Publications by authors named "Minke A E Rab"

Introduction: The unique red blood cell (RBC) properties that characterize the rare neuroacanthocytosis syndromes (NAS) have prompted the exploration of osmotic gradient ektacytometry (Osmoscan) as a diagnostic tool for these disorders. In this exploratory study, we assessed if Osmoscans can discriminate NAS from other neurodegenerative diseases.

Methods: A comprehensive assessment was conducted using Osmoscan on a diverse group of patients, including healthy controls ( = 9), neuroacanthocytosis syndrome patients ( = 6, 2 VPS13A and 4 XK disease), Parkinson's disease patients ( = 6), Huntington's disease patients (n = 5), and amyotrophic lateral sclerosis patients ( = 4).

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Article Synopsis
  • Membranopathies include blood disorders caused by genetic changes in red blood cell membrane proteins, with hereditary spherocytosis and stomatocytosis being key examples, while CDA II shows similar symptoms.
  • Mitapivat, a new drug that activates pyruvate kinase, has shown promise in raising hemoglobin levels and reducing blood cell breakdown in various diseases and is being tested in a trial with around 25 adults who have membranopathies or CDA II.
  • The SATISFY trial aims to determine the safety and effectiveness of mitapivat over an 8-week period, with a focus on measuring its impact on hemoglobin, hemolysis, and patient-reported outcomes.
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The hexokinase (HK) enzyme plays a key role in red blood cell energy production. Hereditary non-spherocytic haemolytic anaemia (HNSHA) caused by HK deficiency is a rare disorder with only 12 different disease-associated variants identified. Here, we describe the clinical features and genotypes of four previously unreported patients with hexokinase 1 (HK1)-related HNSHA, yielding two novel truncating HK1 variants.

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We investigated the potential of the point of sickling (PoS; the pO2 tension at which red cells start to sickle), determined by oxygen gradient ektacytometry to serve as a biomarker associated with the incidence of acute sickle cell disease-related complications in 177 children and 50 adults. In the pediatric cohort, for every 10 mmHg increase in PoS reflecting a greater likelihood of sickling, the likelihood of an individual experiencing >1 type of acute complication increased; the adjusted odds ratio (aOR) was 1.65.

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Targeting the primary pathogenic event of sickle cell disease (SCD), the polymerization of sickle hemoglobin (HbS), may prevent downstream clinical events. Mitapivat, an oral pyruvate kinase (PK) activator, has therapeutic potential by increasing adenosine triphosphate (ATP) and decreasing 2,3-diphosphoglycerate (2,3-DPG), a glycolytic red blood cell (RBC) intermediate. In the previously reported 8-week dose-finding period of this phase 2, investigator-initiated, open-label study, mitapivat was well tolerated and showed efficacy in SCD.

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Adenosine Triphosphatase (ATPase) Phospholipid Transporting 11C gene (ATP11C) encodes the major phosphatidylserine (PS) flippase in human red blood cells (RBCs). Flippases actively transport phospholipids (e.g.

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Novel developments in therapies for various hereditary hemolytic anemias reflect the pivotal role of pyruvate kinase (PK), a key enzyme of glycolysis, in red blood cell (RBC) health. Without PK catalyzing one of the final steps of the Embden-Meyerhof pathway, there is no net yield of adenosine triphosphate (ATP) during glycolysis, the sole source of energy production required for proper RBC function and survival. In hereditary hemolytic anemias, RBC health is compromised and therefore lifespan is shortened.

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Blood flow in the microcirculatory system is crucially affected by intrinsic red blood cell (RBC) properties, such as their deformability. In the smallest vessels of this network, RBCs adapt their shapes to the flow conditions. Although it is known that the age of RBCs modifies their physical properties, such as increased cytosol viscosity and altered viscoelastic membrane properties, the evolution of their shape-adapting abilities during senescence remains unclear.

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As a lymphoid organ, the spleen hosts a wide range of immune cell populations, which not only remove blood-borne antigens, but also generate and regulate antigen-specific immune responses. In particular, the splenic microenvironment has been demonstrated to play a prominent role in adaptive immune responses to enveloped viral infections and alloantigens. During both types of immunizations, antigen-specific immunoglobulins G (IgGs) have been characterized by the reduced amount of fucose present on N-linked glycans of the fragment crystallizable (Fc) region.

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Article Synopsis
  • - The study aimed to compare oxygen gradient ektacytometry parameters in sickle cell patients of different genotypes (SS, SC, S/β) and treatment methods (hydroxyurea vs. chronic red blood cell exchange).
  • - Using a sample of 167 adults and children, the results showed that SC patients had better red blood cell (RBC) deformability and lower sickling susceptibility compared to untreated SS patients; also, SS patients under chronic exchange therapy exhibited improved parameters.
  • - The findings indicate that the various genotypes and treatments influence RBC properties, with notable differences in stability during acute complications among SS patients.
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Bioreactors are increasingly implemented for large scale cultures of various mammalian cells, which requires optimization of culture conditions. Such upscaling is also required to produce red blood cells (RBC) for transfusion and therapy purposes. However, the physiological suitability of RBC cultures to be transferred to stirred bioreactors is not well understood.

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Sickle cell disease (SCD) is a genetic disorder characterized by the production of an abnormal hemoglobin (Hb), which, under deoxygenation, may polymerize and cause a mechanical distortion of red blood cell (RBC) into a crescent-like shape. Recently a method, using ektacytometry principle, has been developed to assess RBC deformability as a function of oxygen tension (pO2) and is called oxygen gradient ektacytometry (oxygenscan). However, standardization of this test is needed to properly assess the tendency of sickling of RBCs under deoxygenation and to allow comparisons between different laboratories.

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Pyruvate kinase (PK) deficiency is a rare hereditary disorder affecting red cell (RBC) glycolysis, causing changes in metabolism including a deficiency in ATP. This affects red cell homeostasis, promoting premature removal of RBCs from the circulation. In this study we characterized and evaluated the effect of AG-348, an allosteric activator of PK that is currently in clinical trials for treatment of PK deficiency, on RBCs and erythroid precursors from PK-deficient patients.

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Article Synopsis
  • * There currently isn’t a reliable lab test to predict the severity of SCD or assess new treatments, but this study introduces a method called oxygen gradient ektacytometry to measure RBC deformability based on oxygen levels.
  • * Key findings include the identification of the point of sickling (PoS), indicating when sickling begins, and minimum elongation index (EImin), which relates to the patient's fetal hemoglobin levels; both
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