev. Biol. 13, 163-181; Cosmos, E., & Butler, J. (1967) in Exploratory Concepts in Muscular Dystrophy and Related Disorders (Milhorat, A. R., Ed.) pp 197-204, Excerpta Medica, Amsterdam], the results are consistent with the hypothesis that there is a general defect in muscle maturation in avian dystrophy.

Aging↗

PubMed2001

Seeing where you are heading: integrating environmental and egocentric reference frames in cardinal direction judgments.

This research focused on how people coordinate the environmental reference frame of a map with the egocentric reference frame of the forward field of view to make cardinal direction judgments. In 3 studies, reference frame misalignment was found to slow response time for cardinal direction judgments and also markedly decrease accuracy. The studies also showed that people often use a nonrotational, analytic strategy for cardinal direction judgments that has not been identified for other navigational tasks, and that interface aids that improve other navigational tasks seem ineffective for cardinal direction judgments. These findings lead to the recommendation that interface aids for improving cardinal direction judgments should integrate heading information from the environmental reference frame into the egocentric frame (forward view).

Adolescent↗

PubMedDate not supplied

Protein changes occurring during storage of platelet concentrates. A two-dimensional gel electrophoretic analysis.

The changes in thrombocyte proteins during 22 degrees C storage of platelet concentrates (PC) were studied. To prepare a reference protein "map" of stored PC, platelet samples were taken on days 1, 7, and 21. The platelet proteins were separated by isoelectric focusing (first-dimension) followed by second-dimension polyacrylamide gradient gel electrophoresis with sodium dodecylsulfate (2D). The silver-stained gels were analyzed by computer to obtain a composite map of stored PC proteins. The pattern seen on day 1 changed during 7 days of storage, with 30 proteins increasing or decreasing in spot density. In general, the spot density for lower-molecular-weight proteins increased, whereas that for higher-molecular-weight proteins decreased. Membrane proteins of intact fresh and stored platelets were labeled with 3H using sodium metaperiodate-[3H]NaBH4 and with 125I using lactoperoxidase-H2O2. A comparison on the fluorographs of 2D gels of [3H]NaBH4-labeled platelet proteins showed several protein spots in the stored Day 7 sample that had not been seen in the Day 1 sample. Similarly, for the autoradiographs, several 125I-labeled proteins detected in Day 7 PC were not seen in the Day 1 samples. The results provide evidence that platelet proteins are altered during PC storage and that these changes involve platelet membrane proteins.

Blood Platelets↗

PubMed1988

HLA class I molecules are associated with CD1a heavy chains on normal human thymus cells.

The molecules encoded by the major histocompatibility complex play a pivotal role in regulatory interactions between cells of the immune system, which can result in the activation and function of T cells. The function of the CD1 molecules, which are homologous to the major histocompatibility complex-encoded molecules but are encoded on human chromosome 1, is not known. HLA class I molecules and CD1a heavy chains share the ability to associate with several different cell-surface molecules. We show here, by several technical approaches, that HLA class I molecules are associated with CD1a heavy chains on the surface of normal thymus cells. The functional significance of this association during T-cell differentiation is discussed.

Antibodies, Monoclonal↗

PubMed1998

Collapsin response mediator protein-2 is associated with neurofibrillary tangles in Alzheimer's disease.

Intraneuronal accumulation of paired helical filaments (PHF) is considered to be closely related to the neuronal loss observed in brains of patients affected with Alzheimer's disease. The central issue is whether PHF formation itself causes or accelerates the neuronal perikaryal and neuritic degeneration or whether they are simply the consequence of preceding degeneration. We sought to address the issue in part by characterizing the PHF-associated molecules and thus raised a number of monoclonal antibodies to neurofibrillary tangles. One monoclonal antibody, 3F4, strongly reacted with neurofibrillary tangles and some plaque neurites but few neuropil threads. This monoclonal antibody labeled a 65-kDa protein, but not tau or ubiquitin, on a Western blot of human brain extract and immunoprecipitated the same protein. The peptides released from the purified 65-kDa protein had the same sequences as those of a newly identified protein, human collapsin response mediator protein-2. Incorporation into neurofibrillary tangles may deplete soluble, cytosolic human collapsin response mediator protein-2 and lead to abnormal neuritic and/or axonal outgrowth of the tangle-bearing neuron, thus accelerating the neuritic degeneration in Alzheimer's disease.

