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  1. Article ; Online: SARS-CoV-2: a storm is raging.

    Pedersen, Savannah F / Ho, Ya-Chi

    The Journal of clinical investigation

    2020  Volume 130, Issue 5, Page(s) 2202–2205

    Abstract: The pandemic coronavirus infectious disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is rapidly spreading across the globe. In this issue of the JCI, Chen and colleagues compared the clinical and immunological ... ...

    Abstract The pandemic coronavirus infectious disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is rapidly spreading across the globe. In this issue of the JCI, Chen and colleagues compared the clinical and immunological characteristics between moderate and severe COVID-19. The authors found that respiratory distress on admission is associated with unfavorable outcomes. Increased cytokine levels (IL-6, IL-10, and TNF-α), lymphopenia (in CD4+ and CD8+ T cells), and decreased IFN-γ expression in CD4+ T cells are associated with severe COVID-19. Overall, this study characterized the cytokine storm in severe COVID-19 and provides insights into immune therapeutics and vaccine design.
    MeSH term(s) Age Factors ; Betacoronavirus/immunology ; COVID-19 ; Coronavirus Infections/complications ; Coronavirus Infections/immunology ; Coronavirus Infections/physiopathology ; Coronavirus Infections/virology ; Cytokines/blood ; Cytokines/immunology ; Disease Progression ; Humans ; Lymphocytes/cytology ; Lymphocytes/immunology ; Pandemics ; Pneumonia, Viral/complications ; Pneumonia, Viral/immunology ; Pneumonia, Viral/physiopathology ; Pneumonia, Viral/virology ; Respiratory Distress Syndrome/etiology ; SARS-CoV-2 ; Severity of Illness Index
    Chemical Substances Cytokines
    Keywords covid19
    Language English
    Publishing date 2020-04-23
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 3067-3
    ISSN 1558-8238 ; 0021-9738
    ISSN (online) 1558-8238
    ISSN 0021-9738
    DOI 10.1172/JCI137647
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Ua VI Zs.184: Show issues Location:
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  2. Article: SARS-CoV-2: a storm is raging

    Pedersen, Savannah F / Ho, Ya-Chi

    J Clin Invest

    Abstract: The pandemic coronavirus infectious disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is rapidly spreading across the globe. In this issue of the JCI, Chen and colleagues compared the clinical and immunological ... ...

    Abstract The pandemic coronavirus infectious disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is rapidly spreading across the globe. In this issue of the JCI, Chen and colleagues compared the clinical and immunological characteristics between moderate and severe COVID-19. The authors found that respiratory distress on admission is associated with unfavorable outcomes. Increased cytokine levels (IL-6, IL-10, and TNF-α), lymphopenia (in CD4+ and CD8+ T cells), and decreased IFN-γ expression in CD4+ T cells are associated with severe COVID-19. Overall, this study characterized the cytokine storm in severe COVID-19 and provides insights into immune therapeutics and vaccine design.
    Keywords covid19
    Publisher WHO
    Document type Article
    Note WHO #Covidence: #17603
    Database COVID19

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  3. Article ; Online: Inhibition of a Chromatin and Transcription Modulator, SLTM, Increases HIV-1 Reactivation Identified by a CRISPR Inhibition Screen.

    Pedersen, Savannah F / Collora, Jack A / Kim, Rachel N / Yang, Kerui / Razmi, Anya / Catalano, Allison A / Yeh, Yang-Hui Jimmy / Mounzer, Karam / Tebas, Pablo / Montaner, Luis J / Ho, Ya-Chi

    Journal of virology

    2022  Volume 96, Issue 13, Page(s) e0057722

    Abstract: Despite effective antiretroviral therapy, HIV-1 persistence in latent reservoirs remains a major obstacle to a cure. We postulate that HIV-1 silencing factors suppress HIV-1 reactivation and that inhibition of these factors will increase HIV-1 ... ...

