Open Access. Powered by Scholars. Published by Universities.®
- Discipline
- Keyword
-
- Sickle cell disease (7)
- Α-synuclein (4)
- Platelets (3)
- Thrombotic thrombocytopenic purpura (3)
- Anemia (2)
-
- COVID-19 (disease) (2)
- Children (2)
- Communicable diseases (2)
- Coronavirus infections (2)
- Lymphopoiesis (2)
- Red cells (2)
- Therapy (2)
- Absolute immature platelet count (1)
- Adamts 13 (1)
- Adhesions (1)
- Adolescents (1)
- Adverse events (1)
- Anti (1)
- Anti-CD20 therapeutic options (1)
- Antibodies (1)
- Antithrombin (1)
- Apheresis (1)
- Atypical hemolytic uremic syndrome (1)
- B cells (1)
- Biomarker (1)
- Biomarkers (1)
- Blood (1)
- Blood transfusion (1)
- CAR T (1)
- CD4 (1)
- Publication Year
- Publication
Articles 1 - 30 of 33
Full-Text Articles in Hematology
Pain Screening In Youth With Sickle Cell Disease: A Quality Improvement Study, Dennis C. Vroom, Samuel N. Rodgers-Melnick, Amma Owusu-Ansah, Jeffery A. Dusek
Pain Screening In Youth With Sickle Cell Disease: A Quality Improvement Study, Dennis C. Vroom, Samuel N. Rodgers-Melnick, Amma Owusu-Ansah, Jeffery A. Dusek
Student Scholarship
Background: Youth with sickle cell disease (SCD) face several challenges as they age, including increased pain frequency, duration, and interference. The purpose of this study was to (i) determine the feasibility of routine pain screening; (ii) identify and describe various clinical pain presentations; and (iii) understand preferences/resources related to engaging in integrative health and medicine (IHM) modalities within an outpatient pediatric SCD clinic. Methods: During routine outpatient visits, patients aged 8–18 completed measures of pain frequency, duration, and chronic pain risk (Pediatric Pain Screening Tool [PPST]). Participants screening positive for (i) persistent or chronic pain or (ii) medium or high …
Point-Of-Care Diagnostic Test For Beta-Thalassemia, Ran An, Umut A. Gurkan
Point-Of-Care Diagnostic Test For Beta-Thalassemia, Ran An, Umut A. Gurkan
Faculty Scholarship
Hemoglobin (Hb) disorders are among the most common monogenic diseases affecting nearly 7% of the world population. Among various Hb disorders, approximately 1.5% of the world population carries β-thalassemia (β-Thal), affecting 40,000 newborns every year. Early screening and a timely diagnosis are essential for β-thalassemia patients for the prevention and management of later clinical complications. However, in Africa, Southern Europe, the Middle East, and Southeast Asia, where β-thalassemia is most prevalent, the diagnosis and screening for β-thalassemia are still challenging due to the cost and logistical burden of laboratory diagnostic tests. Here, we present Gazelle, which is a paper-based microchip …
Apheresis Collection Of Mononuclear Cells For Chimeric-Antigen Receptor Therapies, Robert W. Maitta
Apheresis Collection Of Mononuclear Cells For Chimeric-Antigen Receptor Therapies, Robert W. Maitta
Faculty Scholarship
Collections of lymphocytes to be genetically modified to treat hematologic malignancies have seen a dramatic increase over the last few years as commercial products have been approved. Reports of new products in development that can possibly treat solid organ malignancies represent a massive change in the field. Apheresis is at the center of the collection of cells for the manufacture of these chimeric-antigen receptor therapy products. The expansion of these collections represents one of the areas of apheresis procedures growth. This review will summarize concepts important to this type of collection and variables that need to be optimized to obtain …
Zbtb16::Rara Variant Acute Promyelocytic Leukemia (Vapl) Treated With Gemtuzumab Ozogamicin (Go) With Unique Pathology And Genetic Findings, Jason A. Adler, Ramya Gadde, Benjamin K. Tomlinson, Shahirekha Shetty
Zbtb16::Rara Variant Acute Promyelocytic Leukemia (Vapl) Treated With Gemtuzumab Ozogamicin (Go) With Unique Pathology And Genetic Findings, Jason A. Adler, Ramya Gadde, Benjamin K. Tomlinson, Shahirekha Shetty
Faculty Scholarship
No abstract provided.