Alzheimer Disease↗

PubMed2002

Fluoride exposure attenuates expression of Streptococcus pyogenes virulence factors.

Fluoridation causes an obvious reduction of dental caries by interference with cariogenic streptococci. However, the effect of fluoride on group A streptococci that causes rheumatic fever and acute poststreptococcal glomerulonephritis is not known. We have used proteomic analysis to create a reference proteome map for Streptococcus pyogenes and to determine fluoride-induced protein changes in the streptococci. Cellular and extracellular proteins were resolved by two-dimensional polyacrylamide gel electrophoresis and identified by matrix-assisted laser desorption ionization mass spectrometry. 183 protein spots were visualized, and 74 spots representing 60 unique proteins were identified. A 16-h exposure to sodium fluoride caused decreased expression of proteins required to respond to cellular stress, including anti-oxidants, glycolytic enzymes, transcriptional and translational regulators, and protein folding. Fluoride caused decreased cellular expression of two well-characterized S. pyogenes virulence factors. Fluoride decreased expression of glyceraldehyde-3-phosphate dehydrogenase, which acts to bind fibronectin and promote bacterial adherence. We also performed proteomic analysis of protein released by S. pyogenes into the culture supernatant and observed decreased expression of M proteins following fluoride exposure. These data provide evidence that fluoride causes decreased expression by S. pyogenes proteins used to respond to stress, virulence factors, and implicated in non-suppurative complications of S. pyogenes, including glomerulonephritis and rheumatic fever.

Antioxidants↗

PubMed2005

Quantitative mass spectrometric multiple reaction monitoring assays for major plasma proteins.

Quantitative LC-MS/MS assays were designed for tryptic peptides representing 53 high and medium abundance proteins in human plasma using a multiplexed multiple reaction monitoring (MRM) approach. Of these, 47 produced acceptable quantitative data, demonstrating within-run coefficients of variation (CVs) (n = 10) of 2-22% (78% of assays had CV <10%). A number of peptides gave CVs in the range 2-7% in five experiments (10 replicate runs each) continuously measuring 137 MRMs, demonstrating the precision achievable in complex digests. Depletion of six high abundance proteins by immunosubtraction significantly improved CVs compared with whole plasma, but analytes could be detected in both sample types. Replicate digest and depletion/digest runs yielded correlation coefficients (R(2)) of 0.995 and 0.989, respectively. Absolute analyte specificity for each peptide was demonstrated using MRM-triggered MS/MS scans. Reliable detection of L-selectin (measured at 0.67 microg/ml) indicates that proteins down to the microg/ml level can be quantitated in plasma with minimal sample preparation, yielding a dynamic range of 4.5 orders of magnitude in a single experiment. Peptide MRM measurements in plasma digests thus provide a rapid and specific assay platform for biomarker validation, one that can be extended to lower abundance proteins by enrichment of specific target peptides (stable isotope standards and capture by anti-peptide antibodies (SISCAPA)).

Amino Acid Sequence↗

PubMed1997

Beta A3/A1 crystallin from human cataractous lens contains an intramolecular disulfide bond.

PURPOSE: To develop an experimental approach that can identify amino acid sequences containing cysteine residues involved in disulfide bonding during cataractogenesis of the human lens. METHODS: Total proteins from cataractous and normal human lenses were solubilized anaerobically, followed by carboxy-methylation of free sulfhydryl groups with iodoacetate. Carboxymethylated proteins were partially purified by reverse phase chromatography, then subjected to lys-C endoprotease digestion. Using reverse phase chromatography, each digest was resolved in the presence and absence of dithiothreitol (DTT), to identify peptides that were linked by disulfide bonds. These peptides were further characterized using a combination of Edman degradation and mass spectrometry. RESULTS: The reverse phase chromatography profiles of lys-C peptides from proteins of normal lenses were very similar in the presence and absence of dithiothreitol, while identical analysis of proteins from cataractous lenses demonstrated the presence of a lys-C peptide that corresponded to residues 163-193 of human beta A3/A1, with cysteine 170 and cysteine 185 linked via an intramolecular disulfide bond. CONCLUSIONS: Reverse phase chromatography of complex mixtures of lens protein digests, in the presence and absence of dithiothreitol, provides a rapid method of identifying sequences involved in disulfide bonding. The results of this analysis using the endoprotease lys-C have demonstrated that beta A3/A1 crystallin from cataractous lenses contains an intermolecular disulfide bond involving cysteine residues 170 and 185.

