bluuebunny/crossref_metadata_2025_split huggingface dataset:
14q32 translocations are associated with mixed-lineage expression in childhood acute leukemia
Authors: Hayashi Y , Pui CH , Behm FG , Fuchs AH , Raimondi SC , Kitchingman GR , Mirro J Jr , Williams DL 
Published: October 2019

Abstract
The frequency and characteristics of childhood acute leukemia with a 14q32 translocation [other than the t(8;14)(q24;q32)] were determined in 335 cases of newly diagnosed acute lymphoblastic leukemia (ALL) and 105 cases of acute nonlymphoblastic leukemia (ANLL). Ten children, representing 2.3% of the entire cohort, had this abnormality (1.5% of ALL patients and 4.8% of ANLL patients). By French-American-British (FAB) criteria, 4 cases were classified as L1, 1 as L2, 2 as M1, 1 as M2, and 2 as M5. Remarkably, mixed-lineage expression was found in 6 of these 10 cases, but in only 21 of the other 430 cases without a 14q32 translocation (P less than .001). Leukemic cells from 5 of these 6 cases (4 ANLL, and 1 ALL) coexpressed CD13, a myeloid-associated antigen, and CD2, a T-cell-associated antigen; blasts from the sixth case (ALL) coexpressed CD13 and CD19, a B-lineage-associated antigen. Thus, in addition to the well-described 11q23 translocations and t(9;22), 14q32 translocations also appear to be associated with mixed lineage antigen expression. Break-points of the reciprocal chromosomes from chromosome 14 were identified in five of these cases: 1q23, 6q23- q25, 7p15, 8q11, and 12q13. Of the four mixed-lineage cases that were tested, none showed rearrangement of the immunoglobulin heavy chain (IgH) gene. This suggests that the 14q32 breakpoint does not involve the IgH gene and that an unidentified important gene may reside on 14q32.
Maintenance treatment of patients with myelodysplastic syndromes using recombinant human granulocyte colony-stimulating factor
Authors: Negrin RS , Haeuber DH , Nagler A , Kobayashi Y , Sklar J , Donlon T , Vincent M , Greenberg PL 
Published: October 2019

Abstract
Myelodysplastic syndromes (MDS) are characterized by chronic refractory cytopenias resulting in increased risk of infection, bleeding, and conversion to acute leukemia. In an effort to improve these cytopenias we have treated 18 patients over a 6- to 8-week period with increasing daily subcutaneous doses of recombinant human granulocyte colony- stimulating factor (G-CSF). Sixteen patients responded with improvement in neutrophil counts. On cessation of treatment these counts returned to baseline values over a 2- to 4-week period. To maintain these improved blood counts 11 patients were treated with G-CSF for more prolonged periods. Ten patients again responded with an increase in total leukocyte counts (1.6- to 6.4-fold) and absolute neutrophil counts (ANC) (3.6- to 16.3-fold), with responses persisting for 3 to 16 months. A significantly decreased risk of developing bacterial infections was noted during periods with ANC greater than 1,500/mm3 as compared with periods of time with ANC less than 1,500/mm3. Two anemic patients had a greater than 20% rise in hematocrit over the study period, and 2 additional patients had a decrease in red blood cell transfusion requirements during G-CSF treatment. Bone marrow myeloid maturation improved in 7 of 9 maintenance phase patients. Three patients progressed to acute myeloid leukemia during treatment. The drug was generally well-tolerated and no severe toxicities were noted. These data demonstrated that G-CSF administered to MDS patients by daily subcutaneous administration was well-tolerated and effective in causing persistent improvement of the neutrophil levels and marrow myeloid maturation. These effects were associated with a decreased risk of infection and, in some patients, with decreased red blood cell transfusion requirements.
Effects of injected leukemia inhibitory factor on hematopoietic and other tissues in mice
Authors: Metcalf D , Nicola NA , Gearing DP 
Published: October 2019

