33 results on '"Gural, Alexander"'
Search Results
2. Unit-to-unit variability in the deformability of red blood cells
- Author
-
Barshtein, Gregory, Gural, Alexander, Zelig, Orly, Arbell, Dan, and Yedgar, Saul
- Published
- 2020
- Full Text
- View/download PDF
3. Hemoglobin Binding to the Red Blood Cell (RBC) Membrane Is Associated with Decreased Cell Deformability.
- Author
-
Barshtein, Gregory, Livshits, Leonid, Gural, Alexander, Arbell, Dan, Barkan, Refael, Pajic-Lijakovic, Ivana, and Yedgar, Saul
- Subjects
ERYTHROCYTE deformability ,ERYTHROCYTES ,CELLULAR mechanics ,HEMOGLOBINS ,MASS spectrometry ,SHEARING force - Abstract
The deformability of red blood cells (RBCs), expressing their ability to change their shape as a function of flow-induced shear stress, allows them to optimize oxygen delivery to the tissues and minimize their resistance to flow, especially in microcirculation. During physiological aging and blood storage, or under external stimulations, RBCs undergo metabolic and structural alterations, one of which is hemoglobin (Hb) redistribution between the cytosol and the membrane. Consequently, part of the Hb may attach to the cell membrane, and although this process is reversible, the increase in membrane-bound Hb (MBHb) can affect the cell's mechanical properties and deformability in particular. In the present study, we examined the correlation between the MBHb levels, determined by mass spectroscopy, and the cell deformability, determined by image analysis. Six hemoglobin subunits were found attached to the RBC membranes. The cell deformability was negatively correlated with the level of four subunits, with a highly significant inter-correlation between them. These data suggest that the decrease in RBC deformability results from Hb redistribution between the cytosol and the cell membrane and the respective Hb interaction with the cell membrane. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
4. Preparation of packed red blood cell units in the blood bank: Alteration in red blood cell deformability
- Author
-
Barshtein, Gregory, Gural, Alexander, Zelig, Orly, Arbell, Dan, and Yedgar, Saul
- Published
- 2020
- Full Text
- View/download PDF
5. Red Blood Cell Deformability Is Expressed by a Set of Interrelated Membrane Proteins.
- Author
-
Barshtein, Gregory, Gural, Alexander, Arbell, Dan, Barkan, Refael, Livshits, Leonid, Pajic-Lijakovic, Ivana, and Yedgar, Saul
- Subjects
- *
ERYTHROCYTE deformability , *ERYTHROCYTES , *MEMBRANE proteins , *VASCULAR resistance , *BLOOD circulation disorders , *MASS spectrometry - Abstract
Red blood cell (RBC) deformability, expressing their ability to change their shape, allows them to minimize their resistance to flow and optimize oxygen delivery to the tissues. RBC with reduced deformability may lead to increased vascular resistance, capillary occlusion, and impaired perfusion and oxygen delivery. A reduction in deformability, as occurs during RBC physiological aging and under blood storage, is implicated in the pathophysiology of diverse conditions with circulatory disorders and anemias. The change in RBC deformability is associated with metabolic and structural alterations, mostly uncharacterized. To bridge this gap, we analyzed the membrane protein levels, using mass spectroscopy, of RBC with varying deformability determined by image analysis. In total, 752 membrane proteins were identified. However, deformability was positively correlated with the level of only fourteen proteins, with a highly significant inter-correlation between them. These proteins are involved in membrane rafting and/or the membrane–cytoskeleton linkage. These findings suggest that the reduction of deformability is a programmed (not arbitrary) process of remodeling and shedding of membrane fragments, possibly mirroring the formation of extracellular vesicles. The highly significant inter-correlation between the deformability-expressing proteins infers that the cell deformability can be assessed by determining the level of a few, possibly one, of them. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
6. The Leukemogenicity of AML1-ETO Is Dependent on Site-Specific Lysine Acetylation
- Author
-
Wang, Lan, Gural, Alexander, Sun, Xiao-Jian, Zhao, Xinyang, Perna, Fabiana, Huang, Gang, Hatlen, Megan A., Vu, Ly, Liu, Fan, Xu, Haiming, Asai, Takashi, Xu, Hao, Deblasio, Tony, Menendez, Silvia, Voza, Francesca, Jiang, Yanwen, Cole, Philip A., Zhang, Jinsong, Melnick, Ari, Roeder, Robert G., and Nimer, Stephen D.