Aged↗

PubMed1960

Effect of the method of leading on the recording of the nerve fiber spectrum.

A study has been made of the modifications of the shape of a nerve action potential dependent upon the placement of the two electrodes, always necessary for a lead. In a classic diphasic lead separation of the electrodes brings out, in addition to a separation of the phases, the appearance of a positive deflection traceable to the passage of an impulse between the electrodes. This phenomenon, called the lead separation effect (1.s.e.), must be considered as an expression of a feature of normal nerve fiber biophysics. It regularly appears and it can be analyzed with respect to the position of the sink maximum. Also it cannot be eliminated by a block at the second electrode. The advantage of approximating the leads was shown by the absence of a 1.s.e. following spikes recorded by electronic integration of tangents, which with validity can be derived from threshold fibers. Since tangent leads are not adaptable to recording a spectrum, a block at the second electrode is required. The making of such blocks and the configuration of records obtained with them are described. Conditions for an optimal lead, but not an ideal lead, were delimited. In an optimal lead only two major elevations appear in the spectrum of a skin nerve: those known as alpha and delta. A reference to maps of fiber size analyses shows that the fibers in the delta elevation have velocities of conduction slower than they would have if following in linear sequence the fiber diameters belonging to the alpha elevation.

Electrodes↗

PubMed1990

Assessment of inbreeding by DNA fingerprinting: development of a calibration curve using defined strains of chickens.

By analyzing DNA fingerprints of chickens from seven well-defined genetic groups, a calibration curve was established relating the degree of inbreeding with the average band frequency, allelic frequency and band sharing. The probe used was bacteriophage M13 DNA and digestion of the genomic DNA was carried out with the MspI restriction enzyme. The analysis also provided an estimate of the average allelic frequency at a hypervariable locus and the average mutation frequency per locus and generation. The values of 0.24 and 1.7 X 10(-3), respectively, are similar to the estimates for humans using other probes and hybridization protocols. It is suggested that the calibration curve established can be used for determining inbreeding not only in chickens, but also in other species.

Alleles↗

PubMed1998

A microsatellite map of wheat.

Hexaploid bread wheat (Triticum aestivum L. em. Thell) is one of the world's most important crop plants and displays a very low level of intraspecific polymorphism. We report the development of highly polymorphic microsatellite markers using procedures optimized for the large wheat genome. The isolation of microsatellite-containing clones from hypomethylated regions of the wheat genome increased the proportion of useful markers almost twofold. The majority (80%) of primer sets developed are genome-specific and detect only a single locus in one of the three genomes of bread wheat (A, B, or D). Only 20% of the markers detect more than one locus. A total of 279 loci amplified by 230 primer sets were placed onto a genetic framework map composed of RFLPs previously mapped in the reference population of the International Triticeae Mapping Initiative (ITMI) Opata 85 x W7984. Sixty-five microsatellites were mapped at a LOD >2.5, and 214 microsatellites were assigned to the most likely intervals. Ninety-three loci were mapped to the A genome, 115 to the B genome, and 71 to the D genome. The markers are randomly distributed along the linkage map, with clustering in several centromeric regions.

Base Sequence↗

PubMed1997

Do new cases of rheumatoid arthritis cluster in time or in space?

OBJECTIVES: To examine for evidence of clustering in time, in space and in space/time in the occurrence of rheumatoid arthritis (RA). SETTING: A population-based incidence register of RA in the East Anglian region of the UK: population size 413,000. SUBJECTS: In all 687 new cases of inflammatory joint disease registered between 1 January 1990 and 31 December 1994 were studied. Population data were obtained from postcode areas by age and sex. ANALYSIS: Time trend analysis was conducted over the first 36 months and observed and expected distributions compared. Spatial clustering was based on comparison of observed distribution using map grid references to random expectation based on simulation. A similar procedure was undertaken for time/space clustering. RESULTS: There was no evidence of a time trend. There was only modest evidence of spatial clustering with non-random distribution observed in one area but there was no evidence of time/space clustering. CONCLUSION: Although a viral aetiology is the strongest candidate for RA, no evidence of a localized event in time was associated with disease development in this population.

