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  1. Article: Reticulocyte Maturation.

    Stevens-Hernandez, Christian J / Bruce, Lesley J

    Membranes

    2022  Volume 12, Issue 3

    Abstract: Changes to the membrane proteins and rearrangement of the cytoskeleton must occur for a reticulocyte to mature into a red blood cell (RBC). Different mechanisms of reticulocyte maturation have been proposed to reduce the size and volume of the ... ...

    Abstract Changes to the membrane proteins and rearrangement of the cytoskeleton must occur for a reticulocyte to mature into a red blood cell (RBC). Different mechanisms of reticulocyte maturation have been proposed to reduce the size and volume of the reticulocyte plasma membrane and to eliminate residual organelles. Lysosomal protein degradation, exosome release, autophagy and the extrusion of large autophagic-endocytic hybrid vesicles have been shown to contribute to reticulocyte maturation. These processes may occur simultaneously or perhaps sequentially. Reticulocyte maturation is incompletely understood and requires further investigation. RBCs with membrane defects or cation leak disorders caused by genetic variants offer an insight into reticulocyte maturation as they present characteristics of incomplete maturation. In this review, we compare the structure of the mature RBC membrane with that of the reticulocyte. We discuss the mechanisms of reticulocyte maturation with a focus on incomplete reticulocyte maturation in red cell variants.
    Language English
    Publishing date 2022-03-10
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2614641-1
    ISSN 2077-0375
    ISSN 2077-0375
    DOI 10.3390/membranes12030311
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Reticulocyte Maturation and Variant Red Blood Cells.

    Stevens-Hernandez, Christian J / Flatt, Joanna F / Kupzig, Sabine / Bruce, Lesley J

    Frontiers in physiology

    2022  Volume 13, Page(s) 834463

    Abstract: The bone marrow produces billions of reticulocytes daily. These reticulocytes mature into red blood cells by reducing their plasma membrane by 20% and ejecting or degrading residual internal organelles, membranes and proteins not required by the mature ... ...

    Abstract The bone marrow produces billions of reticulocytes daily. These reticulocytes mature into red blood cells by reducing their plasma membrane by 20% and ejecting or degrading residual internal organelles, membranes and proteins not required by the mature cell. This process occurs by autophagy, protein degradation and vesiculation but is not well understood. We previously reported that Southeast Asian Ovalocytic RBCs demonstrate incomplete reticulocyte maturation and we have now extended this study to a number of other variant RBCs. By comparing the profile of a pure reticulocyte preparation of cultured red cells with these variant cells, we show that the largest of these cells, the overhydrated hereditary stomatocytosis cells, are the least mature, they barely reduced their plasma membrane and contain large amounts of proteins that should have been reduced or removed. Intermediate sized variant RBCs appear to be more mature but retain some endoplasmic reticulum and residual membrane proteins. We propose that the size and composition of these variant cell types correlate with the different stages of reticulocyte maturation and provide insight into the reticulocyte maturation process.
    Language English
    Publishing date 2022-03-07
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2564217-0
    ISSN 1664-042X
    ISSN 1664-042X
    DOI 10.3389/fphys.2022.834463
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Vesiculation in irradiated and cation-leaky-stored red blood cells.

    Stevens-Hernandez, Christian J / Gyorffy, Gyongyver / Meli, Athinoula / New, Helen V / Cardigan, Rebecca / Bruce, Lesley J

    Transfusion

    2023  Volume 64, Issue 1, Page(s) 150–161

    Abstract: Background: Extracellular vesicles (EVs) are released by red blood cells (RBCs) throughout their life-span and also during hypothermic storage when they accumulate in the blood bag. We queried whether stored RBCs with increased cation permeability, ... ...