- Published
- 2011
- Full Text
- View/download PDF
7. Hemolytic Activity of Nanoparticles as a Marker of Their Hemocompatibility.
- Author
-
Yedgar, Saul, Barshtein, Gregory, and Gural, Alexander
- Subjects
ERYTHROCYTES ,NANOPARTICLES ,BLOOD proteins ,BLOOD plasma ,HUMAN ecology - Abstract
The potential use of nanomaterials in medicine offers opportunities for novel therapeutic approaches to treating complex disorders. For that reason, a new branch of science, named nanotoxicology, which aims to study the dangerous effects of nanomaterials on human health and on the environment, has recently emerged. However, the toxicity and risk associated with nanomaterials are unclear or not completely understood. The development of an adequate experimental strategy for assessing the toxicity of nanomaterials may include a rapid/express method that will reliably, quickly, and cheaply make an initial assessment. One possibility is the characterization of the hemocompatibility of nanomaterials, which includes their hemolytic activity as a marker. In this review, we consider various factors affecting the hemolytic activity of nanomaterials and draw the reader's attention to the fact that the formation of a protein corona around a nanoparticle can significantly change its interaction with the red cell. This leads us to suggest that the nanomaterial hemolytic activity in the buffer does not reflect the situation in the blood plasma. As a recommendation, we propose studying the hemocompatibility of nanomaterials under more physiologically relevant conditions, in the presence of plasma proteins in the medium and under mechanical stress. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
8. Double-Facet Effect of Artificial Mechanical Stress on Red Blood Cell Deformability: Implications for Blood Salvage.
- Author
-
Tsohar, Tamir, Beyth, Shaul, Gural, Alexander, Arbell, Dan, Yedgar, Saul, and Barshtein, Gregory
- Subjects
STRAINS & stresses (Mechanics) ,ERYTHROCYTES ,HEMORHEOLOGY ,ERYTHROCYTE deformability ,ARTIFICIAL organs ,CELL populations ,ORTHOPEDIC surgery - Abstract
The use of intra-operative blood salvage, dialysis, and artificial organs are associated with the application of non-physiological mechanical stress on red blood cells (RBCs). To explore the effect of these procedures on red cell deformability, we determined it before and after the mechanical stress application both in an in vitro system and following a blood-saving procedure. RBC from eight healthy donors and fifteen packed RBC units were subjected to mechanical stress. RBCs from five patients undergoing orthopedic surgery were also collected. We measured the percent of undeformable cells (%UDFC) in the red cell samples using our cell flow properties image analyzer, which provides the distribution of RBC deformability in a large cell population. Mechanical stress systematically reduced the cell deformability and increased the %UDFC, while simultaneously causing hemolysis of rigid, undeformable RBCs. Ultimately, the overall result depended on the initial level of the undeformable cells; the stress-induced change in the proportion of rigid cells (Δ%UDFC) increased (Δ%UDFC > 0) when its initial value was low, and decreased (Δ%UDFC < 0) when its initial value was high. This suggests that the final impact of mechanical stress on the percent of rigid cells in the RBC population is primarily determined by their initial concentration in the sample. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
9. Rituximab, methotrexate, procarbazine and lomustine (R-MPL) for the treatment of primary Central nervous system lymphoma.
- Author
-
Lebel, Eyal, Goldschmidt, Neta, Siegal, Tali, Lossos, Alexander, Rosenberg, Shai, Makranz, Chen, Linetski, Eduard, Gatt, Moshe E., Gural, Alexander, Saban, Revital, Lavie, David, Vainstein, Vladimir, Zimran, Eran, Avni, Batia, Grisaro, Sigal, Shaulov, Adir, and Nachmias, Boaz
- Subjects
CENTRAL nervous system ,METHOTREXATE ,RITUXIMAB ,HEALTH facilities ,AUTOGRAFTS - Abstract
The optimal high-dose methotrexate (HDMTX)-based combination therapy for primary central nervous system lymphoma is unknown. We report our experience with rituximab, HDMTX, procarbazine and lomustine (R-MPL) given as first-line treatment in our center. Fifty-two patients between 2006 and 2019 were included. Eighteen patients proceeded to autologous transplant or two cycles of intermediate-dose cytarabine. The median age was 62 y (range 28–94) and the Eastern Cooperative Oncology Group performance status (ECOG-PS) was ≥2 in 62% (32/52). The overall/complete response rates were 79% (41/52) and 52% (27/52), respectively. The median progression-free/overall survival was 19 m/84m, respectively. Grade 3–4 adverse events included infections (17%) and kidney injury (13%). Ten patients (19%) discontinued therapy for toxicity. There were no treatment-related deaths. In summary, in a cohort enriched in frail patients, R-MPL achieved good responses and OS and was safe for all ages. The PFS was sub-optimal, possibly explained by a low proportion of consolidation. This regimen should be evaluated prospectively. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
10. case series of eosinophilic myocarditis: different faces of the same coin.
- Author
-
Mengesha, Bethlehem, Meir, Karen, Gural, Alexander, and Asleh, Rabea
- Subjects
MYOCARDITIS ,SYMPTOMS ,TREATMENT delay (Medicine) ,COINS ,CARDIOVASCULAR diseases - Abstract
Background Eosinophilic myocarditis (EM) is a rare form of myocarditis with various aetiologies and dire consequences if not diagnosed and treated expeditiously. Case summary We report three cases of EM at different stages of the disease with differing clinical manifestations. We highlight the diagnostic workup including the role of multimodality imaging and endomyocardial biopsy (EMB), and the treatment strategies. Discussion EM is an underdiagnosed and potentially life-threatening disease. Therefore, a high clinical suspicion for EM should arise when patients with signs and symptoms of cardiovascular disease develop hypereosinophilia or vice versa. Early identification of this condition using multimodality imaging and EMB is of paramount importance as the disease may progress to the irreversible late fibrotic stage if treatment is delayed. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