    Abstract Despite effective antiretroviral therapy, HIV-1 persistence in latent reservoirs remains a major obstacle to a cure. We postulate that HIV-1 silencing factors suppress HIV-1 reactivation and that inhibition of these factors will increase HIV-1 reactivation. To identify HIV-1 silencing factors, we conducted a genome-wide CRISPR inhibition (CRISPRi) screen using four CRISPRi-ready, HIV-1-d6-GFP-infected Jurkat T cell clones with distinct integration sites. We sorted cells with increased green fluorescent protein (GFP) expression and captured single guide RNAs (sgRNAs) via targeted deep sequencing. We identified 18 HIV-1 silencing factors that were significantly enriched in HIV-1-d6-GFP
    MeSH term(s) Antiretroviral Therapy, Highly Active ; CD4-Positive T-Lymphocytes ; Chromatin/genetics ; Chromatin/metabolism ; Clustered Regularly Interspaced Short Palindromic Repeats/genetics ; Gene Knockdown Techniques ; HIV Infections/physiopathology ; HIV Seropositivity/genetics ; HIV-1/physiology ; Humans ; Jurkat Cells ; Matrix Attachment Region Binding Proteins/antagonists & inhibitors ; Matrix Attachment Region Binding Proteins/metabolism ; Virus Activation/genetics
    Chemical Substances Chromatin ; Matrix Attachment Region Binding Proteins
    Language English
    Publishing date 2022-06-22
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 80174-4
    ISSN 1098-5514 ; 0022-538X
    ISSN (online) 1098-5514
    ISSN 0022-538X
    DOI 10.1128/jvi.00577-22
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 609: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

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  4. Article ; Online: Restriction of SARS-CoV-2 replication by targeting programmed -1 ribosomal frameshifting.

    Sun, Yu / Abriola, Laura / Niederer, Rachel O / Pedersen, Savannah F / Alfajaro, Mia M / Silva Monteiro, Valter / Wilen, Craig B / Ho, Ya-Chi / Gilbert, Wendy V / Surovtseva, Yulia V / Lindenbach, Brett D / Guo, Junjie U

    Proceedings of the National Academy of Sciences of the United States of America

    2021  Volume 118, Issue 26

    Abstract: Translation of open reading frame 1b (ORF1b) in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) requires a programmed -1 ribosomal frameshift (-1 PRF) promoted by an RNA pseudoknot. The extent to which SARS-CoV-2 replication may be sensitive ...

    Abstract Translation of open reading frame 1b (ORF1b) in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) requires a programmed -1 ribosomal frameshift (-1 PRF) promoted by an RNA pseudoknot. The extent to which SARS-CoV-2 replication may be sensitive to changes in -1 PRF efficiency is currently unknown. Through an unbiased, reporter-based high-throughput compound screen, we identified merafloxacin, a fluoroquinolone antibacterial, as a -1 PRF inhibitor for SARS-CoV-2. Frameshift inhibition by merafloxacin is robust to mutations within the pseudoknot region and is similarly effective on -1 PRF of other betacoronaviruses. Consistent with the essential role of -1 PRF in viral gene expression, merafloxacin impedes SARS-CoV-2 replication in Vero E6 cells, thereby providing proof-of-principle for targeting -1 PRF as a plausible and effective antiviral strategy for SARS-CoV-2 and other coronaviruses.
    MeSH term(s) Animals ; Antiviral Agents/pharmacology ; Betacoronavirus ; Chlorocebus aethiops ; Fluoroquinolones/pharmacology ; Frameshifting, Ribosomal/drug effects ; Frameshifting, Ribosomal/genetics ; Mutation ; Nucleic Acid Conformation ; RNA, Viral/chemistry ; RNA, Viral/genetics ; SARS-CoV-2/drug effects ; SARS-CoV-2/physiology ; Vero Cells ; Virus Replication/drug effects
    Chemical Substances Antiviral Agents ; Fluoroquinolones ; RNA, Viral ; CI 934 (91188-00-0)
    Language English
    Publishing date 2021-06-29
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 209104-5
    ISSN 1091-6490 ; 0027-8424
    ISSN (online) 1091-6490
    ISSN 0027-8424
    DOI 10.1073/pnas.2023051118
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 1148: Show issues Location:
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  5. Article ; Online: Correction: Defactinib, Pembrolizumab, and Gemcitabine in Patients with Advanced Treatment Refractory Pancreatic Cancer: a Phase I Dose Escalation and Expansion Study.