    Abstract Background: Extracellular vesicles (EVs) are released by red blood cells (RBCs) throughout their life-span and also during hypothermic storage when they accumulate in the blood bag. We queried whether stored RBCs with increased cation permeability, either from donors with familial pseudohyperkalaemia (FP) or caused by irradiation, vesiculate more readily.
    Study design and methods: Recent technical advances have revealed at least two sub-populations of MVs in RBC storage units: macrovesicles (2-6 μm) and microvesicles (1-2 μm). Using nanoparticle tracking analysis, imaging flow cytometry, and protein quantification methods, we measured and characterized vesicles released by RBCs from control and FP individuals at three different storage time-points (day 4, day 17, and day 29). The RBCs had either been stored untreated or irradiated on either day 1 or day 14 of storage.
    Results: We found no difference in the number or size of vesicles released between cation-leaky FP RBCs and non-FP controls. Similarly, irradiated and non-irradiated RBCs showed very similar patterns of vesicle release to during cold-storage. The only significant difference in vesicle release was the increase in accumulated vesicles with length of storage time which has been reported previously.
    Discussion: EVs in stored blood are potential contributors to adverse transfusion reactions. The number of vesicles released during 35-day hypothermic storage varies between donors and increases with storage duration. However, increased cation permeability and irradiation do not appear to affect vesicle formation during RBC cold-storage.
    MeSH term(s) Humans ; Erythrocytes/metabolism ; Blood Transfusion ; Extracellular Vesicles ; Anemia, Hemolytic, Congenital ; Tissue Donors ; Blood Preservation/methods
    Language English
    Publishing date 2023-11-12
    Publishing country United States
    Document type Journal Article
    ZDB-ID 208417-x
    ISSN 1537-2995 ; 0041-1132
    ISSN (online) 1537-2995
    ISSN 0041-1132
    DOI 10.1111/trf.17593
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Commentary.

    Stevens-Hernandez, Christian J / Bradbury, Wayne H / Oakes, Roderick / Bruce, Lesley J

    Clinical chemistry

    2019  Volume 65, Issue 3, Page(s) 381–382

    MeSH term(s) Humans ; Male ; Potassium ; Siblings
    Chemical Substances Potassium (RWP5GA015D)
    Language English
    Publishing date 2019-02-25
    Publishing country England
    Document type Journal Article ; Comment
    ZDB-ID 80102-1
    ISSN 1530-8561 ; 0009-9147
    ISSN (online) 1530-8561
    ISSN 0009-9147
    DOI 10.1373/clinchem.2018.297325
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: The compound effect of irradiation and familial pseudohyperkalemia on potassium leak from red blood cells.

    Meli, Athinoula / Linger, Rachel / Stevens-Hernandez, Christian J / Gyongyver, Gyorffy / Marks, Denese C / Aung, Htet Htet / Tan, Joanne C G / Cardigan, Rebecca / Bruce, Lesley J / New, Helen V

    Transfusion

    2022  Volume 62, Issue 12, Page(s) 2587–2595

    Abstract: Background: Familial pseudohyperkalemia (FP) is a rare asymptomatic condition characterized by an increased rate of potassium leak from red blood cells (RBC) on refrigeration. Gamma irradiation compromises RBC membrane integrity and accelerates ... ...

