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  1. Article ; Online: Inverse Relationship Between Lipopolysaccharide Concentration and Monocyte and Dendritic Cells Inflammatory Response.

    Perros, Alexis J / Flower, Robert L / Dean, Melinda M

    Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research

    2020  Volume 40, Issue 7, Page(s) 349–356

    Abstract: Dendritic cells (DCs) and monocytes are key immunoregulatory cells that link the innate and adaptive immune response. However, understanding of human cell-specific responses to different doses of stimuli including lipopolysaccharide (LPS) is limited. ... ...

    Abstract Dendritic cells (DCs) and monocytes are key immunoregulatory cells that link the innate and adaptive immune response. However, understanding of human cell-specific responses to different doses of stimuli including lipopolysaccharide (LPS) is limited. This study investigated the monocyte and classical DC (cDC)-specific, as well as the overall inflammatory response after exposure to varying doses of LPS. Fresh peripheral whole blood (
    MeSH term(s) Cells, Cultured ; Cytokines/biosynthesis ; Cytokines/blood ; Cytokines/immunology ; Dendritic Cells/drug effects ; Dendritic Cells/immunology ; Dose-Response Relationship, Drug ; Humans ; Inflammation/immunology ; Lipopolysaccharides/pharmacology ; Monocytes/drug effects ; Monocytes/immunology
    Chemical Substances Cytokines ; Lipopolysaccharides
    Language English
    Publishing date 2020-05-27
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1226675-9
    ISSN 1557-7465 ; 1079-9907
    ISSN (online) 1557-7465
    ISSN 1079-9907
    DOI 10.1089/jir.2019.0244
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 1748: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
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    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

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  2. Article ; Online: Intraoperative cell salvage: The impact on immune cell numbers.

    Roets, Michelle / Sturgess, David / Tran, Thu / Obeysekera, Maheshi / Perros, Alexis / Tung, John-Paul / Flower, Robert / van Zundert, Andre / Dean, Melinda

    PloS one

    2023  Volume 18, Issue 8, Page(s) e0289177

    Abstract: Background: Patient outcomes are influenced by many confounding factors peri-operatively, including the type of surgery, anaesthesia, transfusion, and immune competence. We have previously demonstrated (in-vitro) that compared to allogeneic blood ... ...

