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PubMed2001

The facilitated component of intestinal glucose absorption.

Over the last decade, a debate has developed about the mechanism of the passive or 'diffusive' component of intestinal glucose absorption and, indeed, whether it even exists. Pappenheimer and colleagues have proposed that paracellular solvent drag contributes a passive component, which, at high concentrations of sugars similar to those in the jejunal lumen immediately after a meal, is severalfold greater than the active component mediated by the Na+-glucose cotransporter SGLT1. On the other hand, Ferraris & Diamond maintain that the kinetics of glucose absorption can be explained solely in terms of SGLT1 and that a passive or paracellular component plays little, if any, part. Recently, we have provided new evidence that the passive component of glucose absorption exists, but is in fact facilitated since it is mediated by the rapid, glucose-dependent activation and recruitment of the facilitative glucose transporter GLUT2 to the brush-border membrane; regulation involves a protein kinase C (PKC)-dependent pathway activated by glucose transport through SGLT1 and also involves mitogen-activated protein kinase (MAP kinase) signalling pathways. This topical review seeks to highlight the significant points of the debate, to show how our proposals on GLUT2 impact on different aspects of the debate and to look at the regulatory events that are likely to be involved in the short-term regulation of sugar absorption during the assimilation of a meal.

Absorption↗
PubMed2001

The sentinel node biopsy in melanoma patients.

A palpable node is the first and most frequent sign of regional metastasis of malignant melanoma (MM). Nevertheless, the role of the elective lymph node dissection in patients with cutaneous melanoma remains one of the most debated topics of surgical oncology. Lymphatic mapping and sentinel node (SN) biopsy are supported as the standard of surgical care of MM by the World Health Organization and the Sunbelt Melanoma Clinical Trial. The only way to identify patients harboring microscopic nodal metastases is the elective complete regional lymphadenectomy or, as preferred today for its high specificity and minimal morbidity, the SN biopsy, which provides a histologic representative sample of the entire basin.

Humans↗
PubMed2005

DIG--a system for gene annotation and functional discovery.

SUMMARY: We describe a database and information discovery system named DIG (Duke Integrated Genomics) designed to facilitate the process of gene annotation and the discovery of functional context. The DIG system collects and organizes gene annotation and functional information, and includes tools that support an understanding of genes in a functional context by providing a framework for integrating and visualizing gene expression, protein interaction and literature-based interaction networks.

Chromosome Mapping↗
PubMed2001

Map position and expression of the genes in the 38 region of Drosophila.

With the completion of the Drosophila genome sequence, an important next step is to extract its biological information by systematic functional analysis of genes. We have produced a high-resolution genetic map of cytological region 38 of Drosophila using 41 deficiency stocks that provide a total of 54 breakpoints within the region. Of a total of 45 independent P-element lines that mapped by in situ hybridization to the region, 14 targeted 7 complementation groups within the 38 region. Additional EMS, X-ray, and spontaneous mutations define a total of 17 complementation groups. Because these two pools partially overlap, the completed analysis revealed 21 distinct complementation groups defined by point mutations. Seven additional functions were defined by trans-heterozygous combinations of deficiencies, resulting in a total of 28 distinct functions. We further produced a developmental expression profile for the 760 kb from 38B to 38E. Of 135 transcription units predicted by GENSCAN, 22 have at least partial homology to mobile genetic elements such as transposons and retroviruses and 17 correspond to previously characterized genes. We analyzed the developmental expression pattern of the remaining genes using poly(A)(+) RNA from ovaries, early and late embryos, larvae, males, and females. We discuss the correlation between GENSCAN predictions and experimentally confirmed transcription units, the high number of male-specific transcripts, and the alignment of the genetic and physical maps in cytological region 38.

Animals↗
PubMed2003

The informatics of a C57BL/6J mouse brain atlas.

The Mouse Atlas Project (MAP) aims to produce a framework for organizing and analyzing the large volumes of neuroscientific data produced by the proliferation of genetically modified animals. Atlases provide an invaluable aid in understanding the impact of genetic manipulations by providing a standard for comparison. We use a digital atlas as the hub of an informatics network, correlating imaging data, such as structural imaging and histology, with text-based data, such as nomenclature, connections, and references. We generated brain volumes using magnetic resonance microscopy (MRM), classical histology, and immunohistochemistry, and registered them into a common and defined coordinate system. Specially designed viewers were developed in order to visualize multiple datasets simultaneously and to coordinate between textual and image data. Researchers can navigate through the brain interchangeably, in either a text-based or image-based representation that automatically updates information as they move. The atlas also allows the independent entry of other types of data, the facile retrieval of information, and the straight-forward display of images. In conjunction with centralized servers, image and text data can be kept current and can decrease the burden on individual researchers' computers. A comprehensive framework that encompasses many forms of information in the context of anatomic imaging holds tremendous promise for producing new insights. The atlas and associated tools can be found at http://www.loni.ucla.edu/MAP.

