bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expression of the c-raf protooncogene in human hematopoietic cells and cell lines
Authors: Sariban E , Mitchell T , Kufe D 
Published: October 2019

Abstract
The murine sarcoma virus 3611 contains the transforming v-raf gene that has partial nucleotide homology with the src family of tyrosine kinase- encoding oncogenes. Although this virus induces fibrosarcomas in mice, a recombinant murine retrovirus carrying both the raf and myc oncogenes induces immunoblastic lymphomas and immortalizes mouse macrophages in vitro. The present study has thus monitored the expression of c-raf in human hematopoietic cells. The results demonstrate the presence of a 3.6-kb c-raf transcript in HL-60 promyelocytic leukemic cells. The induction of HL-60 cell differentiation along the monocytic or granulocytic lineages had no detectable effect on the level of c-raf transcripts. Furthermore, in contrast to c-myc and c-fms expression, inhibition of protein synthesis with cycloheximide had no detectable effect on c-raf expression. Similar levels of c-rafRNA were also found in other human cell lines derived from myeloid, B cell, and T cell tumors, as well as in normal granulocytes, monocytes, and macrophages. These findings suggest that the c-raf protooncogene is widely expressed in multiple hematopoietic lineages.
Synergism between recombinant growth factors, GM-CSF and G-CSF, acting on the blast cells of acute myeloblastic leukemia [published erratum appears in Blood 1987 Jul;70(1):339]
Authors: Kelleher C , Miyauchi J , Wong G , Clark S , Minden MD , McCulloch EA 
Published: October 2019

Abstract
The genes for the hemopoietic growth factors, GM colony-stimulating factor (CSF) and G-CSF have been cloned, and recombinant material is available for both. We tested these recombinant factors for their effects on the blast cells of acute myeloblastic leukemia (AML). Culture methods are available that support both colony formation by AML blasts and the growth of blast stem cells in suspension. Recombinant GM- CSF is active in both culture systems, although to a varying degree. We found that recombinant G-CSF was also effective; however, the two recombinant factors showed striking synergism for the stimulation of blast growth of cells from five of eight AML patients. In these cases, the combination was equivalent to the stimulating activity of supernatants from the continuous cell line 5637. This conditioned medium (HTB9-CM) is considered the standard for blast growth. Blasts from one of the patients grew without added factor. In another instance, recombinant GM-CSF alone was almost as effective as HTB9-CM. In the third case, both recombinant factors were active, but synergism was not observed and their combined effect was not equivalent to that of HTB9-CM. Both GM-CSF and G-CSF were active on normal bone marrow granulopoietic progenitors, but synergism was not observed. We conclude that the marked heterogeneity observed when AML blasts are examined by other criteria is also observed when their response to growth factors is evaluated.
Activities of four purified growth factors on highly enriched human hematopoietic progenitor cells
Authors: Strife A , Lambek C , Wisniewski D , Gulati S , Gasson JC , Golde DW , Welte K , Gabrilove JL , Clarkson B 
Published: October 2019