    Abstract Background: Patient outcomes are influenced by many confounding factors peri-operatively, including the type of surgery, anaesthesia, transfusion, and immune competence. We have previously demonstrated (in-vitro) that compared to allogeneic blood transfusion (ABT), intraoperative cell salvage (ICS) improves immune competence. The peri-operative immune response is complex. Altered or impaired immune responses may predispose patients to develop adverse outcomes (i.e., post-operative wound infection, pneumonia, urinary tract infection etc.) Surgical patients may develop infection, even without the confirmed presence of a definite microbiological pathogen. With all these factors in mind it is important to consider changes in immune cell numbers (and sub-populations) and functional capacity during peri-operative transfusion.
    Methods: In this TRIMICS-Cell (Transfusion Related Immune Modulation and Intraoperative Cell Salvage-Cell numbers) study (n = 17, October 2018-November 2019) we prioritized and analysed peri-operative changes in the number and proportions of immune cell populations and sub-populations (B cells (CD20+), NK (natural killer) cells (CD56+), monocytes (CD14+), T cells (total CD3+ and sub-populations: T helper cells (CD4+), cytotoxic T cells (CD8+), effector T cells (CD4+ CD127+), activated effector T cells (CD4+ CD25+ CD127+) and regulatory T cells (CD4+ CD25+ CD127-)), plasmacytoid dendritic cells (pDC; Lineage-, HLA-DR+, CD11c-, CD123+), classical dendritic cell (cDC) (Lineage-, HLA-DR+, CD11c+), and cDC activation (Lineage-, HLA-DR+, CD11c+), co-stimulatory/adhesion molecules and pDC (CD9+, CD38+, CD80+, CD83+, CD86+, CD123+). Firstly we analysed the whole cohort of study patients and secondly according to the relevant transfusion modality (i.e., three study groups: those who received no transfusion, received ICS only (ICS), or both ICS and allogeneic packed red blood cells (pRBC) (ICS&RBC)), during major orthopaedic surgery.
    Results: For the whole study cohort (all patients), changes in immune cell populations were significant: leucocytes and specifically neutrophils increased post-operatively, returning towards pre-operative numbers by 48h post-operatively (48h), and lymphocytes reduced post-operatively returning to pre-operative numbers by 48h. When considering transfusion modalities, there were no significant peri-operative changes in the no transfusion group for all immune cell populations studied (cell numbers and proportions (%)). Significant changes in cell population numbers (i.e., leucocytes, neutrophils and lymphocytes) were identified in both transfused groups (ICS and ICS&RBC). Considering all patients, changes in immune cell sub-populations (NK cells, monocytes, B cells, T cells and DCs) and functional characteristics (e.g., co-stimulation markers, adhesion, activation, and regulation) were significant peri-operatively and when considering transfusion modalities. Interestingly DC numbers and functional capacity were specifically altered following ICS compared to ICS&RBC and pDCs were relatively preserved post-operatively following ICS.
    Conclusion: A transient peri-operative alteration with recovery towards pre-operative numbers by 48h post-surgery was demonstrated for many immune cell populations and sub-populations throughout. Immune cell sub-populations and functional characteristics were similar peri-operatively in those who received no transfusion but changed significantly following ICS and ICS&RBC. Interesting changes that require future study are a post-operative monocyte increase in the ICS&RBC group, changes in cDC considering transfusion modalities, and possibly preserved pDC numbers post-operatively following ICS. Future studies to assess changes in immune cell sub-populations, especially during peri-operative transfusion, while considering post-operative adverse outcomes, is recommended.
    MeSH term(s) Humans ; Interleukin-3 Receptor alpha Subunit ; HLA-DR Antigens ; T-Lymphocytes, Regulatory ; Blood Transfusion ; Cell Count ; Dendritic Cells
    Chemical Substances Interleukin-3 Receptor alpha Subunit ; HLA-DR Antigens
    Language English
    Publishing date 2023-08-01
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2267670-3
    ISSN 1932-6203 ; 1932-6203
    ISSN (online) 1932-6203
    ISSN 1932-6203
    DOI 10.1371/journal.pone.0289177
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Next generation sequencing to identify iron status and individualise blood donors' experience.

    Jacko, Georgina / Sivakaanthan, Aarany / Obeysekera, Maheshi / Welvaert, Marijke / Viennet, Elvina / Hyland, Catherine / Tung, John-Paul / Perros, Alexis J / Flower, Robert L / Roulis, Eileen

    Blood transfusion = Trasfusione del sangue

    2023  Volume 21, Issue 6, Page(s) 463–471

    Abstract: Background: Young adults form the majority of first-time blood donors to Australian Red Cross Lifeblood. However, these donors pose unique challenges for donor safety. Young blood donors, who are still undergoing neurological and physical development, ... ...

    Abstract Background: Young adults form the majority of first-time blood donors to Australian Red Cross Lifeblood. However, these donors pose unique challenges for donor safety. Young blood donors, who are still undergoing neurological and physical development, have been found to have lower iron stores, and have higher risks of iron deficiency anaemia when compared to older adults and non-donors. Identifying young donors with higher iron stores may improve donor health and experience, increase donor retention, and reduce the burden on product donation. In addition, these measures could be used to individualise donation frequency.
    Materials and methods: Stored DNA samples from young male donors (18-25 years; No.=47) were sequenced using a custom panel of genes identified in the literature to be associated with iron homeostasis. The custom sequencing panel used in this study identified and reported variants to human genome version 19 (Hg19).
    Results: 82 gene variants were analysed. Only one of which, rs8177181, was found to have a statistically significant (p<0.05) association with plasma ferritin level. Heterozygous alleles of this Transferrin gene variant, rs8177181T>A, significantly predicted a positive effect on ferritin levels (p=0.03).
    Discussion: This study identified gene variants involved in iron homeostasis using a custom sequencing panel and analysed their association with ferritin levels in a young male blood donor population. Additional studies of factors associated with iron deficiency in blood donors are required if a goal of personalised blood donation protocols is to be achieved.
    MeSH term(s) Young Adult ; Male ; Humans ; Aged ; Iron ; Blood Donors ; Ferritins ; High-Throughput Nucleotide Sequencing ; Australia ; Hemoglobins
    Chemical Substances Iron (E1UOL152H7) ; Ferritins (9007-73-2) ; Hemoglobins
    Language English
    Publishing date 2023-04-28
    Publishing country Italy
    Document type Journal Article
    ZDB-ID 2135732-8
    ISSN 2385-2070 ; 0041-1787 ; 1723-2007
    ISSN (online) 2385-2070
    ISSN 0041-1787 ; 1723-2007
    DOI 10.2450/BloodTransfus.499
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 798: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
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    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

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  4. Article ; Online: Soluble Mediators in Platelet Concentrates Modulate Dendritic Cell Inflammatory Responses in an Experimental Model of Transfusion.