Editorial: Developments In Sickle Cell Disease Therapy And Potentials For Gene Therapy, Robert W. Maitta, Hollie M. Reeves
Editorial: Developments In Sickle Cell Disease Therapy And Potentials For Gene Therapy, Robert W. Maitta, Hollie M. Reeves
Faculty Scholarship
No abstract provided.
Membrane Bending And Sphingomyelinase-Associated, Sulfatide-Dependent Hypoxic Adhesion Of Sickle Mature Erythrocytes, Utku Goreke, Erdem Kucukal, Fang Wang, Ran An, Nicole Arnold, Erina Quinn, Charlotte Yuan, Allison Bode, Ailis Hill, Yuncheng Man, Bryan C. Hambley, Robert Schilz, Mahazarin Ginwalla, Umut A. Gurkan, Umut A. Gurkan
Membrane Bending And Sphingomyelinase-Associated, Sulfatide-Dependent Hypoxic Adhesion Of Sickle Mature Erythrocytes, Utku Goreke, Erdem Kucukal, Fang Wang, Ran An, Nicole Arnold, Erina Quinn, Charlotte Yuan, Allison Bode, Ailis Hill, Yuncheng Man, Bryan C. Hambley, Robert Schilz, Mahazarin Ginwalla, Umut A. Gurkan, Umut A. Gurkan
Faculty Scholarship
Abnormal erythrocyte adhesion owing to polymerization of sickle hemoglobin is central to the pathophysiology of sickle cell disease (SCD). Mature erythrocytes constitute >80% of all erythrocytes in SCD; however, the relative contributions of erythrocytes to acute and chronic vasculopathy in SCD are not well understood. Here, we showed that bending stress exerted on the erythrocyte plasma membrane by polymerization of sickle hemoglobin under hypoxia, enhances sulfatide-mediated abnormal mature erythrocyte adhesion. We hypothesized that sphingomyelinase (SMase) activity, which is upregulated by accumulated bending energy, leads to elevated membrane sulfatide availability, and thus, hypoxic mature erythrocyte adhesion. We found that mature erythrocyte …
Kindlin-3 Deficiency Leads To Impaired Erythropoiesis And Erythrocyte Cytoskeleton, Chloe Turpin, Utku Goreke, Utku Goreke, Katarzyna Bialkowska, Kamila M. Bledzka, Dmitriy Verbovetskiy, Umut A. Gurkan, Jun Qin, Edward F. Plow, Elzbieta Pluskota
Kindlin-3 Deficiency Leads To Impaired Erythropoiesis And Erythrocyte Cytoskeleton, Chloe Turpin, Utku Goreke, Utku Goreke, Katarzyna Bialkowska, Kamila M. Bledzka, Dmitriy Verbovetskiy, Umut A. Gurkan, Jun Qin, Edward F. Plow, Elzbieta Pluskota
Faculty Scholarship
Kindlin-3 (K3) is critical for the activation of integrin adhesion receptors in hematopoietic cells. In humans and mice, K3 deficiency is associated with impaired immunity and bone development, bleeding, and aberrant erythrocyte shape. To delineate how K3 deficiency (K3KO) contributes to anemia and misshaped erythrocytes, mice deficient in erythroid (K3KO\EpoR-cre) or myeloid cell K3 (K3KO\Lyz2cre), knockin mice expressing mutant K3 (Q597W598 to AA) with reduced integrin-activation function (K3KI), and control wild-type (WT) K3 mice were studied. Both K3-deficient strains and K3KI mice showed anemia at baseline, reduced response to erythropoietin stimulation, and compromised recovery after phenylhydrazine (PHZ)-induced hemolytic anemia as …
Microfluidic Concurrent Assessment Of Red Blood Cell Adhesion And Microcapillary Occlusion: Potential Hemorheological Biomarkers In Sickle Cell Disease, Yuncheng Man, Douglas H. Wu, Ran An, Karamoja Monchamp, Utku Goreke, Zoe Sekyonda, William J. Wulftange, Chiara Federici, Allison Bode, Lalitha V. Nayak, Umut A. Gurkan
Microfluidic Concurrent Assessment Of Red Blood Cell Adhesion And Microcapillary Occlusion: Potential Hemorheological Biomarkers In Sickle Cell Disease, Yuncheng Man, Douglas H. Wu, Ran An, Karamoja Monchamp, Utku Goreke, Zoe Sekyonda, William J. Wulftange, Chiara Federici, Allison Bode, Lalitha V. Nayak, Umut A. Gurkan
Faculty Scholarship