Abstract
The activities of four purified human growth factors: biosynthetic (recombinant) granulocyte-macrophage colony-stimulating factor (GM- CSF); recombinant erythroid-potentiating activity (EPA); natural and recombinant pluripoietin (Ppo); and natural pluripoietin alpha (Ppo alpha), were compared on the growth of hematopoietic colonies from enriched populations of human marrow and blood progenitor cells. Conditioned medium from the Mo T cell line (MoCM) was used as a standard positive control. We found that activities of GM-CSF and Ppo alpha on the growth of hematopoietic colonies were indistinguishable; Ppo alpha is now believed to be identical to GM-CSF. Both factors were able to promote the growth of colonies derived from subpopulations of CFU-GM, BFU-E, and CFU-GEM. Colonies derived from CFU-GM and CFU-GEM in cultures stimulated by GM-CSF and Ppo alpha were much smaller than in cultures stimulated by MoCM. In contrast to previous reports in which less highly enriched progenitors were used as target cells, Ppo had no detectable activity on the growth of colonies derived from BFU-E or CFU- GEM but promoted the growth of a subpopulation of CFU-GM derived colonies. Ppo is now recognized to be identical to G-CSF. The GM colonies in cultures stimulated by G-CSF (Ppo) were much smaller than in cultures stimulated by MoCM. EPA had no detectable activity on either the size or number of colonies derived from CFU-GM, BFU-E, or CFU-GEM. Results from experiments using target cell populations of marrow fractions separated by velocity sedimentation and marrow populations following freezing suggested that GM-CSF (Ppo alpha) and G- CSF (Ppo) primarily affect the growth of relatively mature subpopulations of progenitor cells. It is clear from these results that additional factor(s) are present in MoCM that are necessary to stimulate CFU-GM, BFU-E, and CFU-GEM maximally in vitro.
Glucose-6-phosphate dehydrogenase of malaria parasite Plasmodium falciparum
Authors: Yoshida A , Roth EF Jr 
Published: October 2019

Abstract
Plasmodium falciparum growth is impaired in glucose-6-phosphate dehydrogenase (G6PD)-deficient red blood cells (RBCs), and malaria has been implicated in the spreading of deficient variants in malaria- endemic areas. Recent reports suggest that the malaria parasite can adapt itself to grow in these variant RBCs by producing its own G6PD, but studies on parasite G6PD are very limited. In this report, we define the properties of the parasite G6PD. G6PD was partially purified from infected and uninfected variant RBCs associated with severe G6PD deficiency. G6PD from infected RBCs contained two components separable by starch gel electrophoresis: a major component (approximately 90% activity) with a very slow anodal electrophoretic mobility and a minor component (approximately 10% activity) with the same mobility as the host G6PD. Parasite G6PD exhibited much higher affinity (low Km) to G6P and nicotinamide-adenine dinucleotide phosphate (NADP) than did human G6PD. Southern blot hybridization indicated that the parasite genome contained nucleotide sequences that were hybridizable with the human G6PD cDNA. These data indicate that the parasite is capable of adapting to G6PD-deficient RBCs by producing its own G6PD.
Human plasma protein Z antigen: range in normal subjects and effect of warfarin therapy
Authors: Miletich JP , Broze GJ Jr 
Published: October 2019

Abstract
In contrast to the other well-studied vitamin K-dependent proteins that circulate in plasma, protein Z antigen is much more variable. The concentration in plasmas collected in EDTA from 455 normal, healthy donors is normally distributed with a mean of 2.9 micrograms/mL (46 nmol/L) and a SD of 1.0 microgram/mL (95% interval of 32% to 168% of the mean). No significant correlation to age or sex could be detected. In comparison, the concentration of protein C antigen measured with the same type of assay on the same 455 samples has a log normal distribution with a mean of 4.0 micrograms/mL (65 nmol/L) and a 95% interval of 70% to 138% of the mean. Also in marked contrast to other plasma vitamin K-dependent proteins, the total protein Z antigen level is extremely low in patients on stable warfarin therapy (range 1% to 16% of normal). Moreover, even though greater than 95% of the antigen in normal plasmas adsorbs to barium citrate (a crude reflection of the presence of gamma-carboxyglutamic acid (Gla) residues), in the patients taking warfarin almost all of the small amount of the antigen failed to adsorb, suggesting that virtually no protein Z had its full complement of Gla residues. Total protein C antigen in the same 25 patients averaged 53% of normal (34% to 72%) and 54% (average) of the total remaining antigen still adsorbed to barium citrate. The concentration of protein Z antigen in the plasma of a normal individual given a loading dose of warfarin fell at an initial rate of approximately 20% a day, indicating a plasma half-life (t1/2) of 2 to 3 days.
Development of large numbers of mast cells at sites of idiopathic chronic dermatitis in genetically mast cell-deficient WBB6F1-W/Wv mice
Authors: Galli SJ , Arizono N , Murakami T , Dvorak AM , Fox JG 
Published: October 2019

