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  1. Article ; Online: Comparing viral metagenomics methods using a highly multiplexed human viral pathogens reagent.

    Li, Linlin / Deng, Xutao / Mee, Edward T / Collot-Teixeira, Sophie / Anderson, Rob / Schepelmann, Silke / Minor, Philip D / Delwart, Eric

    Journal of virological methods

    2014  Volume 213, Page(s) 139–146

    Abstract: Unbiased metagenomic sequencing holds significant potential as a diagnostic tool for the simultaneous detection of any previously genetically described viral nucleic acids in clinical samples. Viral genome sequences can also inform on likely phenotypes ... ...

    Abstract Unbiased metagenomic sequencing holds significant potential as a diagnostic tool for the simultaneous detection of any previously genetically described viral nucleic acids in clinical samples. Viral genome sequences can also inform on likely phenotypes including drug susceptibility or neutralization serotypes. In this study, different variables of the laboratory methods often used to generate viral metagenomics libraries were compared for their abilities to detect multiple viruses and generate full genome coverage. A biological reagent consisting of 25 different human RNA and DNA viral pathogens was used to estimate the effect of filtration and nuclease digestion, DNA/RNA extraction methods, pre-amplification and the use of different library preparation kits on the detection of viral nucleic acids. Filtration and nuclease treatment led to slight decreases in the percentage of viral sequence reads and number of viruses detected. For nucleic acid extractions silica spin columns improved viral sequence recovery relative to magnetic beads and Trizol extraction. Pre-amplification using random RT-PCR while generating more viral sequence reads resulted in detection of fewer viruses, more overlapping sequences, and lower genome coverage. The ScriptSeq library preparation method retrieved more viruses and a greater fraction of their genomes than the TruSeq and Nextera methods. Viral metagenomics sequencing was able to simultaneously detect up to 22 different viruses in the biological reagent analyzed including all those detected by qPCR. Further optimization will be required for the detection of viruses in biologically more complex samples such as tissues, blood, or feces.
    MeSH term(s) Humans ; Indicators and Reagents ; Metagenomics/methods ; Specimen Handling/methods ; Virology/methods ; Virus Diseases/diagnosis ; Virus Diseases/virology ; Viruses/isolation & purification
    Chemical Substances Indicators and Reagents
    Keywords covid19
    Language English
    Publishing date 2014-12-11
    Publishing country Netherlands
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 8013-5
    ISSN 1879-0984 ; 0166-0934
    ISSN (online) 1879-0984
    ISSN 0166-0934
    DOI 10.1016/j.jviromet.2014.12.002
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: CD36 N-terminal cytoplasmic domain is not required for the internalization of oxidized low-density lipoprotein.

    McDermott-Roe, Chris / Martin, Juliette / Collot-Teixeira, Sophie / McGregor, John L

    Bioscience reports

    2008  Volume 28, Issue 3, Page(s) 145–151

    Abstract: The uptake of OxLDLs (oxidized low density lipoproteins) by CD36-expressing macrophages in the arterial intima and the subsequent 'foam cell' formation represents a crucial step in the initiation and development of atherosclerotic plaques. The present ... ...