11. Cold Agglutinin-Mediated Autoimmune Hemolytic Anemia in Association with Antiphospholipid Syndrome.
- Author
-
Gelman, Ram, Kharouf, Fadi, Ishay, Yuval, and Gural, Alexander
- Subjects
AUTOIMMUNE hemolytic anemia ,ANTIPHOSPHOLIPID syndrome ,COMPLEMENT activation ,HEMOLYTIC anemia - Abstract
Antiphospholipid syndrome and cold agglutinin-mediated autoimmune hemolytic anemia are 2 distinct immune-mediated hematologic disorders. While no clear association exists between these 2 entities, complement activation is known to occur in both of them. Herein, we report a unique case of cold agglutinin hemolytic anemia in a patient with a known primary antiphospholipid syndrome. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
12. A trifungal infection of the mandible: Case report and literature review
- Author
-
Lador, Nilly, Polacheck, Itzhack, Gural, Alexander, Sanatski, Ekatrina, and Garfunkel, Adrian
- Published
- 2006
13. Age related microsatellite instability in T cells from healthy individuals
- Author
-
Krichevsky, Svetlana, Pawelec, Graham, Gural, Alexander, Effros, Rita B, Globerson, Amiela, Yehuda, Dina Ben, and Yehuda, Arie Ben
- Published
- 2004
- Full Text
- View/download PDF
14. Venetoclax combinations induce high response rates in newly diagnosed acute myeloid leukemia patients ineligible for intensive chemotherapy in routine practice.
- Author
-
Apel, Arie, Moshe, Yakir, Ofran, Yishai, Gural, Alexander, Wolach, Ofir, Ganzel, Chezi, Canaani, Jonathan, Zektser, Miri, Duek, Adrian, Stemer, Galia, Hellman, Ilana, Basood, May, Frisch, Avraham, Leibovitch, Chiya, and Koren‐Michowitz, Maya
- Published
- 2021
- Full Text
- View/download PDF
15. Venetoclax is safe and efficacious in relapsed/refractory AML.
- Author
-
Ganzel, Chezi, Ram, Ron, Gural, Alexander, Wolach, Ofir, Gino-Moor, Sharon, Vainstein, Vladimir, Nachmias, Boaz, Apel, Arie, Koren-Michowitz, Maya, Pasvolsky, Oren, Yerushalmi, Ronit, Danylesko, Ivetta, Cohen, Yosef, Peretz, Galit, Moshe, Yakir, Zektser, Miri, Yeganeh, Shay, Rowe, Jacob M., and Ofran, Yishai
- Subjects
ACUTE myeloid leukemia ,PLATELET count ,BONE marrow examination - Abstract
Data from 11 Israeli centers, where venetoclax was used for relapsed/refractory AML after intensive chemotherapy, were retrospectively collected. During 2016–2019, forty patients were identified. Median age was 67 years (21–82), 60% males, median of 2(1–4) prior lines of treatment and 42% relapsed after allogeneic transplant. 62.5% of the patients received the venetoclax with hypomethylating agents and 22.5% with low dose cytarabine. Median follow-up was 5.5 months. Of the 29 patients who survived for more than two cycles of therapy, 22 (76%) achieved neutrophil recovery and 59% (n = 17) recovered also their platelet count. In 15 (52% of those who survived > 2 months), CR/CRi was confirmed by bone marrow examination. The median OS from venetoclax initiation of all the patients and of those who survived more than 2 months was 5.5 and 6.5 months, respectively. In conclusion, this study demonstrates that venetoclax is safe and active also in AML patients with advanced disease. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
16. Methylation of RUNX1 by PRMT1 abrogates SIN3A binding and potentiates its transcriptional activity
- Author
-
Xinyang Zhao, Jankovic, Vladimir, Gural, Alexander, Gang Huang, Pardanani, Animesh, Menendez, Silvia, Jin Zhang, Dunne, Richard, Xiao, Andrew, Erdjument-Bromage, Hediye, Allis, C. David, Tempst, Paul, and Nimer, Stephen D.
- Subjects
Arginine -- Research ,Leukemia -- Genetic aspects ,Methylation -- Analysis ,Genetic transcription -- Analysis ,Biological sciences - Abstract
The identification of two arginine residues (R206 and R210) within the region of RUNX1 that interact with the corepressor SIN3A and are methylated by PRMT1 is reported. Results provide insight into the arginine methylation sites and the loss of dynamic regulation of corepressor binding in the leukemia-associated RUNX1-ETO fusion protein, which contributes to its dominant inhibitory activity.
- Published
- 2008
17. Romidepsin-Bendamustine Combination for Relapsed/Refractory T Cell Lymphoma.
- Author
-
Nachmias, Boaz, Shaulov, Adir, Lavie, David, Goldschmidt, Neta, Gural, Alexander, Saban, Revital, Lebel, Eyal, and Gatt, Moshe E.