Abstract
Purified bacterially synthesized recombinant murine leukemia inhibitory factor (LIF) was injected in varying doses for up to 2 weeks into adult DBA/2 and C3H/HeJ mice. At high doses (2 micrograms, three times daily) LIF exhibited toxic effects seen as behavioral changes, loss of body fat, and thymus atrophy. Dose-related rises were observed in blood platelets, erythrocyte sedimentation rates, and serum calcium to albumin ratios, including dose schedules with no toxic effects. LIF induced a decrease in bone marrow cell numbers, particularly in marrow lymphocytes, and a moderate increase in spleen weight with a reduction in spleen lymphocytes and an elevation of erythroid populations. LIF- injected mice showed a rise in megakaryocytes up to twofold in the marrow and fivefold in the spleen, with an associated 10-fold rise in megakaryocyte progenitor cells in the spleen. Comparable rises in other types of progenitor cells were also observed in the spleen. The observed changes indicate the biologic activity of LIF in vivo and are consistent with the known wide range of in vitro actions of this molecule. The ability of LIF to elevate megakaryocyte and platelet levels suggests a potential clinical application of LIF in the treatment of thrombocytopenias.
Evaluation of leukocyte removal filters modelled by use of HIV-infected cells and DNA amplification
Authors: Rawal BD , Schwadron R , Busch MP , Endow R , Vyas GN 
Published: October 2019

Abstract
The concept of reducing cell-associated blood-borne viruses (BBVs) by filtration of the vector leukocytes from blood collected for transfusion has led to the development of high efficiency filters. Improved filtration technology demands newer methodology to accurately estimate the residual cells. We have developed an experimental model based on the hemocytometer counts and the polymerase chain reaction (PCR), performed on the lymphocytes derived from the units of red cell mass inoculated with marker cells (H9) persistently carrying cell- associated human immunodeficiency virus DNA (CA-HIV). We measured the efficiency of 6 units of a prototype filter using our model and found an estimated mean of less than 4 residual cells per milliliter in the filtered blood. This represents a mean 5.84 log10 reduction of normal PBMC and CA-HIV in pre- and post-filtration aliquots and exemplifies the application of our model for evaluating a new generation of blood filters. Our model illustrates that a biological tracer (ie, DNA) is a better measure of the efficacy of a leukocyte filter than the hemocytometric enumeration of pre- and post-filtration PBMC concentrates.
Potentiation of the erythropoietin response by dimethyl sulfoxide priming of erythroleukemia cells: evidence for interaction of two signaling pathways
Authors: Chern Y , Yonekura S , Sytkowski AJ 
Published: October 2019

Abstract
Erythropoietin (Epo) and dimethyl sulfoxide (DMSO) are believed to induce the differentiation of transformed erythroid cells by different signal transduction pathways. We have now obtained evidence for the interaction of these pathways. We used a Rauscher murine erythroleukemia cell line with a relatively low (8% to 10%) hemoglobinization response to Epo alone. Pretreatment of these cells for 1 day with DMSO followed by its removal and the addition of Epo resulted in a marked enhancement of the Epo specific hemoglobinization. We have designated this effect “DMSO priming.” This priming effect of DMSO on the Epo response was both time-dependent and DMSO concentration- dependent. DMSO priming potentiated the Epo response in three ways. Firstly, DMSO priming increased the total number of Epo responsive cells from 8% to 10% to 40% to 60%. Secondly, DMSO priming reduced the time required to reach the optimal Epo-induced response from 4 days to 2 days. Thirdly, the Epo dose-response curve was left-shifted approximately 20-fold. DMSO priming was also associated with a marked increase in Epo receptor density characterized by an apparently new receptor population and by the appearance of positive cooperativity between receptors. Our results suggest that the DMSO priming effect is due to potentiation of the Epo signaling pathway, thus resulting in a much more rapid and dramatic Epo-induced hemoglobinization response.
Species specificity of human interleukin-3 demonstrated by cloning and expression of the homologous rhesus monkey (Macaca mulatta) gene
Authors: Burger H , van Leen RW , Dorssers LC , Persoon NL , Lemson PJ , Wagemaker G 
Published: October 2019

Abstract
To enable preclinical studies on homologous interleukin-3 (IL-3) in primate species, we isolated the gene encoding Rhesus monkey IL-3 (RhIL- 3). The nucleotide sequence of the RhIL-3 gene displayed 92.9% homology with that of the human IL-3 (hIL-3) gene. The isolated RhIL-3 gene encodes a 143-amino acid (aa) precursor polypeptide, nine C-terminal residues shorter than the human protein. Protein homology was found to be 89.5% for the signal peptide (19 aa) and 80.5% for the mature protein (124 aa). Comparison of the human and RhIL-3 coding sequences showed that the majority of substitutions had occurred at amino acid replacement sites indicating a rapid evolution of the IL-3 protein. After expression of a genomic fragment in COS cells, RhIL-3 cDNA was constructed, which enabled large-scale production of the RhIL-3 polypeptide, RhIL-3 produced by Bacillus licheniformis and purified to homogeneity appeared to be approximately 100-fold more effective in stimulating Rhesus monkey hematopoietic progenitors than hIL-3, whereas RhIL-3 and hIL-3 showed comparable stimulatory activity on normal as well as malignant human hematopoietic cells. Thus, the rapid evolution of hIL-3 has resulted in a unidirectional species specificity, which most likely restricts the in vivo effects of hIL-3 in Macaca species.
Fibrinogen Baltimore I: polymerization defect associated with a gamma 292Gly----Val (GGC----GTC) mutation
Authors: Bantia S , Mane SM , Bell WR , Dang CV 
Published: October 2019

