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  1. Article ; Online: Investigating and imaging platelets in inflammation.

    Cleary, Simon J / Conrad, Catharina

    The international journal of biochemistry & cell biology

    2023  Volume 157, Page(s) 106373

    Abstract: Blood platelets are best known for their roles in hemostasis and thrombosis, but platelets also make important contributions to inflammation, immunity, and inflammatory resolution. Experiments involving depletion, genetic modification, and live imaging ... ...

    Abstract Blood platelets are best known for their roles in hemostasis and thrombosis, but platelets also make important contributions to inflammation, immunity, and inflammatory resolution. Experiments involving depletion, genetic modification, and live imaging of platelets in animal models have increased our mechanistic understanding of platelet contributions to inflammation. In this minireview, we provide a critical overview of experimental techniques for manipulating and imaging platelets in inflammation models. We then highlight studies using innovative approaches to elucidate molecular mechanisms through which platelet subsets, platelet Fc gamma receptors, and pro-resolution platelet functions influence inflammatory responses. We also propose future technologies and research directions which might move us closer to harnessing of platelet functions for improved therapeutic modulation of inflammatory diseases.
    MeSH term(s) Animals ; Blood Platelets ; Hemostasis ; Inflammation ; Thrombosis
    Language English
    Publishing date 2023-01-27
    Publishing country Netherlands
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 1228429-4
    ISSN 1878-5875 ; 1357-2725
    ISSN (online) 1878-5875
    ISSN 1357-2725
    DOI 10.1016/j.biocel.2023.106373
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 431: 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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  2. Article ; Online: Chewing the fat on TRALI.

    Cleary, Simon J / Looney, Mark R

    Blood

    2021  Volume 137, Issue 5, Page(s) 586–587

    MeSH term(s) Acute Lung Injury ; Extracellular Vesicles ; Humans ; Sphingolipids ; Transfusion Reaction ; Transfusion-Related Acute Lung Injury
    Chemical Substances Sphingolipids
    Language English
    Publishing date 2021-02-23
    Publishing country United States
    Document type Journal Article ; Comment
    ZDB-ID 80069-7
    ISSN 1528-0020 ; 0006-4971
    ISSN (online) 1528-0020
    ISSN 0006-4971
    DOI 10.1182/blood.2020010034
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    Uh III Zs.140: Show issues Location:
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    Zs.MO 364: Show issues

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  3. Article ; Online: Gustav Born: pioneer in imaging platelet and leukocyte biology.

    Cleary, Simon J / Page, Clive P

    Platelets

    2018  Volume 29, Issue 8, Page(s) 766–770

    Abstract: Gustav Born achieved scientific fame for his application of light transmission aggregometry to the study of platelet function, but also led interdisciplinary research teams in pioneering quantitative in vivo imaging studies of platelet aggregation and ... ...

    Abstract Gustav Born achieved scientific fame for his application of light transmission aggregometry to the study of platelet function, but also led interdisciplinary research teams in pioneering quantitative in vivo imaging studies of platelet aggregation and leukocyte adhesion, and in conducting the first research into the biomechanical factors underlying atherosclerotic plaque rupture. Gus Born also communicated both current research findings and an integrated understanding of cardiovascular biology to a wide audience through acting as scientific advisor on several television productions. Using footage from two of these films, we discuss Gustav Born's scientific achievements and legacy.
    MeSH term(s) Blood Platelets ; Cell Adhesion ; History, 20th Century ; History, 21st Century ; Humans ; Leukocytes ; Plaque, Atherosclerotic/history ; Platelet Aggregation ; Platelet Function Tests/history
    Language English
    Publishing date 2018-11-09
    Publishing country England
    Document type Biography ; Historical Article ; Journal Article
    ZDB-ID 1034283-7
    ISSN 1369-1635 ; 0953-7104
    ISSN (online) 1369-1635
    ISSN 0953-7104
    DOI 10.1080/09537104.2018.1535001
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 2888: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
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    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

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  4. Article ; Online: Optimizing anesthesia and delivery approaches for dosing into lungs of mice.

    Seo, Yurim / Qiu, Longhui / Magnen, Mélia / Conrad, Catharina / Moussavi-Harami, S Farshid / Looney, Mark R / Cleary, Simon J

    American journal of physiology. Lung cellular and molecular physiology

    2023  Volume 325, Issue 2, Page(s) L262–L269

    Abstract: Microbes, toxins, therapeutics, and cells are often instilled into lungs of mice to model diseases and test experimental interventions. Consistent pulmonary delivery is critical for experimental power and reproducibility, but we observed variation in ... ...