Anatomy, Artistic↗
PubMed2001

Maps of the brain.

We review recent developments in brain mapping and computational anatomy that have greatly expanded our ability to analyze brain structure and function. The enormous diversity of brain maps and imaging methods has spurred the development of population-based digital brain atlases. These atlases store information on how the brain varies across age and gender, across time, in health and disease, and in large human populations. We describe how brain atlases, and the computational tools that align new datasets with them, facilitate comparison of brain data across experiments, laboratories, and from different imaging devices. The major methods are presented for the construction of probabilistic atlases, which store information on anatomic and functional variability in a population. Algorithms are reviewed that create composite brain maps and atlases based on multiple subjects. We show that group patterns of cortical organization, asymmetry, and disease-specific trends can be resolved that may not be apparent in individual brain maps. Finally, we describe the creation of four-dimensional (4D) maps that store information on the dynamics of brain change in development and disease. Digital atlases that correlate these maps show considerable promise in identifying general patterns of structural and functional variation in human populations, and how these features depend on demographic, genetic, cognitive, and clinical parameters.

Algorithms↗
PubMed1997

Direct effects of ropivacaine and bupivacaine on spinal pial vessels in canine. Assessment with closed spinal window technique.

BACKGROUND: Ropivacaine produces a vasoconstriction of cutaneous vessels in contrast to vasodilation produced by bupivacaine. To evaluate direct spinal microvascular actions of these local anesthetics, the authors investigated the concentration-related effects of ropivacaine and bupivacaine on spinal pial vascular diameters using the spinal window technique. METHODS: Anesthetized dogs (n = 14) divided into two groups (ropivacaine, n = 7; bupivacaine, n = 7) were prepared for measurement of spinal pial vessel diameters by intravital microscopy in a spinal window preparation. The authors administered six concentrations of each drug (10(-8)-10(-3) M) under the window and directly measured the spinal pial arteriolar and venular diameters at sequential times. Physiologic data including mean arterial blood pressure (MAP) and heart rate (HR) were determined before and after topical application of each concentration of the drugs. In additional experiments (n = 18), the action of topical ropivacaine and bupivacaine solution on spinal vessels was evaluated in the presence of yohimbine, prazosin, and propranolol. RESULTS: Ropivacaine significantly constricted whereas bupivacaine dilated pial arterioles and venules, both in a concentration-dependent manner. Microvascular alteration was not blocked with any of the adrenoceptor antagonists tested (yohimbine, prazosin, propranolol), each of which per se did not affect pial vessel diameters. Topical application of ropivacaine or bupivacaine did not induce any change in MAP or HR. CONCLUSIONS: The present results indicate that ropivacaine constricts and bupivacaine dilates the pial vessels of the spinal cord in a concentration-dependent fashion, and the mechanisms involved in such actions do not seem to be mediated via alpha- or beta-adrenoceptor of spinal vasculature.

Amides↗
PubMed2002

Imaging databases and neuroscience.

Brain atlases are equivalent to neuroimage databases provided an appropriate coordinate system to enable multisubject comparisons, along with comprehensive descriptions of the data, are included. Warping tools, visualization, and statistical analyses that accommodate the various neuroimaging modalities can be used to integrate diverse data and form comprehensive maps describing a particular subpopulation's brain structure and function. By linking task performance and genetic information to brain morphology, complex interrelations between genotype, phenotype, and behavior can be established. Several examples of these multimodal, multisubject atlases, including those that are dynamic, are presented.

Animals↗
PubMedDate not supplied

Text mining biomedical literature for discovering gene-to-gene relationships: a comparative study of algorithms.