Adolescent↗

PubMed2006

Intra- and interpopulation genotype reconstruction from tagging SNPs.

The optimal method to be used for tSNP selection, the applicability of a reference LD map to unassayed populations, and the scalability of these methods to genome-wide analysis, all remain subjects of debate. We propose novel, scalable matrix algorithms that address these issues and we evaluate them on genotypic data from 38 populations and four genomic regions (248 SNPs typed for approximately 2000 individuals). We also evaluate these algorithms on a second data set consisting of genotypes available from the HapMap database (1336 SNPs for four populations) over the same genomic regions. Furthermore, we test these methods in the setting of a real association study using a publicly available family data set. The algorithms we use for tSNP selection and unassayed SNP reconstruction do not require haplotype inference and they are, in principle, scalable even to genome-wide analysis. Moreover, they are greedy variants of recently developed matrix algorithms with provable performance guarantees. Using a small set of carefully selected tSNPs, we achieve very good reconstruction accuracy of "untyped" genotypes for most of the populations studied. Additionally, we demonstrate in a quantitative manner that the chosen tSNPs exhibit substantial transferability, both within and across different geographic regions. Finally, we show that reconstruction can be applied to retrieve significant SNP associations with disease, with important genotyping savings.

Algorithms↗

PubMed2003

The mammalian protein-protein interaction database and its viewing system that is linked to the main FANTOM2 viewer.

Here, we describe the development of a mammalian protein-protein interaction (PPI) database and of a PPI Viewer application to display protein interaction networks (http://fantom21.gsc.riken.go.jp/PPI/). In the database, we stored the mammalian PPIs identified through our PPI assays (internal PPIs), as well as those we extracted and processed (external PPIs) from publicly available data sources, the DIP and BIND databases and MEDLINE abstracts by using FACTS, a new functional inference and curation system. We integrated the internal and external PPIs into the PPI database, which is linked to the main FANTOM2 viewer. In addition, we incorporated into the PPI Viewer information regarding the luciferase reporter activity of internal PPIs and the data confidence of external PPIs; these data enable visualization and evaluation of the reliability of each interaction. Using the described system, we successfully identified several interactions of biological significance. Therefore, the PPI Viewer is a useful tool for exploring FANTOM2 clone-related protein interactions and their potential effects on signaling and cellular communication.

Animals↗

PubMed2004

RAGS: Region-aided Geometric Snake.

An enhanced, region-aided, geometric active contour that is more tolerant toward weak edges and noise in images is introduced. The proposed method integrates gradient flow forces with region constraints, composed of image region vector flow forces obtained through the diffusion of the region segmentation map. We refer to this as the Region-aided Geometric Snake or RAGS. The diffused region forces can be generated from any reliable region segmentation technique, greylevel or color. This extra region force gives the snake a global complementary view of the boundary information within the image which, along with the local gradient flow, helps detect fuzzy boundaries and overcome noisy regions. The partial differential equation (PDE) resulting from this integration of image gradient flow and diffused region flow is implemented using a level set approach. We present various examples and also evaluate and compare the performance of RAGS on weak boundaries and noisy images.

Algorithms↗

PubMed1990

Computer-enhanced mapping of activation sequences in the surgical treatment of supraventricular arrhythmias.

Surgical treatment of accessory pathways and ectopic foci requires accurate information on the physical locations of the arrhythmogenic substrates. Although electrophysiology studies during cardiac catheterization frequently provide accurate and reliable data, the physical locations of the sites to be ablated must be verified in situ by electrical activity mapping. We have developed a microcomputer-based system that facilitates creation of electrical activity maps, supplanting the manual method formerly used. Signals produced by mapping and reference electrodes, as well as cardiac diagrams with grid coordinates and times, are presented on a monitor in formats that are easily interpreted by the surgeon and cardiologist. The system is rapid, accurate, and reliable, and has reduced the time required to localize conduction abnormalities from 30 to 45 minutes for the manual method, down to an average of 12 minutes per case. The system is simple to operate, requiring only minimal training. All of the components of the system are commercially available; no specialized hardware is required.

Adolescent↗