    Abstract Microbes, toxins, therapeutics, and cells are often instilled into lungs of mice to model diseases and test experimental interventions. Consistent pulmonary delivery is critical for experimental power and reproducibility, but we observed variation in outcomes between handlers using different anesthetic approaches for intranasal dosing in mice. We therefore used a radiotracer to quantify lung delivery after intranasal dosing under inhalational (isoflurane) versus injectable (ketamine/xylazine) anesthesia in C57BL/6 mice. We found that ketamine/xylazine anesthesia resulted in delivery of a greater proportion (52 ± 9%) of an intranasal dose to lungs relative to isoflurane anesthesia (30 ± 15%). This difference in pulmonary dose delivery altered key outcomes in models of viral and bacterial pneumonia, with mice anesthetized with ketamine/xylazine for intranasal infection with influenza A virus or
    MeSH term(s) Animals ; Mice ; Anesthesia/methods ; Anesthetics ; Isoflurane ; Ketamine ; Lung ; Mice, Inbred C57BL ; Reproducibility of Results ; Xylazine
    Chemical Substances Anesthetics ; Isoflurane (CYS9AKD70P) ; Ketamine (690G0D6V8H) ; Xylazine (2KFG9TP5V8)
    Language English
    Publishing date 2023-07-04
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 1013184-x
    ISSN 1522-1504 ; 1040-0605
    ISSN (online) 1522-1504
    ISSN 1040-0605
    DOI 10.1152/ajplung.00046.2023
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Uc I Zs.89: Show issues Location:
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    Zs.A 2749: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
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    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

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  5. Article ; Online: IgG hexamers initiate complement-dependent acute lung injury.

    Cleary, Simon J / Seo, Yurim / Tian, Jennifer J / Kwaan, Nicholas / Bulkley, David P / Bentlage, Arthur E H / Vidarsson, Gestur / Boilard, Éric / Spirig, Rolf / Zimring, James C / Looney, Mark R

    The Journal of clinical investigation

    2024  

    Abstract: Antibodies can initiate lung injury in a variety of disease states such as autoimmunity, transfusion reactions, or after organ transplantation, but the key factors determining in vivo pathogenicity of injury-inducing antibodies are unclear. Harmful ... ...

    Abstract Antibodies can initiate lung injury in a variety of disease states such as autoimmunity, transfusion reactions, or after organ transplantation, but the key factors determining in vivo pathogenicity of injury-inducing antibodies are unclear. Harmful antibodies often activate the complement cascade. A model for how IgG antibodies trigger complement activation involves interactions between IgG Fc domains driving assembly of IgG hexamer structures that activate C1 complexes. The importance of IgG hexamers in initiating injury responses was unclear, so we tested their relevance in a mouse model of alloantibody and complement-mediated acute lung injury. We used three approaches to block alloantibody hexamerization (antibody carbamylation, the K439E Fc mutation, or treatment with domain B from Staphylococcal protein A), all of which reduced acute lung injury. Conversely, Fc mutations promoting spontaneous hexamerization made a harmful alloantibody into a more potent inducer of acute lung injury and rendered an innocuous alloantibody pathogenic. Treatment with a recombinant Fc hexamer 'decoy' therapeutic protected mice from lung injury, including in a model with transgenic human FCGR2A expression that exacerbated pathology. These results indicate an in vivo role of IgG hexamerization in initiating acute lung injury and the potential for therapeutics that inhibit or mimic hexamerization to treat antibody-mediated diseases.
    Language English
    Publishing date 2024-03-26
    Publishing country United States
    Document type Journal Article
    ZDB-ID 3067-3
    ISSN 1558-8238 ; 0021-9738
    ISSN (online) 1558-8238
    ISSN 0021-9738
    DOI 10.1172/JCI178351
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: IgG hexamers initiate acute lung injury.

    Cleary, Simon J / Seo, Yurim / Tian, Jennifer J / Kwaan, Nicholas / Bulkley, David P / Bentlage, Arthur E H / Vidarsson, Gestur / Boilard, Éric / Spirig, Rolf / Zimring, James C / Looney, Mark R

    bioRxiv : the preprint server for biology

    2024  

    Abstract: Antibodies can initiate lung injury in a variety of disease states such as autoimmunity, transfusion reactions, or after organ transplantation, but the key factors determining in vivo pathogenicity of injury-inducing antibodies are unclear. A previously ... ...

    Abstract Antibodies can initiate lung injury in a variety of disease states such as autoimmunity, transfusion reactions, or after organ transplantation, but the key factors determining in vivo pathogenicity of injury-inducing antibodies are unclear. A previously overlooked step in complement activation by IgG antibodies has been elucidated involving interactions between IgG Fc domains that enable assembly of IgG hexamers, which can optimally activate the complement cascade. Here, we tested the in vivo relevance of IgG hexamers in a complement-dependent alloantibody model of acute lung injury. We used three approaches to block alloantibody hexamerization (antibody carbamylation, the K439E Fc mutation, or treatment with domain B from Staphylococcal protein A), all of which reduced acute lung injury. Conversely, Fc mutations promoting spontaneous hexamerization made a harmful alloantibody into a more potent inducer of acute lung injury and rendered an innocuous alloantibody pathogenic. Treatment with a recombinant Fc hexamer 'decoy' therapeutic protected mice from lung injury, including in a model with transgenic human FCGR2A expression that exacerbated pathology. These results indicate a direct in vivo role of IgG hexamerization in initiating acute lung injury and the potential for therapeutics that inhibit or mimic hexamerization to treat antibody-mediated diseases.
    Language English
    Publishing date 2024-01-27
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2024.01.24.577129
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article: Optimizing anesthesia and delivery approaches for dosing into lungs of mice.

