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    2617 results match your criteria Werner Syndrome

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    Progerin impairs vascular smooth muscle cell growth via the DNA damage response pathway.
    Oncotarget 2017 Mar 7. Epub 2017 Mar 7.
    Department of Cardiovascular Biology and Medicine, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
    Mutations of the lamin A gene cause various premature aging syndromes, including Hutchinson-Gilford progeria syndrome (HGPS) and atypical Werner syndrome. In HGPS (but not atypical Werner syndrome), extensive loss of vascular smooth muscle cells leads to myocardial infarction with premature death. The underlying mechanisms how single gene mutations can cause various phenotypes are largely unknown. Read More

    [Hereditary bone tumors].
    Pathologe 2017 Apr 18. Epub 2017 Apr 18.
    Institut für Pathologie, Knochentumor-Referenzzentrum, Universitätsspital Basel, Schönbeinstrasse 40, 4031, Basel, Schweiz.
    Hereditary bone tumors are rare and result from mutations affecting cell cycle regulation (e.g. retinoblastoma syndrome/RB1 and Li-Fraumeni syndrome/TP53, Gardner syndrome/APC), energy metabolism (enchondromatosis/IDH1/2), complex signaling cascades (multiple hereditary exostoses/EXT1/2) and DNA integrity (Rothmund-Thomson/RECQL4, Werner/WRN and Bloom syndromes/BLM). Read More

    Auditory processing following infantile spasms: An event-related potential study.
    Epilepsia 2017 Apr 12. Epub 2017 Apr 12.
    Young Epilepsy, Surrey, United Kingdom.
    Objectives: To investigate acoustic auditory processing in patients with recent infantile spasms (IS).

    Methods: Patients (n = 22; 12 female; median age 8 months; range 5-11 months) had normal preceding development, brain magnetic resonance imaging (MRI), and neurometabolic testing (West syndrome of unknown cause, uWS). Controls were healthy babies (n = 22; 11 female; median age 6 months; range 3-12 months). Read More

    Rare copy number variants in patients with congenital conotruncal heart defects.
    Birth Defects Res 2017 Mar 13;109(4):271-295. Epub 2017 Feb 13.
    Division of Cardiology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
    Background: Previous studies using different cardiac phenotypes, technologies and designs suggest a burden of large, rare or de novo copy number variants (CNVs) in subjects with congenital heart defects. We sought to identify disease-related CNVs, candidate genes, and functional pathways in a large number of cases with conotruncal and related defects that carried no known genetic syndrome.

    Methods: Cases and control samples were divided into two cohorts and genotyped to assess each subject's CNV content. Read More

    Recent Trends in WRN Gene Mutation Patterns in Individuals with Werner Syndrome.
    J Am Geriatr Soc 2017 Apr 10. Epub 2017 Apr 10.
    Department of Clinical Cell Biology and Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan.
    Objectives: To determine recent trends in mutation patterns in the WRN gene, which cause Werner syndrome (WS), a rare, inheritable progeroid syndrome in Japan.

    Design: Retrospective cohort.

    Setting: Longitudinal survey of WS and literature search for case reports. Read More

    [A Familial Non Medullary Thyroid Carcinoma (FNMTC) : a clinical and genetic update].
    Rev Med Liege 2016 Dec;71(12):557-561
    Service d'Endocrinologie, CHU de Liège, Site du Sart Tilman, Liège, Belgique.
    The syndrome of Familial Non Medullary Thyroid Carcinoma (FNMTC) includes two or more patients with an isolated non-medullary thyroid cancer (papillary, follicular, anaplastic) within the same family. To diagnose FNMTC, the clinician must exclude a syndromic presentation such as the syndromes of Cowden, Gardner or Werner, and the Carney Complex. Up to now, a hundred families with FNMTC have been genetically studied, including forms with (Ch19p13. Read More

    Accelerated epigenetic aging in Werner syndrome.
    Aging (Albany NY) 2017 Apr 4. Epub 2017 Apr 4.
    Department of Human Genetics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA.
    Individuals suffering from Werner syndrome (WS) exhibit many clinical signs of accelerated aging. While the underlying constitutional mutation leads to accelerated rates of DNA damage, it is not yet known whether WS is also associated with an increased epigenetic age according to a DNA methylation based biomarker of aging (the "Epigenetic Clock"). Using whole blood methylation data from 18 WS cases and 18 age matched controls, we find that WS is associated with increased extrinsic epigenetic age acceleration (p=0. Read More