    Abstract The uptake of OxLDLs (oxidized low density lipoproteins) by CD36-expressing macrophages in the arterial intima and the subsequent 'foam cell' formation represents a crucial step in the initiation and development of atherosclerotic plaques. The present study has addressed the function of the CD36 N-terminal cytoplasmic domain in the binding and internalization of OxLDL. A selection of CD36 N-terminal cytoplasmic domain mutants were generated and stably expressed in HEK-293 (human embryonic kidney) cells. The capacity of three mutants [CD36_C3/7-A (CD36-C3A/C7A), CD36_D4/R5-A (CD36-D4A/R5A) and CD36_nCPD(-) (CD36 lacking the N-terminal cytoplasmic domain)] to bind and endocytose OxLDL was then studied using immunofluorescence microscopy and quantitative fluorimetry. Each of the CD36 constructs was expressed at differing levels at the cell surface, as measured by flow cytometry and Western blotting. Following incubation with DiI (1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate)-OxLDL, cells bearing the CD36_wt (wild-type CD36), CD36_C3/7-A, CD36_D4/R5-A and CD36_nCPD(-) constructs all internalized DiI-OxLDL into endosomal structures, whereas empty-vector-transfected cells failed to do so, indicating that, unlike the C-terminal cytoplasmic domain, the N-terminal cytoplasmic domain is not essential for the endocytosis of OxLDL. In conclusion, the uptake of OxLDL by CD36 is not reliant on the presence of the CD36 N-terminal cytoplasmic domain. However, the N-terminal cytoplasmic domain may conceivably be implicated in the maturation of CD36.
    MeSH term(s) CD36 Antigens/chemistry ; CD36 Antigens/genetics ; CD36 Antigens/physiology ; Carbocyanines/metabolism ; Cell Line ; Endocytosis ; Fluorescent Dyes/metabolism ; Fluorometry ; Humans ; Lipoproteins, LDL/metabolism ; Microscopy, Fluorescence ; Protein Binding ; Protein Interaction Mapping ; Protein Structure, Tertiary ; Recombinant Fusion Proteins/chemistry ; Recombinant Fusion Proteins/physiology
    Chemical Substances CD36 Antigens ; Carbocyanines ; Fluorescent Dyes ; Lipoproteins, LDL ; Recombinant Fusion Proteins ; oxidized low density lipoprotein ; 3,3'-dioctadecylindocarbocyanine (40957-95-7)
    Language English
    Publishing date 2008-06
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 764946-0
    ISSN 1573-4935 ; 0144-8463
    ISSN (online) 1573-4935
    ISSN 0144-8463
    DOI 10.1042/BSR20080045
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Scavenger receptor A and CD36 are implicated in mediating platelet activation induced by oxidized low- density lipoproteins.

    Collot-Teixeira, Sophie / De Lorenzo, Ferrucio / Delorenzo, Ferrucio / McGregor, John L

    Arteriosclerosis, thrombosis, and vascular biology

    2007  Volume 27, Issue 12, Page(s) 2491–2492

    MeSH term(s) Animals ; Blood Platelets/enzymology ; Blood Platelets/immunology ; Blood Platelets/metabolism ; CD36 Antigens/metabolism ; Humans ; Kinetics ; LDL-Receptor Related Proteins ; Lipoproteins, LDL/metabolism ; Mice ; Phenotype ; Phosphorylation ; Platelet Activation ; Receptors, Lipoprotein/metabolism ; Receptors, Lysophosphatidic Acid/metabolism ; Scavenger Receptors, Class A/metabolism ; Signal Transduction ; Thrombosis/blood ; Thrombosis/immunology ; Thrombosis/metabolism ; p38 Mitogen-Activated Protein Kinases/metabolism
    Chemical Substances CD36 Antigens ; LDL-Receptor Related Proteins ; Lipoproteins, LDL ; Receptors, Lipoprotein ; Receptors, Lysophosphatidic Acid ; Scavenger Receptors, Class A ; low density lipoprotein receptor-related protein 8 ; oxidized low density lipoprotein ; p38 Mitogen-Activated Protein Kinases (EC 2.7.11.24)
    Language English
    Publishing date 2007-12
    Publishing country United States
    Document type Editorial ; Research Support, Non-U.S. Gov't ; Comment
    ZDB-ID 1221433-4
    ISSN 1524-4636 ; 1079-5642
    ISSN (online) 1524-4636
    ISSN 1079-5642
    DOI 10.1161/ATVBAHA.107.154864
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Comparing viral metagenomics methods using a highly multiplexed human viral pathogens reagent

    Li, Linlin / Deng, Xutao / Mee, Edward T / Collot-Teixeira, Sophie / Anderson, Rob / Schepelmann, Silke / Minor, Philip D / Delwart, Eric

    Journal of virological methods. 2015 Mar. 01, v. 213

    2015  

    Abstract: Unbiased metagenomic sequencing holds significant potential as a diagnostic tool for the simultaneous detection of any previously genetically described viral nucleic acids in clinical samples. Viral genome sequences can also inform on likely phenotypes ... ...