Deformability and non-adherence are two fundamental functional properties of red blood cells (RBCs), which allow them to move unimpeded through the microvasculature. In sickle cell disease (SCD), polymerization of abnormal sickle hemoglobin leads to decreased deformability and increased membrane adhesiveness in RBCs. This contributes to abnormal blood vessel occlusion, which is central to the underlying pathophysiology. RBC deformability and adhesiveness are, therefore key hemorheological biomarkers in characterizing disease states as well as in evaluating novel therapeutics. To date, these important interrelated biomarkers have been assessed in distinct laboratory assays, without integration or concurrent assessment in vitro. To this end, we …
Massage Therapy For Children, Adolescents, And Young Adults: Clinical Delivery And Effectiveness In Hematology And Oncology, Samuel N. Rodgers-Melnick, Mandy Bartolovich, Neha J. Desai, Smitha Hosahalli Vasanna, Amma Owusu-Ansah, Sanjay P. Ahuja, Jeffery A. Dusek, David W. Miller
Massage Therapy For Children, Adolescents, And Young Adults: Clinical Delivery And Effectiveness In Hematology And Oncology, Samuel N. Rodgers-Melnick, Mandy Bartolovich, Neha J. Desai, Smitha Hosahalli Vasanna, Amma Owusu-Ansah, Sanjay P. Ahuja, Jeffery A. Dusek, David W. Miller
Student Scholarship
Background: Children, adolescents, and young adults with hematologic and/or oncologic conditions experience multiple, significant symptoms (e.g., pain, stress, and anxiety), which may be addressed by nonpharmacologic approaches such as massage therapy (MT). The purpose of this study was to describe the clinical delivery of MT provided by a certified pediatric massage therapist and assess effectiveness in two patient groups: those with sickle cell disease (SCD) or hematologic and/or oncologic conditions excluding SCD (HemOnc). Methods: Investigators conducted a retrospective review of MT sessions provided to patients 0–39 years with hematologic and/or oncologic conditions at a large pediatric academic medical center. Results: …
Sickle Red Blood Cell-Derived Extracellular Vesicles Activate Endothelial Cells And Enhance Sickle Red Cell Adhesion Mediated By Von Willebrand Factor, Ran An, Yuncheng Man, Kevin Cheng, Tianyi Zhang, Fang Wang, Erdem Kucukal, William J. Wulftange, Utku Goreke, Allison Bode, Lalitha V. Nayak, Jane A. Little, Umut A. Gurkan
Sickle Red Blood Cell-Derived Extracellular Vesicles Activate Endothelial Cells And Enhance Sickle Red Cell Adhesion Mediated By Von Willebrand Factor, Ran An, Yuncheng Man, Kevin Cheng, Tianyi Zhang, Fang Wang, Erdem Kucukal, William J. Wulftange, Utku Goreke, Allison Bode, Lalitha V. Nayak, Jane A. Little, Umut A. Gurkan
Faculty Scholarship
Endothelial activation and sickle red blood cell (RBC) adhesion are central to the pathogenesis of sickle cell disease (SCD). Quantitatively, RBC-derived extracellular vesicles (REVs) are more abundant from SS RBCs compared with healthy RBCs (AA RBCs). Sickle RBC-derived REVs (SS REVs) are known to promote endothelial cell (EC) activation through cell signalling and transcriptional regulation at longer terms. However, the SS REV-mediated short-term non-transcriptional response of EC is unclear. Here, we examined the impact of SS REVs on acute microvascular EC activation and RBC adhesion at 2 h. Compared with AA REVs, SS REVs promoted human pulmonary microvascular ECs (HPMEC) …
Pum1 Mediates The Posttranscriptional Regulation Of Human Fetal Hemoglobin, Yuncheng Man, Amma Owusu-Ansah, Omar Y. Mian, Umut A. Gurkan, Anton A. Komar, Merlin Nithya Gnanapragasam
Pum1 Mediates The Posttranscriptional Regulation Of Human Fetal Hemoglobin, Yuncheng Man, Amma Owusu-Ansah, Omar Y. Mian, Umut A. Gurkan, Anton A. Komar, Merlin Nithya Gnanapragasam
Faculty Scholarship