    Are "normal hips" being labeled as femoroacetabular impingement due to EE angle?
    Medicine (Baltimore) 2017 Mar;96(13):e6410
    aDepartment of Sports Medicine and Rehabilitation, Peking University Shenzhen Hospital bNanshan Maternity & Child Healthcare Hospital of Shenzhen, Shenzhen, China.
    Gluteal muscle contracture (GMC) is a clinical syndrome characterized by gait abnormality and limb dysfunction, as well as secondary deformities of pelvis and femur. Femoroacetabular impingement (FAI) typically could be diagnosed on the basis of computed tomography (CT) such as the equatorial-edge angle (EE angle), but it did not work well in GMC patients. In this study, we retrospected all image data and found small EE angles in GMCs, which meant retroverted acetabulum; however, none of them showed no symptoms and signs of FAI. Read More

    Locally advanced adenocarcinoma of the cervix on uterus didelphys: a case report.
    J Contemp Brachytherapy 2017 Feb 31;9(1):71-76. Epub 2017 Jan 31.
    Department of Radiotherapy, Oscar Lambret Comprehensive Cancer Center, Lille, France.
    In November 2013, a woman with Herlyn-Werner-Wunderlich (HWW) syndrome was diagnosed with a locally advanced left cervical adenocarcinoma. The patient's malformation consisted of two uteri with two cervixes, a obstructed vagina, and a left renal agenesis. Classification FIGO: stage IIIa because of infiltration of the inferior third of the vagina wall. Read More

    IMMUNE RECONSTITUTION INFLAMMATORY SYNDROME CAUSING PROGRESSIVE OPTIC NERVE EDEMA IN CRYPTOCOCCAL MENINGITIS.
    Retin Cases Brief Rep 2017 Mar 22. Epub 2017 Mar 22.
    *Department of Ophthalmology, Tufts New England Eye Center, Boston, Massachusetts; †Neuro-Ophthalmology Service, Department of Ophthalmology, Tufts New England Eye Center, Boston, Massachusetts; and ‡Retina Service, Department of Ophthalmology, Tufts New England Eye Center, Boston, Massachusetts.
    Purpose: To report an human immunodeficiency virus-positive patient undergoing therapy for cryptococcal meningitis who developed progressive optic disc edema that was steroid responsive.

    Methods: Observational case report.

    Results: One month after commencing antifungal treatment for cryptococcal meningitis, the patient developed bilateral, progressive, recurrent optic disc edema with subretinal fluid that coincided with initiation of highly active antiretroviral therapy and recovery of CD4 cell counts. Read More

    MRI in the evaluation of obstructive reproductive tract anomalies in paediatric patients.
    Clin Radiol 2017 Mar 7. Epub 2017 Mar 7.
    Department of Radiology, West China Second University Hospital, Sichuan University, Sichuan, China.
    Aim: To outline the anatomical variations of obstructive reproductive tract anomalies (ORTA) using magnetic resonance imaging (MRI) and its role in preoperative evaluation.

    Materials And Methods: MRI and treatment of 21 paediatric patients with ORTA were reviewed and analysed. MRI findings were correlated with ultrasound and surgical findings. Read More

    Homozygosity for the WRN Helicase-Inactivating Variant, R834C, does not confer a Werner syndrome clinical phenotype.
    Sci Rep 2017 Mar 9;7:44081. Epub 2017 Mar 9.
    INMEGEN, National Institute of Genomic Medicine, Periferico Sur No.4809, Col. Arenal Tepepan, Del. Tlalpan Mèxico, D.F, C.P. 14610, Mexico.
    Loss-of-function mutations in the WRN helicase gene cause Werner syndrome- a progeroid syndrome with an elevated risk of cancer and other age-associated diseases. Large numbers of single nucleotide polymorphisms have been identified in WRN. We report here the organismal, cellular, and molecular phenotypes of variant rs3087425 (c. Read More

    Single-molecule studies reveal reciprocating of WRN helicase core along ssDNA during DNA unwinding.
    Sci Rep 2017 Mar 7;7:43954. Epub 2017 Mar 7.
    College of Life Sciences, Northwest A&F University, Yangling 712100, China.
    Werner syndrome is caused by mutations in the WRN gene encoding WRN helicase. A knowledge of WRN helicase's DNA unwinding mechanism in vitro is helpful for predicting its behaviors in vivo, and then understanding their biological functions. In the present study, for deeply understanding the DNA unwinding mechanism of WRN, we comprehensively characterized the DNA unwinding properties of chicken WRN helicase core in details, by taking advantages of single-molecule fluorescence resonance energy transfer (smFRET) method. Read More

