DOCSLIB.ORG

Hepcidin (Hepc) Are Important Iron-Related Protein and Regulative Peptide

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Hepcidin (Hepc) Are Important Iron-Related Protein and Regulative Peptide CONSTRUCTION OF ADENOVIRUSES AND RETROVIRUSES OF RECOMBINANT IRON METABOLISM GENES AND THEIR APPLICATION IN THE STUDIES ON IRON METABOLISM GE XIAOHU THE DEGREE OF DOCTOR OF PHILOSOPHY THE HONG KONG POLYTECHNIC UNIVERSITY 2010 The Hong Kong Polytechnic University Department of Applied Biology & Chemical Technology CONSTRUCTION OF ADENOVIRUSES AND RETROVIRUSES OF RECOMBINANT IRON METABOLISM GENES AND THEIR APPLICATION IN THE STUDIES ON IRON METABOLISM GE XIAOHU A THESIS SUBMITTED IN PARTIAL FULFILMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY June 2009 2 CERTIFICATE OF ORIGINALITY I hereby declare that this thesis in my own work and that, to the best of my knowledge and belief, it reproduces no material previously published or written nor material which has been accepted for the award of any other degree or diploma, except where due acknowledgement has been made in the text. …………………………………………. (Signed) ………………………………………….. (Name of Student) 3 Abstract of thesis entitled ‘construction of adenoviruses and retroviruses of recombinant iron metabolism genes and their application in the studies on iron metabolism’ Submitted by Ge Xiaohu For the degree of Doctor of Philosophy At The Hong Kong Polytechnic University in June 2009 Abstract Human iron metabolism is the set of chemical reactions that maintains human homeostasis of iron. Iron is essential for most lives on earth, including human beings. Iron participates in a series of cellular metabolic processes in the brain, for example, as tyrosine hydroxylase, and cofactor for the enzymes. Iron is also essential for the biosynthesis of CNS lipids and cholesterol. In oligodendroglia, it plays an important role in action of metabolic enzymes as a co-factor. But excessive iron is damaging to the brain and may lead to many neurodegenerative diseases. The existence of excessive total brain iron, a common feature of some neurodegenerative diseases, is thought to be a cause of many such diseases. A significant increased concentration of brain iron is found in the neuronal systems 4 or some specific brain regions in some neurodegenerative diseases. In iron metabolism, Divalent metal transporter 1 (DMT1), Transferrin receptors 1 (TfR1), Ferroportin1 (FPN1), Hephaestin (Heph), hepcidin (Hepc) are important iron-related protein and regulative peptide. In order to investigate the effects of these iron-related genes on neurodegenerative diseases, we constructed a series of recombinant adenoviruses and retroviruses, including rAd-DMT1 (+), rAd-DMT1 (-), rAd-FPN1, rAd-Heph, rAd-Hepc, Retro-DMT1, Retro-FPN1, Retro-Heph, and Retro-Hepc through molecular biological technology. All these recombinant virus products were applied to primary culture neurons or some cell lines. Our results proved that there are high biological expression activities of these recombinant adenoviruses and retroviruses in cells. In this study, we also provided solid evidence for the first time for the association of DMT1-IRE with neurotoxicity induced by L-DOPA. We believe that inhibition of DMT1-IRE expression or neuronal iron uptake might be an effective approach to prevent or delay the development of neurotoxicity induced by L-DOPA in PD patients through the retrovirus gene knockout system. Furthermore, we investigated the regulating effects of hepcidin, an iron regulatory peptide, in neurons through rAd-hepc and retro-hepc. Our results suggested that hepcidin has the ability to regulate the expression of some iron related genes as an upstream regulatory factor, such as FPN1, DMT1 (+), DMT1 (-) etc. This thesis consists of 9 chapters, beginning with a general introduction, followed by the methodology section, and 6 chapters on results, and ends with suggestions on future work. LIST OF PUBLICATIONS 5 1. Ge Xiaohu, Wang qin, Qian zhongming et al. The iron regulatory hormone hepcidin reduces ferroportin 1 content band iron release in H9C2 cardiomyocytes, Journal of Nutritional biochemistry, 2008. Article in Press. (IF 3.5) 2. Wang, Q., Du, F., Qian, Z.M., Ge, X.H., Zhu, L., Yung, W.H., Yang, L., and Ke, Y. (2008). Lipopolysaccharide induces a significant increase in expression of iron regulatory hormone hepcidin in the cortex and substantia nigra in rat brain. Endocrinology 149, 3920-3925 (IF 6.0) 3. Qian, Z.M., Chang, Y.Z., Zhu, L., Yang, L., Du, J.R., Ho, K.P., Wang, Q., Li, L.Z., Wang, C.Y., Ge, X., et al. Development and iron-dependent expression of hephaestin in different brain regions of rats. J Cell Biochem (2007)102, 1225-1233. 4. Ke, Y., Ho, K., Du, J., Zhu, L., Xu, Y., Wang, Q., Wang, C.Y., Li, L., Ge, X., Chang, Y., et al. Role of soluble ceruloplasmin in iron uptake by midbrain and hippocampus neurons. J Cell Biochem (2006). 