Abstract
Fibrinogen Baltimore I is one of the very first congenital abnormal fibrinogens reported over several decades ago; however, the molecular defect of this dysfibrinogen has eluded identification. In fact, several reports misidentified the functional defect of Baltimore I, which has impaired fibrin monomer polymerization. Reversed-phase high- performance liquid chromatography analysis of lysyl endopeptidase digest of the purified Baltimore I gamma-chain showed an abnormal peptide not found in the co-existing normal gamma-chain of this heterozygote. Amino acid sequencing of this peptide indicated that gamma-chain Gly292 is replaced by valine. This observation was confirmed, and the genetic defect was determined by direct nucleotide sequencing of a polymerase chain reaction product containing codon gamma 292, which is mutated: GGC----GTC. The molecular defect of Fibrinogen Baltimore I lies in a region of the gamma-chain required for fibrin polymerization, suggesting that the integrity of gamma Gly292 is critical for fibrin assembly.
Differential expression of CD24-related epitopes in mycosis fungoides/Sezary syndrome: a potential marker for circulating Sezary cells
Authors: Pirruccello SJ , Lang MS 
Published: October 2019

Abstract
In the hematopoietic system, the B-cell associated antigen CD24 is expressed at high density on B cells, B-cell precursors, and B-cell malignancies as well as at low density on peripheral blood polymorphonuclear leukocytes. The 42-Kd sialoglycoprotein has not been previously demonstrated to be expressed on T cells, thymocytes, or T- cell malignancies. We identified three patients with mycosis fungoides/Sezary syndrome that showed low density expression of the CD24-related epitope recognized by antibody BA-1 on circulating T cells. All three patients had Sezary cells by morphologic assessment and clonal T-cell populations in the peripheral blood by gene rearrangement studies. In two of these patients, indirect immunofluorescence with a panel of six anti-CD24 monoclonal antibodies demonstrated reactivity for two of six antibodies in one case and only one of six antibodies in the other. The biologic significance of CD24- related epitope expression on circulating T cells in mycosis fungoides/Sezary syndrome is unclear. However, these findings suggest that differential, low density expression of CD24-related epitopes (BA- 1+, OKB2-) may be a useful phenotypic marker for identifying circulating Sezary cells.
Down's syndrome and acute leukemia in children: an analysis of phenotype by use of monoclonal antibodies and electron microscopic platelet peroxidase reaction [see comments]
Authors: Kojima S , Matsuyama T , Sato T , Horibe K , Konishi S , Tsuchida M , Hayashi Y , Kigasawa H , Akiyama Y , Okamura J 
Published: October 2019

Abstract
The clinical, hematologic, and immunophenotypic features in 20 patients with Down's syndrome (DS) and acute leukemia were analyzed. Of the 20 patients, all 14 patients who were 3 years old and less were diagnosed as having acute megakaryoblastic leukemia (AMKL) by use of platelet- specific monoclonal antibodies and platelet peroxidase (PPO) reaction in electron microscopy. They were characterized by the presence of bone marrow fibrosis, having a history of myelodysplastic syndrome (MDS) and a poor response to chemotherapy. Only one patient has remained in continuous complete remission for more than 1 year. Acute leukemia in six patients who were older than 4 years was classified as common acute lymphoblastic leukemia antigen (CALLA)-positive acute lymphoblastic leukemia (ALL). In one of six patients classified as ALL, the leukemic blasts simultaneously expressed myeloid-associated surface antigens. All six patients achieved a complete remission and have remained in continuous complete remission and have remained in continuous complete remission from 10 to 52 months from the initial diagnosis. Although it has been suggested that the distribution of types of acute leukemia in patients with DS is similar to that in normal children, the present study shows that the distribution of acute leukemia types is quite different from that in patients without Down's syndrome.
Immunochemical and electrophoretic analyses of phosphorylated native and recombinant neutrophil oxidase component p47-phox
Authors: Nauseef WM , Volpp BD , Clark RA 
Published: October 2019