    Pyogenic arthritis, pyoderma gangrenosum, and acne (PAPA) syndrome: differential diagnosis of septic arthritis by regular detection of exceedingly high synovial cell counts.
    Infection 2017 Mar 1. Epub 2017 Mar 1.
    Allgemeinmedizin und Sportmedizin Nymphenburg, Nymphenburger Str. 108a, 80636, Munich, Germany.
    Pyogenic arthritis, pyoderma gangrenosum and acne syndrome was diagnosed in a 42-year-old patient, after an unusual persistency of high synovial cell counts had been noticed. Clinical peculiarities and problems with diagnosing septic versus non-septic arthritis are discussed. Read More

    A helical bundle in the N-terminal domain of the BLM helicase mediates dimer and potentially hexamer formation.
    J Biol Chem 2017 Apr 22;292(14):5909-5920. Epub 2017 Feb 22.
    From the College of Life Sciences, Northwest A&F University, Yangling, Shaanxi 712100, China,
    Helicases play a critical role in processes such as replication or recombination by unwinding double-stranded DNA; mutations of these genes can therefore have devastating biological consequences. In humans, mutations in genes of three members of the RecQ family helicases (blm, wrn, and recq4) give rise to three strikingly distinctive clinical phenotypes: Bloom syndrome, Werner syndrome, and Rothmund-Thomson syndrome, respectively. However, the molecular basis for these varying phenotypic outcomes is unclear, in part because a full mechanistic description of helicase activity is lacking. Read More

    Case Report: A Rare Cause of Complicated Urinary Tract Infection in a Woman with Herlyn-Werner-Wunderlich Syndrome.
    Iran Red Crescent Med J 2016 Nov 30;18(11):e40267. Epub 2016 Oct 30.
    MD, Division of Nephrology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; School of Medicine, China Medical University, Taichung, Taiwan; Department of Life Science, Tunghai University, Taichung, Taiwan.
    Introduction: Urinary tract infection is a common disease in the general population. However, in patients with frequent urinary tract infection, it is important to determine any treatable cause to avoid recurrence.

    Case Presentation: Herlyn-Werner-Wunderlich syndrome or OHVIRA syndrome is a very rare congenital anomaly with uterus didelphys, obstructed hemivagina, and ipsilateral renal agenesis. Read More

    WRN is recruited to damaged telomeres via its RQC domain and tankyrase1-mediated poly-ADP-ribosylation of TRF1.
    Nucleic Acids Res 2017 Apr;45(7):3844-3859
    University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, 5117 Centre Avenue, Pittsburgh, PA 15213, USA.
    Werner syndrome (WS) is a progeroid-like syndrome caused by WRN gene mutations. WS cells exhibit shorter telomere length compared to normal cells, but it is not fully understood how WRN deficiency leads directly to telomere dysfunction. By generating localized telomere-specific DNA damage in a real-time fashion and a dose-dependent manner, we found that the damage response of WRN at telomeres relies on its RQC domain, which is different from the canonical damage response at genomic sites via its HRDC domain. Read More

    Cognitive deficit in hippocampal-dependent tasks in Werner syndrome mouse model.
    Behav Brain Res 2017 Apr 21;323:68-77. Epub 2017 Jan 21.
    Université de Toulouse, France; Centre de Recherches sur la Cognition Animale (CRCA), Centre de Biologie Intégrative (CBI), CNRS, UPS,118 route de Narbonne, F-31062 Toulouse, Cedex 9, France. Electronic address:
    Mammalian aging is often characterized by metabolic disturbances, cognitive declines and DNA repairs deficiency, but the underlying molecular mechanisms are still not well understood. Alterations in DNA repair can significantly exacerbate aging. Mammalian neuronal cells which accumulate unrepaired DNA damage over time could potentially lead to brain functions disorders. Read More

    The role of WRNIP1 in genome maintenance.
    Cell Cycle 2017 Mar 24;16(6):515-521. Epub 2017 Jan 24.
    a Molecular Cell Biology Laboratory , Research Institute of Pharmaceutical Sciences, Faculty of Pharmacy, Musashino University , Nishitokyo-shi Tokyo , Japan.
    WRNIP1 interacts with WRN helicase, which is defective in the premature aging disease Werner syndrome. WRNIP1 belongs to the AAA+ ATPase family and is conserved from Escherichia coli to human. The protein contains an ubiquitin-binding zinc finger (UBZ) domain at the N terminus and an ATPase domain in the middle region. Read More

    Is There an Association Between Hemoglobin A1C and Deep Postoperative Infection After TKA?
    Clin Orthop Relat Res 2017 Jan 23. Epub 2017 Jan 23.
    Department of Orthopaedic Surgery, University of Virginia Health System, PO Box 800159 HSC, Charlottesville, VA, 22908, USA.
    Background: Despite substantial research into the use of glycemic markers to stratify infection risk in patients with diabetes mellitus, there is little evidence to support a perioperative hemoglobin A1c (HbA1c) level associated with an increased risk of deep postoperative infection after TKA.