- Abstract
Background: The treatment of relapsed/refractory (R/R) peripheral T cell lymphoma (PTCL) is limited to a few agents. Romidepsin, a histone deacetylase inhibitor, was approved for PTCL treatment as a single agent in the R/R setting, yet with partial efficacy. Several attempts to combine romidepsin with other chemotherapy regimens have been reported, however, with significant toxicity. Objectives: To study the romidepsin-bendamustine combination in PTCL in an attempt to maximize efficacy while minimizing toxicity. Methods: We report on a series of 7 heavily pretreated PTCL patients (2–5 previous lines of therapy) treated with a romidepsin-bendamustine combination. Results: Four patients were not previously exposed to either drug. Of these, 2 achieved complete remission. Interestingly, 1 patient continued treatment with a prolonged progression-free survival of more than 4 years. Toxicity was minimal and no treatment-related deaths or discontinuation were noted. Significant nausea and vomiting were reported in over 50% of patients. Hematological toxicity was mild and lower than that reported for other romidepsin-chemotherapy combinations and was correlated with bone marrow involvement by lymphoma. Conclusions: Although reporting a small number of patients, our data suggest that the combination of romidepsin and bendamustine may be a feasible therapeutic option in R/R PTCL patients and merits further study. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
18. A Bortezomib-Based Protocol Induces a High Rate of Complete Remission with Minor Toxicity in Adult Patients with Relapsed/Refractory Acute Lymphoblastic Leukemia.
- Author
-
Nachmias, Boaz, Shaulov, Adir, Gatt, Moshe E., Shapira, Michael, and Gural, Alexander
- Subjects
BORTEZOMIB ,BONE marrow transplantation ,CANCER chemotherapy ,HEMATOLOGIC malignancies ,GRAFT versus host disease - Abstract
The treatment of relapsed/refractory acute lymphoblastic leukemia (RR-ALL) presents a true clinical challenge. In 2012, a protocol combining bortezomib, dexamethasone, asparaginase, doxorubicin, and vincristine administered to children with RR-ALL was published with encouraging results. Over the past 5 years, we have implemented this protocol in the adult RR-ALL population (> 18 years) and addressed its feasibility in terms of remission rate and toxicity. Here, we present the results of our experience in 9 patients, all of whom received multiple previous chemotherapy protocols, two of them relapsing after an allogeneic bone marrow transplantation. All of the five B-ALL patients, and two of the four T-ALL achieved complete remission. Of the seven patients achieving complete remission, two patients were referred for allogeneic bone marrow transplantation, two patients were subsequently given blinatumomab, and one patient subsequently received donor lymphocyte infusion followed by blinatumomab. Thus, five out of nine patients treated (55%) were able to proceed to best available therapy in a complete remission. We observed minimal adverse effects, mainly hematological toxicity. We conclude that the bortezomib-based protocol should be evaluated as an effective and well-tolerated treatment option for adult patients either unfit for or failing standard salvage chemotherapy, as a bridge to immunotherapy or allogeneic bone marrow transplantation. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
19. Is It Possible to Reverse the Storage-Induced Lesion of Red Blood Cells?
- Author
-
Barshtein, Gregory, Arbell, Dan, Livshits, Leonid, and Gural, Alexander
- Subjects
ERYTHROCYTES ,BLOOD banks ,BLOOD transfusion ,BLOOD cell deformability ,ERYTHROCYTE membranes - Abstract
Cold-storage of packed red blood cells (PRBCs) in the blood bank is reportedly associated with alteration in a wide range of RBC features, which change cell storage each on its own timescale. Thus, some of the changes take place at an early stage of storage (during the first 7 days), while others occur later. We still do not have a clear understanding what happens to the damaged PRBC following their transfusion. We know that some portion (from a few to 10%) of transfused cells with a high degree of damage are removed from the bloodstream immediately or in the first hour(s) after the transfusion. The remaining cells partially restore their functionality and remain in the recipient’s blood for a longer time. Thus, the ability of transfused cells to recover is a significant factor in PRBC transfusion effectiveness. In the present review, we discuss publications that examined RBC lesions induced by the cold storage, aiming to offer a better understanding of the time frame in which these lesions occur, with particular emphasis on the question of their reversibility. We argue that transfused RBCs are capable (in a matter of a few hours) of restoring their pre-storage levels of ATP and 2,3-DPG, with subsequent restoration of cell functionality, especially of those properties having a more pronounced ATP-dependence. The extent of reversal is inversely proportional to the extent of damage, and some of the changes cannot be reversed. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
20. Daratumumab resistance is frequent in advanced‐stage multiple myeloma patients irrespective of CD38 expression and is related to dismal prognosis.
- Author
-
Pick, Marjorie, Vainstein, Vladimir, Goldschmidt, Neta, Lavie, David, Libster, Diana, Gural, Alexander, Grisariu, Sigal, Avni, Batia, Ben Yehuda, Dina, and Gatt, Moshe E.