98, 912-919. 5. Chang, Y.Z., Qian, Z.M., Du, J.R., Zhu, L., Xu, Y., Li, L.Z., Wang, C.Y., Wang, Q., Ge, X.H., Ho, K.P., et al. Ceruloplasmin expression and its role in iron transport in C6 cells. Neurochem Int (2007).50, 726-733. PATENTS 6 1. Inventors:ZM qian, Xiaohu G, The application and construction of anti-HJV retrovirus. Accepted. Application NO.: 200710075360.8 Publication NO. : CN101307085 2. Inventors:ZM qian, Xiaohu G, The application and methodology of FPN recombinant adenovirus, Accepted. Application NO. : 200710125467.9 Publication NO. : CN101210255 3. Inventors:ZM qian,Xiaohu G，The application and methodology of hepcidin recombinant adenovirus, Accepted. Application NO. : 200710075462.X 4. Inventors:ZM qian, Xiaohu G ， The application and construction of anti-hecpcidin retroviru, Accepted. Application NO. : 200810141910.6 5. Inventors: ZM qian, Xiaohu G， The application and construction of anti-DMT1 retrovirus, Accepted. Application NO. : 200810141912.5 6. Inventors:ZM qian, Xiaohu G ， The application and construction of anti-FPN1 retrovirus, Accepted. Application NO. : 200810141911.0 7. Inventors: ZM qian, Xiaohu G， The application and methodology of two kinds of DMT1 recombinant adenovirus, Accepted. Application NO. : 200810141913. ACKNOWLEDGEMENTS 7 The investigations described in this thesis were carried out in the Laboratory of Iron Metabolism in the Department of Applied Biology and Chemical Technology (ABCT), The Hong Kong Polytechnic University. I am especially indebted to my Chief Supervisor, Prof. Qian Zhong-ming, for his outstanding guidance, sincere encouragement, and helpful advice throughout the course of this work. It would have been impossible for me to complete this thesis without him. I am also grateful to Prof. Wong Kwok-Yin, Prof. Lau Chak-po, Prof. Lo Chun-lap and Dr. Chow Ming-cheung for their encouragement and valuable suggestions. I am much indebted to the Departmental Research Committee of the ABCT Department and the Research Committee of The Hong Kong Polytechnic University for giving me a Research Scholarship and supporting my study in this university. I would also like to thank Dr. Ke Ya, Dr. Li Lian-zhi, Dr. Wang Cheng-yuan, Dr. Wang Qin, Ms. Wang Xiao-yun and all other colleagues in our research group for their kind help and strong support. With all my heart, I would like to thank my parents, Ge Chu-xing and Shi Feng-yi, my wife, Liang Yong-hong, my sisters and brothers-in-law, Ge Xiao-hong, Cai Li-ming and Ge Xiao-ni, Zhong Tao for their unconditional love, endless encouragement and understanding. I am also grateful to all those who encouraged and supported me throughout my life. Finally, I hope to dedicate this thesis to my darling daughter YoYo. The List of Content 8 1 CHAPTER 1 INTRODUCTION ................................................................................................ 28 1.1 INTRODUCTORY STATEMENT ................................................................................................... 28 1.2 GENERAL DESCRIPTION OF IRON METABOLISM ....................................................................... 28 1.2.1 Iron absorption .................................................................................................................. 29 1.2.2 Genetic Insights into Mammalian Iron Absorption ........................................................... 32 1.2.3 Erythropoiesis and Iron Absorption .................................................................................. 33 1.2.4 Body iron stores ................................................................................................................. 34 1.2.5 Cells iron uptake from body .............................................................................................. 35 1.2.5.1 Tf and TfR Dependent Iron Uptake ..................................................................................... 37 1.2.5.2 Tf and TfR Independent Iron Uptake .................................................................................. 38 1.2.6 Iron efflux .......................................................................................................................... 42 1.3 BRAIN IRON METABOLISM PROTEINS ...................................................................................... 43 1.3.1 Transferrin Receptor 1 ...................................................................................................... 43 1.3.1.1 Transferrin Receptor and Transferrin Receptor 2 ............................................................. 44 1.3.1.2 Molecular Characterization and Expression of TfR1 and TfR2 ....................................... 44 1.3.1.3 Regulation of TfR and TfR2 Gene Expression .................................................................... 46 1.3.1.4 Transferrin Receptor in the Brain ......................................................................................