The fetal-to-adult hemoglobin switching at about the time of birth involves a shift in expression from γ-globin to β-globin in erythroid cells. Effective re-expression of fetal γ-globin can ameliorate sickle cell anemia and β-thalassemia. Despite the physiological and clinical relevance of this switch, its posttranscriptional regulation is poorly understood. Here, we identify Pumilo 1 (PUM1), an RNA-binding protein with no previously reported functions in erythropoiesis, as a direct posttranscriptional regulator of β-globin switching. PUM1, whose expression is regulated by the erythroid master transcription factor erythroid Krüppel-like factor (EKLF/KLF1), peaks during erythroid differentiation, binds γ-globin messenger RNA (mRNA), and reduces γ-globin …
Multispectral Imaging For Microchip Electrophoresis Enables Point-Of-Care Newborn Hemoglobin Variant Screening, Ran An, Yuning Huang, Anne Rocheleau, Qiaochu Zhang, Yuncheng Man, Zoe Sekyonda, Amma Owusu-Ansah, Umut A. Gurkan
Multispectral Imaging For Microchip Electrophoresis Enables Point-Of-Care Newborn Hemoglobin Variant Screening, Ran An, Yuning Huang, Anne Rocheleau, Qiaochu Zhang, Yuncheng Man, Zoe Sekyonda, Amma Owusu-Ansah, Umut A. Gurkan
Faculty Scholarship
Hemoglobin (Hb) disorders affect nearly 7% of the world's population. Globally, around 400,000 babies are born annually with sickle cell disease (SCD), primarily in sub-Saharan Africa where morbidity and mortality rates are high. Screening, early diagnosis, and monitoring are not widely accessible due to technical challenges and cost. We hypothesized that multispectral imaging will allow sensitive hemoglobin variant identification in existing affordable paper-based Hb electrophoresis. To test this hypothesis, we developed the first integrated point-of-care multispectral Hb variant test: Gazelle-Multispectral. Here, we evaluated the accuracy of Gazelle-Multispectral for Hb variant newborn screening in 265 newborns with known hemoglobin variants including …
Catch Bonds In Sickle Cell Disease: Shear-Enhanced Adhesion Of Red Blood Cells To Laminin, Utku Goreke, Shamreen Iram, Gundeep Singh, Sergio Domínguez-Medina, Yuncheng Man, Allison Bode, Ran An, Jane A. Little, Christopher L. Wirth, Michael Hinczewski, Umut A. Gurkan
Catch Bonds In Sickle Cell Disease: Shear-Enhanced Adhesion Of Red Blood Cells To Laminin, Utku Goreke, Shamreen Iram, Gundeep Singh, Sergio Domínguez-Medina, Yuncheng Man, Allison Bode, Ran An, Jane A. Little, Christopher L. Wirth, Michael Hinczewski, Umut A. Gurkan
Faculty Scholarship
Could the phenomenon of catch bonding—force-strengthened cellular adhesion—play a role in sickle cell disease, where abnormal red blood cell (RBC) adhesion obstructs blood flow? Here we investigate the dynamics of sickle RBCs adhering to a surface functionalized with the protein laminin (a component of the extracellular matrix around blood vessels) under physiologically relevant micro-scale flow. First, using total internal reflectance microscopy we characterize the spatial fluctuations of the RBC membrane above the laminin surface before detachment. The complex dynamics we observe suggest the possibility of catch bonding, where the mean detachment time of the cell from the surface initially increases …
Chronic Red Cell Exchange In Sickle Cell Patients With Iron Overload May Not Affect Mortality, Yi Yuan Zhou, Hollie M. Reeves, Robert W. Maitta
Chronic Red Cell Exchange In Sickle Cell Patients With Iron Overload May Not Affect Mortality, Yi Yuan Zhou, Hollie M. Reeves, Robert W. Maitta
Faculty Scholarship
Sickle cell disease (SCD) is an inherited blood disorder that affects ~100,000 Americans (1, 2). In SCD, red blood cells (RBC) containing aberrant sickle hemoglobin (HgbS) become sickle-shaped at low oxygen tension and stick together leading to obstructed blood flow. The resulting decrease in tissue oxygenation causes chronic complications such as vasculo-occlusive pain crises among others that require frequent hospitalizations (3). Chronic RBC transfusions play a prominent role in the treatment of this disease by improving oxygenation through addition of normal RBC and dilution of RBC containing HgbS (4, 5). However, the major disadvantage of management with simple transfusion is …