Partitioning closely related genes into clusters has become an important element of practically all statistical analyses of microarray data. A number of computer algorithms have been developed for this task. Although these algorithms have demonstrated their usefulness for gene clustering, some basic problems remain. This paper describes our work on extracting functional keywords from MEDLINE for a set of genes that are isolated for further study from microarray experiments based on their differential expression patterns. The sharing of functional keywords among genes is used as a basis for clustering in a new approach called BEA-PARTITION in this paper. Functional keywords associated with genes were extracted from MEDLINE abstracts. We modified the Bond Energy Algorithm (BEA), which is widely accepted in psychology and database design but is virtually unknown in bioinformatics, to cluster genes by functional keyword associations. The results showed that BEA-PARTITION and hierarchical clustering algorithm outperformed k-means clustering and self-organizing map by correctly assigning 25 of 26 genes in a test set of four known gene groups. To evaluate the effectiveness of BEA-PARTITION for clustering genes identified by microarray profiles, 44 yeast genes that are differentially expressed during the cell cycle and have been widely studied in the literature were used as a second test set. Using established measures of cluster quality, the results produced by BEA-PARTITION had higher purity, lower entropy, and higher mutual information than those produced by k-means and self-organizing map. Whereas BEA-PARTITION and the hierarchical clustering produced similar quality of clusters, BEA-PARTITION provides clear cluster boundaries compared to the hierarchical clustering. BEA-PARTITION is simple to implement and provides a powerful approach to clustering genes or to any clustering problem where starting matrices are available from experimental observations.

Abstracting and Indexing↗
PubMed1980

The effects of topical and oral slow-release nitroglycerin on anterior myocardial infarction size assessed by precordial ST segment mapping.

The effect of slow-release nitroglycerin and nitroglycerin ointment in reducing anterior myocardial infarction size was assessed in 18 patients by means of epicardial mapping. The sum of all ST elevations (sigma ST), the number of leads with ST elevations greater than 1 mm (NST), the sum of the ST segment elevations of those leads with ST elevations greater than 1 mm (sigma STmm) and the average ST segment elevations (ST) were evaluated. No statistically significant difference between the two forms of nitroglycerin and placebo was found over a 72-h period. These data suggest that no benefit in terms of reduction in myocardial infarction size, assessed by epicardial mapping, is obtained from therapy with oral slow release nitroglycerin and nitroglycerin ointment.

Administration, Oral↗
PubMed2003

The neural basis of autobiographical and semantic memory: new evidence from three PET studies.

A novel, neuropsychologically informed paradigm (extended retrieval of events in response to a cue word) was used to investigate the neural basis of autobiographical and semantic memory. Contrasting retrieval of autobiographical memories with retrieval of semantic facts (ABM-SEM) in 24 subjects across three PET studies revealed bilateral involvement of the middle temporal gyrus (BA 21) and medial frontal cortex (BA 9/10). The opposite contrast, SEM-ABM, resulted in increased regional cerebral blood flow in left posterior temporal regions (BA 37) and left prefrontal cortex (BA 45/46). Laterality maps suggest that the bilateral pattern seen in our studies, but not often in other neuroimaging investigations, reflects the use of a task stressing retrieval of specific personal events. Further comparisons revealed that the activation in the right anterior temporal lobe during autobiographical recall was virtually identical to that seen during retrieval of information about famous people or events in contrast with retrieval of general semantic facts. These findings suggest that the retrieval of an autobiographical event requires participation from conceptual knowledge, and that this type of knowledge is bilaterally distributed in the temporal lobes.

Adult↗
PubMed1996

Human type 1 diabetes and the insulin gene: principles of mapping polygenes.

We review the strategy used to identify a susceptibility locus (IDDM2) for type 1 (insulin dependent) diabetes mellitus. As type 1 diabetes is becoming the paradigm for dissecting multifactorial disease genetics, the approach described provides important general guidelines for positional cloning of human disease polygenes. Main topics include: (a) historical conspectus of the mapping and identification of IDDM2--a critical survey of the work leading up to the conclusion that IDDM2 most likely corresponds to allelic variation at the insulin gene minisatellite (VNTR) locus; (b) the nature of allelic (length and sequence) variation at the VNTR locus; (c) gene interactions and disease pathogenesis; (d) mechanism of action of the INS VNTR in type 1 diabetes--insulin gene expression, parent-of-origin effects (genomic imprinting); and (e) summary and future prospects--alleles of the insulin VNTR that are protective for type 1 diabetes appear to encode susceptibility to type 2 diabetes.

Alleles↗
PubMed2006

A hybrid approach to shape-based interpolation of stereotactic atlases of the human brain.