    Questions/purposes: (1) Is there an association between perioperative HbA1c level in patients with diabetes and deep postoperative infection after primary TKA? (2) Is the perioperative HbA1c level in patients with diabetes a useful test as an independent predictor for postoperative infection after TKA?

    Methods: We queried the PearlDiver Patient Records Database Humana dataset for patients who underwent primary TKA. This is a for-fee insurance patient-records database that contains records for more than 20 million patients with orthopaedic diagnoses from 2007 to the second quarter of 2015. Read More

    Risk factors for revision surgery following isolated ulnar nerve release at the cubital tunnel: a study of 25,977 cases.
    J Shoulder Elbow Surg 2017 Apr 13;26(4):710-715. Epub 2017 Jan 13.
    Department of Orthopedic Surgery, University of Virginia School of Medicine, Charlottesville, VA, USA. Electronic address:
    Background: The literature investigating risk factors for failure after decompression of the ulnar nerve at the elbow (cubital tunnel release [CuTR]) is limited. The purpose of this study was to identify risk factors for failure of isolated CuTR, defined as progression to subsequent ipsilateral revision surgery.

    Methods: The 100% Medicare Standard Analytic Files from 2005 to 2012 were queried for patients undergoing CuTR. Read More

    Transcatheter aortic valve implantation leads to a restoration of von Willebrand factor (VWF) abnormalities in patients with severe aortic stenosis - Incidence and relevance of clinical and subclinical VWF dysfunction in patients undergoing transfemoral TAVI.
    Thromb Res 2017 Mar 7;151:23-28. Epub 2017 Jan 7.
    Med. Klinik und Poliklinik II, Universitätsklinikum Bonn, Bonn, Germany. Electronic address:
    Background: In this study, we sought to analyze the incidence and relevance of von Willebrand factor (VWF) abnormalities in patients undergoing transcatheter aortic valve implantation (TAVI), especially on perioperative bleeding. Furthermore, we hypothesized that, similar to aortic valve surgery, TAVI results in a restoration of VWF abnormalities.

    Methods And Results: We performed a prospective analysis of periinterventional VWF parameters in 74 patients (80±7years, female in 37. Read More

    Neuroimaging findings of congenital Zika virus infection: a pictorial essay.
    Jpn J Radiol 2017 Mar 10;35(3):89-94. Epub 2017 Jan 10.
    Department of Obstetrics, Paulista School of Medicine, Federal University of São Paulo (EPM-UNIFESP), São Paulo, SP, Brazil.
    Zika virus (ZIKV) is a mosquito-borne arbovirus from the Flaviviridae family. It had caused several epidemics since its discovery in 1947, but there was no significant attention to this virus until the recent outbreak in Brazil in 2015. The main concern is the causal relationship between prenatal ZIKV infection and congenital microcephaly, which has been confirmed recently. Read More

    Residues in the RecQ C-terminal Domain of the Human Werner Syndrome Helicase Are Involved in Unwinding G-quadruplex DNA.
    J Biol Chem 2017 Feb 9;292(8):3154-3163. Epub 2017 Jan 9.
    From the Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205-7199 and
    The structural and biophysical properties typically associated with G-quadruplex (G4) structures render them a significant block for DNA replication, which must be overcome for cell division to occur. The Werner syndrome protein (WRN) is a RecQ family helicase that has been implicated in the efficient processing of G4 DNA structures. The aim of this study was to identify the residues of WRN involved in the binding and ATPase-driven unwinding of G4 DNA. Read More

    Genetic variation in WRN and ischemic stroke: General population studies and meta-analyses.
    Exp Gerontol 2017 Mar 4;89:69-77. Epub 2017 Jan 4.
    Department of Clinical Biochemistry, Rigshospitalet, Blegdamsvej 9, DK-2100 Copenhagen, Denmark; The Copenhagen General Population Study, Herlev and Gentofte Hospital, Herlev Ringvej 75, DK-2730 Herlev, Denmark; The Copenhagen City Heart Study, Frederiksberg Hospital, Nordre Fasanvej 57, DK-2000 Frederiksberg, Denmark; Copenhagen University Hospitals and Faculty of Health and Medical Sciences, University of Copenhagen, Denmark. Electronic address:
    Background: Werner syndrome, a premature genetic aging syndrome, shares many clinical features reminiscent of normal physiological aging, and ischemic vascular disease is a frequent cause of death. We tested the hypothesis that genetic variation in the WRN gene was associated with risk of ischemic vascular disease in the general population.