Occlusionchip: A Functional Microcapillary Occlusion Assay Complementary To Ektacytometry For Detection Of Small-Fraction Red Blood Cells With Abnormal Deformability, Yuncheng Man, Ran An, Karamoja Monchamp, Zoe Sekyonda, Erdem Kucukal, Chiara Federici, William J. Wulftange, Utku Goreke, Allison Bode, Umut A. Gurkan
Occlusionchip: A Functional Microcapillary Occlusion Assay Complementary To Ektacytometry For Detection Of Small-Fraction Red Blood Cells With Abnormal Deformability, Yuncheng Man, Ran An, Karamoja Monchamp, Zoe Sekyonda, Erdem Kucukal, Chiara Federici, William J. Wulftange, Utku Goreke, Allison Bode, Umut A. Gurkan
Faculty Scholarship
Red blood cell (RBC) deformability is a valuable hemorheological biomarker that can be used to assess the clinical status and response to therapy of individuals with sickle cell disease (SCD). RBC deformability has been measured by ektacytometry for decades, which uses shear or osmolar stress. However, ektacytometry is a population based measurement that does not detect small-fractions of abnormal RBCs. A single cell-based, functional RBC deformability assay would complement ektacytometry and provide additional information. Here, we tested the relative merits of the OcclusionChip, which measures RBC deformability by microcapillary occlusion, and ektacytometry. We tested samples containing glutaraldehyde-stiffened RBCs for up …
Antithrombin-Iii Mitigates Thrombin-Mediated Endothelial Cell Contraction And Sickle Red Blood Cell Adhesion In Microscale Flow, William J. Wulftange, Erdem Kucukal, Yuncheng Man, Ran An, Karamoja Monchamp, Charlotte D. Sevrain, Himanshu R. Dashora, Allison Bode, Jane A. Little, Umut A. Gurkan
Antithrombin-Iii Mitigates Thrombin-Mediated Endothelial Cell Contraction And Sickle Red Blood Cell Adhesion In Microscale Flow, William J. Wulftange, Erdem Kucukal, Yuncheng Man, Ran An, Karamoja Monchamp, Charlotte D. Sevrain, Himanshu R. Dashora, Allison Bode, Jane A. Little, Umut A. Gurkan
Faculty Scholarship
Individuals with sickle cell disease (SCD) have persistently elevated thrombin generation that results in a state of systemic hypercoagulability. Antithrombin-III (ATIII), an endogenous serine protease inhibitor, inhibits several enzymes in the coagulation cascade, including thrombin. Here, we utilize a biomimetic microfluidic device to model the morphology and adhesive properties of endothelial cells (ECs) activated by thrombin and examine the efficacy of ATIII in mitigating the adhesion of SCD patient-derived red blood cells (RBCs) and EC retraction. Microfluidic devices were fabricated, seeded with ECs, and incubated under physiological shear stress. Cells were then activated with thrombin with or without an ATIII …
Anti‐Cd20 Therapeutic Options In Immune‐Mediated Thrombotic Thrombocytopenic Purpura, Robert W. Maitta
Anti‐Cd20 Therapeutic Options In Immune‐Mediated Thrombotic Thrombocytopenic Purpura, Robert W. Maitta
Faculty Scholarship
Immunosuppression with rituximab in immune-mediated thrombotic thrombocytopenic purpura helps decrease production of autoantibody mediating ADAMTS13 clearance from circulation. Failure to respond to rituximab in a satisfactory way or made difficult by adverse events to the medication does not represent a reason to stop considering anti-CD20 therapies to control antibody production. Therefore, both of atumumab and obinutuzumab with specificity to CD20, represent potentially valuable therapeutic tools in patients who are not candidates for rituximab. Commentary on: Doyle et al. The use of obinutuzumab and ofatumumab in the treatment of immune thrombotic thrombocytopenic purpura. Br J Haematol. 2022;198:391-396.1.