    Abstract Background: Familial pseudohyperkalemia (FP) is a rare asymptomatic condition characterized by an increased rate of potassium leak from red blood cells (RBC) on refrigeration. Gamma irradiation compromises RBC membrane integrity and accelerates potassium leakage. Here, we compared the effect of irradiation, applied early or late in storage, on FP versus non-FP RBC.
    Study design: Five FP and 10 non-FP individuals from the National Institute for Health Research Cambridge BioResource, UK, and three FP and six non-FP individuals identified by Australian Red Cross Lifeblood consented to the study. Blood was collected according to standard practice in each center, held overnight at 18-24°C, leucocyte-depleted, and processed into red cell concentrates (RCC) in Saline Adenine Glucose Mannitol. On Day 1, RCC were split equally into six Red Cell Splits (RCS). Two RCS remained non-irradiated, two were irradiated on Day 1 and two were irradiated on Day 14. RBCs were tested over cold storage for quality parameters.
    Results: As expected, non-irradiated FP RCS had significantly higher supernatant potassium levels than controls throughout 28 days of storage (p < .001). When irradiated early, FP RCS released potassium at similar rates to control. When irradiated late, FP RCS supernatants had higher initial post-irradiation potassium concentration than controls but were similar to controls by the end of storage (14 days post-irradiation). No other parameters studied showed a significant difference between FP and control.
    Discussion: FP does not increase the rate of potassium leak from irradiated RBCs. Irradiation may cause a membrane defect similar to that in FP RBCs.
    MeSH term(s) Humans ; Potassium ; Australia ; Erythrocytes
    Chemical Substances Potassium (RWP5GA015D)
    Language English
    Publishing date 2022-10-26
    Publishing country United States
    Document type Journal Article
    ZDB-ID 208417-x
    ISSN 1537-2995 ; 0041-1132
    ISSN (online) 1537-2995
    ISSN 0041-1132
    DOI 10.1111/trf.17159
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Familial pseudohyperkalemia induces significantly higher levels of extracellular potassium in early storage of red cell concentrates without affecting other standard measures of quality: A case control and allele frequency study.

    Meli, Athinoula / McAndrew, Margaret / Frary, Amy / Rehnstrom, Karola / Stevens-Hernandez, Christian J / Flatt, Joanna F / Griffiths, Alexandra / Stefanucci, Luca / Astle, William / Anand, Rekha / New, Helen V / Bruce, Lesley J / Cardigan, Rebecca

    Transfusion

    2021  Volume 61, Issue 8, Page(s) 2439–2449

    Abstract: Background: Familial pseudohyperkalemia (FP) is characterized by an increased rate of potassium leakage in refrigerated red cells and is associated with the minor allele of the single nucleotide polymorphism rs148211042 (R723Q) in the ABCB6 gene. The ... ...

    Abstract Background: Familial pseudohyperkalemia (FP) is characterized by an increased rate of potassium leakage in refrigerated red cells and is associated with the minor allele of the single nucleotide polymorphism rs148211042 (R723Q) in the ABCB6 gene. The study aims were to obtain the minor allele frequencies of ABCB6 variants and to measure supernatant potassium accumulation, and other red cell storage parameters, in red cell concentrates (RCC) from carriers of variant rs148211042 under standard blood bank conditions.
    Study design: Whole blood units were collected from 6 FP individuals and 11 controls and processed into RCC in additive solution. RCC were sampled and tested over cold storage for full blood count, extracellular potassium, glucose, lactate, microvesicle release, deformability, hemolysis, pH, adenosine triphosphate, and 2,3-diphosphoglycerate.
    Results: Screening of genotyped cohorts identified that variant rs148211042 is present in 1 in 394 British citizens of European ancestry. FP RCC had significantly higher supernatant potassium at all time points from day 3 onwards (p < .001) and higher mean cell volume (p = .032) than controls. The initial rate of potassium release was higher in FP RCC; supernatant potassium reached 46.0 (23.8-57.6) mmol/L (mean [range]) by day 5, increasing to 68.9 (58.8-73.7) mmol/L by day 35. Other quality parameters were not significantly different between FP RCC and controls.
    Conclusion: These data suggest that if a blood donor has FP, reducing the RCC shelf-life to 5 days may be insufficient to reduce the risk of hyperkalemia in clinical scenarios such as neonatal large volume transfusion.
    MeSH term(s) ATP-Binding Cassette Transporters/genetics ; Blood Preservation/methods ; Erythrocytes/cytology ; Erythrocytes/metabolism ; Female ; Gene Frequency ; Humans ; Hyperkalemia/congenital ; Hyperkalemia/genetics ; Male ; Polymorphism, Single Nucleotide ; Potassium/analysis
    Chemical Substances ABCB6 protein, human ; ATP-Binding Cassette Transporters ; Potassium (RWP5GA015D)
    Language English
    Publishing date 2021-05-07
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 208417-x
    ISSN 1537-2995 ; 0041-1132
    ISSN (online) 1537-2995
    ISSN 0041-1132
    DOI 10.1111/trf.16440
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article: Expression of South East Asian Ovalocytic Band 3 Disrupts Erythroblast Cytokinesis and Reticulocyte Maturation.