    Methods: We included 58,284 participants from two general population cohorts, the Copenhagen City Heart Study (CCHS) and the Copenhagen General Population Study (CGPS). Read More

    The Herlyn-Werner-Wunderlich Syndrome - A Case Report with Radiological Review.
    Pol J Radiol 2016 24;81:395-400. Epub 2016 Aug 24.
    Department of Radiology, Dr. DY Patil Medical College & Research Center, Pimpri, Pune, Maharashtra, India.
    Background: HWW syndrome is a very rare congenital anomaly of urogenital tract involving Mullerian ducts and mesonephric ducts. It is characterised by a triad of symptoms - uterus didelphys, obstructed hemivagina and ipsilateral renal agenesis. It can be classified based on a completely or incompletely obstructed hemivagina. Read More

    Long-term health-related quality of life and psychological adjustment in children after haemolytic-uraemic syndrome.
    Pediatr Nephrol 2017 May 23;32(5):869-878. Epub 2016 Dec 23.
    Paediatric Nephrology Unit, University Children's Hospital Zurich, Steinwiesstrasse 75, CH-8032, Zurich, Switzerland.
    Background: In children after haemolytic-uraemic syndrome (HUS), little is known about long-term health-related quality of life (HRQoL) and psychological adjustment as defined by behavioural problems, depressive symptoms and post-traumatic stress symptoms.

    Methods: Sixty-two paediatric patients with a history of HUS were included in this study. Medical data of the acute HUS episode were retrieved retrospectively from hospital records. Read More

    Anti-histone Properties of C1 Esterase Inhibitor Protect Against Lung Injury.
    Am J Respir Crit Care Med 2016 Dec 22. Epub 2016 Dec 22.
    University of Giessen Lung Center, Department of Internal Medicine, Pneumology and Intensive Care Medicine , Klinikstrasse 36 , Giessen, Hesse, Germany , 35392 ;
    Rationale: Acute respiratory distress syndrome (ARDS) is characterized by alveolar epithelial cell injury, edema formation, and intraalveolar contact phase activation.

    Objectives: To explore whether C1 esterase inhibitor (C1INH), an endogenous inhibitor of the contact phase, may protect from lung injury in vivo and to decipher the possible underlying mechanisms mediating protection.

    Methods: The ability of C1INH to control the inflammatory processes was studied in vitro and in vivo. Read More

    Pyometra and Pregnancy with Herlyn-Werner-Wunderlich Syndrome.
    Rev Bras Ginecol Obstet 2016 Dec 21;38(12):623-628. Epub 2016 Dec 21.
    Department of Obstetrics and Gynecology and Department of Maternal Fetal Medicine, Hospital Dr. José de Almeida, Lisbon, Portugal.
    We describe a Herlyn-Werner-Wunderlich syndrome (HWWS) patient with previous history of infertility who got pregnant without treatment and presented a pyometra in the contralateral uterus throughout the gestational period, despite multiple antibiotic treatments. Due to the uterus' congenital anomaly and the possibility of ascending infection with subsequent abortion, this pregnancy was classified as high-risk. We believe that the partial horizontal septum in the vagina may have contributed to the closure of the gravid uterus cervix, thus ensuring that the pregnancy came to term, with an uneventful vaginal delivery. Read More

    Radiographic presentation of musculoskeletal involvement in Werner syndrome (adult progeria).
    Diagn Interv Imaging 2016 Dec 5. Epub 2016 Dec 5.
    Service central de radiologie et imagerie médicale, Hôtel Dieu, CHU de Nantes, 1, place Alexis-Ricordeau, 44093 Nantes cedex 1, France.
    Werner syndrome (i.e., adult progeria) is a rare autosomal recessive disorder caused by mutations of the WRN gene, which is characterized by the premature appearance of features associated with normal aging and cancer predisposition. Read More

