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      Comprehensive Screening of Gene Function and Networks by DNA Microarray Analysis in Japanese Patients with Idiopathic Portal Hypertension

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          Abstract

          The functions of genes involved in idiopathic portal hypertension (IPH) remain unidentified. The present study was undertaken to identify the functions of genes expressed in blood samples from patients with IPH through comprehensive analysis of gene expression using DNA microarrays. The data were compared with data from healthy individuals to explore the functions of genes showing increased or decreased expression in patients with IPH. In cluster analysis, no dominant probe group was shown to differ between patients with IPH and healthy controls. In functional annotation analysis using the Database for Annotation Visualization and Integrated Discovery tool, clusters showing dysfunction in patients with IPH involved gene terms related to the immune system. Analysis using network-based pathways revealed decreased expression of adenosine deaminase, ectonucleoside triphosphate diphosphohydrolase 4, ATP-binding cassette, subfamily C, member 1, transforming growth factor- β, and prostaglandin E receptor 2; increased expression of cytochrome P450, family 4, subfamily F, polypeptide 3, and glutathione peroxidase 3; and abnormalities in the immune system, nucleic acid metabolism, arachidonic acid/leukotriene pathways, and biological processes. These results suggested that IPH involved compromised function of immunocompetent cells and that such dysfunction may be associated with abnormalities in nucleic acid metabolism and arachidonic acid/leukotriene-related synthesis/metabolism.

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          Most cited references33

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          Use of a cDNA microarray to analyse gene expression patterns in human cancer.

          The development and progression of cancer and the experimental reversal of tumorigenicity are accompanied by complex changes in patterns of gene expression. Microarrays of cDNA provide a powerful tool for studying these complex phenomena. The tumorigenic properties of a human melanoma cell line, UACC-903, can be suppressed by introduction of a normal human chromosome 6, resulting in a reduction of growth rate, restoration of contact inhibition, and suppression of both soft agar clonogenicity and tumorigenicity in nude mice. We used a high density microarray of 1,161 DNA elements to search for differences in gene expression associated with tumour suppression in this system. Fluorescent probes for hybridization were derived from two sources of cellular mRNA [UACC-903 and UACC-903(+6)] which were labelled with different fluors to provide a direct and internally controlled comparison of the mRNA levels corresponding to each arrayed gene. The fluorescence signals representing hybridization to each arrayed gene were analysed to determine the relative abundance in the two samples of mRNAs corresponding to each gene. Previously unrecognized alterations in the expression of specific genes provide leads for further investigation of the genetic basis of the tumorigenic phenotype of these cells.
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            Idiopathic noncirrhotic portal hypertension.

            Idiopathic noncirrhotic portal hypertension (INCPH) is characterized by an increased portal venous pressure gradient in the absence of a known cause of liver disease and portal vein thrombosis. In contrast to the high prevalence of this disorder in India, INCPH is a rare disease in the Western world. The etiology of INCPH can be divided in five categories: chronic infections, exposure to medication or toxins, thrombophilia, immunological disorders, and genetic disorders. Multifactorial etiology can also be encountered. Chronic abdominal infection is incriminated as the most important etiological factor in Eastern patients and thrombophilia in Western patients. The majority of patients with INCPH initially present with signs or complications of portal hypertension (mainly variceal bleeding and splenomegaly). These patients usually have preserved liver function. Liver function impairment occurs mainly in the context of intercurrent conditions. Patients with INCPH are often clinically and radiologically misdiagnosed as liver cirrhosis, so that a liver biopsy is indispensable to discriminate cirrhosis from INCPH. Histopathological characteristics of INCPH are heterogeneous, demonstrating overlap between several pathological entities (e.g., hepatoportal sclerosis, nodular regenerative hyperplasia, and incomplete septal cirrhosis). Even though hemodynamical changes in INCPH patients are not comparable to those in cirrhotics, prophylaxis and treatment of variceal bleeding are recommended to be similar. Anticoagulation therapy must be considered only in patients who develop portal vein thrombosis. INCPH has been considered a disorder with a relatively benign disease course. However, liver failure, hepatic encephalopathy, and hepatopulmonary syndrome can occur and are considered indications for liver transplantation. Copyright © 2011 American Association for the Study of Liver Diseases.
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              The role of leukotrienes in inflammation.

              To review the biochemistry and biological activities of leukotrienes, focusing on their role in the mediation of inflammatory diseases. MEDLINE (1966-1994), EMBASE (Excerpta Medica; 1974-1994), and other biomedical and drug directory databases (such as Pharmaprojects and IMSworld R&D Focus [1991-1994]) were searched to identify English-language articles (basic science, clinical trial research, and review articles) and abstracts of conference proceedings on leukotrienes and related terms. Basic science studies on leukotrienes and clinical research studies on the use of leukotriene inhibitors and antagonists in the treatment of inflammatory diseases such as asthma, psoriasis, rheumatoid arthritis, and ulcerative colitis. Detailed summaries of data from basic science studies on the formation and actions of leukotrienes and from clinical studies of drugs that block the synthesis or receptor-mediated actions of leukotrienes. Leukotrienes are biologically active 5-lipoxygenase products of arachidonic acid metabolism that are involved in the mediation of various inflammatory disorders. Of these, leukotriene B4 (a potent chemoattractant for leukocytes) and the sulfidopeptide leukotrienes C4, D4, and E4 (which increase vascular permeability and constrict smooth muscle) exert their biological actions through specific ligand-receptor interactions. Selective leukotriene inhibitors and receptor antagonists are currently under evaluation in the treatment of various inflammatory diseases. Further data on the in vitro and in vivo activities of the leukotriene inhibitors and antagonists should clarify the role of leukotrienes in the pathogenesis of such inflammatory diseases as asthma, rheumatoid arthritis, and inflammatory bowel disease. Leukotriene inhibitors and antagonists will probably become important agents in the group of anti-inflammatory drugs.
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                Author and article information

                Journal
                Mediators Inflamm
                Mediators Inflamm
                MI
                Mediators of Inflammation
                Hindawi Publishing Corporation
                0962-9351
                1466-1861
                2015
                4 October 2015
                : 2015
                : 349215
                Affiliations
                1Department of Nuclear Medicine, Graduate School of Medicine, Osaka City University, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585, Japan
                2Department of Hepatology, Graduate School of Medicine, Osaka City University, Osaka 545-8585, Japan
                3Department of Disaster and Emergency Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan
                Author notes

                Academic Editor: Ekihiro Seki

                Article
                10.1155/2015/349215
                4609492
                26549939
                79e8d22c-4396-4e95-a966-7798faf69c73
                Copyright © 2015 Kohei Kotani et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 10 June 2015
                : 5 August 2015
                : 11 August 2015
                Categories
                Research Article

                Immunology
                Immunology

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