    Flatt, Joanna F / Stevens-Hernandez, Christian J / Cogan, Nicola M / Eggleston, Daniel J / Haines, Nicole M / Heesom, Kate J / Picard, Veronique / Thomas, Caroline / Bruce, Lesley J

    Frontiers in physiology

    2020  Volume 11, Page(s) 357

    Abstract: Southeast Asian Ovalocytosis results from a heterozygous deletion of 9 amino acids in the erythrocyte anion exchange protein AE1 (band 3). The report of the first successful birth of an individual homozygous for this mutation showed an association with ... ...

    Abstract Southeast Asian Ovalocytosis results from a heterozygous deletion of 9 amino acids in the erythrocyte anion exchange protein AE1 (band 3). The report of the first successful birth of an individual homozygous for this mutation showed an association with severe dyserythropoietic anemia. Imaging of the proband's erythrocytes revealed the presence of band 3 at their surface, a reduction in Wr(b) antigen expression, and increases in glycophorin C, CD44, and CD147 immunoreactivity. Immunoblotting of membranes from heterozygous Southeast Asian Ovalocytosis red cells showed a quantitative increase in CD44, CD147, and calreticulin suggesting a defect in reticulocyte maturation, as well as an increase in phosphorylation at residue Tyr359 of band 3, and peroxiredoxin-2 at the membrane, suggesting altered band 3 trafficking and oxidative stress, respectively.
    Language English
    Publishing date 2020-04-28
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2564217-0
    ISSN 1664-042X
    ISSN 1664-042X
    DOI 10.3389/fphys.2020.00357
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Blood group type A secretors are associated with a higher risk of COVID-19 cardiovascular disease complications.

    Mankelow, Tosti J / Singleton, Belinda K / Moura, Pedro L / Stevens-Hernandez, Christian J / Cogan, Nicola M / Gyorffy, Gyongyver / Kupzig, Sabine / Nichols, Luned / Asby, Claire / Pooley, Jennifer / Ruffino, Gabriella / Hosseini, Faroakh / Moghaddas, Fiona / Attwood, Marie / Noel, Alan / Cooper, Alex / Arnold, David T / Hamilton, Fergus / Hyams, Catherine /
    Finn, Adam / Toye, Ashley M / Anstee, David J

    EJHaem

    2021  Volume 2, Issue 2, Page(s) 175–187

    Abstract: The SARS-CoV-2 virus causes COVID-19, an infection capable of causing severe disease and death but which can also be asymptomatic or oligosymptomatic. We investigated whether ABO blood group or secretor status was associated with COVID-19 severity. We ... ...

    Abstract The SARS-CoV-2 virus causes COVID-19, an infection capable of causing severe disease and death but which can also be asymptomatic or oligosymptomatic. We investigated whether ABO blood group or secretor status was associated with COVID-19 severity. We investigated secretor status because expression of ABO glycans on secreted proteins and non-erythroid cells are controlled by a fucosyltransferase (FUT2), and inactivating FUT2 mutations result in a non-secretor phenotype which protects against some viral infections. Data combined from healthcare records and our own laboratory tests (
    Language English
    Publishing date 2021-04-02
    Publishing country United States
    Document type Journal Article
    ISSN 2688-6146
    ISSN (online) 2688-6146
    DOI 10.1002/jha2.180
    Database MEDical Literature Analysis and Retrieval System OnLINE

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