Load more

Recommended publications
  • Association Between Hereditary Hemochromatosis and Hepatocellular Carcinoma: a Comprehensive Review
    Jayachandran et al. Hepatoma Res 2020;6:8 Hepatoma Research DOI: 10.20517/2394-5079.2019.35 Review Open Access Association between hereditary hemochromatosis and hepatocellular carcinoma: a comprehensive review Aparna Jayachandran1,2, Ritu Shrestha1,2, Kim R. Bridle1,2, Darrell H. G. Crawford1,2 1The University of Queensland, Faculty of Medicine, Brisbane, QLD 4006, Australia. 2Gallipoli Medical Research Institute, Greenslopes Private Hospital, Brisbane, QLD 4120, Australia. Correspondence to: Prof. Darrell H. G. Crawford, Gallipoli Medical Research Institute, The University of Queensland, Faculty of Medicine, Lower Lobby Level, Administration Building, Greenslopes Private Hospital, Greenslopes, QLD 4120, Australia. E-mail: [email protected] How to cite this article: Jayachandran A, Shrestha R, Bridle KR, Crawford DHG. Association between hereditary hemochromatosis and HCC: a comprehensive review. Hepatoma Res 2020;6:8. http://dx.doi.org/10.20517/2394-5079.2019.35 Received: 15 Nov 2019 First Decision: 10 Dec 2019 Revised: 4 Feb 2020 Accepted: 18 Feb 2020 Published: 6 Mar 2020 Science Editor: Guang-Wen Cao Copy Editor: Jing-Wen Zhang Production Editor: Tian Zhang Abstract Hepatocellular carcinoma (HCC) is a significant global health problem with high morbidity and mortality. Its incidence is increasing exponentially worldwide with a close overlap between annual incidence and death rates. Even though significant advances have been made in HCC treatment, fewer than 20% of patients with HCC are suitable for potentially curative treatment. Hereditary hemochromatosis (HH) is an important genetic risk factor for HCC. HH is an autosomal recessive disorder of iron metabolism, characterised by elevated iron deposition in most organs including the liver, leading to progressive organ dysfunction.
