bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phenotypic Characterization of Human CD34+ Cells Selected from G-CSF Mobilized Leukopheresis Using Baxter’s Isolex™ 300i Magnetic Cell Selection System (v2.5)
Authors: Cohen Amy , Motlagh Delara , Amrani David 
Published: April 2020

Abstract
Baxter’s Isolex™ 300i Magnetic Cell Selection System (v2.5) is used to select CD34+ cells from G-CSF mobilized leukopheresis units. This study focused on evaluating the cellular composition of the post-Isolex product as well as producing a detailed characterization of the CD34+ cells. A multi-color flow cytometry assay was developed to characterize the Isolex product with a detailed focus on the CD34+ cells. A hematopoietic colony-forming assay was used to determine the clonal potential of the selected cells. Cell function was evaluated by measuring the migration potential of the CD34+ cells toward SDF-1. The post-Isolex cell suspension product contained an average of 96.44% ± 0.84% CD34+ cells. The majority of the remaining cells present were T and B cell lymphocytes with an average 1.74% ± 0.78% CD3 positive T-Cells and 1.61% ± 0.23% CD19 positive B-Cells. The platelets comprised 1.92% ± 0.92% of the product and 99% of this population were co-aggregated to the CD34+ cells. Non-CD34, immature white blood cells averaged less than 0.5% of the total post-Isolex population. A majority of the CD34+ stem cells are lineage-committed HPCs as determined by KDR-CD34+ (94.90% ± 1.99%) and CD38+CD34+ (93.87% ± 2.76%). Commitment to a myeloid cell line (CD33+CD34+) was determined to be 34.75% ± 23.10%. Migration potential of the stem cells toward SDF-1 as defined by dual positivity for CXCR4 and CD34 averaged 1.95% ± 2.49%. While the CXCR4 receptor positivity appears low, the migratory response of the CD34+ cells toward SDF-1 was robust. An examination of VEGF populations in the post-Isolex product averaged 0.32% ± 0.17% for VEGF R2 (KDR) and 34.25% ± 12.74% for VEGF R1. Several adhesion markers were assayed and the positivity was equal to or less than 1% for CD146, CD144, CD73, and CD29. Other adhesion markers, such as CD105 (endoglin) averaged 34.04% ± 20.64% and CD99 averaged 66.33% ± 13.25%. CD117, which binds to the receptor for stem cell factor (SCF), averaged 69.63% ± 6.38%. CD133, which is considered an early HPC marker, averaged 73.90% ± 5.97%. CD90, which is useful for defining a population of highly proliferative cells capable of long-term culture, averaged 60.50% ± 8.50%. The EPC phenotypic profile combination, KDR+CD34+CD133+, averaged 0.30% ± 0.22% in our post-Isolex population. In the hematopoietic colony-forming assay, the Isolex-selected CD34+ cells were able to produce colonies with an efficiency of 20% with CFU-GM forming a majority of the colonies. By utilizing multi-color flow cytometry, we were able to account for the cell populations found in the Isolex product and to further characterize the CD34+ selected cell population. The hematopoietic colony-forming assay gave insight into the efficiency and growth potential of the CD34+ selected cells. The functional migration assay determined that the CD34+ selected cells exhibited a robust migratory response toward SDF-1.
A Hypoxic Niche in the Mouse Bone Marrow Diminishes Proliferation and Differentiation of Hematopoietic Stem Cells
Authors: Eliasson Pernilla M , Jönsson Jan-Ingvar 
Published: April 2020

Abstract
In the bone marrow hematopoietic stem cells (HSCs) reside in specialized niches in close contact with stromal cells and endosteal osteoblasts. It is thought that this environment is hypoxic in nature, where HSCs are maintained in a quiescent state to prevent their depletion. Hypoxia stabilizes the transcription factor HIF-1α which triggers angiogenesis as well as genes slowering the cell cycle, promoting cell survival, and leading to a decrease in cellular metabolism. In this study, hypoxic effects of the maintenance of Lin−Sca1+c-kit+* (LSK) cells derived from mouse bone marrow and the involvement of the transcription factor hypoxia inducible factor 1 α (HIF-1α) were investigated. Hypoxic culture conditions led to an increase in numbers of primitive colony-forming progenitor cells and a preferential expansion of immature blast-like appearing cells. Concurrently, the immature c-kit Sca-1 phenotype was better maintained in hypoxia compared to ambient oxygen levels. Moreover, hypoxia decreased the proliferation of HSCs as measured by CFSE or PKH26 staining. This was confirmed by cell cycle analysis, and hypoxic cultivation decreased the percentage of cells in S-phase whereas cells in G0/G1 phase increased. Cells infected with a constitutively active form of HIF-1α showed the same pattern as cells cultured in hypoxia. To verify that the effect is HIF-1α mediated, we silenced HIF-1α in LSK cells with shRNA. The decrease in proliferation in hypoxic cultivation of cells infected with shRNA against HIF-1α was markedly diminished, indicating that HIF-1α play an important role in controlling proliferation of hematopoietic stem cells. These results suggest that a major function of hypoxia is to counteract proliferation and possibly differentiation, thereby sustaining maintenance. Furthermore, hypoxic culture conditions may have beneficial clinical implications for ex vivo purposes and may improve the yields of stem cells. In our ongoing-studies, we are investigating whether HIF-1α and hypoxia is an absolute prerequisite for the proper maintenance of HSCs in the bone marrow.
Hematopoietic Stem - and Progenitor Cells Are Differentially Mobilized in Response to Flt3-Ligand
Authors: de Kruijf Evert-Jan F. M. , van Pel Melissa , Fibbe Willem E. 
Published: April 2020