Editorial: Thrombotic Microangiopathies, Diagnostic And Therapeutic Advances, Robert W. Maitta, Hollie M. Reeves
Editorial: Thrombotic Microangiopathies, Diagnostic And Therapeutic Advances, Robert W. Maitta, Hollie M. Reeves
Faculty Scholarship
Thrombotic microangiopathies (TMAs) as a disease group represent a diagnostic and clinical challenge to practitioners. Presentations, which at times have overlapping symptomatology or have undetermined etiologies, emphasize the need for a constant reassessment of what is known about this disease group in order to determine not only how to best treat patients but also to develop targeted approaches to test for a given etiology. Likewise, in those instances when excluding diagnoses is the only available option, timely adjustment of therapy due to lack of therapeutic response needs to be achieved in the most efficient way. It is with this in …
Immature Platelet Dynamics In Immune-Mediated Thrombocytopenic States, Hollie M. Reeves, Robert W. Maitta
Immature Platelet Dynamics In Immune-Mediated Thrombocytopenic States, Hollie M. Reeves, Robert W. Maitta
Faculty Scholarship
A major challenge encountered by clinicians is differentiating presentations characterized by significant thrombocytopenia due to overlapping clinical symptoms and signs in the setting of ambiguous laboratory results. Immature platelets represent the youngest platelets that can be measured in peripheral blood by current hematology analyzers. These young platelets are larger, with higher RNA content recently released from the bone marrow. Thrombocytopenic presentations caused directly or indirectly by immune responses can lead to compensatory bone marrow responses seeking to normalize the platelet count; thus obtaining absolute immature platelet counts may be informative while triaging patients. Over the last decade, their use has …
Is G-Csf Dangerous In Covid-19: Why Not Use Gm-Csf?, Hillard M. Lazarus
Is G-Csf Dangerous In Covid-19: Why Not Use Gm-Csf?, Hillard M. Lazarus
Faculty Scholarship
No abstract provided.
G-Csf And Gm-Csf Are Different. Which One Is Better For Covid-19?, Hillard M. Lazarus
G-Csf And Gm-Csf Are Different. Which One Is Better For Covid-19?, Hillard M. Lazarus
Faculty Scholarship
No abstract provided.
Red Blood Cell Adhesion To Icam-1 Is Mediated By Fibrinogen And Is Associated With Right-To-Left Shunts In Sickle Cell Disease, Erdem Kucukal, Yuncheng Man, Erina Quinn, Neil Tewari, Ran An, Jane A. Little, Umut A. Gurkan
Red Blood Cell Adhesion To Icam-1 Is Mediated By Fibrinogen And Is Associated With Right-To-Left Shunts In Sickle Cell Disease, Erdem Kucukal, Yuncheng Man, Erina Quinn, Neil Tewari, Ran An, Jane A. Little, Umut A. Gurkan
Faculty Scholarship
Sickle cell disease (SCD), which afflicts 100 000 Americans, as well as millions worldwide, is associated with anemia, lifelong morbidity, and early mortality. Abnormal adhesion of sickle red blood cells (RBCs) to activated vascular endothelium may contribute acutely to the initiation of painful vaso-occlusive crises and chronically to endothelial damage in SCD. Sickle RBCs adhere to activated endothelium through several adhesion mechanisms. In this study, using whole blood from 17 people with heterozygous SCD (HbS variant) and 55 people with homozygous SCD (HbSS) analyzed in an in vitro microfluidic assay, we present evidence for the adhesion of sickle RBCs to …
Whole Blood Viscosity And Red Blood Cell Adhesion: Potential Biomarkers For Targeted And Curative Therapies In Sickle Cell Disease, Erdem Kucukal, Yuncheng Man, Ailis Hill, Shichen Liu, Allison Bode, Ran An, Jaikrishnan Kadambi, Jane A. Little, Umut A. Gurkan
Whole Blood Viscosity And Red Blood Cell Adhesion: Potential Biomarkers For Targeted And Curative Therapies In Sickle Cell Disease, Erdem Kucukal, Yuncheng Man, Ailis Hill, Shichen Liu, Allison Bode, Ran An, Jaikrishnan Kadambi, Jane A. Little, Umut A. Gurkan
Faculty Scholarship