    Abstract Unbiased metagenomic sequencing holds significant potential as a diagnostic tool for the simultaneous detection of any previously genetically described viral nucleic acids in clinical samples. Viral genome sequences can also inform on likely phenotypes including drug susceptibility or neutralization serotypes. In this study, different variables of the laboratory methods often used to generate viral metagenomics libraries were compared for their abilities to detect multiple viruses and generate full genome coverage. A biological reagent consisting of 25 different human RNA and DNA viral pathogens was used to estimate the effect of filtration and nuclease digestion, DNA/RNA extraction methods, pre-amplification and the use of different library preparation kits on the detection of viral nucleic acids. Filtration and nuclease treatment led to slight decreases in the percentage of viral sequence reads and number of viruses detected. For nucleic acid extractions silica spin columns improved viral sequence recovery relative to magnetic beads and Trizol extraction. Pre-amplification using random RT-PCR while generating more viral sequence reads resulted in detection of fewer viruses, more overlapping sequences, and lower genome coverage. The ScriptSeq library preparation method retrieved more viruses and a greater fraction of their genomes than the TruSeq and Nextera methods. Viral metagenomics sequencing was able to simultaneously detect up to 22 different viruses in the biological reagent analyzed including all those detected by qPCR. Further optimization will be required for the detection of viruses in biologically more complex samples such as tissues, blood, or feces.
    Keywords DNA ; RNA ; blood ; diagnostic techniques ; drugs ; feces ; filtration ; genome ; humans ; magnetism ; metagenomics ; neutralization ; nucleotide sequences ; pathogens ; phenotype ; quantitative polymerase chain reaction ; reverse transcriptase polymerase chain reaction ; serotypes ; silica ; tissues ; viruses ; covid19
    Language English
    Dates of publication 2015-0301
    Size p. 139-146.
    Publishing place Elsevier B.V.
    Document type Article
    ZDB-ID 8013-5
    ISSN 1879-0984 ; 0166-0934
    ISSN (online) 1879-0984
    ISSN 0166-0934
    DOI 10.1016/j.jviromet.2014.12.002
    Database NAL-Catalogue (AGRICOLA)

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  5. Article ; Online: Prevention of atherosclerosis in patients living with HIV.

    De Lorenzo, Ferruccio / Boffito, Marta / Collot-Teixeira, Sophie / Gazzard, Brian / McGregor, John L / Shotliff, Kevin / Xiao, Han

    Vascular health and risk management

    2009  Volume 5, Issue 1, Page(s) 287–300

    Abstract: INVESTIGATIONAL PRODUCT: Rosuvastatin (Crestor; Astra Zeneca).: Active ingredients: Rosuvastatin (5 mg).: Study title: Prevention of Atherosclerosis in Patients Living with HIV.: Phase of study: Phase III.: Aims: PRIMARY AIM: To assess ... ...