Stereotactic human brain atlases, either in print or electronic form, are useful not only in functional neurosurgery, but also in neuroradiology, human brain mapping, and neuroscience education. The existing atlases represent structures on 2D plates taken at variable, often large intervals, which limit their applications. To overcome this problem, we propose a hybrid interpolation approach to build high-resolution brain atlases from the existing ones. In this approach, all section regions of each object are grouped into two types of components: simple and complex. A NURBS-based method is designed for interpolation of the simple components, and a distance map-based method for the complex components. Once all individual objects in the atlas are interpolated, the results are combined hierarchically in a bottom-up manner to produce the interpolation of the entire atlas. In the procedure, different knowledge-based and heuristic strategies are used to preserve various topological relationships. The proposed approach has been validated quantitatively and used for interpolation of two stereotactic brain atlases: the Talairach-Tournoux atlas and Schaltenbrand-Wahren atlas. The interpolations produced are of high resolution and feature high accuracy, 3D consistency, smooth surface, and preserved topology. They potentially open new applications for electronic stereotactic brain atlases, such as atlas reformatting, accurate 3D display, and 3D nonlinear warping against normal and pathological scans. The proposed approach is also potentially useful in other applications, which require interpolation and 3D modeling from sparse and/or variable intersection interval data. An example of 3D modeling of an infarct from MR diffusion images is presented.

Algorithms↗
PubMed2003

The Cerefy Neuroradiology Atlas: a Talairach-Tournoux atlas-based tool for analysis of neuroimages available over the internet.

The article introduces an atlas-assisted method and a tool called the Cerefy Neuroradiology Atlas (CNA), available over the Internet for neuroradiology and human brain mapping. The CNA contains an enhanced, extended, and fully segmented and labeled electronic version of the Talairach-Tournoux brain atlas, including parcelated gyri and Brodmann's areas. To our best knowledge, this is the first online, publicly available application with the Talairach-Tournoux atlas. The process of atlas-assisted neuroimage analysis is done in five steps: image data loading, Talairach landmark setting, atlas normalization, image data exploration and analysis, and result saving. Neuroimage analysis is supported by a near-real-time, atlas-to-data warping based on the Talairach transformation. The CNA runs on multiple platforms; is able to process simultaneously multiple anatomical and functional data sets; and provides functions for a rapid atlas-to-data registration, interactive structure labeling and annotating, and mensuration. It is also empowered with several unique features, including interactive atlas warping facilitating fine tuning of atlas-to-data fit, navigation on the triplanar formed by the image data and the atlas, multiple-images-in-one display with interactive atlas-anatomy-function blending, multiple label display, and saving of labeled and annotated image data. The CNA is useful for fast atlas-assisted analysis of neuroimage data sets. It increases accuracy and reduces time in localization analysis of activation regions; facilitates to communicate the information on the interpreted scans from the neuroradiologist to other clinicians and medical students; increases the neuroradiologist's confidence in terms of anatomy and spatial relationships; and serves as a user-friendly, public domain tool for neuroeducation. At present, more than 700 users from five continents have subscribed to the CNA.

Atlases as Topic↗
PubMed1999

No relationship between the size of the deletion and the level of developmental delay in cri-du-chat syndrome.

Molecular cytogenetic and developmental assessment was performed on 50 individuals with cri-du-chat syndrome. Fluorescent in situ hybridization analysis was used to confirm a terminal deletion karyotype and map more precisely the location of the deletion breakpoint. We identified terminal deletion breakpoints mapping from 5p15.2 to 5p13. Developmental assessment was performed using the Vineland Adaptive Behavior Scales test. Composite Vineland Scores ranged from 20-75. In general, the communication score was higher than the composite score. Comparison of the size of the deletion with the composite Vineland score, as well as the Vineland Communication score, demonstrated that there was no correlation between the size of the deletion and the level of developmental delay. These results demonstrate that patients with cri-du-chat syndrome show high variability in the level of developmental achievement.

Chromosome Deletion↗
PubMed2004

Analyzing protein-protein interactions in cell membranes.

Interactions among membrane proteins regulate numerous cellular processes, including cell growth, cell differentiation and apoptosis. We need to understand which proteins interact, where they interact and to which extent they interact. This article describes a set of novel approaches to measure, on the surface of living cells, the number of clusters of proteins, the number of proteins per cluster, the number of clusters or membrane domains that contain pairs of interacting proteins and the fraction of one protein species that interacts with another protein within these domains. These data can then be interpreted in terms of the function of the protein-protein interactions.

Cell Membrane↗