Sickle cell disease (SCD) is a recessive genetic blood disorder exhibiting abnormal blood rheology. Polymerization of sickle hemoglobin, due to a point mutation in the β-globin gene of hemoglobin, results in aberrantly adhesive and stiff red blood cells (RBCs). Hemolysis, abnormal RBC adhesion, and abnormal blood rheology together impair endothelial health in people with SCD, which leads to cumulative systemic complications. Here, we describe a microfluidic assay combined with a micro particle image velocimetry technique for the integrated in vitro assessment of whole blood viscosity (WBV) and RBC adhesion. We examined WBV and RBC adhesion to laminin (LN) in microscale …
Use Of A Whole-Cell Elisa To Detect Additional Antibodies In Setting Of Suspected Heparin-Induced Thrombocytopenia, Eva M. Bashover, Catherine M. Stefaniuk, Clifford V. Harding, Robert W. Maitta
Use Of A Whole-Cell Elisa To Detect Additional Antibodies In Setting Of Suspected Heparin-Induced Thrombocytopenia, Eva M. Bashover, Catherine M. Stefaniuk, Clifford V. Harding, Robert W. Maitta
Faculty Scholarship
OBJECTIVES: Type II heparin-induced thrombocytopenia (HIT) is mediated by formation of antibodies to platelet factor 4 (PF4)-heparin complexes. We evaluated anti-PF4-heparin-negative samples for the presence of additional anti-platelet and anti-red blood cell (RBC) antibodies using whole-cell platelet/ RBC ELISAs we developed. METHODS: Seventy-three samples tested for anti-PF4-heparin by ELISA were included: 62 tested negative, 9 tested positive, and 2 had equivocal results. Plasma specimens from healthy donors were used as controls. RESULTS: 100% (9/9) anti-PF4-positive samples had anti-platelet antibodies detected by whole-cell platelet ELISA. 42.2% (27/64) anti-PF4-heparin-negative samples were negative for anti-platelet and anti-RBC antibodies. 32.8% (21/64) negative samples showed …
Ultrastructural Changes In Peripheral Blood Leukocytes In Α-Synuclein Knockout Mice, Hammad Tashkandi, Afshin Shameli, Clifford V. Harding, Robert W. Maitta
Ultrastructural Changes In Peripheral Blood Leukocytes In Α-Synuclein Knockout Mice, Hammad Tashkandi, Afshin Shameli, Clifford V. Harding, Robert W. Maitta
Faculty Scholarship
Effects of α-synuclein deficiency on cellular blood components have not been extensively investigated. This study evaluated ultrastructural changes of leukocytes in α-synuclein knockout (KO) mice using electron microscopy (EM). The following ultrastructural characteristics were quantified in leukocytes: mitochondria, primary granules, specific granules (SG), Golgi apparatus (GA), inclusions, rough-endoplasmic reticulum (RER), smooth-endoplasmic reticulum (SER), and cellular projections (CP). EM showed increased numbers or amounts of SG, inclusions, and SER in KO group (5.3 ± 4.5 in WT vs. 14.1 ± 10.3 in KO, p = 0.02; 0.4 ± 0.9 in WT vs. 3.2 ± 2.8 in KO, p = 0.007; and …
Α-Synuclein Concentration Increases Over Time In Plasma Supernatant Of Single Donor Platelets, Catherine M. Stefaniuk, Clifford V. Harding, Robert W. Maitta
Α-Synuclein Concentration Increases Over Time In Plasma Supernatant Of Single Donor Platelets, Catherine M. Stefaniuk, Clifford V. Harding, Robert W. Maitta
Faculty Scholarship
OBJECTIVES: In platelets, α-synuclein is important in calcium-dependent granule release. Notably, cells release α-synuclein in setting of cell damage or death. Therefore, we investigated α-synuclein levels in plasma of single donor platelet (SDP) units during storage. METHODS: Aliquots were obtained from same SDP units for 7 days from day of donation. Additionally, randomly sampled SDP units at same storage time points were also assayed by enzyme-linked immunosorbent assay. RESULTS: α-Synuclein in SDP plasma increased continuously over time at each assayed time point. Significant increases were measured on day 3 (11.7 ± 9.6 ng/mL, P = 0.025), day 5 (15.3 ± …
Biomimetic Post-Capillary Venule Expansions For Leukocyte Adhesion Studies, Bryan L. Benson, Lucy Li, Jay T. Myers, R. Dixon Dorand, Umut A. Gurkan, Alex Y. Huang