Abstract
The normal skin and other tissues of adult mast cell-deficient WBB6F1- W/Wv or WCB6F1-Sl/Sld mice contain less than 1.0% the number of mast cells present in the corresponding tissues of the congenic normal (+/+) mice. As a result, genetically mast cell-deficient WBB6F1-W/Wv or WCB6F1-Sl/Sld mice are widely used for studies of mast cell differentiation and function. We found that mast cells developed at sites of idiopathic chronic dermatitis in WBB6F1-W/Wv mice and that the number of mast cells present in the skin of WBB6F1-W/Wv mice was proportional to the severity of the dermatitis (in ear skin, there were 33 +/- 4 mast cells/mm2 of dermis at sites of severe dermatitis v 9 +/- 3 at sites of mild dermatitis, 0.8 +/- 0.3 in skin without dermatitis, and 100 +/- 7 in the normal skin of congenic WBB6F1-+/+ mice; in back skin, the corresponding values were 2.0 +/- 0.6, 1.1 +/- 0.9, 0.025 +/- 0.025, and 26.2 +/- 3.2). The development of mast cells was a local, not systemic, consequence of the dermatitis. Thus, WBB6F1-W/Wv mice with severe dermatitis lacked mast cells in skin not showing signs of dermatitis and also in the peritoneal cavity, stomach, cecum, and tongue. Idiopathic chronic dermatitis was not associated with the local development of mast cells in WCB6F1-Sl/Sld mice, a mutant whose mast cell deficiency is due to a mechanism distinct from that of WBB6F1-W/Wv mice. These findings may have implications for understanding the nature of the mast cell deficiency in WBB6F1-W/Wv and WCB6F1-Sl/Sld mice and for the use of these mutants to analyze mast cell differentiation and function.
The effect of ABO blood group on the diagnosis of von Willebrand disease
Authors: Gill JC , Endres-Brooks J , Bauer PJ , Marks WJ Jr , Montgomery RR 
Published: October 2019

Abstract
In order to firmly establish a normal range for von Willebrand factor antigen (vWF:Ag), we determined plasma vWF:Ag concentrations in 1,117 volunteer blood donors by quantitative immunoelectrophoresis. The presence of the ABO blood group has a significant influence on vWF:Ag values; individuals with blood group O had the lowest mean vWF:Ag level (74.8 U/dL), followed by group A (105.9 U/dL), then group B (116.9 U/dL), and finally group AB (123.3 U/dL). Multiple regression analysis revealed that age significantly correlated with vWF:Ag levels in each blood group. We then performed reverse ABO typing on stored plasma from 142 patients with the diagnosis of von Willebrand disease (vWd). Of 114 patients with type I vWd, blood group O was found in 88 (77%), group A in 21 (18%), group B in 5 (4%), and group AB in none (0%), whereas the frequency of these blood groups in the normal population is significantly different (45%, 45%, 7% and 3%, respectively) (P less than .001). Patients with type II or III vWd had ABO blood group frequencies that were not different from the expected distribution. There may be a subset of symptomatic vWd patients with decreased concentrations of structurally normal vWf (vWd, type I) on the basis of blood group O. Some individuals of blood group AB with a genetic defect of vWF may have the diagnosis overlooked because vWF levels are elevated due to blood type.
Type beta transforming growth factor is a potent inhibitor of murine megakaryocytopoiesis in vitro
Authors: Ishibashi T , Miller SL , Burstein SA 
Published: October 2019