    WRN regulates pathway choice between classical and alternative non-homologous end joining.
    Nat Commun 2016 Dec 6;7:13785. Epub 2016 Dec 6.
    Laboratory of Molecular Gerontology, Biomedical Research Center, 251 Bayview Boulevard, National Institute on Aging, NIH, Baltimore, Maryland 21224, USA.
    Werner syndrome (WS) is an accelerated ageing disorder with genomic instability caused by WRN protein deficiency. Many features seen in WS can be explained by the diverse functions of WRN in DNA metabolism. However, the origin of the large genomic deletions and telomere fusions are not yet understood. Read More

    Different non-synonymous polymorphisms modulate the interaction of the WRN protein to its protein partners and its enzymatic activities.
    Oncotarget 2016 Dec;7(52):85680-85696
    Centre de Recherche du CHU de Québec, Pavillon CHUL Université Laval, Faculté de Médecine, Québec, Canada.
    Werner syndrome (WS) is characterized by the premature onset of several age-associated pathologies including cancer. The protein defective in WS patients (WRN) is a helicase/exonuclease involved in DNA replication and repair. Here, we present the results of a large-scale proteome analysis that has been undertaken to determine protein partners of different polymorphic WRN proteins found with relatively high prevalence in the human population. Read More

    Human RECQ Helicase Pathogenic Variants, Population Variation and "Missing" Diseases.
    Hum Mutat 2017 Feb 9;38(2):193-203. Epub 2016 Dec 9.
    Department of Genome Sciences, University of Washington, Seattle, Washington.
    Heritable loss of function mutations in the human RECQ helicase genes BLM, WRN, and RECQL4 cause Bloom, Werner, and Rothmund-Thomson syndromes, cancer predispositions with additional developmental or progeroid features. In order to better understand RECQ pathogenic and population variation, we systematically analyzed genetic variation in all five human RECQ helicase genes. A total of 3,741 unique base pair-level variants were identified, across 17,605 potential mutation sites. Read More

    The Werner Syndrome Helicase Coordinates Sequential Strand Displacement and FEN1-Mediated Flap Cleavage during Polymerase δ Elongation.
    Mol Cell Biol 2017 Feb 19;37(3). Epub 2017 Jan 19.
    Department of Molecular Microbiology and Immunology, Institute for Genetic Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA
    The Werner syndrome protein (WRN) suppresses the loss of telomeres replicated by lagging-strand synthesis by a yet to be defined mechanism. Here, we show that whereas either WRN or the Bloom syndrome helicase (BLM) stimulates DNA polymerase δ progression across telomeric G-rich repeats, only WRN promotes sequential strand displacement synthesis and FEN1 cleavage, a critical step in Okazaki fragment maturation, at these sequences. Helicase activity, as well as the conserved winged-helix (WH) motif and the helicase and RNase D C-terminal (HRDC) domain play important but distinct roles in this process. Read More

    WRN-targeted therapy using inhibitors NSC 19630 and NSC 617145 induce apoptosis in HTLV-1-transformed adult T-cell leukemia cells.
    J Hematol Oncol 2016 Nov 9;9(1):121. Epub 2016 Nov 9.
    Department of Pathology and Laboratory Medicine, Center for Viral Oncology, University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, KS, 66160, USA.
    Background: Human T-cell leukemia virus type 1 (HTLV-1) infection is associated with adult T-cell leukemia/lymphoma (ATLL), a lymphoproliferative malignancy with a dismal prognosis and limited therapeutic options. Recent evidence shows that HTLV-1-transformed cells present defects in both DNA replication and DNA repair, suggesting that these cells might be particularly sensitive to treatment with a small helicase inhibitor. Because the "Werner syndrome ATP-dependent helicase" encoded by the WRN gene plays important roles in both cellular proliferation and DNA repair, we hypothesized that inhibition of WRN activity could be used as a new strategy to target ATLL cells. Read More

    Predictors of survival in critically ill patients with acute respiratory distress syndrome (ARDS): an observational study.
    BMC Anesthesiol 2016 Nov 8;16(1):108. Epub 2016 Nov 8.
    Department of Anesthesiology and Intensive Care Medicine, Charité - Universitätsmedizin Berlin, Campus Virchow-Klinikum / Campus Charité Mitte, Augustenburger Platz 1, D-13353, Berlin, Germany.
    Background: Currently there is no ARDS definition or classification system that allows optimal prediction of mortality in ARDS patients. This study aimed to examine the predictive values of the AECC and Berlin definitions, as well as clinical and respiratory parameters obtained at onset of ARDS and in the course of the first seven consecutive days.