Abstract
Human polymorphonuclear neutrophils (PMNs) possess a potent oxygen- dependent microbicidal system that depends on the activity of a stimulus-activated multicomponent nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. Patients with chronic granulomatous disease (CGD) lack activity of this oxidase and consequently suffer severe and frequent infections. Components of the oxidase include both membrane- bound factors (most notably, cytochrome b559, which is absent in the X- linked form of CGD) and at least two cytosolic factors, one or the other of which is absent in autosomal CGD. Patients with CGD, particularly the autosomal type, have defective phosphorylation of proteins in the 44 to 48 Kd range. A polyclonal antiserum (B-1) that recognizes cytosolic oxidase components of 47 and 67 Kd was used to identify phosphoproteins in a cell-free oxidase system. Two-dimensional gel electrophoresis showed the identity of the 47-Kd cytosolic protein (p47-phox) recognized by B-1 and the cationic 47-Kd protein that is phosphorylated in normal but not p47-phox-deficient CGD cytosol during activation of the NADPH-dependent oxidase. All full-length and C- terminal recombinant p47-phox proteins augmented the superoxide- generating capacity of the cell-free system and were phosphorylated when added to cytosol from normal subjects or from a patient with p47- deficient autosomal CGD. These studies provide compelling evidence that the 47-Kd cationic protein that is a substrate for phosphorylation during the activation of PMNs is, in fact, p47-phox, a cytosolic protein previously shown to be critical for normal activity of the NADPH-dependent oxidase of PMNs.
The C gamma 1-encoded disulphide-linked and the C gamma 2-encoded nondisulphide-linked forms of the gamma/delta heterodimer use different gamma and delta variable regions [see comments]
Authors: Fagioli M , Ciccone E , Bottino C , Falini B , Grignani F , Moretta A , Moretta L , Pelicci PG 
Published: October 2019

Abstract
We identified two types of gamma/delta T-cell clones: (1) BB3+ clones, which express the disulphide-linked form of the gamma/delta heterodimer (type 1 receptor) and carry rearrangements of the C gamma 1 gene; and (2) delta TCS1+ clones, which express the nondisulphide-linked form of the gamma/delta heterodimer (type 2 receptor) and carry rearrangements of the C gamma 2 gene. To determine the joining (J) and variable (V) region usage of the two receptor types, T gamma and T delta gene rearrangements and expression were analyzed in each gamma/delta T-cell clone. The results showed that the J and V regions used by the two receptor types are distinct: clones that express the type 1 receptor carry potentially functional rearrangements in J gamma P-V gamma 9 for gamma and in J delta 1-V delta 2 for delta; and clones that express the type 2 receptor had potentially functional rearrangements in J gamma 2- V gamma 2/V gamma 4 for gamma and in J delta 1-V delta 1 for delta. Therefore, two clearly different gamma/delta receptors (V gamma 9-J gamma P-C gamma 1/V delta 2-J delta 1-C delta and V gamma 2/V gamma 4-J gamma 2-C gamma 2/V delta 1-J delta 1-C delta) predominate in peripheral blood.
Regulation of proto-oncogene and tumor necrosis factor gene expression by ethanol in HL-60 myeloid leukemia cells
Authors: Datta R , Sherman ML , Kufe DW 
Published: October 2019

Abstract
Previous studies have shown that certain low molecular weight polar solvents downregulate c-myc gene expression and induce terminal differentiation of human HL-60 myeloid leukemia cells. We have examined the effects of ethanol on gene expression in this cell line. The results show that while ethanol induces a more differentiated phenotype, this agent has little effect on the self-renewal capacity of HL-60 cells. Ethanol treatment was also associated with a concentration- dependent and transient downregulation of c-myc transcripts. Similar effects were observed for c-myb mRNA levels. The results further show that ethanol exposure is associated with induction of tumor necrosis factor gene expression. These findings indicate that ethanol induces changes in specific gene expression during non-terminal differentiation of HL-60 cells. The clinical effects of this agent could thus be related to altered patterns of gene expression in hematopoietic or other cells.
Subcutaneous recombinant granulocyte-macrophage colony-stimulating factor used as a single agent and in an alternating regimen with azidothymidine in leukopenic patients with severe human immunodeficiency virus infection [see comments]
Authors: Pluda JM , Yarchoan R , Smith PD , McAtee N , Shay LE , Oette D , Maha M , Wahl SM , Myers CE , Broder S 
Published: October 2019