    Abstract INVESTIGATIONAL PRODUCT: Rosuvastatin (Crestor; Astra Zeneca).
    Active ingredients: Rosuvastatin (5 mg).
    Study title: Prevention of Atherosclerosis in Patients Living with HIV.
    Phase of study: Phase III.
    Aims: PRIMARY AIM: To assess whether rosuvastatin therapy could slow the progression of the carotid intima-media thickness (C-IMT; as measured by the change in the mean IMT of the near and far walls of the distal common carotid arteries) over 2 years in HIV-infected patients (HIV-IP).
    Secondary aims: To assess whether rosuvastatin therapy could reduce highly sensitive C reactive protein (hs-CRP) inflammatory marker that is increased in HIV-IP.To assess the effect of rosuvastatin therapy on serum lipid levels (total cholesterol [TC], low-density lipoprotein [LDL] cholesterol, high-density lipoprotein [HDL] cholesterol and triglycerides [TG]) and apolipoproteins (APO A1, APO B and APO B/A1).To assess the safety of rosuvastatin in HIV-IP through the evaluation of clinical laboratory analyses (liver function tests and creatine kinase) and adverse events (AEs).
    Study design: Two-year randomized, double-blind, placebo-controlled, parallel group study.
    Planned sample size: 320 HIV-IP.
    Summary of eligibility criteria: HIV-IP who are aged between 30 and 60 years, with a CD4 count. greater than 200 cells/mm(3). Patients must be stable on combination antiretroviral therapy (cART) for at least 12 months and have a 10-year CVD risk of less than 20% (using the Framingham risk score).
    Number of study centers: One.
    Duration of treatment: Two years (5 mg rosuvastatin or placebo once daily).
    Dose and route of administration: Oral rosuvastatin (5 mg) once daily. The incidence of cardiovascular disease (CVD) in HIV-IP is at least three times higher than in the general population and further increases each year with combination anti-retroviral therapy (cART). The carotid atherosclerosis progression rate is 10 times higher in HIV-IP than in uninfected individuals. The aim of this study is to assess whether therapy with 5 mg rosuvastatin could: 1) Slow the progression in the mean IMT of the distal common carotid arteries over two years in HIV-IP.2) Change the concentration in the inflammatory marker--hs-CRP, which is increased in HIV-IP.3) Change the concentrations of TC, LDL cholesterol, HDL cholesterol, TG, apolipoproteins (APO) B, APO A1 and APO B/A1.4) Be administered safely in the study population. Pharmacological intervention with rosuvastatin will be evaluated in a double-blind, placebo-controlled, randomized clinical trial in HIV-IP treated with cART not matching the published selection criteria for lipid-lowering therapy. For the first time, this study will investigate anti-inflammatory and anti-atherogenic effects of a pharmacological lipid-lowering agent in HIV-IP that may lead to the reduction of CVD.
    MeSH term(s) Administration, Oral ; Adult ; Antiretroviral Therapy, Highly Active ; Atherosclerosis/blood ; Atherosclerosis/pathology ; Atherosclerosis/prevention & control ; Atherosclerosis/virology ; Biomarkers/blood ; C-Reactive Protein/metabolism ; Carotid Artery Diseases/blood ; Carotid Artery Diseases/pathology ; Carotid Artery Diseases/prevention & control ; Carotid Artery Diseases/virology ; Disease Progression ; Double-Blind Method ; Fluorobenzenes/administration & dosage ; Fluorobenzenes/adverse effects ; Fluorobenzenes/therapeutic use ; HIV Infections/complications ; HIV Infections/drug therapy ; HIV Infections/virology ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use ; Lipids/blood ; Middle Aged ; Pyrimidines/administration & dosage ; Pyrimidines/adverse effects ; Pyrimidines/therapeutic use ; Research Design ; Rosuvastatin Calcium ; Sulfonamides/administration & dosage ; Sulfonamides/adverse effects ; Sulfonamides/therapeutic use ; Time Factors ; Treatment Outcome
    Chemical Substances Biomarkers ; Fluorobenzenes ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Lipids ; Pyrimidines ; Sulfonamides ; Rosuvastatin Calcium (83MVU38M7Q) ; C-Reactive Protein (9007-41-4)
    Language English
    Publishing date 2009-04-08
    Publishing country New Zealand
    Document type Clinical Trial, Phase III ; Journal Article ; Randomized Controlled Trial
    ZDB-ID 2186568-1
    ISSN 1178-2048 ; 1176-6344
    ISSN (online) 1178-2048
    ISSN 1176-6344
    DOI 10.2147/vhrm.s5206
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: A role for TRPV1 in influencing the onset of cardiovascular disease in obesity.

    Marshall, Nichola J / Liang, Lihuan / Bodkin, Jennifer / Dessapt-Baradez, Cecile / Nandi, Manasi / Collot-Teixeira, Sophie / Smillie, Sarah-Jane / Lalgi, Kamal / Fernandes, Elizabeth S / Gnudi, Luigi / Brain, Susan D

    Hypertension (Dallas, Tex. : 1979)

    2012  Volume 61, Issue 1, Page(s) 246–252

    Abstract: Obesity induced by Western diets is associated with type 2 diabetes mellitus and cardiovascular diseases, although underlying mechanisms are unclear. We investigated a murine model of diet-induced obesity to determine the effect of transient potential ... ...