    [Show full text]
  • Nr EC Aandoening Orphacode Patiëntenorganisatie Vragenlijst
    Nr EC Aandoening Orphacode Patiëntenorganisatie Vragenlijst P PNR ingediend? G-24-12 ABeta amyloidosis, Dutch type ORPHA:100006 Vereniging HCHWA-D Nee P 14 G-8-7 Tubular duplication of the esophagus ORPHA:100048 Vereniging voor Ouderen en Kinderen met Slokdarmafsluiting (VOKS) Ja P 124 G-17-10 Neurogenic thoracic outlet syndrome ORPHA:100073 RSI-vereniging Nee P 305 G-11-43 Laryngeal neuroendocrine tumor ORPHA:100083 St NET-Groep Ja P 62 G-11-43 Middle ear neuroendocrine tumor ORPHA:100084 St NET-Groep Ja P 62 G-11-1 Thyroid tumor ORPHA:100087 Schildklier Organisatie NL (SON) Ja P 60 G-11-13 Thyroid tumor ORPHA:100087 Schildklier Organisatie NL (SON) Ja P 60 G-11-35 Thyroid Tumor ORPHA:100087 Schildklier Organisatie NL (SON) Ja P 60 G-11-13 Thyroid carcinoma ORPHA:100088 Schildklier Organisatie NL (SON) Ja P 60 G-11-35 Thyroid carcinoma ORPHA:100088 Schildklier Organisatie NL (SON) Ja P 60 G-3-11 Thyroid carcinoma ORPHA:100088 Schildklier Organisatie NL (SON) Ja P 60 G-3-17 Thyroid carcinoma ORPHA:100088 Schildklier Organisatie NL (SON) Ja P 60 G-3-13 Adrenal/paraganglial tumor ORPHA:100091 Nlse Vereniging voor patiënten met Paragangliomen (NVPG) Ja P 29 G-3-13 Adrenal/paraganglial tumor ORPHA:100091 Bijniervereniging (NVACP) Nee P 64 G-3-2 Adrenal/paraganglial tumor ORPHA:100091 Nlse Vereniging voor Patiënten met Paragangliomen (NVPG) Ja P 29 G-3-2 Adrenal/paraganglial tumor ORPHA:100091 Bijniervereniging (NVACP) Nee P 64 G-11-29 Gastroenteropancreatic neuroendocrine neoplasm ORPHA:100092 St NET-Groep Ja P 62 G-11-27 Thymic tumor ORPHA:100100
    [Show full text]
  • Do Pregnancies Reduce Iron Overload In
    Scotet et al. BMC Pregnancy and Childbirth (2018) 18:53 https://doi.org/10.1186/s12884-018-1684-6 RESEARCH ARTICLE Open Access Do pregnancies reduce iron overload in HFE hemochromatosis women? results from an observational prospective study Virginie Scotet1*†, Philippe Saliou1,2†, Marianne Uguen1, Carine L’Hostis1, Marie-Christine Merour3, Céline Triponey3, Brigitte Chanu3, Jean-Baptiste Nousbaum1,4, Gerald Le Gac1,5 and Claude Ferec1,3,5 Abstract Background: HFE hemochromatosis is an inborn error of iron metabolism linked to a defect in the regulation of hepcidin synthesis. This autosomal recessive disease typically manifests later in women than men. Although it is commonly stated that pregnancy is, with menses, one of the factors that offsets iron accumulation in women, no epidemiological study has yet supported this hypothesis. The aim of our study was to evaluate the influence of pregnancy on expression of the predominant HFE p.[Cys282Tyr];[Cys282Tyr] genotype. Methods: One hundred and forty p.Cys282Tyr homozygous women enrolled in a phlebotomy program between 2004 and 2011 at a blood centre in western Brittany (France) were included in the study. After checking whether the disease expression was delayed in women than in men in our study, the association between pregnancy and iron overload was assessed using multivariable regression analysis. Results: Our study confirms that women with HFE hemochromatosis were diagnosed later than men cared for during the same period (52.6 vs. 47.4 y., P < 0.001). Compared to no pregnancy, having at least one pregnancy was not associated with lower iron markers. In contrast, the amount of iron removed by phlebotomies appeared significantly higher in women who had at least one pregnancy (eβ = 1.50, P = 0.047).
    [Show full text]
  • Current and Potential Therapeutic Strategies for Hemodynamic Cardiorenal Syndrome
    Cardiorenal Med 2016;6:83–98 DOI: 10.1159/000441283 © 2015 S. Karger AG, Basel Published online: November 6, 2015 1664–3828/15/0062–0083$39.50/0 www.karger.com/crm Review Current and Potential Therapeutic Strategies for Hemodynamic Cardiorenal Syndrome a, c a, c, f d b Yoshitsugu Obi Taehee Kim Csaba P. Kovesdy Alpesh N. Amin a, c, e Kamyar Kalantar-Zadeh a b Division of Nephrology and Hypertension and Department of Medicine, University of c California Irvine, and Harold Simmons Center for Kidney Disease Research and d Epidemiology, Orange, Calif., Division of Nephrology, University of Tennessee Health e Sciences Center, Memphis, Tenn. , and Department of Medicine, VA Long Beach f Health Care System, Long Beach, Calif., USA; Department of Medicine, Inje University, Busan , South Korea Key Words Cardiorenal syndrome · Chronic kidney disease · Heart failure · Acute kidney injury · Dobutamine · Ultrafiltration Abstract Background: Cardiorenal syndrome (CRS) encompasses conditions in which cardiac and renal disorders co-exist and are pathophysiologically related. The newest classification of CRS into seven etiologically and clinically distinct types for direct patient management pur- poses includes hemodynamic, uremic, vascular, neurohumoral, anemia- and/or iron metab- olism-related, mineral metabolism-related and protein-energy wasting-related CRS. This classification also emphasizes the pathophysiologic pathways. The leading CRS category remains hemodynamic CRS, which is the most commonly encountered type in patient care settings and in which acute or chronic heart failure leads to renal impairment. Summary: This review focuses on selected therapeutic strategies for the clinical management of he- modynamic CRS. This is often characterized by an exceptionally high ratio of serum urea to creatinine concentrations.