    Perros, Alexis J / Christensen, Anne-Marie / Flower, Robert L / Dean, Melinda M

    Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research

    2015  Volume 35, Issue 10, Page(s) 821–830

    Abstract: The transfusion of platelet concentrates (PCs) is widely used to treat thrombocytopenia and severe trauma. Ex vivo storage of PCs is associated with a storage lesion characterized by partial platelet activation and the release of soluble mediators, such ... ...

    Abstract The transfusion of platelet concentrates (PCs) is widely used to treat thrombocytopenia and severe trauma. Ex vivo storage of PCs is associated with a storage lesion characterized by partial platelet activation and the release of soluble mediators, such as soluble CD40 ligand (sCD40L), RANTES, and interleukin (IL)-8. An in vitro whole blood culture transfusion model was employed to assess whether mediators present in PC supernatants (PC-SNs) modulated dendritic cell (DC)-specific inflammatory responses (intracellular staining) and the overall inflammatory response (cytometric bead array). Lipopolysaccharide (LPS) was included in parallel cultures to model the impact of PC-SNs on cell responses following toll-like receptor-mediated pathogen recognition. The impact of both the PC dose (10%, 25%) and ex vivo storage period was investigated [day 2 (D2), day 5 (D5), day 7 (D7)]. PC-SNs alone had minimal impact on DC-specific inflammatory responses and the overall inflammatory response. However, in the presence of LPS, exposure to PC-SNs resulted in a significant dose-associated suppression of the production of DC IL-12, IL-6, IL-1α, tumor necrosis factor-α (TNF-α), and macrophage inflammatory protein (MIP)-1β and storage-associated suppression of the production of DC IL-10, TNF-α, and IL-8. For the overall inflammatory response, IL-6, TNF-α, MIP-1α, MIP-1β, and inflammatory protein (IP)-10 were significantly suppressed and IL-8, IL-10, and IL-1β significantly increased following exposure to PC-SNs in the presence of LPS. These data suggest that soluble mediators present in PCs significantly suppress DC function and modulate the overall inflammatory response, particularly in the presence of an infectious stimulus. Given the central role of DCs in the initiation and regulation of the immune response, these results suggest that modulation of the DC inflammatory profile is a probable mechanism contributing to transfusion-related complications.
    MeSH term(s) Biomarkers ; Blood Platelets/metabolism ; Blood Transfusion ; Cytokines/metabolism ; Dendritic Cells/immunology ; Dendritic Cells/metabolism ; Humans ; Inflammation Mediators/metabolism ; Platelet Transfusion
    Chemical Substances Biomarkers ; Cytokines ; Inflammation Mediators
    Language English
    Publishing date 2015-10
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1226675-9
    ISSN 1557-7465 ; 1079-9907
    ISSN (online) 1557-7465
    ISSN 1079-9907
    DOI 10.1089/jir.2015.0029
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 1748: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
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  5. Article ; Online: Intraoperative Cell Salvage as an Alternative to Allogeneic (Donated) Blood Transfusion: A Prospective Observational Evaluation of the Immune Response Profile.

    Roets, Michelle / Sturgess, David John / Obeysekera, Maheshi Prabodani / Tran, Thu Vinh / Wyssusek, Kerstin Hildegard / Punnasseril, Jaisil Eldo Jos / da Silva, Diana / van Zundert, Andre / Perros, Alexis Jacqueline / Tung, John Paul / Flower, Robert Lewis Powell / Dean, Melinda Margaret

    Cell transplantation

    2020  Volume 29, Page(s) 963689720966265

    Abstract: Allogeneic blood transfusion (ABT) is associated with transfusion-related immune modulation (TRIM) and subsequent poorer patient outcomes including perioperative infection, multiple organ failure, and mortality. The precise mechanism(s) underlying TRIM ... ...