    Abstract Obesity induced by Western diets is associated with type 2 diabetes mellitus and cardiovascular diseases, although underlying mechanisms are unclear. We investigated a murine model of diet-induced obesity to determine the effect of transient potential receptor vanilloid 1 (TRPV1) deletion on hypertension and metabolic syndrome. Wild-type and TRPV1 knockout mice were fed normal or high-fat diet from 3 to 15 weeks. High-fat diet-fed mice from both genotypes became obese, with similar increases in body and adipose tissue weights. High-fat diet-fed TRPV1 knockout mice showed significantly improved handling of glucose compared with high-fat diet-fed wild-type mice. Hypertension, vascular hypertrophy, and altered nociception were observed in high-fat diet-fed wild-type but not high-fat diet-fed TRPV1 knockout mice. Wild-type, but not high-fat diet-fed TRPV1 knockout, mice demonstrated remodeling in terms of aortic vascular hypertrophy and increased heart and kidney weight, although resistance vessel responses were similar in each. Moreover, the wild-type mice had significantly increased plasma levels of leptin, interleukin 10 and interleukin 1β, whereas samples from TRPV1 knockout mice did not show significant increases. Our results do not support the concept that TRPV1 plays a major role in influencing weight gain. However, we identified a role of TRPV1 in the deleterious effects observed with high-fat feeding in terms of inducing hypertension, impairing thermal nociception sensitivity, and reducing glucose tolerance. The observation of raised levels of adipokines in wild-type but not TRPV1 knockout mice is in keeping with TRPV1 involvement in stimulating the proinflammatory network that is central to obesity-induced hypertension and sensory neuronal dysfunction.
    MeSH term(s) Adipose Tissue/metabolism ; Animals ; Blood Glucose/metabolism ; Blood Pressure/physiology ; Cardiovascular Diseases/complications ; Cardiovascular Diseases/genetics ; Cardiovascular Diseases/metabolism ; Diet, High-Fat ; Hypertension/complications ; Hypertension/genetics ; Hypertension/metabolism ; Insulin Resistance ; Interleukin-10/blood ; Interleukin-1beta/blood ; Leptin/blood ; Metabolic Syndrome/complications ; Metabolic Syndrome/genetics ; Metabolic Syndrome/metabolism ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Obesity/complications ; Obesity/genetics ; Obesity/metabolism ; TRPV Cation Channels/genetics ; TRPV Cation Channels/metabolism
    Chemical Substances Blood Glucose ; Interleukin-1beta ; Leptin ; TRPV Cation Channels ; TRPV1 protein, mouse ; Interleukin-10 (130068-27-8)
    Language English
    Publishing date 2012-11-12
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 423736-5
    ISSN 1524-4563 ; 0194-911X ; 0362-4323
    ISSN (online) 1524-4563
    ISSN 0194-911X ; 0362-4323
    DOI 10.1161/HYPERTENSIONAHA.112.201434
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article: CD36 and macrophages in atherosclerosis.

    Collot-Teixeira, Sophie / Martin, Juliette / McDermott-Roe, Chris / Poston, Robin / McGregor, John Louis

    Cardiovascular research

    2007  Volume 75, Issue 3, Page(s) 468–477

    Abstract: CD36 is a multi-ligand scavenger receptor present on the surface of a number of cells such as platelets, monocytes/macrophages, endothelial and smooth muscle cells. Monocyte/macrophage CD36 has been shown to play a critical role in the development of ... ...

    Abstract CD36 is a multi-ligand scavenger receptor present on the surface of a number of cells such as platelets, monocytes/macrophages, endothelial and smooth muscle cells. Monocyte/macrophage CD36 has been shown to play a critical role in the development of atherosclerotic lesions by its capacity to bind and endocytose oxidized low density lipoproteins (OxLDL), and it is implicated in the formation of foam cells. However, the significance of CD36 in atherosclerosis has recently been called into question by different studies, and therefore its exact role still needs to be clarified. The aim of this article is to carefully review the importance of CD36 as an essential component in the pathogenesis of atherosclerosis.
    MeSH term(s) Animals ; Atherosclerosis/immunology ; Atherosclerosis/pathology ; Blood Vessels/immunology ; Blood Vessels/pathology ; CD36 Antigens/metabolism ; Humans ; Lipoproteins, LDL/metabolism ; Macrophages/metabolism ; Mice ; Mice, Transgenic ; Models, Animal ; Structure-Activity Relationship
    Chemical Substances CD36 Antigens ; Lipoproteins, LDL ; oxidized low density lipoprotein
    Language English
    Publishing date 2007-08-01
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 80340-6
    ISSN 1755-3245 ; 0008-6363
    ISSN (online) 1755-3245
    ISSN 0008-6363
    DOI 10.1016/j.cardiores.2007.03.010
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article: Statin therapy-evidence beyond lipid lowering contributing to plaque stability.