Abstract
Flt3 is a tyrosine kinase receptor expressed mainly on primitive hematopoietic cells and its ligand, Flt3-ligand (FL), is a slowly mobilizing agent in mice when administered for 5–10 days. This provides a time-frame to study the HPC and HSC migration kinetics in detail. BALB/c mice were injected for 3, 5, 7 and 10 days with FL (10 ug/day, intraperitoneally). Mobilization of hematopoietic stem- and progenitor cells was studied using colony-forming-unit granulocyte/monocyte (CFU-GM) and cobblestone-area-forming-cell (CAFC) assays. The radioprotective capacity of mobilized peripheral blood mononuclear cells (PBMC) was studied by transplantation of 1.5 × 106 FL-mobilized PBMNC into lethally irradiated (9.5 Gy) recipients. Hematopoietic progenitor cell mobilization was detected from day 3 onwards and prolonged administration of FL showed a steady increase in mobilized progenitor cells (CFU-GM; 23.1±20.1 [PBS], 219.0±213.7 [3 days FL, n=10], 1,007.8±742 [5 days FL, n=21], 3,526.6±1,406 [7 days FL, n=10] and 19,149±2,338 [10 days FL, n=10]). Administration of FL for 10 days lead to a 5.5-fold increase in CAFC-week 4, compared to FL administration for 5 days (0.69 vs 0.13 CAFC per 105 PBMC respectively) and a 5.0-fold increase in CAFC-week 5 (0.27 vs 0.05 CAFC per 105 PBMC respectively). No CAFC week 4/5 were found in PBMC obtained from PBS-injected control mice. Transplantation of 5-day FL-mobilized PBMC did not radioprotect lethally irradiated recipients (mean survival time (MST): 66 days; MST PBS: 13 days). In contrast, transplantation of PBMC obtained from a 10-day FL mobilization regime radioprotected 100% of the recipients (Table 1). These results indicate that HPC and HSC show different mobilization kinetics in response to FL, resulting in preferential mobilization of HPC at day 5, followed by HSC mobilization at day 10. We speculate that this difference in mobilization kinetics might be due to the selective recruitment of HPC and HSC from their respective bone marrow compartments.
Table 1. HPC and HSC frequencies in peripheral blood following Flt3-ligand-induced mobilization
CFU-GM per ml PB CAFC-day 28 per 105cells CAFC-day 35 per 105cells % Radioprotection day 150 * fold increase compared to 5 day FL 5 days Flt3-L 1,007 (n=21) 0.126 0.054 0 (n=10) 10 days Flt3-L 19,149 (n=10) (19.0)* 0.694 (5.5)* 0.272 (5.0)* 100 (n=10)
Hemodynamic Monitoring during Erythrocytapheresis in Sickle Cell Disease Patients Using Impedance Cardiography
Authors: Das Bibhuti B , Kemparajurs Samyuktha , Bertolone Salvatore , Kong Maiying , Raj Ashok B. 
Published: April 2020