Biomimetic Post-Capillary Venule Expansions For Leukocyte Adhesion Studies, Bryan L. Benson, Lucy Li, Jay T. Myers, R. Dixon Dorand, Umut A. Gurkan, Alex Y. Huang
Faculty Scholarship
Leukocyte adhesion and extravasation are maximal near the transition from capillary to post-capillary venule, and are strongly influenced by a confluence of scale-dependent physical effects. Mimicking the scale of physiological vessels using in vitro microfluidic systems allows the capture of these effects on leukocyte adhesion assays, but imposes practical limits on reproducibility and reliable quantification. Here we present a microfluidic platform that provides multiple (54–512) technical replicates within a 15-minute sample collection time, coupled with an automated computer vision analysis pipeline that captures leukocyte adhesion probabilities as a function of shear and extensional stresses. We report that in post-capillary channels …
Prevalence Of Stroke In Children Admitted With Sickle Cell Anaemia To Mulago Hospital, Samden Lhatoo, Martha Sajatovic
Prevalence Of Stroke In Children Admitted With Sickle Cell Anaemia To Mulago Hospital, Samden Lhatoo, Martha Sajatovic
Faculty Scholarship
Background: Stroke is a major complication of sickle cell anaemia (SCA). It occurs commonly in childhood with about 10 % of children with sickle cell anaemia getting affected by this complication. In Uganda, there is paucity of data on the prevalence of stroke in children admitted in a tertiary institution. We determined the prevalence of stroke amongst children with SCA admitted to Mulago National Referral Hospital in Uganda and described the ir co-morbidities. Methods: We conducted a retrospective record review of children with SCA admitted from August 2012 to August 2014 to the Paediatric Haematology Ward of Mulago Hospital in …
A Critical Role For Alpha-Synuclein In Development And Function Of T Lymphocytes, Afshin Shameli, Wenbin Xiao, Yan Zheng, Susan Shyu, John Sumodi, Howard J. Meyerson, Clifford V. Harding, Robert W. Maitta
A Critical Role For Alpha-Synuclein In Development And Function Of T Lymphocytes, Afshin Shameli, Wenbin Xiao, Yan Zheng, Susan Shyu, John Sumodi, Howard J. Meyerson, Clifford V. Harding, Robert W. Maitta
Faculty Scholarship
Alpha-synuclein is highly expressed in the central nervous system and plays an important role in pathogenesis of neurodegenerative disorders such as Parkinson's disease and Lewy body dementia. Previous studies have demonstrated the expression of α-synuclein in hematopoietic elements and peripheral blood mononuclear cells, although its roles in hematopoiesis and adaptive immunity are not studied. Using an α-synuclein knock out (KO) mouse model, we have recently shown that α-synuclein deficiency is associated with a mild defect in late stages of hematopoiesis. More importantly, we demonstrated a marked defect in B lymphocyte development and IgG, but not IgM production in these mice. …
Re-Examination Of 30-Day Survival And Relapse Rates In Patients With Thrombotic Thrombocytopenic Purpura-Hemolytic Uremic Syndrome, Cassiana E. Bittencourt, Jennifer P. Ha, Robert W. Maitta
Re-Examination Of 30-Day Survival And Relapse Rates In Patients With Thrombotic Thrombocytopenic Purpura-Hemolytic Uremic Syndrome, Cassiana E. Bittencourt, Jennifer P. Ha, Robert W. Maitta
Faculty Scholarship
Background and Objectives: Thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS) are characterized by microangiopathic hemolytic anemia and thrombocytopenia. Interestingly, markedly different survival rates have been reported despite increases in survivability. We studied TTP-HUS 30-day mortality and relapse rates of patients who received TPE at our institution and compared them to published data. Patients and Methods: Retrospective study analyzed 30-day mortality and relapse rates attributed to TTP-HUS from 01/01/2008 to 12/31/2012 and compared them to comparable literature reporting mortality and survival. Studies describing other etiologies for TPE and different mortality time interval were excluded. Results: Fifty-nine patients were analyzed …