    de Lorenzo, Ferruccio / Feher, Michael / Martin, Juliette / Collot-Teixeira, Sophie / Dotsenko, Olena / McGregor, John Louis

    Current medicinal chemistry

    2006  Volume 13, Issue 28, Page(s) 3385–3393

    Abstract: Primarily statin drugs inhibit hepatic 3-hydroxy 3-methylglutaryl coenzyme A (HMG-CoA) reductase, which is responsible for the reduction in circulating low-density lipoprotein (LDL) cholesterol. Several findings from recent research studies indicate that ...

    Abstract Primarily statin drugs inhibit hepatic 3-hydroxy 3-methylglutaryl coenzyme A (HMG-CoA) reductase, which is responsible for the reduction in circulating low-density lipoprotein (LDL) cholesterol. Several findings from recent research studies indicate that statins have multiple actions that favorably influence key factors involved in the atherogenic process. These so-called pleiotropic properties affect various aspects of cell function, inflammation, coagulation, and vasomotor activity. These effects are mediated either indirectly through LDL cholesterol reduction or via a direct effect on cellular functions. Such actions may contribute to the early cardiovascular benefit observed in several outcome trials with statin drugs therapy. Although many of the pleiotropic properties of statins may be a class effect, some may be unique to certain agents and account for differences in their pharmacological activity. This review summarise the results of the major outcome trials of statins and non-statins therapy and the possible mechanisms beyond lipid lowering contributing to plaque stability.
    MeSH term(s) Arteriosclerosis/drug therapy ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use ; Hypercholesterolemia/drug therapy
    Chemical Substances Hydroxymethylglutaryl-CoA Reductase Inhibitors
    Language English
    Publishing date 2006
    Publishing country United Arab Emirates
    Document type Journal Article ; Review
    ZDB-ID 1319315-6
    ISSN 1875-533X ; 0929-8673
    ISSN (online) 1875-533X
    ISSN 0929-8673
    DOI 10.2174/092986706779010324
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Investigation of low-dose ritonavir on human peripheral blood mononuclear cells using gene expression whole genome microarrays.

    Yilmaz, Saliha / Boffito, Marta / Collot-Teixeira, Sophie / De Lorenzo, Ferruccio / Waters, Laura / Fletcher, Carl / Back, David / Pozniak, Anton / Gazzard, Brian / McGregor, John Louis

    Genomics

    2010  Volume 96, Issue 1, Page(s) 57–65

    Abstract: Ritonavir is a protease inhibitor associated with metabolic abnormalities and cardiovascular disease. We have investigated the effects of low-dose ritonavir treatment on gene expression in peripheral blood mononuclear cells (PBMC) of 10 healthy donors. ... ...