    Seo, Yurim / Qiu, Longhui / Magnen, Mélia / Conrad, Catharina / Moussavi-Harami, S Farshid / Looney, Mark R / Cleary, Simon J

    bioRxiv : the preprint server for biology

    2023  

    Abstract: Microbes, toxins, therapeutics and cells are often instilled into lungs of mice to model diseases and test experimental interventions. Consistent pulmonary delivery is critical for experimental power and reproducibility, but we observed variation in ... ...

    Abstract Microbes, toxins, therapeutics and cells are often instilled into lungs of mice to model diseases and test experimental interventions. Consistent pulmonary delivery is critical for experimental power and reproducibility, but we observed variation in outcomes between handlers using different anesthetic approaches for intranasal dosing into mice. We therefore used a radiotracer to quantify lung delivery after intranasal dosing under inhalational (isoflurane) versus injectable (ketamine/xylazine) anesthesia in C57BL/6 mice. We found that ketamine/xylazine anesthesia resulted in delivery of a greater proportion (52±9%) of an intranasal dose to lungs relative to isoflurane anesthesia (30±15%). This difference in pulmonary dose delivery altered key outcomes in models of viral and bacterial pneumonia, with mice anesthetized with ketamine/xylazine for intranasal infection with influenza A virus or Pseudomonas aeruginosa developing more robust lung inflammation responses relative to control animals randomized to isoflurane anesthesia. Pulmonary dosing efficiency through oropharyngeal aspiration was not affected by anesthetic method and resulted in delivery of 63±8% of dose to lungs, and a non-surgical intratracheal dosing approach further increased lung delivery to 92±6% of dose. Use of either of these more precise dosing methods yielded greater experimental power in the bacterial pneumonia model relative to intranasal infection. Both anesthetic approach and dosing route can impact pulmonary dosing efficiency. These factors affect experimental power and so should be considered when planning and reporting studies involving delivery of fluids to lungs of mice.
    Language English
    Publishing date 2023-06-29
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.02.01.526706
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Update on animal models for COVID-19 research.

    Cleary, Simon J / Magnen, Mélia / Looney, Mark R / Page, Clive P

    British journal of pharmacology

    2020  Volume 177, Issue 24, Page(s) 5679–5681

    MeSH term(s) Angiotensin-Converting Enzyme 2/metabolism ; Animals ; COVID-19/transmission ; Disease Models, Animal ; Masks ; Mesocricetus ; Mice ; SARS-CoV-2
    Chemical Substances Angiotensin-Converting Enzyme 2 (EC 3.4.17.23)
    Keywords covid19
    Language English
    Publishing date 2020-11-02
    Publishing country England
    Document type Letter
    ZDB-ID 80081-8
    ISSN 1476-5381 ; 0007-1188
    ISSN (online) 1476-5381
    ISSN 0007-1188
    DOI 10.1111/bph.15266
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article: Decoding functional hematopoietic progenitor cells in the adult human lung.

    Conrad, Catharina / Magnen, Melia / Tsui, Jessica / Wismer, Harrison / Naser, Mohammad / Venkataramani, Urmila / Samad, Bushra / Cleary, Simon J / Qiu, Longhui / Tian, Jennifer J / De Giovanni, Marco / Mende, Nicole / Passegue, Emmanuelle / Laurenti, Elisa / Combes, Alexis J / Looney, Mark R

    Research square

    2024  

    Abstract: The bone marrow is the main site of blood cell production in adults, however, rare pools of hematopoietic stem and progenitor cells with self-renewal and differentiation potential have been found in extramedullary organs. The lung is primarily known for ... ...

    Abstract The bone marrow is the main site of blood cell production in adults, however, rare pools of hematopoietic stem and progenitor cells with self-renewal and differentiation potential have been found in extramedullary organs. The lung is primarily known for its role in gas exchange but has recently been described as a site of blood production in mice. Here, we show that functional hematopoietic precursors reside in the extravascular spaces of the human lung, at a frequency similar to the bone marrow, and are capable of proliferation and engraftment. The organ-specific gene signature of pulmonary and medullary CD34
    Language English
    Publishing date 2024-02-16
    Publishing country United States
    Document type Preprint
    DOI 10.21203/rs.3.rs-3576483/v2
    Database MEDical Literature Analysis and Retrieval System OnLINE

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