    Abstract Allogeneic blood transfusion (ABT) is associated with transfusion-related immune modulation (TRIM) and subsequent poorer patient outcomes including perioperative infection, multiple organ failure, and mortality. The precise mechanism(s) underlying TRIM remain largely unknown. During intraoperative cell salvage (ICS) a patient's own (autologous) blood is collected, anticoagulated, processed, and reinfused. One impediment to understanding the influence of the immune system on transfusion-related adverse outcomes has been the inability to characterize immune profile changes induced by blood transfusion, including ICS. Dendritic cells and monocytes play a central role in regulation of immune responses, and dysfunction may contribute to adverse outcomes. During a prospective observational study (
    MeSH term(s) Blood Transfusion/methods ; Humans ; Immunity/physiology ; Monocytes/physiology ; Prospective Studies
    Language English
    Publishing date 2020-10-06
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1135816-6
    ISSN 1555-3892 ; 0963-6897
    ISSN (online) 1555-3892
    ISSN 0963-6897
    DOI 10.1177/0963689720966265
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 3556: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
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    Jg. 1995 - 2021: Lesesall (2.OG)
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  6. Article ; Online: Coronary artery bypass grafting is associated with immunoparalysis of monocytes and dendritic cells.

    Perros, Alexis J / Esguerra-Lallen, Arlanna / Rooks, Kelly / Chong, Fenny / Engkilde-Pedersen, Sanne / Faddy, Helen M / Hewlett, Elise / Naidoo, Rishendran / Tung, John-Paul / Fraser, John F / Tesar, Peter / Ziegenfuss, Marc / Smith, Susan / O'Brien, Donalee / Flower, Robert L / Dean, Melinda M

    Journal of cellular and molecular medicine

    2020  Volume 24, Issue 8, Page(s) 4791–4803

    Abstract: Coronary artery bypass grafting (CABG) triggers a systemic inflammatory response that may contribute to adverse outcomes. Dendritic cells (DC) and monocytes are immunoregulatory cells potentially affected by CABG, contributing to an altered immune state. ...

    Abstract Coronary artery bypass grafting (CABG) triggers a systemic inflammatory response that may contribute to adverse outcomes. Dendritic cells (DC) and monocytes are immunoregulatory cells potentially affected by CABG, contributing to an altered immune state. This study investigated changes in DC and monocyte responses in CABG patients at 5 time-points: admission, peri-operative, ICU, day 3 and day 5. Whole blood from 49 CABG patients was used in an ex vivo whole blood culture model to prospectively assess DC and monocyte responses. Lipopolysaccharide (LPS) was added in parallel to model responses to an infectious complication. Co-stimulatory and adhesion molecule expression and intracellular mediator production was measured by flow cytometry. CABG modulated monocyte and DC responses. In addition, DC and monocytes were immunoparalysed, evidenced by failure of co-stimulatory and adhesion molecules (eg HLA-DR), and intracellular mediators (eg IL-6) to respond to LPS stimulation. DC and monocyte modulation was associated with prolonged ICU length of stay and post-operative atrial fibrillation. DC and monocyte cytokine production did not recover by day 5 post-surgery. This study provides evidence that CABG modulates DC and monocyte responses. Using an ex vivo model to assess immune competency of CABG patients may help identify biomarkers to predict adverse outcomes.
    MeSH term(s) Aged ; Cell Adhesion Molecules/genetics ; Coronary Artery Bypass/adverse effects ; Dendritic Cells/drug effects ; Dendritic Cells/immunology ; Female ; Gene Expression Regulation/drug effects ; HLA-DR Antigens/blood ; HLA-DR Antigens/genetics ; Humans ; Interleukin-6/blood ; Interleukin-6/genetics ; Lipopolysaccharides/pharmacology ; Male ; Monocytes/drug effects ; Monocytes/immunology ; Paralysis/blood ; Paralysis/immunology ; Paralysis/pathology ; Thoracic Surgery
    Chemical Substances Cell Adhesion Molecules ; HLA-DR Antigens ; Interleukin-6 ; Lipopolysaccharides
    Language English
    Publishing date 2020-03-17
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2074559-X
    ISSN 1582-4934 ; 1582-4934 ; 1582-1838
    ISSN (online) 1582-4934
    ISSN 1582-4934 ; 1582-1838
    DOI 10.1111/jcmm.15154
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    Zs.A 5752: Show issues Location:
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