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research-article
Author(s):
Harvey J. Alter a ,
Judy A. Mikovits b ,
William M. Switzer c ,
Francis W. Ruscetti d ,
Shyh-Ching Lo e ,
Nancy Klimas f,g ,
Anthony L. Komaroff h ,
Jose G. Montoya i ,
Lucinda Bateman j ,
Susan Levine k ,
Daniel Peterson l ,
Bruce Levin m ,
Maureen R. Hanson n ,
Afia Genfi o ,
Meera Bhat o ,
HaoQiang Zheng c ,
Richard Wang a ,
Bingjie Li e ,
Guo-Chiuan Hung e ,
Li Ling Lee n ,
Stephen Sameroff o ,
Walid Heneine c ,
John Coffin p ,
Mady Hornig o ,
W. Ian Lipkin o
Publication date (Electronic): 18 September 2012
Journal: mBio
Publisher: American Society of Microbiology
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The disabling disorder known as chronic fatigue syndrome or myalgic encephalomyelitis (CFS/ME) has been linked in two independent studies to infection with xenotropic murine leukemia virus-related virus (XMRV) and polytropic murine leukemia virus (pMLV). Although the associations were not confirmed in subsequent studies by other investigators, patients continue to question the consensus of the scientific community in rejecting the validity of the association. Here we report blinded analysis of peripheral blood from a rigorously characterized, geographically diverse population of 147 patients with CFS/ME and 146 healthy subjects by the investigators describing the original association. This analysis reveals no evidence of either XMRV or pMLV infection. Chronic fatigue syndrome/myalgic encephalomyelitis has an estimated prevalence of 42/10,000 in the United States, with annual direct medical costs of $7billion. Here, the original investigators who found XMRV and pMLV (polytropic murine leukemia virus) in blood of subjects with this disorder report that this association is not confirmed in a blinded analysis of samples from rigorously characterized subjects. The increasing frequency with which molecular methods are used for pathogen discovery poses new challenges to public health and support of science. It is imperative that strategies be developed to rapidly and coherently address discoveries so that they can be carried forward for translation to clinical medicine or abandoned to focus resource investment more productively. Our study provides a paradigm for pathogen dediscovery that may be helpful to others working in this field. ABSTRACT
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Most cited references33
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The RAND-36 measure of health-related quality of life.
William Hays, David Morales (2001)
The RAND-36 is perhaps the most widely used health-related quality of life (HRQoL) survey instrument in the world today. It is comprised of 36 items that assess eight health concepts: physical functioning, role limitations caused by physical health problems, role limitations caused by emotional problems, social functioning, emotional well-being, energy/fatigue, pain, and general health perceptions. Physical and mental health summary scores are also derived from the eight RAND-36 scales. This paper provides example applications of the RAND-36 cross-sectionally and longitudinally, provides information on what a clinically important difference is for the RAND-36 scales, and provides guidance for summarizing the RAND-36 in a single number. The paper also discusses the availability of the RAND-36 in multiple languages and summarizes changes that are incorporated in the latest version of the survey.
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Detection of an infectious retrovirus, XMRV, in blood cells of patients with chronic fatigue syndrome.
Vincent Lombardi, Francis Ruscetti, Jaydip Das Gupta … (2009)
Chronic fatigue syndrome (CFS) is a debilitating disease of unknown etiology that is estimated to affect 17 million people worldwide. Studying peripheral blood mononuclear cells (PBMCs) from CFS patients, we identified DNA from a human gammaretrovirus, xenotropic murine leukemia virus-related virus (XMRV), in 68 of 101 patients (67%) as compared to 8 of 218 (3.7%) healthy controls. Cell culture experiments revealed that patient-derived XMRV is infectious and that both cell-associated and cell-free transmission of the virus are possible. Secondary viral infections were established in uninfected primary lymphocytes and indicator cell lines after their exposure to activated PBMCs, B cells, T cells, or plasma derived from CFS patients. These findings raise the possibility that XMRV may be a contributing factor in the pathogenesis of CFS.
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Failure to Detect the Novel Retrovirus XMRV in Chronic Fatigue Syndrome
Otto Erlwein, Steve Kaye, Myra O McClure … (2010)
Background In October 2009 it was reported that 68 of 101 patients with chronic fatigue syndrome (CFS) in the US were infected with a novel gamma retrovirus, xenotropic murine leukaemia virus-related virus (XMRV), a virus previously linked to prostate cancer. This finding, if confirmed, would have a profound effect on the understanding and treatment of an incapacitating disease affecting millions worldwide. We have investigated CFS sufferers in the UK to determine if they are carriers of XMRV. Methodology Patients in our CFS cohort had undergone medical screening to exclude detectable organic illness and met the CDC criteria for CFS. DNA extracted from blood samples of 186 CFS patients were screened for XMRV provirus and for the closely related murine leukaemia virus by nested PCR using specific oligonucleotide primers. To control for the integrity of the DNA, the cellular beta-globin gene was amplified. Negative controls (water) and a positive control (XMRV infectious molecular clone DNA) were included. While the beta-globin gene was amplified in all 186 samples, neither XMRV nor MLV sequences were detected. Conclusion XMRV or MLV sequences were not amplified from DNA originating from CFS patients in the UK. Although we found no evidence that XMRV is associated with CFS in the UK, this may be a result of population differences between North America and Europe regarding the general prevalence of XMRV infection, and might also explain the fact that two US groups found XMRV in prostate cancer tissue, while two European studies did not.
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Author and article information
Journal
Journal ID (nlm-ta): mBio
Journal ID (iso-abbrev): MBio
Journal ID (hwp): mbio
Journal ID (pmc): mbio
Journal ID (publisher-id): mBio
Title: mBio
Publisher: American Society of Microbiology (1752 N St., N.W., Washington, DC )
ISSN (Electronic): 2150-7511
Publication date (Electronic): 18 September 2012
Publication date Collection: Sep-Oct 2012
Volume: 3
Issue: 5
Electronic Location Identifier: e00266-12
Affiliations
Department of Transfusion Medicine, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, Maryland, USA [ a ];
Division of HIV/AIDS Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia, USA [ c ];
Cancer and Inflammation Program, Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA [ d ];
Author notes
Address correspondence to W. Ian Lipkin, wil2001@ 123456columbia.edu .
Article
Publisher ID: mBio00266-12
DOI: 10.1128/mBio.00266-12
PMC ID: 3448165
PubMed ID: 22991430
SO-VID: 15c07639-0ff3-4ce6-9ccf-9c535de26edb
Copyright © Copyright © 2012 Alter et al.
License:
This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported License, which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original author and source are credited.
History
Date received : 1 August 2012
Date accepted : 20 August 2012
Page count
Pages: 7
Categories
Subject: Research Article
Custom metadata
cover-date September/October 2012
ScienceOpen disciplines: Life sciences
Data availability:
ScienceOpen disciplines: Life sciences
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