- Subjects
MULTIPLE myeloma ,CD38 antigen ,AMYLOIDOSIS ,MULTIPLE myeloma treatment ,FLOW cytometry ,DRUG administration ,DARATUMUMAB - Abstract
Abstract: Objective: Daratumumab is a promising new antimyeloma agent. We report a single center “real‐world” series of multiple myeloma (MM) and amyloidosis (AL) patients treated with daratumumab. Methods: Forty‐one patients were included: 7 second‐line MM, 30 heavily pretreated (median number of therapies of 5) advanced MM, and 4 with AL. Results: Second‐line patients and advanced AL showed high rate of durable overall responses. However, advanced MM patients had a dismal prognosis with an overall response rate (ORR) of 36%, and a short median progression‐free and overall survival of 2.3 and 6.6 months, respectively. Responses were particularly poor in patients with extramedullary plasmacytomas. Neither the addition of another agent to daratumumab nor changing to the next line of therapy produced significant durable responses in this patient population. Flow cytometry analysis demonstrated that CD38 expression level was not predictive of response. We show that CD38 expression dynamics by a commercially available anti‐CD38 antibody after daratumumab administration was hindered by competitive binding of daratumumab. Conclusions: Responses to daratumumab and combinations in patients with advanced MM, particularly with extramedullary disease, are low and short‐lived, stressing the administration of this agent should be early in the course of the disease. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
21. Alopecia Areata as a Manifestation of Systemic Lymphoma: Report of Two Cases.
- Author
-
Ramot, Yuval, Gural, Alexander, and Zlotogorski, Abraham
- Published
- 2016
- Full Text
- View/download PDF
22. A Randomized Controlled Study to Determine the Efficacy of Garlic Compounds in Patients With Hematological Malignancies at Risk for Chemotherapy-Related Febrile Neutropenia.
- Author
-
Gatt, Moshe E., Strahilevitz, Jacob, Sharon, Nir, Lavie, David, Goldschmidt, Neta, Kalish, Yossef, Gural, Alexander, and Paltiel, Ora B.
- Abstract
Background. Patients receiving chemotherapy for hematological malignancies are at high risk for febrile neutropenia (FN). Garlic extracts (GEs) are natural food substances showing antimicrobial effects in vivo. Objectives. We explored whether adding GE may be efficacious in reducing the risk or severity of infections. Design. This was a placebo-controlled double-blind randomized study. Results. Of 95 patients randomized to receive GE or placebo following chemotherapy, a febrile episode was documented in 50% of patients receiving GE and 63.3% receiving placebo (P = .89). There was a higher risk of developing a third and fourth febrile episode in the GE group (P = .01). However, among those at a lower risk for FN, those receiving GE developed fewer FN episodes (P = .075), especially those with severe neutropenia (P = .05). Major adverse events were distributed equally, but nonadherence was more common in the GE than in the placebo group: 19.5% versus 4%, respectively (P = .05). Conclusions. GE was safe and did not reduce FN risk in the entire cohort, but yet appeared to exert a protective effect in the lower-risk subgroup. We do not recommend the use of GE for FN prevention in higher-risk patients. A larger-scale clinical trial for the lower-risk subgroup of patients is advocated. (This trial was registered at
www.clinicaltrials.gov as NCT00247039.) [ABSTRACT FROM AUTHOR]- Published
- 2015
- Full Text
- View/download PDF
23. Polymorphisms in the human organic cation transporter and the multidrug resistance gene: correlation with imatinib levels and clinical course in patients with chronic myeloid leukemia.
- Author
-
Vine, Jacob, Cohen, Sara Bar, Ruchlemer, Rosa, Goldschmidt, Neta, Levin, Moshe, Libster, Diana, Gural, Alexander, Gatt, Moshe E., Lavie, David, Ben-Yehuda, Dina, and Rund, Deborah
- Subjects
CHRONIC myeloid leukemia ,GENETIC polymorphism research ,MULTIDRUG resistance ,CATIONS ,IMATINIB ,PROTEIN-tyrosine kinases ,PHARMACOGENOMICS ,HEALTH outcome assessment - Abstract
The optimal tyrosine kinase inhibitor for any individual patient with chronic myeloid leukemia (CML) is not predictable. Pharmacogenetic parameters and trough levels of imatinib (IM) have each been independently correlated with response. We therefore studied the human organic cation transporter (h OCT1) and multidrug resistance ( MDR1) single nucleotide polymorphisms (SNPs) and correlated these with IM levels and major molecular response (MMR) (3-log reduction) in 84 patients with CML, the first such study performed in Caucasians. We studied MDR1 G2677T and C3435T, and for h OCT1, C480G and A1222G. IM levels varied significantly with dose (< or > 400 mg/day) ( p = 0.038) and were significantly lower in 20 patients who lost MMR ( p = 0.042). Adjusting for dose, trough IM levels were not significantly correlated with SNPs. Patients with MDR1 3435 TT had significantly longer times to MMR compared to CC/CT genotypes ( p = 0.047). Genotypes did not predict treatment failure when controlling for IM levels. We conclude that IM levels, but not the SNPs studied here, determine IM failure. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