    Wang-Gillam, Andrea / Lim, Kian-Huat / McWilliams, Robert / Suresh, Rama / Lockhart, Albert C / Brown, Amberly / Breden, Marcus / Belle, Jad I / Herndon, John / Bogner, Savannah J / Pedersen, Katrina / Tan, Benjamin / Boice, Nicholas / Acharya, Abhi / Abdiannia, Mina / Gao, Feng / Yoon, Harry H / Zhu, Mojun / Trikalinos, Nikolaos A /
    Ratner, Lee / Aranha, Olivia / Hawkins, William G / Herzog, Brett H / DeNardo, David G

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

    2023  Volume 29, Issue 22, Page(s) 4698

    Language English
    Publishing date 2023-11-14
    Publishing country United States
    Document type Published Erratum
    ZDB-ID 1225457-5
    ISSN 1557-3265 ; 1078-0432
    ISSN (online) 1557-3265
    ISSN 1078-0432
    DOI 10.1158/1078-0432.CCR-23-2993
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 4223: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
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  6. Article ; Online: Defactinib, Pembrolizumab, and Gemcitabine in Patients with Advanced Treatment Refractory Pancreatic Cancer: A Phase I Dose Escalation and Expansion Study.

    Wang-Gillam, Andrea / Lim, Kian-Huat / McWilliams, Robert / Suresh, Rama / Lockhart, Albert C / Brown, Amberly / Breden, Marcus / Belle, Jad I / Herndon, John / Bogner, Savannah J / Pedersen, Katrina / Tan, Benjamin / Boice, Nicholas / Acharya, Abhi / Abdiannia, Mina / Gao, Feng / Yoon, Harry H / Zhu, Mojun / Trikalinos, Nikolaos A /
    Ratner, Lee / Aranha, Olivia / Hawkins, William G / Herzog, Brett H / DeNardo, David G

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

    2022  Volume 28, Issue 24, Page(s) 5254–5262

    Abstract: Purpose: Targeting focal adhesion kinase (FAK) renders checkpoint immunotherapy effective in pancreatic ductal adenocarcinoma (PDAC) mouse model. Defactinib is a highly potent oral FAK inhibitor that has a tolerable safety profile.: Patients and ... ...

    Abstract Purpose: Targeting focal adhesion kinase (FAK) renders checkpoint immunotherapy effective in pancreatic ductal adenocarcinoma (PDAC) mouse model. Defactinib is a highly potent oral FAK inhibitor that has a tolerable safety profile.
    Patients and methods: We conducted a multicenter, open-label, phase I study with dose escalation and expansion phases. In dose escalation, patients with refractory solid tumors were treated at five escalating dose levels of defactinib and gemcitabine to identify a recommended phase II dose (RP2D). In expansion phase, patients with metastatic PDAC who progressed on frontline treatment (refractory cohort) or had stable disease (SD) after at least 4 months of standard gemcitabine/nab-paclitaxel (maintenance cohort) were treated at RP2D. Pre- and posttreatment tumor biopsies were performed to evaluate tumor immunity.
    Results: The triple drug combination was well-tolerated, with no dose-limiting toxicities. Among 20 treated patients with refractory PDAC, the disease control rate (DCR) was 80%, with one partial response (PR) and 15 SDs, and the median progression-free survival (PFS) and overall survival (OS) were 3.6 and 7.8 months, respectively. Among 10 evaluable patients in the maintenance cohort, DCR was 70% with one PR and six SDs. Three patients with SD came off study due to treatment- or disease-related complications. The median PFS and OS on study treatment were 5.0 and 8.3 months, respectively.
    Conclusions: The combination of defactinib, pembrolizumab, and gemcitabine was well-tolerated and safe, had promising preliminary efficacy, and showed biomarker activity in infiltrative T lymphocytes. Efficacy of this strategy may require incorporation of more potent chemotherapy in future studies.
    MeSH term(s) Animals ; Mice ; Gemcitabine ; Deoxycytidine ; Albumins ; Paclitaxel ; Antineoplastic Combined Chemotherapy Protocols/adverse effects ; Pancreatic Neoplasms/pathology ; Adenocarcinoma/pathology ; Pancreatic Neoplasms
    Chemical Substances Gemcitabine ; defactinib (53O87HA2QU) ; Deoxycytidine (0W860991D6) ; pembrolizumab (DPT0O3T46P) ; Albumins ; Paclitaxel (P88XT4IS4D)
    Language English
    Publishing date 2022-10-14
    Publishing country United States
    Document type Clinical Trial, Phase I ; Multicenter Study ; Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 1225457-5
    ISSN 1557-3265 ; 1078-0432
    ISSN (online) 1557-3265
    ISSN 1078-0432
    DOI 10.1158/1078-0432.CCR-22-0308
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 4223: Show issues Location:
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    Jg. 1995 - 2021: Lesesall (2.OG)
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