    [Show full text]
  • Orphanet Aandoening Orphacode Patiëntenorganisatie P
    Cluster(s) Orphanet Aandoening Orphacode Patiëntenorganisatie P PNR -U UNR Rare genetic diseases ABeta amyloidosis, Dutch type ORPHA:100006 Vereniging HCHWA-D P 14 U 2003 Rare neurological diseases Rare respiratory diseases Tubular duplication of the esophagus ORPHA:100048 Vereniging voor Ouderen en Kinderen met Slokdarmafsluiting (VOKS) P 124 U 495 Rare surgical thoracic diseases Rare surgical thoracic diseases Neurogenic thoracic outlet syndrome ORPHA:100073 RSI-vereniging P 305 U 6 Rare neurological diseases Neurogenic thoracic outlet syndrome ORPHA:100073 Spierziekten NL P 43 U 1418 Rare neoplastic diseases Laryngeal neuroendocrine tumor ORPHA:100083 ST NET-Groep P 62 U 1199 Rare odontological diseases Rare bone diseases Rare otorhinolaryngological diseases Rare skin diseases Rare surgical maxillo-facial diseases Rare neoplastic diseases Middle ear neuroendocrine tumor ORPHA:100084 ST NET-Groep P 62 U 1200 Rare odontological diseases Rare bone diseases Rare otorhinolaryngological diseases Rare skin diseases Rare surgical maxillo-facial diseases Rare endocrine diseases Thyroid tumor ORPHA:100087 Schildklier Organisatie NL (SON) P 60 U 1214 Rare neoplastic diseases Rare endocrine diseases Thyroid tumor ORPHA:100087 Schildklier Organisatie NL (SON) P 60 U 1213 Rare endocrine diseases Thyroid Tumor ORPHA:100087 Schildklier Organisatie NL (SON) P 60 U 1215 Rare neoplastic diseases Rare endocrine diseases Thyroid carcinoma ORPHA:100088 Schildklier Organisatie NL (SON) P 60 U 1216 Rare endocrine diseases Thyroid carcinoma ORPHA:100088 Schildklier
    [Show full text]
  • WO 2014/121298 A2 7 August 2014 (07.08.2014) P O P C T
    (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date WO 2014/121298 A2 7 August 2014 (07.08.2014) P O P C T (51) International Patent Classification: VULIC, Marin; c/o Seres Health, Inc., 161 First Street, A61K 39/02 (2006.01) Suite 1A, Cambridge, MA 02142 (US). (21) International Application Number: (74) Agents: HUBL, Susan, T. et al; Fenwick & West LLP, PCT/US2014/014738 Silicon Valley Center, 801 California Street, Mountain View, CA 94041 (US). (22) International Filing Date: 4 February 2014 (04.02.2014) (81) Designated States (unless otherwise indicated, for every kind of national protection available): AE, AG, AL, AM, English (25) Filing Language: AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, (26) Publication Language: English BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, (30) Priority Data: HN, HR, HU, ID, IL, IN, IR, IS, JP, KE, KG, KN, KP, KR, 61/760,584 4 February 2013 (04.02.2013) US KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, ME, 61/760,585 4 February 2013 (04.02.2013) US MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, 61/760,574 4 February 2013 (04.02.2013) us OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, 61/760,606 4 February 2013 (04.02.2013) us SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, 61/926,918 13 January 2014 (13.01.2014) us TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, (71) Applicant: SERES HEALTH, INC.