24. Storage-Induced Damage to Red Blood Cell Mechanical Properties Can Be Only Partially Reversed by Rejuvenation.
- Author
-
Barshtein, Gregory, Gural, alexander, Manny, Noga, Zelig, Orly, Yedgar, Saul, and arbell, Dan
- Abstract
Background: The storage of red blood cells (RBC) is associated with impairment of their properties that can induce a circulatory risk to recipients. In a preceding study (2009), we reported that post-storage rejuvenation (RJ) of stored RBC (St-RBC) efficiently reduced the storage-induced RBC/endothelial cell interaction, while only partially reversing the level of intracellular Ca2+, reactive oxygen species, and surface phosphatidylserine. In the present study, we examined the RJ effectiveness in repairing St-RBC mechanical properties. Methods: RBC, stored in CPDA-1 without pre-storage leukoreduction, were subjected to post-storage RJ, and the deformability, osmotic fragility (OF), and mechanical fragility (MF) of the rejuvenated St-RBC (St-RBCRj) were compared to those of untreated St-RBC and of freshly-collected RBC (F-RBC). Results: 5-week storage considerably increased OF and MF, and reduced the deformability of St-RBC. All alterations were only partially (40-70%) reversed by RJ, depending on the extent of the damage: the greater the damage, the lesser the relative effect of RJ. Conclusion: The findings of the present and preceding studies suggest that different St-RBC properties are differentially reversed by RJ, implying that some of the changes occur during storage and are irreversible. © 2014 S. Karger GmbH, Freiburg [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
25. Short communication: bendamustine-related hemolytic anemia in chronic lymphocytic leukemia.
- Author
-
Goldschmidt, Neta, Gural, Alexander, Ben-Yehuda, Dina, and Gatt, Moshe
- Subjects
- *
NITROGEN mustards , *DRUG side effects , *HEMOLYTIC anemia , *HEMOLYTIC anemia treatment , *CHRONIC lymphocytic leukemia , *THERAPEUTIC complications , *PURINES - Abstract
Purpose: Immune hemolytic anemia (IHA) may complicate the course of chronic lymphocytic leukemia (CLL), especially in patients with advanced disease, and as a complication of treatment with chlorambucil or fludarabine. Bendamustine, a novel agent with both alkylating and purine-analog properties, was approved in the USA for use in CLL in 2008. Since then, clinical data on its adverse events are accumulating. IHA related to bendamustine was seldom described and is thus reported and reviewed. Methods: We assessed five cases of CLL patients complicated by IHA, out of 31 treated with bendamustine for a relapse of their disease. Also reviewed are previous case reports in the literature. Results and conclusions: Bendamustine-related IHA is more common than suspected (16 %). No such cases were found in non-CLL patients. Personal history of fludarabine-triggered AIHA may be a risk factor for this complication (recorded in 4/5 patients, 80 %). The mechanism is thought to be related to the loss of T cell regulatory control as described for other agents. Physicians using bendamustine for the treatment for CLL should be aware of this complication. [ABSTRACT FROM AUTHOR]
- Published
- 2013
- Full Text
- View/download PDF
26. The Leukemogenicity of AML1-ETO Is Dependent on Site-Specific Lysine Acetylation.
- Author
-
Lan Wang, Gural, Alexander, Xiao-Jian Sun, Xinyang Zhao, Perna, Fabiana, Gang Huang, Hatlen, Megan A., Ly Vu, Fan Liu, Haiming Xu, Asai, Takashi, Hao Xu, Deblasio, Tony, Menendez, Silvia, Voza, Francesca, Yanwen Jiang, Cole, Philip A., Zhang, Jinsong, Melnick, Ari, and Roeder, Robert G.
- Subjects
- *
ACUTE myeloid leukemia , *LEUKEMIA etiology , *ACETYLTRANSFERASES , *CHROMOSOMAL translocation , *GENETIC transcription , *TRANSCRIPTION factors , *ACETYLATION ,LEUKEMIA genetics - Abstract
The chromosomal translocations found in acute myelogenous leukemia (AMD generate oncogenic fusion transcription factors with aberrant transcriptional regulatory properties. Although therapeutic targeting of most leukemia fusion proteins remains elusive, the posttranslational modifications that control their function could be targetable. We found that AML1-ETO, the fusion protein generated by the t(8;21) translocation, is acetylated by the transcriptional coactivator p300 in leukemia cells isolated from t(8;21) AML patients, and that this acetylation is essential for its self-renewal--promoting effects in human cord blood CD34+ cells and its leukemogenicity in mouse models. Inhibition of p300 abrogates the acetylation of AML1-ETO and impairs its ability to promote leukemic transformation. Thus, lysine acetyltransferases represent a potential therapeutic target in AML. [ABSTRACT FROM AUTHOR]