Abstract
BACKGROUND: Erythrocytapheresis procedures are increasingly used in the treatment of severe acute complications of sickle cell disease (SCD). Some patients who undergo erythrocytapheresis experience dizziness during or after the procedure. There is no data in literature for hemodynamic monitoring of cardiac index (CI) and systemic vascular resistance index (SVRI) during erythrocytapheresis. We have previously shown that impedance cardiography (ICG) and invasive measures of CI by thermodilution techniques are significantly correlated in children.
OBJECTIVES: We wanted to evaluate changes in CI and SVRI using ICG and to correlate these with systolic blood pressure (SBP) measurements in SCD patients while undergoing erythrocytapheresis.
METHODS: Thirty one SCD patients who had 70 consecutive erythrocytapheresis procedures were included in this IRB approved study. ICG measurements (CI, SVRI, and blood pressure) were taken pre-erythrocytapheresis, 30 minutes after initiation of the procedure, one hour into erythrocytapheresis, and at the end of the procedure. ICG measurements were repeated in symptomatic patients before and after intervention with fluid administration.
RESULTS: We evaluated hemodynamic data on 31 SCD patients, average age 12.8±5.2 years and 56% are female. SBP decreased below the base line during 33 procedures and increased above the baseline during 37 procedures. Among patients who had a decrease in SBP, 28/33 (84%) had decreased CI. Among them 22/28 (78%) had increased SVRI. Among patients who had an increase in SBP, 5/37 (14%) had increased CI. Among them 4/5 (80%) also had increased SVRI. Using paired t test, the changes in CI (P &lt;0.001) and SVRI (P=0.0002) comparing to baseline are statistically significant. CI is negatively correlated with change in SVRI (Pearson correlation coefficient −0.8).
CONCLUSIONS:In summary, the hemodynamic changes during erythrocytapheresis are probably multifactorial in origin and may include a combination of SVRI and CI changes. Confirmation of these findings may allow early intervention in some patients and minimize the risk of developing overt clinical symptoms during erythrocytapheresis.
Association of Pulmonary Hypertension with Sickle Cell Disease Subtypes
Authors: Cohen Alice J. , Tuckman-Vernon Chaim 
Published: April 2020

Abstract
Pulmonary hypertension (PH) is a common complication of sickle cell disease (SD) and a significant cause of morbidity and mortality. PH, measured by Doppler echocardiography and defined as a tricuspid regurgitant jet velocity (TRV) &gt; 2.5 m per second (m/s), is hypothesized to be related to the chronic hemolytic anemia of SD, but causality is unproven. If so, the presence of hemoglobin C, which reduces hemolysis, would be expected to have a reduced likelihood of PH. This study reviewed the prevalence of PH in 3 categories of patients with SD: homozygous S (SS), sickle-beta thalassemia (SB), and SC.
Methods: Sickle cell disease patients registered at a state funded community comprehensive care adult sickle cell center were routinely screened for PH by Doppler echocardiography. The presence of PH, the incidence of a related complication, acute chest syndrome (ACS), and baseline hemoglobin (hgb) were reviewed.
Results: 16 patients with SC type, 30 with SS and 39 with SB disease underwent screening. The prevalence of PH, ACS and hgb are listed in the table below.
Conclusion: SC patients have PH and ACS similar to patients with SS and SB patients. These patients have higher baseline hemoglobin and may have hyperviscosity as a cause of PH and ACS as opposed to hemolytic anemia. Further study of PH and ACS in SC patients is warranted.
SC SS SB p value PH 6/16 (38%) 12/40 (40%) 11/39 (28%) p= NS ACS 7/16 (44%) 10/30 (33%) 19/39 (49%) p=NS PH + ACS 4/16 (25%) 5/30 (17%) 4/39 (10%) p=NS ACS in PH patients 4/6 (67%) 5/12 (42%) 4/11 (36%) p-=NS Hgb 10.8 7.89 8.57 p=0.000
Marijuana Use and Sickle Cell Disease
Authors: Gotlieb Vladimir K. , Oo Khine Z. 
Published: April 2020