    [Show full text]
  • Wjcc.V8.I23.5962 ISSN 2307-8960 (Online)
    World Journal of W J C C Clinical Cases Submit a Manuscript: https://www.f6publishing.com World J Clin Cases 2020 December 6; 8(23): 5962-5975 DOI: 10.12998/wjcc.v8.i23.5962 ISSN 2307-8960 (online) ORIGINAL ARTICLE Observational Study Genetic diagnosis history and osteoarticular phenotype of a non- transfusion secondary hemochromatosis Dan-Dan Ruan, Yu-Mian Gan, Tao Lu, Xiao Yang, Yao-Bin Zhu, Qing-Hua Yu, Li-Sheng Liao, Ning Lin, Xin Qian, Jie-Wei Luo, Fa-Qiang Tang ORCID number: Dan-Dan Ruan Dan-Dan Ruan, Yu-Mian Gan, Tao Lu, Qing-Hua Yu, Li-Sheng Liao, Ning Lin, Xin Qian, Jie-Wei Luo, 0000-0001-9611-2979; Yu-Mian Gan Fa-Qiang Tang, Shengli Clinical Medical College, Fujian Medical University, Fuzhou 350001, 0000-0003-3676-1242; Tao Lu 0000- Fujian Province, China 0002-6807-9152; Xiao Yang 0000- 0003-2091-7126; Yao-Bin Zhu 0000- Xiao Yang, Department of Management, Fujian Health College, Fuzhou 350101, Fujian 0003-2186-2286; Qing-Hua Yu 0000- Province, China 0002-3465-6417; Li-Sheng Liao 0000- 0001-7364-4366; Ning Lin 0000- Yao-Bin Zhu, Department of Traditional Chinese Medicine, The First Affiliated Hospital, Fujian 0003-4911-7309; Xin Qian 0000- Medical University, Fuzhou 350005, Fujian Province, China 0001-7239-7295; Jie-Wei Luo 0000- 0003-4271-4848; Fa-Qiang Tang Fa-Qiang Tang, Department of Orthopedics, Fujian Provincial Hospital, Fuzhou 350001, Fujian 0000-0002-0625-8470. Province, China Author contributions: Ruan DD, Corresponding author: Fa-Qiang Tang, MD, Chief Physician, Doctor, Shengli Clinical Medical Gan YM, Lu T, Yang X and Zhu YB College, Fujian Medical University, No.
    [Show full text]
  • Abnormal Serum Iron Markers in Chronic Hepatitis B Virus Infection May Be Because of Liver Injury Weilin Maoa, Ying Hub, Yufeng Loua, Yuemei Chena and Juanwen Zhanga
    130 Original article Abnormal serum iron markers in chronic hepatitis B virus infection may be because of liver injury WeiLin Maoa, Ying Hub, YuFeng Loua, YueMei Chena and JuanWen Zhanga Objective In patients with chronic hepatitis B virus (HBV) inversely related to both end-stage liver disease scores infection, it is not known whether altered serum iron and iron levels (all P < 0.01). markers are directly because of the infection or the Conclusion Serum iron markers tended to be aberrant in associated liver injury. We determined the serum iron status chronic HBV-infected patients with cirrhosis. The liver injury of patients with chronic HBV infection, and investigated associated with HBV infection, but not chronic HBV infection whether it is HBV infection or HBV-related liver injury that directly, is likely the main cause for iron metabolism likely causes abnormal serum iron markers in chronic HBV disorder. Eur J Gastroenterol Hepatol 27:130–136 © 2015 infection. Wolters Kluwer Health | Lippincott Williams & Wilkins. Materials and methods For a retrospective study, chronic European Journal of Gastroenterology & Hepatology 2015, 27:130–136 HBV-infected patients (80 patients with cirrhosis and 76 patients without cirrhosis) and 58 healthy controls were Keywords: ferritin, liver cirrhosis, liver injury, serum iron, transferrin enrolled. Serum alanine transaminase levels were Departments of aClinical Laboratory and bUltrasonography, the First Affiliated measured to ascertain liver damage. Indicators of iron Hospital, College of Medicine,
    [Show full text]
  • Topics Symposia