    Abstract Ritonavir is a protease inhibitor associated with metabolic abnormalities and cardiovascular disease. We have investigated the effects of low-dose ritonavir treatment on gene expression in peripheral blood mononuclear cells (PBMC) of 10 healthy donors. Results using whole genome Illumina microarrays show that ritonavir modulates a number of genes implicated in lipid metabolism, inflammation and atherosclerosis. These candidate genes are dual specificity phosphatase 1 DUSP1), Kelch domain containing 3 (KLHDC3), neutral cholesterol ester hydrolase 1 (NCEH1) and acyl-CoA synthetase short-chain family member 2 (ACSS2). Validation experiments using quantitative PCR showed that ritonavir (at 100 mg once daily and 100 mg twice daily significantly down-regulated these 4 selected candidate genes in 20 healthy individuals. Lower expression levels of these 4 candidate genes, known to play a critical role in inflammation, lipid metabolism and atherosclerosis, may explain ritonavir adverse effects in patients.
    MeSH term(s) Acetate-CoA Ligase/genetics ; Adolescent ; Adult ; Biomarkers ; Carboxylic Ester Hydrolases/genetics ; Computational Biology ; Down-Regulation/drug effects ; Dual Specificity Phosphatase 1/genetics ; Female ; Gene Expression Profiling ; Gene Expression Regulation/drug effects ; HIV Protease Inhibitors/pharmacology ; Humans ; Leukocytes, Mononuclear/drug effects ; Leukocytes, Mononuclear/metabolism ; Male ; Middle Aged ; Ritonavir/pharmacology
    Chemical Substances Biomarkers ; HIV Protease Inhibitors ; Carboxylic Ester Hydrolases (EC 3.1.1.-) ; NCEH1 protein, human (EC 3.1.1.13) ; DUSP1 protein, human (EC 3.1.3.48) ; Dual Specificity Phosphatase 1 (EC 3.1.3.48) ; Acetate-CoA Ligase (EC 6.2.1.1) ; Ritonavir (O3J8G9O825)
    Language English
    Publishing date 2010-03-28
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 356334-0
    ISSN 1089-8646 ; 0888-7543
    ISSN (online) 1089-8646
    ISSN 0888-7543
    DOI 10.1016/j.ygeno.2010.03.011
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article: Involvement of human herpesvirus-6 variant B in classic Hodgkin's lymphoma via DR7 oncoprotein.

    Lacroix, Aurélie / Collot-Teixeira, Sophie / Mardivirin, Laurent / Jaccard, Arnaud / Petit, Barbara / Piguet, Christophe / Sturtz, Franck / Preux, Pierre-Marie / Bordessoule, Dominique / Ranger-Rogez, Sylvie

    Clinical cancer research : an official journal of the American Association for Cancer Research

    2010  Volume 16, Issue 19, Page(s) 4711–4721

    Abstract: Purpose: Hodgkin's lymphoma (HL) is associated with the presence of EBV in Reed-Sternberg (RS) cells in ∼40% of cases. Here, we studied the presence of human herpesvirus type 6 (HHV-6) variant B in RS cells of HL patients and correlated results with ... ...

    Abstract Purpose: Hodgkin's lymphoma (HL) is associated with the presence of EBV in Reed-Sternberg (RS) cells in ∼40% of cases. Here, we studied the presence of human herpesvirus type 6 (HHV-6) variant B in RS cells of HL patients and correlated results with clinical parameters. We then examined the implication of HHV-6 DR7B protein in cell deregulation.
    Experimental design: HHV-6 DR7B protein was produced in a Semliki Forest virus system. Polyclonal antibodies were then generated and used for immunochemical HHV-6 localization in HL biopsies. Binding between DR7B and p53 was studied using a double-hybrid system. Transactivation of NFκB was observed after transient transfection using reporter gene assays. We looked for Id2 factor expression after stable transfection of the BJAB cell line by reverse transcription-PCR and Western blot analysis.
    Results: HHV-6 was more common in nodular sclerosis subtype HL, and DR7B oncoprotein was detected in RS cells for 73.7% of EBV-negative patients. Colocalization of EBV and HHV-6 was observed in RS cells of doubly infected patients. DR7B protein bound to human p53 protein. p105-p50/p65 mRNA expression and activation of the NFκB complex were increased when DR7B was expressed. Stable expression of DR7B exhibited a strong and uniform expression of Id2. A slightly higher percentage of remission was observed in patients with RS cells testing positive for DR7B than in those testing negative.
    Conclusions: Collectively, these data provide evidence for the implication of a novel agent, HHV-6, in cases of nodular sclerosis HL.
    MeSH term(s) Adolescent ; Adult ; Aged ; Aged, 80 and over ; Female ; Herpesvirus 6, Human/metabolism ; Hodgkin Disease/metabolism ; Humans ; Male ; Middle Aged ; Multiple Sclerosis/metabolism ; Oncogenes ; Trans-Activators/metabolism ; Young Adult
    Chemical Substances ORF-1 protein, Human herpesvirus 6 ; Trans-Activators
    Language English
    Publishing date 2010-10-01
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1225457-5
    ISSN 1557-3265 ; 1078-0432
    ISSN (online) 1557-3265
    ISSN 1078-0432
    DOI 10.1158/1078-0432.CCR-10-0470
    Database MEDical Literature Analysis and Retrieval System OnLINE

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