70 research outputs found

    A Proposal to Perform High Contrast Imaging of Human Palatine Tonsil with Cross Polarized Optical Coherence Tomography

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    The palatine tonsils provide the first line of immune defense against foreign pathogens inhaled or ingested. However, a disruption in the epithelial layer within the tonsil crypts can lead to recurrent acute tonsillitis (RAT). Current imaging techniques suffer from poor resolution and contrast and do not allow a classification of the severity of RAT. We have developed a cross-polarized optical coherence tomography system. The system can detect a change in the polarization of the light after the light-tissue interaction. We demonstrate improved resolution and contrast in tonsil imaging with the developed method. Intensity, as well as retardance images of the excised tonsil tissue, were acquired. Features such as crypt epithelium, lymphoid follicles, and dense connective tissue were observed with improved contrast. Cross polarized optical coherence tomography can be a valuable tool in the clinic to evaluate palatine tonsils as it would allow visualizing common tonsil features without the need for any external contrast agent

    Computing the shortest elementary flux modes in genome-scale metabolic networks

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    This article is available open access through the publisher’s website through the link below. Copyright @ The Author 2009.Motivation: Elementary flux modes (EFMs) represent a key concept to analyze metabolic networks from a pathway-oriented perspective. In spite of considerable work in this field, the computation of the full set of elementary flux modes in large-scale metabolic networks still constitutes a challenging issue due to its underlying combinatorial complexity. Results: In this article, we illustrate that the full set of EFMs can be enumerated in increasing order of number of reactions via integer linear programming. In this light, we present a novel procedure to efficiently determine the K-shortest EFMs in large-scale metabolic networks. Our method was applied to find the K-shortest EFMs that produce lysine in the genome-scale metabolic networks of Escherichia coli and Corynebacterium glutamicum. A detailed analysis of the biological significance of the K-shortest EFMs was conducted, finding that glucose catabolism, ammonium assimilation, lysine anabolism and cofactor balancing were correctly predicted. The work presented here represents an important step forward in the analysis and computation of EFMs for large-scale metabolic networks, where traditional methods fail for networks of even moderate size. Contact: [email protected] Supplementary information: Supplementary data are available at Bioinformatics online (http://bioinformatics.oxfordjournals.org/cgi/content/full/btp564/DC1).Fundação Calouste Gulbenkian, Fundação para a Ciência e a Tecnologia (FCT) and Siemens SA Portugal

    The search for the primary tumor in metastasized gastroenteropancreatic neuroendocrine neoplasm.

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    Gastroenteropancreatic neuroendocrine tumors (NETs) often present as liver metastasis from a carcinoma of unknown primary. We recently showed that primary NETs from the pancreas, small intestine and stomach as well as their respective liver metastases differ from each other by the expression profile of the three genes CD302, PPWD1 and ABHB14B. The gene and protein expression of CD302, PPWD1, and ABHB14B was studied in abdominal NET metastases to identify the site of the respective primary tumors. Cryopreserved tissue from NET metastases collected in different institutions (group A: 29, group B: 50, group C: 132 specimens) were examined by comparative genomic hybridization (Agilent 105 K), gene expression analysis (Agilent 44 K) (groups A and B) and immunohistochemistry (group C). The data were blindly evaluated, i.e. without knowing the site of the primary. Gene expression analysis correctly revealed the primary in the ileum in 94 % of the cases of group A and in 58 % of group B. A pancreatic primary was predicted in 83 % (group A) and 20 % (group B), respectively. The combined sensitivity of group A and B was 75 % for ileal NETs and 38 % for pancreatic NETs. Immunohistochemical analysis of group C revealed an overall sensitivity of 80 %. Gene and protein expression analysis of CD302 and PPWD1 in NET metastases correctly identifies the primary in the pancreas or the ileum in 80 % of the cases, provided that the tissue is well preserved. Immunohistochemical profiling revealed CD302 as the best marker for ileal and PPWD1 for pancreatic detection

    Identification of sex hormone-binding globulin in the human hypothalamus

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    Gonadal steroids are known to influence hypothalamic functions through both genomic and non-genomic pathways. Sex hormone-binding globulin ( SHBG) may act by a non-genomic mechanism independent of classical steroid receptors. Here we describe the immunocytochemical mapping of SHBG-containing neurons and nerve fibers in the human hypothalamus and infundibulum. Mass spectrometry and Western blot analysis were also used to characterize the biochemical characteristics of SHBG in the hypothalamus and cerebrospinal fluid (CSF) of humans. SHBG-immunoreactive neurons were observed in the supraoptic nucleus, the suprachiasmatic nucleus, the bed nucleus of the stria terminalis, paraventricular nucleus, arcuate nucleus, the perifornical region and the medial preoptic area in human brains. There were SHBG-immunoreactive axons in the median eminence and the infundibulum. A partial colocalization with oxytocin could be observed in the posterior pituitary lobe in consecutive semithin sections. We also found strong immunoreactivity for SHBG in epithelial cells of the choroid plexus and in a portion of the ependymal cells lining the third ventricle. Mass spectrometry showed that affinity-purified SHBG from the hypothalamus and choroid plexus is structurally similar to the SHBG identified in the CSF. The multiple localizations of SHBG suggest neurohypophyseal and neuroendocrine functions. The biochemical data suggest that CSF SHBG is of brain rather than blood origin. Copyright (c) 2005 S. Karger AG, Base

    Benchmark datasets for 3D MALDI- and DESI-imaging mass spectrometry

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    BACKGROUND: Three-dimensional (3D) imaging mass spectrometry (MS) is an analytical chemistry technique for the 3D molecular analysis of a tissue specimen, entire organ, or microbial colonies on an agar plate. 3D-imaging MS has unique advantages over existing 3D imaging techniques, offers novel perspectives for understanding the spatial organization of biological processes, and has growing potential to be introduced into routine use in both biology and medicine. Owing to the sheer quantity of data generated, the visualization, analysis, and interpretation of 3D imaging MS data remain a significant challenge. Bioinformatics research in this field is hampered by the lack of publicly available benchmark datasets needed to evaluate and compare algorithms. FINDINGS: High-quality 3D imaging MS datasets from different biological systems at several labs were acquired, supplied with overview images and scripts demonstrating how to read them, and deposited into MetaboLights, an open repository for metabolomics data. 3D imaging MS data were collected from five samples using two types of 3D imaging MS. 3D matrix-assisted laser desorption/ionization imaging (MALDI) MS data were collected from murine pancreas, murine kidney, human oral squamous cell carcinoma, and interacting microbial colonies cultured in Petri dishes. 3D desorption electrospray ionization (DESI) imaging MS data were collected from a human colorectal adenocarcinoma. CONCLUSIONS: With the aim to stimulate computational research in the field of computational 3D imaging MS, selected high-quality 3D imaging MS datasets are provided that could be used by algorithm developers as benchmark datasets

    Epigenetic assays for chemical biology and drug discovery

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