Abstract
We investigated the effects of recombinant human granulocyte-macrophage colony-stimulating factor (rGM-CSF) administered by the subcutaneous route, first alone and then alternating with azidothymidine (AZT), in leukopenic patients with severe human immunodeficiency virus (HIV) infection. Ten patients with acquired immunodeficiency syndrome (AIDS) or related disorders, five of whom could not tolerate conventional doses of AZT, were administered rGM-CSF subcutaneously for 12 days. They then were administered an alternating regimen using AZT for 1 week, followed by 5 days of subcutaneous rGM-CSF and 2 days without any medication. During the initial 12 days of GM-CSF administration, there was an increase in the mean white blood cell (WBC) value. In addition, rGM-CSF stimulated circulating monocytes as evidenced by an increase in superoxide anion production and expression of surface HLA-DR antigen. However, at the same time rGM-CSF increased the serum HIV p24 antigen in each of the six evaluable patients from 189 x/divided by 2.02 pg/mL (geometric mean x/divided by SEM) at entry to 375 x/divided by 2.11 pg/mL (P less than .05). During the subsequent period of alternating AZT and rGM-CSF treatment, serum HIV p24 antigen fell below the day 14 value in most patients, particularly after the weeks of AZT administration. The mean T4 cell value increased in patients who had not previously received AZT, but generally did not change in those who had prior AZT exposure. Hematologic toxicity appeared to be somewhat reduced compared with continuous full-dose AZT therapy, and two patients with previous AZT hematologic toxicity tolerated this alternating regimen for 25 weeks. Additional regimens simultaneously combining these two agents are worth exploring.
Prolonged thrombocytosis in mice after 5-fluorouracil results from failure to down-regulate megakaryocyte concentration. An experimental model that dissociates regulation of megakaryocyte size and DNA content from megakaryocyte concentration
Authors: Chenaille PJ , Steward SA , Ashmun RA , Jackson CW 
Published: October 2019

Abstract
Rodents treated with 150 mg/kg of 5-fluorouracil (5-FU) exhibit a marked and prolonged rebound thrombocytosis, suggesting that feedback control of one or more megakaryocyte characteristics (size, polyploidy, or concentration) is altered. To determine the changes in megakaryocytes that lead to such a profound thrombocytosis, C3H mice were injected with 150 mg/kg 5-FU, and platelet and megakaryocyte responses were examined at frequent intervals from days 1 through 25. After 5-FU injection, all megakaryocyte indices decreased, as did platelet number. However, the decrease in platelets to one third of control was greater than the decreases in megakaryocyte indices, suggesting that thrombocytopoiesis was ineffective from days 3 through 7 post 5-FU. Megakaryocyte size began to recover on day 4, followed by polyploid DNA content on day 5, and megakaryocyte concentration and platelets at 7.5 days. Megakaryocyte size peaked on days 6 through 8 (1.25 x normal), followed by megakaryocyte polyploid DNA content on day 8, megakaryocyte concentration on days 9 through 12 (2 1/2 to 3x normal), and platelets on days 12 through 15 (2x normal). Platelet levels are thought to be important in the feedback regulation of megakaryocytes; however, only polyploid DNA content distributions showed a close inverse relationship to platelet counts during both the recovery and rebound thrombocytosis phases after 5-FU. In contrast, megakaryocyte size peaked before platelet recovery commenced, while megakaryocyte concentration increased in parallel with platelets from 7.5 to 10 days post 5-FU and continued to be maintained at 2 to 3 times normal through day 13, despite platelet levels that were more than twice normal. Both megakaryocyte size and polyploid DNA content distributions shifted toward lower values in response to the rebound thrombocytosis (DNA content on day 10 and size on days 12 and 13). Splenectomy did not substantially alter the pattern of post 5-FU rebound thrombocytosis or megakaryocyte response from that seen in intact mice, indicating that splenic megakaryocytes are not responsible for the prolonged thrombocytosis seen after this drug. In summary, the prolonged thrombocytosis after 5-FU administration results from failure to down-regulate the number of precursors entering the differentiating megakaryocyte compartment. These data indicate that megakaryocyte size and DNA content are responsive to different feedback controls than megakaryocyte concentration in this model system.