- Published
- 2011
- Full Text
- View/download PDF
27. A new point-of-care method for monitoring anti-platelet therapy: Application of the cone and plate(let) analyzer.
- Author
-
Spectre, Galia, Brill, Alexander, Gural, Alexander, Shenkman, Boris, Touretsky, Natalia, Mosseri, Elinor, Savion, Naphtali, and Varon, David
- Subjects
POINT-of-care testing ,DIAGNOSIS ,MEDICAL technology ,DRUGS ,ASPIRIN ,NONSTEROIDAL anti-inflammatory agents ,ANALGESICS - Abstract
Recent studies suggest that anti-platelet agents are not equally effective in all individuals. We have developed a new method to evaluate the effect of anti-platelet drugs using the cone and plate(let) analyzer (CPA) test. The method is based on the ability of activators to reduce platelet adhesion under flow conditions. Treatment of a blood sample with arachidonic acid (AA) or ADP in vitro significantly decreased platelet deposition to a surface coverage (SC) of 2.1?±?0.4 and 1.3?±?0.6%, respectively, compared with the basic SC of 12.3?±?6.8%. The effect of AA was prevented by aspirin (SC 8.1?±?3.8%) and that of ADP was reduced by 2-methylthio-AMP, a P2Y12 ADP receptor inhibitor (SC 4.8?±?2.0%). Pre-incubation with AA of whole blood samples from untreated healthy volunteers resulted in a marked decline of SC (from SC 9.8?±?2.2 to 0.6?±?0.3%). In contrast, in volunteers treated with 100, 300, and 500?mg aspirin per day, AA (but not ADP) decreased SC only to 3.5?±?1.3, 4.4?±?1.7, and 4.1?±?2.0%, respectively ( P <0.001 versus SC with AA before treatment). A good correlation was observed between the modified CPA and aggregometry ( R 2 ?=?0.55). In conclusion, the modified CPA test is a useful tool to evaluate the efficacy of anti-platelet therapy. [ABSTRACT FROM AUTHOR]
- Published
- 2005
- Full Text
- View/download PDF
28. Extensive Splenic Infarction, Deep Vein Thrombosis and Pulmonary Emboli Complicating Induction Therapy with All-trans-retinoic Acid (ATRA) for Acute Promyelocytic Leukemia.
- Author
-
Goldschmidt, Neta, Gural, Alexander, and Yehuda, Dina Ben
- Subjects
- *
HEMORRHAGE , *LEUKEMIA treatment , *THROMBOSIS , *PATHOLOGICAL physiology - Abstract
Bleeding is a common complication during initial induction treatment for acute promyelocytic leukemia (APL). Administration of all-transretinoic acid (ATRA), which is in routine use for APL in the past decade improves the bleeding tendency dramatically. Nevertheless, thrombotic events have still been reported in a small proportion of APL patients treated with ATRA. Here we describe a case of splenic infarction and life threatening thrombosis in a young patient with APL treated with ATRA. We review the relevant literature and discuss the pathophysiology, risk factors and treatment of this complication occurring during therapy, for APL. [ABSTRACT FROM AUTHOR]
- Published
- 2003
- Full Text
- View/download PDF
29. Do We Store Packed Red Blood Cells under "Quasi-Diabetic" Conditions?
- Author
-
Livshits, Leonid, Barshtein, Gregory, Arbell, Dan, Gural, Alexander, Levin, Carina, and Guizouarn, Hélène
- Subjects
ERYTHROCYTES ,TYPE 2 diabetes ,BLOOD group antigens ,ERYTHROCYTE deformability ,COLD storage - Abstract
Red blood cell (RBC) transfusion is one of the most common therapeutic procedures in modern medicine. Although frequently lifesaving, it often has deleterious side effects. RBC quality is one of the critical factors for transfusion efficacy and safety. The role of various factors in the cells' ability to maintain their functionality during storage is widely discussed in professional literature. Thus, the extra- and intracellular factors inducing an accelerated RBC aging need to be identified and therapeutically modified. Despite the extensively studied in vivo effect of chronic hyperglycemia on RBC hemodynamic and metabolic properties, as well as on their lifespan, only limited attention has been directed at the high sugar concentration in RBCs storage media, a possible cause of damage to red blood cells. This mini-review aims to compare the biophysical and biochemical changes observed in the red blood cells during cold storage and in patients with non-insulin-dependent diabetes mellitus (NIDDM). Given the well-described corresponding RBC alterations in NIDDM and during cold storage, we may regard the stored (especially long-stored) RBCs as "quasi-diabetic". Keeping in mind that these RBC modifications may be crucial for the initial steps of microvascular pathogenesis, suitable preventive care for the transfused patients should be considered. We hope that our hypothesis will stimulate targeted experimental research to establish a relationship between a high sugar concentration in a storage medium and a deterioration in cells' functional properties during storage. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
30. Diagnostic and Management Difficulty of Bleeding Aorto-Duodenal Fistula Associated with Hodgkin's Lymphoma.
- Author
-
Nachmias, Boaz, Bloom, Allan I., Gural, Alexander, and Filippiadis, Dimitrios
- Subjects
HODGKIN'S disease ,FISTULA ,BLOOD transfusion ,DIAGNOSIS ,INTERVENTIONAL radiology - Abstract
Primary aorto-enteric fistula (AEF) resulting from abdominal malignancy is a rare and often fatal complication. The few reports to date are mostly secondary to solid tumors. We present a case of a patient with refractory Hodgkin's lymphoma who developed life-threatening AEF. We describe the diagnostic and therapeutic efforts, requiring a multi-disciplinary team of interventional radiology, gastroenterology, and transfusion medicine, resulting in a favorable outcome. Importantly, we offer several insights regarding the identification and management of high-risk patients, with an emphasis on pre-treatment considerations and urgent diagnosis and intervention. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
31. Blinatumomab as a bridge to further therapy in cases of overwhelming toxicity in pediatric B-cell precursor acute lymphoblastic leukemia: Report from the Israeli Study Group of Childhood Leukemia.