    Methods: The observational study was conducted at a 14-bed intensive care unit specialized on treatment of ARDS. Read More

    Identification of an AR Mutation-Negative Class of Androgen Insensitivity by Determining Endogenous AR Activity.
    J Clin Endocrinol Metab 2016 Nov 1;101(11):4468-4477. Epub 2016 Sep 1.
    Department of Pediatrics (N.C.H., M.U., J.D., P.R., A.E.K., P.-M.H.), Division of Pediatric Endocrinology and Diabetes, and Institute of Human Genetics (L.W., R.S., O.A.), Christian-Albrechts-University Kiel and University Hospital Schleswig-Holstein, Campus Kiel, Schwanenweg 20, 24105 Kiel, Germany; Rheinische Friedrich-Wilhelms-Universität Bonn, Department of Medicine III (H.U.S., G.W.), Institute for Biochemistry and Molecular Biology, Nussallee 11, 53115 Bonn, Germany; Department of Pediatrics (O.H., R.W.), Division of Experimental Pediatric Endocrinology, University of Luebeck, 23538 Luebeck, Germany; Department of Pediatrics (S.L.S.D.), Division of Pediatric Endocrinology, Sophia Childreńs Hospital, Erasmus Medical Center, 's-Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands; Department of Pediatric Endocrinology (Medical Center), Ghent University Hospital, Ghent University, 9000 Ghent, Belgium; Department of Pediatrics (I.A.H.), University of Cambridge, Cambridge CB2 0QQ, United Kingdom; Pediatric Endocrinology Research Unit (L.A.), Vall d'Hebron Institut de Recerca, Hospital Universitari Vall d'Hebron, Centro de Investigación Biomédica en Red Enfermedades Raras, Instituto de Salud Carlos III, Passeig Vall d'Hebron 119, 08035 Barcelona, Spain; Developmental Endocrinology Research Group (S.F.A.), School of Medicine, University of Glasgow, Yorkhill Glasgow G3 8SJ, United Kingdom; Kinderklinik (D.D.), Klinikum Augsburg, 86156 Augsburg, Germany; Klinikum Esslingen (E.M.-R.), 73730 Esslingen, Germany; Department of Pediatrics (T.R.), Division of Pediatric Endocrinology, Diabetes, and Nutrition, University Witten/Herdecke, 45711 Datteln, Germany; Hypospadiezentrum (A.T.H.), 63500 Seligenstadt, Germany; Gemeinschaftspraxis für Kinderchirurgie (A.K.E.), 24119 Kronshagen, Germany; Urologische Gemeinschaftspraxis (C.v.d.H), and UROLOGIE Zentrum Kiel (C.S.), 24103 Kiel, Germany; and Institute of Human Genetics (R.S.), University of Ulm and University Hospital of Ulm, 89081 Ulm, Germany.
    Context: Only approximately 85% of patients with a clinical diagnosis complete androgen insensitivity syndrome and less than 30% with partial androgen insensitivity syndrome can be explained by inactivating mutations in the androgen receptor (AR) gene.

    Objective: The objective of the study was to clarify this discrepancy by in vitro determination of AR transcriptional activity in individuals with disorders of sex development (DSD) and male controls.

    Design: Quantification of DHT-dependent transcriptional induction of the AR target gene apolipoprotein D (APOD) in cultured genital fibroblasts (GFs) (APOD assay) and next-generation sequencing of the complete coding and noncoding AR locus. Read More

    Neurodegeneration in accelerated aging.
    Dan Med J 2016 Nov;63(11)
    The growing proportion of elderly people represents an increasing economic burden, not least because of age-associated diseases that pose a significant cost to the health service. Finding possible interventions to age-associated disorders therefore have wide ranging implications. A number of genetically defined accelerated aging diseases have been characterized that can aid in our understanding of aging. Read More

    Familial non-medullary thyroid cancer: unraveling the genetic maze.
    Endocr Relat Cancer 2016 Dec 2;23(12):R577-R595. Epub 2016 Nov 2.
    Cancer Genetics ServiceDivision of Medical Oncology, National Cancer Centre, Singapore, Singapore
    Familial non-medullary thyroid cancer (FNMTC) constitutes 3-9% of all thyroid cancers. Out of all FNMTC cases, only 5% in the syndromic form has well-studied driver germline mutations. These associated syndromes include Cowden syndrome, familial adenomatous polyposis, Gardner syndrome, Carney complex type 1, Werner syndrome and DICER1 syndrome. Read More

    Laparoscopic Hemi-hysterectomy and Trachelectomy in a Case of Herlyn-Werner-Wunderlich Syndrome.
    Surg Technol Int 2016 Oct;XXIX:181-184
    Department of Obstetrics and Gynecology, University of South Florida Morsani College of Medicine, Tampa, Florida.
    Background: Herlyn-Werner-Wunderlich Syndrome (HWWS) is a rare Müllerian anomaly characterized by uterus didelphys coexisting with an obstructed hemivagina and ipsilateral renal agenesis.