Abstract
A 45-year old Jamaican man with sickle cell disease came to our clinic complaining of chronic left ankle ulcer for one year. He stated that when he was a young boy he had had several hospital admissions for sickle cell crisis, usually precipitated by physical activity or infection, once or twice per month. We were surprised to find out that he had never had a crisis since the age of fifteen. We doubted his diagnosis yet his hemoglobin electrophoresis revealed HbS was 94.7%, HbF was 0.6% and HbA2 was 4.7%. He denied taking any medication. However, he admitted smoking 4 to 5 cigarettes of marijuana a day for the past 30 years. Cannabis has been used as a medicine even before the Christian era in Asia, first in China then mainly in India. Its use was later spread to the West.
The general indications for marijuana were reported as severe nausea and vomiting, weight loss associated with debilitating illnesses, spasticity, pain syndrome, and glaucoma.
Numerous Phase I–III studies in 2000 subjects with exposure of Sativex by GW Pharmaceuticals from United Kingdom demonstrated that the patients attained good sleep quality, which may improve patients’ quality of life in disabling chronic pain syndromes.
We reviewed the literature on any report that cannabinoids could change the severity of sickle cell disease. We found the study from West Indies, which investigated the perception that marijuana use ameliorated the complications of sickle cell disease, in year 2000 and 2004. The study concluded that marijuana smoking is common in adults with sickle cell disease but its usage is unrelated to clinical severity of the disease.
We also found a report, from Central Middlesex Hospital in London, United Kingdom, which observed 86 young adults with HbSS, HbSC and HbSbetathalassemia disease, median age being 30 years.
Results of this study showed that 31 (36%) had used cannabis in the previous 12 months to relieve the symptoms associated with sickle cell disease. Symptoms related to sedation and mood effects were reported in 77% of patients. The main reasons for use of cannabis were to reduce pain in 52% and to induce relaxation or relieve anxiety and depression in 39%. (5) We wondered if any physicians had observed similar effects of marijuana in sickle cell disease patients in their practice. Could ‘Marijuana Use has beneficial effect on Sickle Cell Disease’ be an interesting topic for a broader clinical trial or a retrospective analysis?
Codanin-1, the Protein Encoded by the Gene Mutated in Congenital Dyserythropoietic Anemia Type I (CDAN1), Is Cell Cycle Regulated
Authors: Noy-Lotan Sharon , Dgany Orly , Lahmi Roxane , Marcoux Nathaly , Krasnov Tanya , Yissachar Nissan , Ginsberg Doron , Motro Benny , Resnitzky Peretz , Yaniv Isaac , Kupfer Gary , Tamary Hannah 
Published: April 2020

Abstract
Congenital dyserythropoietic anemia (CDA) type I is an inherited autosomal recessive macrocytic anemia associated with ineffective erythropoiesis and the development of secondary hemochromatosis. Distinct erythroid precursors with inter-nuclear chromatin bridges and spongy heterochromatin are pathognomonic for the disease. The mutated gene (CDAN1) encodes a ubiquitously expressed protein of unknown function, codanin-1. Based on the morphological features of CDA type I erythroblasts and the preliminary data on the Drosophila homolog, dlt, which was found to be required for cell survival and cell cycle progression, we investigated the location and the behavior of codanin-1 during the cell cycle. Using immunofluorescence and immune electron microscopy, we localized codanin-1 to the heterochromatin in interphase cells. During the cell cycle, high levels of codanin-1 were observed in S phase. At mitosis, codanin-1 underwent phosphorylation, which coincided with exclusion from condensed chromosomes. The proximal CDAN1 gene promoter region, never before characterized, was found to contain 5 putative E2F1 binding sites. E2F transcription factors are the main regulators of G1/S transition. Cotransfection of an E2F1 expression plasmid increased luciferase activity, confirming that E2F1 activates the transcription of CDAN1, and chromatin immunoprecipitation identified the codanin-1 promoter as a direct target of E2F1. Taken together, these data suggest that codanin-1 is a cell cycle-regulated protein active in S-phase. Based on the localization of codanin-1 to the heterochromatin and the spongy appearance of heterochromatin in CDA I, we suggest that codanin-1 may be involved in heterochromatin organization during DNA replication. This represents the first work towards understanding the function of the proteins involved in CDAs.
Hodgkin Disease and Nephrotic Syndrome, a Rare Paraneoplastic Complication in Children with Literature Review
Authors: Dsilva Sehba , Karayalcin Gungor , Singh Sharon 
Published: April 2020

Abstract
The association between Hodgkin Disease (HD) and paraneoplastic Nephrotic Syndrome is well documented in adults but is relatively uncommon in the pediatric population. We describe two children with HD who initially presented with Nephrotic Syndrome. Case 1: 12- year-old boy who presented with a two-week history of periorbital edema, proteinuria and hypertension and was diagnosed with Nephrotic Syndrome. The renal biopsy showed minimal change disease. Since the patient developed dyspnea, further work-up was done and he was found to have a large mediastinal mass. Core needle biopsy of the mass was consistent with HD, nodular sclerosing type. Case 2: 14-year-old boy diagnosed to have Nephrotic Syndrome with biopsy proven minimal change disease and was treated intermittently with steroids over 6 months. He subsequently developed dyspnea and was found to have a right paratracheal mass and excisinal biopsy was consistent with HD, nodular sclerosing type. Both these patients initially presented with Nephrotic Syndrome which completely resolved after the first course of chemotherapy for HD. Upon review of literature, there have been 23 pediatric cases of Nephrotic Syndrome associated with HD in patients ranging in age between 2–15 years. The renal biopsy was not done for 8 of these patients and the diagnosis was established clinically. Fifteen patients had biopsies, 9 had minimal change disease, 1 mesangial hypercellularity, 1 glomerulosclerosis, 1 undetermined histology and 3 were normal. In all cases, the Nephrotic Syndrome was refractory to steroids and resolved with treatment of the HD. Pathogenesis of the Nephrotic Syndrome associated with HD is not known, however there are speculations about T-cell involvement and production of lymphokines and humoral factors which may be responsible for the glomerular damage.
Caspofungin for the Treatment of Candidemia in patients with Hematological Malignancies
Authors: Fianchi Luana , Fanci Rosa , Candoni Anna , Caira Morena , Valentini Caterina Giovanna , Posteraro Brunella , Morselli Monica , Farina Giuliana , Mitra Maria Enza , Offidani Massimo , Sanguinetti Maurizio , Tosti Maria Elena , Nosari Annamaria , Viale Pierluigi , Leone Giuseppe , Pagano Livio 
Published: April 2020