    Abstracts Topics Symposia Symposia S_1 Structural variation S 1 Structural variation S 2 Low risk cancer genes S1_01 S 3 Transgeneration effects and Molecular Mechanisms and Clinical Consequences of Genomic Disor- epigenetic programming ders. Implementation of array CGH in Genetic Diagnostics. The Baylor S 4 Ciliopathies Experience S 5 Systems biology Pawel Stankiewicz S 6 Molecular processes in meiosis Dept. of Molecular & Human Genetics, Baylor College of Medicine, Hous- ton, TX, USA Genomic disorders are a group of human genetic diseases caused by Selected Presentations DNA rearrangements, ranging in size from an average exon (~100 bp) to megabases and affecting dosage sensitive genes. Three major mo- lecular mechanisms: non-allelic homologous recombination (NAHR), Workshops non-homologous end joining (NHEJ), and the fork stalling and tem- W 1 Clinical genetics plate switching (FoSTeS)/microhomology-mediated breakage-induced W 2 Molecular basis of disease I repair (MMBIR) have been described as causative for the vast majority W 3 Cancer genetics of genomic disorders. Recurrent rearrangements are typically mediated W 4 Molecular basis of disease II by NAHR between low-copy repeats that are usually >10 kb in size with >97% DNA sequence identity. Nonrecurrent CNVs have been found to W 5 Imprinting be formed by NAHR between highly homologous repetitive elements W 6 Genomics technology / bioinformatics (e.g. Alu, LINE) and more often by NHEJ and FoSTeS/MMBIR stimu- W 7 Complex diseases lated, but not mediated, by genomic architectural features. Further- W 8 Cytogenetics / prenatal genetics more, simple repeating DNA sequences that have a potential of adopt- ing non-B DNA conformations (e.g.
    [Show full text]
  • U UNR Aandoening Orphacode Patiëntenorganisatie P 296
    P PNR -U UNR Aandoening Orphacode Patiëntenorganisatie P 296 U 21 Anterior cutaneous nerve entrapment syndrome ORPHA:51890 ACNES Foundation P 296 U 22 Anterior cutaneous nerve entrapment syndrome ORPHA:51890 ACNES Foundation P 1 U 1837 Rare ataxia ORPHA:102002 ADCA-Ataxie Vereniging P 1 U 1838 Rare ataxia ORPHA:102002 ADCA-Ataxie Vereniging P 1 U 1839 Autosomal recessive cerebellar ataxia ORPHA:1172 ADCA-Ataxie Vereniging P 1 U 1840 Epilepsy and/or ataxia with myoclonus as major feature ORPHA:306756 ADCA-Ataxie Vereniging P 1 U 1841 Autosomal dominant cerebellar ataxia ORPHA:99 ADCA-Ataxie Vereniging P 1 U 1842 Autosomal dominant cerebellar ataxia ORPHA:99 ADCA-Ataxie Vereniging P 1 U 1907 CLIPPERS ORPHA:284448 ADCA-Ataxie vereniging P 268 U 90 Amyotrophic lateral sclerosis ORPHA:803 ALS Patients Connected P 268 U 91 Amyotrophic lateral sclerosis ORPHA:803 ALS Patients Connected P 268 U 92 amyotrophic lateral sclerosis-parkinsonism-dementia complex ORPHA:90020 ALS Patients Connected P 2 U 1821 Cerebral autosomal dominant arteriopathy-subcortical infarcts-leukoencephalopathy ORPHA:136 Alzheimer NL P 2 U 1822 Pantothenate kinase-associated neurodegeneration ORPHA:157850 Alzheimer NL P 2 U 1823 Cerebral autosomal recessive arteriopathy-subcortical infarcts-leukoencephalopathy ORPHA:199354 Alzheimer NL P 2 U 1827 neuronal intranuclear inclusion disease ORPHA:2289 Alzheimer NL P 2 U 1828 Frontotemporal dementia with motor neuron disease ORPHA:275872 Alzheimer NL P 2 U 1829 Frontotemporal dementia ORPHA:282 Alzheimer NL P 2 U 1830 Neurodegeneration
    [Show full text]
  • (12) STANDARD PATENT (11) Application No. AU 2010202722 B2 (19) AUSTRALIAN PATENT OFFICE