    Case: A 13-year-old female presented one-year after menarche with severe dysmenorrhea and a right-sided pelvic mass. Imaging identified a right uterus with hematometra, hematocolpos, absent right kidney, normal left kidney, ureter, left uterus, and vagina compressed to the left by right hematocolpos. Read More

    Genetic risk score based on the lifetime prevalence of femoral fracture in 924 consecutive autopsies of Japanese males.
    J Bone Miner Metab 2016 Nov 13;34(6):685-691. Epub 2015 Oct 13.
    Local Independent Administrative Agency, Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology, Tokyo, Japan.
    A genetic risk score (GRS) was developed for predicting fracture risk based on lifetime prevalence of femoral fractures in 924 consecutive autopsies of Japanese males. A total of 922 non-synonymous single nucleotide polymorphisms (SNPs) located in 62 osteoporosis susceptibility genes were genotyped and evaluated for their association with the prevalence of femoral fracture in autopsy cases. GRS values were calculated as the sum of risk allele counts (unweighted GRS) or the sum of weighted scores estimated from logistic regression coefficients (weighted GRS). Read More

    Metabolic Syndrome After HIV Acquisition in South African Women.
    J Acquir Immune Defic Syndr 2016 Dec;73(4):438-445
    *Centre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu-Natal, Durban, South Africa; †Division of Infectious Disease, Department of Medicine, Columbia University, New York, NY; ‡Department of Medical Microbiology, University of KwaZulu-Natal, Durban, South Africa; §National Health Laboratory Service, Durban, South Africa; Divisions of ‖Medical Virology, ¶Immunology, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, South Africa; and #Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY.
    Background: Noncommunicable diseases are common among chronically infected patients with HIV in the developed world, but little is known about these conditions in African cohorts. We assessed the epidemiology of metabolic syndrome among young South African women during the first 3 years after HIV acquisition.

    Methods: A total of 160 women were followed prospectively in the CAPRISA 002 Acute Infection study. Read More

    Case of sarcomatoid carcinoma occurring in a patient with Werner syndrome.
    J Dermatol 2016 Nov 14;43(11):1362-1364. Epub 2016 Apr 14.
    Department of Dermatology, Federation of National Public Service Personnel Mutual Aid Associations, Hamanomachi Hospital, Fukuoka, Japan.

    The adaptive drop foot stimulator - Multivariable learning control of foot pitch and roll motion in paretic gait.
    Med Eng Phys 2016 Nov 7;38(11):1205-1213. Epub 2016 Jul 7.
    Control Systems Group, Technische Universität Berlin, Germany.
    Many stroke patients suffer from the drop foot syndrome, which is characterized by a limited ability to lift (the lateral and/or medial edge of) the foot and leads to a pathological gait. In this contribution, we consider the treatment of this syndrome via functional electrical stimulation (FES) of the peroneal nerve during the swing phase of the paretic foot. A novel three-electrodes setup allows us to manipulate the recruitment of m. Read More

    Periodontal Ehlers-Danlos Syndrome Is Caused by Mutations in C1R and C1S, which Encode Subcomponents C1r and C1s of Complement.
    Am J Hum Genet 2016 Nov 13;99(5):1005-1014. Epub 2016 Oct 13.
    Division of Human Genetics, Medical University of Innsbruck, Innsbruck 6020, Austria. Electronic address:
    Periodontal Ehlers-Danlos syndrome (pEDS) is an autosomal-dominant disorder characterized by early-onset periodontitis leading to premature loss of teeth, joint hypermobility, and mild skin findings. A locus was mapped to an approximately 5.8 Mb region at 12p13. Read More

    Resuscitation with polymeric plasma substitutes is permissive for systemic inflammatory response syndrome and sepsis in multiply injured patients: a retrospective cohort study.
    Eur J Med Res 2016 Oct 13;21(1):39. Epub 2016 Oct 13.
    Division of Trauma Surgery, University Hospital of Zürich, Rämistrasse 100, 8091, Zurich, Switzerland.
    Objective: Multiple trauma is often accompanied by systemic inflammatory response syndrome (SIRS). The aim of this study was to investigate the impact of polymeric plasma substitutes on the development of SIRS or sepsis.

    Methods: We included 2969 patients aged ≥16 years with an Injury Severity Score (ISS) >16 in this study. Read More

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