- Author
-
Elitzur, Sarah, Arad‐Cohen, Nira, Barzilai‐Birenboim, Shlomit, Ben‐Harush, Miriam, Bielorai, Bella, Elhasid, Ronit, Feuerstein, Tamar, Gilad, Gil, Gural, Alexander, Kharit, Mira, Litichever, Naomi, Nirel, Ronit, Weinreb, Sigal, Wolach, Ofir, Toren, Amos, Izraeli, Shai, Jacoby, Elad, Arad-Cohen, Nira, Barzilai-Birenboim, Shlomit, and Ben-Harush, Miriam
- Published
- 2019
- Full Text
- View/download PDF
32. Clinical considerations and key issues in the management of patients with Erdheim-Chester Disease: a seven case series.
- Author
-
Mazor, Roei D, Manevich-Mazor, Mirra, Kesler, Anat, Aizenstein, Orna, Eshed, Iris, Jaffe, Ronald, Pessach, Yakov, Goldberg, Ilan, Sprecher, Eli, Yaish, Iris, Gural, Alexander, Ganzel, Chezi, and Shoenfeld, Yehuda
- Abstract
Background: Erdheim-Chester Disease (ECD), a non Langerhans' cell histiocytosis of orphan nature and propensity for multi-systemic presentations, comprises an intricate medical challenge in terms of diagnosis, treatment and complication management.Objectives: The objectives are to report the clinical, radiological and pathological characteristics, as well as cardinal therapeutic approaches to ECD patients and to provide clinical analyses of the medical chronicles of these complex patients.Methods: Patients with biopsy proven ECD were audited by a multi-disciplinary team of specialists who formed a coherent timeline of all the substantial clinical events in the evolution of their patients' illness.Results: Seven patients (five men, two women) were recruited to the study. The median age at presentation was 53 years (range: 39 to 62 years). The median follow-up time was 36 months (range: 1 to 72 months). Notable ECD involvement sites included the skeleton (seven), pituitary gland (seven), retroperitoneum (five), central nervous system (four), skin (four), lungs and pleura (four), orbits (three), heart and great vessels (three) and retinae (one). Prominent signs and symptoms were fever (seven), polyuria and polydipsia (six), ataxia and dysarthria (four), bone pain (four), exophthalmos (three), renovascular hypertension (one) and dyspnea (one). The V600E BRAF mutation was verified in three of six patients tested. Interferon-α treatment was beneficial in three of six patients treated. Vemurafenib yielded dramatic neurological improvement in a BRAF mutated patient. Infliximab facilitated pericardial effusion volume reduction. Cladribine improved cerebral blood flow originally compromised by perivenous lesions.Conclusions: ECD is a complex, multi-systemic, clonal entity coalescing both neoplastic and inflammatory elements and strongly dependent on impaired RAS/RAF/MEK/ERK signaling. [ABSTRACT FROM AUTHOR]- Published
- 2014
- Full Text
- View/download PDF
33. Non-oxidative band-3 clustering agents cause the externalization of phosphatidylserine on erythrocyte surfaces by a calcium-independent mechanism.
- Author
-
Koshkaryev, Alexander, Livshits, Leonid, Pajic-Lijakovic, Ivana, Gural, Alexander, Barshtein, Gregory, and Yedgar, Saul
- Subjects
- *
ERYTHROCYTES , *ACRIDINE orange , *INFORMED consent (Medical law) - Abstract
Aging of red blood cells (RBCs) is associated with alteration in a wide range of RBC features, occurring each on its own timescale. A number of these changes are interrelated and initiate a cascade of biochemical and structural transformations, including band-3 clustering and phosphatidylserine (PS) externalization. Using specific band-3 clustering agents (acridine orange (AO) and ZnCl 2), we examined whether treatment of RBCs with these agents may affects PS externalization and whether this process is Ca2+-dependent. RBCs were isolated from the blood of eight healthy donors upon obtaining their informed consent. The suspension was supplemented with increasing concentrations of AO or ZnCl 2 (from 0.5 to 2.0 mM) and incubated at 25 °C for 60 min. To detect PS at the RBC surface, we used allophycocyanin-conjugated recombinant human Annexin V. We demonstrated, that treatment of RBCs with both clustering agents caused an elevation in the percent of cells positively labeled by Annexin-V (RBCPS), and that this value was not dependent on the presence of calcium in the buffer: RBCs treated with AO in the presence of either EDTA, EGTA or calcium exhibited similar percentage of RBCPS. Moreover, the active influx of Zn2+ into RBCs induced by their co-incubation with both ZnCl 2 and A23187 did not increase the percent of RBCPS as compared to RBCs incubated with ZnCl 2 alone. Taken together, these results demonstrate that the band-3 clustering agents (AO or ZnCl 2) induce PS externalization in a Ca2+ independent manner, and we hereby suggest a possible scenario for this phenomenon. Unlabelled Image • The clustering of band-3 induces phosphatidylserine externalization on RBC surface. • The externalization of phosphatidylserine to the RBC surface can be Ca2+ independent. • We propose the scenario that binds band-3 clustering with phosphatidylserine translocation. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.