    (12) STANDARD PATENT (11) Application No. AU 2010202722 B2 (19) AUSTRALIAN PATENT OFFICE (54) Title Juvenile hemochromatosis gene (HFE2A), expression products and uses thereof (51) International Patent Classification(s) C12Q 1/68 (2006.01) G01N 33/50 (2006.01) C07K 14/47 (2006.01) (21) Application No: 2010202722 (22) Date of Filing: 2010.06.29 (43) Publication Date: 2010.07.15 (43) Publication Journal Date: 2010.07.15 (44) Accepted Journal Date: 2012.12.20 (62) Divisional of: 2004231122 (71) Applicant(s) Xenon Pharmaceuticals, Inc. (72) Inventor(s) Ludwig, Erwin H.;Papanikolaou, George;MacDonald, Marcia L.E.;Samuels, Mark E.;Franchini, Patrick;Kamboj, Rajender K.;Goldberg, Yigal Paul (74) Agent / Attorney Spruson & Ferguson, L 35 St Martins Tower 31 Market St, SYDNEY, NSW, 2000 (56) Related Art WO 2000/073801 WO 2002/051438 GenBank Accession No: BAB26407 JUVENILE HEMOCHROMATOSIS GENE (HFE2A), EXPRESSION PRODUCTS 2010 AND USES THEREOF Jun Abstract 29 5 Polynucleotide and polypeptide sequences for HFE2A, as well as mutations associated with juvenile hemochromatosis, and methods of utilizing these for screening and identification of agents for the treatment of diseases of iron metabolism, including small organic compounds, are disclosed along with methods of treating and/or io ameliorating diseases of iron metabolism, especially in human patients are disclosed. 2010202722 Diagnostic compounds, kits and methods using HFE2A are also described. S&FRef: 739254D1 AUSTRALIA 2010 PATENTS ACT 1990 COMPLETE SPECIFICATION Jun 29 FOR A STANDARD PATENT 2010202722 Name and Address Xenon Pharmaceuticals, Inc., of 3650 Gilmore Way, of Applicant: Burnaby, British Columbia, V5G 4W8, Canada Actual Inventor(s): Erwin H.
    [Show full text]
  • Thi Na Utaliblat in Un Minune Talk
    THI NA UTALIBLATUS010064900B2 IN UN MINUNE TALK (12 ) United States Patent ( 10 ) Patent No. : US 10 , 064 ,900 B2 Von Maltzahn et al . ( 45 ) Date of Patent: * Sep . 4 , 2018 ( 54 ) METHODS OF POPULATING A (51 ) Int. CI. GASTROINTESTINAL TRACT A61K 35 / 741 (2015 . 01 ) A61K 9 / 00 ( 2006 .01 ) (71 ) Applicant: Seres Therapeutics, Inc. , Cambridge , (Continued ) MA (US ) (52 ) U . S . CI. CPC .. A61K 35 / 741 ( 2013 .01 ) ; A61K 9 /0053 ( 72 ) Inventors : Geoffrey Von Maltzahn , Boston , MA ( 2013. 01 ); A61K 9 /48 ( 2013 . 01 ) ; (US ) ; Matthew R . Henn , Somerville , (Continued ) MA (US ) ; David N . Cook , Brooklyn , (58 ) Field of Classification Search NY (US ) ; David Arthur Berry , None Brookline, MA (US ) ; Noubar B . See application file for complete search history . Afeyan , Lexington , MA (US ) ; Brian Goodman , Boston , MA (US ) ; ( 56 ) References Cited Mary - Jane Lombardo McKenzie , Arlington , MA (US ); Marin Vulic , U . S . PATENT DOCUMENTS Boston , MA (US ) 3 ,009 ,864 A 11/ 1961 Gordon - Aldterton et al. 3 ,228 ,838 A 1 / 1966 Rinfret (73 ) Assignee : Seres Therapeutics , Inc ., Cambridge , ( Continued ) MA (US ) FOREIGN PATENT DOCUMENTS ( * ) Notice : Subject to any disclaimer , the term of this patent is extended or adjusted under 35 CN 102131928 A 7 /2011 EA 006847 B1 4 / 2006 U .S . C . 154 (b ) by 0 days. (Continued ) This patent is subject to a terminal dis claimer. OTHER PUBLICATIONS ( 21) Appl . No. : 14 / 765 , 810 Aas, J ., Gessert, C . E ., and Bakken , J. S . ( 2003) . Recurrent Clostridium difficile colitis : case series involving 18 patients treated ( 22 ) PCT Filed : Feb . 4 , 2014 with donor stool administered via a nasogastric tube .
    [Show full text]