Abstract
Objective: To evaluate the efficacy of Caspofungin in patients with hematological malignancies (HM) and candidemia
Design: The study was prospectively conducted in 11 Hematology Divisions in a tertiary care or university hospital setting.; neutropenic hematological patients with clinical evidence of infection and a positive blood culture for Candida were enrolled.
Patients and results: Between January 2005 and November 2007, 38 episodes of candidemia among patients with HM were registered. Among these, 24 eligible neutropenic patients, collected in 8/11 participating centers, were evaluated. All these patients had received chemotherapy for their underlying hematological diseases: acute myeloid leukemia (AML) in 11 patients (46%); non Hodgkin’s lymphoma (NHL) in 6 patients (25%); acute lymphoblastic leukemia (ALL) in 4 patients (16%); multiple myeloma (MM) in 2 patients (8%); chronic lymphoblastic leukemia (CLL) in 1 patient. In 11 patients (46%) the infection onset after a HSCT procedure (7 allogeneic and 4 autologous). Before the infection onset, all patients were neutropenic (ANC&lt;0.5×109/l) for a median average of 12 days (range 2–41). Candidemia diagnosis was made after a median time of 3 days from the onset of fever. Candida isolated species were: C.albicans 46%, C. parapsilosis 17%, C. krusei 12.5%, C. tropicalis in 8%, C. lusitanae, C. guillermondii, C. dubliniensis, C. famata in 4% of patients each. Caspofungin at standard dosage was the first-line therapy in 17 pts (71%); in the other 7 pts, previous antifungal therapy (4 L-AmB, 1 itraconazole, 1 fluconazole, 1 voriconazole) was changed to Caspofungin at candidemia diagnosis after no more than 48 hours of treatment. The median duration of Caspofungin therapy was 12 days (range 3–26). No side effects were registered. A complete response to therapy of 58% was obtained. At 30 days following candidemia onset, 11 pts had died (41%), but the candidemia was responsible for the mortality in only 6 pts (overall attributable mortality 25%).
Conclusions: Our data confirm the efficacy of Caspofungin in the treatment of neutropenic pts with HM and concomitant candidemia as well as it was reported for non hematological subgroups. Caspofungin was well tolerated also in very compromised pts.
Do Deletions in 9p Reflect Prognosis in Adult Precursor B-Cell ALL? a Multi-Centre Study of 381 Patients
Authors: Nahi Hareth , Smedmyr Bengt , Hallböök Helene , Hagglund Hans 
Published: April 2020

Abstract
Despite the fact that the outcome among patients with acute lymphoblastic leukaemia (ALL) has improved, the majority of adult patients relapse and die of their disease. Besides age and white cell count at diagnosis, the cytogenetic abnormalities t(9,22)/BCR-ABL and t(4,11) are important prognostic markers and are often included in the treatment stratification of patients with adult ALL. Deletions in 9p are seen in about 9% of cases of adult ALL, but their prognostic impact has been controversial.
Methods: Cytogenetic data from 381 patients diagnosed with B-precursor ALL were reviewed. Chromosomal analysis was successful in 240 cases. Of these cases, 18 (8%) had abnormalities in 9p and they were compared with patients with normal karyotypes and patients with t(9;22)/BCR-ABL.
Results: Patients with abnormalities of chromosome 9 showed significantly shorter overall survival compared with patients with normal karyotypes. In fact, overall survival was similar to that in the poor prognosis t(9;22)/BCR-ABL-positive group.
Conclusions: The data suggest that chromosomal abnormalities involving 9p may have a significant negative impact on survival in adult B-precursor ALL.