Abstract
To investigate the potential role of platelets in the inhibition of megakaryocytopoiesis, freeze-thawed extracts of human platelets were added to serumless liquid cultures of murine marrow. When acetylcholinesterase (AchE), a marker of megakaryocytic differentiation in mice, was assayed, a significant inhibition of enzymatic activity was noted in cultures containing the equivalent of greater than 5 X 10(6) solubilized platelets per milliliter. Freeze-thawed extracts of granulocytes had significantly less inhibitory effect than did platelets. Transforming growth factor beta (TGF-beta), a growth factor known to be inhibitory to some cell lineages and to be found at relatively high concentrations in platelets, was then added to liquid marrow cultures. A similar inhibition of AchE activity was detected when cultures were stimulated with mitogen-stimulated conditioned medium. The effect was potent with 50% inhibition of AchE activity observed at 4 pmol TGF-beta/L. To determine if TGF-beta inhibited specifically one aspect of megakaryocytic differentiation, the factor was added to isolated single megakaryocytes in serumless culture induced by interleukin 3 (IL3) to increase in size. The number of megakaryocytes increasing in size in response to IL 3 exposure was reduced from 68% to 20% when both factors were simultaneously added to cultures. Colony assays showed that megakaryocytic and granulocyte- macrophage colony detection was inhibited at picomolar concentrations of the factor. These data suggest that TGF-beta is a potent in vitro inhibitor of the murine megakaryocytic lineage, although its effects are not limited to this lineage.
Spectrin oxidation correlates with membrane vesiculation in stored RBCs
Authors: Wagner GM , Chiu DT , Qju JH , Heath RH , Lubin BH 
Published: October 2019

Abstract
An increase in spectrin oxidation in a variety of erythrocytes displaying a tendency to vesiculate has been previously described. To explore this relationship in more detail, we have studied blood stored in citrate-phosphate-dextrose-adenine under blood bank conditions because, in this system, vesiculation occurs slowly. Vesiculation was quantitated by measuring acetylcholinesterase release, and the extent of spectrin oxidation was detected by using thiol-disulfide exchange chromatography. A strong correlation (r = .92) was found between the extent of spectrin oxidation and vesiculation when blood from five donors was analyzed at weekly intervals during storage. This strongly suggests that spectrin oxidation plays a role in the formation of spectrin-free vesicles, thereby limiting the shelf life of stored blood.
Identification of an erythropoietin-sensitive cell line
Authors: Branch DR , Turc JM , Guilbert LJ 
Published: October 2019

Abstract
The murine lymphoblastic cell line DA-1 has been characterized as dependent upon both interleukin-3 (IL-3, multicolony-stimulating factor [multi-CSF]) and granulocyte-macrophage colony-stimulating factor (GM- CSF) for survival and growth. Here we demonstrate that it is responsive to a third hematopoietic factor, the erythroid-specific hormone, erythropoietin (Epo). DA-1 cells are stimulated to proliferate by partly purified natural murine and human Epo, and pure recombinant human Epo. Antibody to Epo specifically blocks Epo-stimulated growth. Maximal growth stimulated by Epo and GM-CSF is similar, and considerably less than that stimulated by multi-CSF. Proliferation stimulated by Epo and GM-CSF is transient, decreasing within 24 to 48 hours of exposure. However, Epo acts cooperatively with GM-CSF to sustain proliferation. With or without GM-CSF, no obvious erythroid differentiation of DA-1 cells occurs after exposure to Epo for up to 72 hours. This is the first report of a growth factor-dependent cell line also responsive to Epo for survival and growth. The availability of this cell line model should greatly facilitate biochemical analysis of the mechanism of Epo growth-stimulating action.
Endothelial cell interactions with sickle cell, sickle trait, mechanically injured, and normal erythrocytes under controlled flow
Authors: Barabino GA , McIntire LV , Eskin SG , Sears DA , Udden M 
Published: October 2019

Abstract
Increased adhesive forces between sickle erythrocytes and endothelial cells (EC) have been hypothesized to play a role in the initiation of vasoocclusion in sickle cell anemia. Erythrocyte/human umbilical vein EC interactions were studied under controlled flow conditions for normal (AA), homozygous sickle cell (SS), sickle cell trait (AS), mechanically injured normal, and “high-reticulocyte control” RBC by using video microscopy and digital image processing. The number of adherent RBC was determined at ten-minute intervals during a washout period. Results indicate that SS RBC were more adherent than AA RBC. Mechanically injured (sheared) AA RBC were also more adherent than control normal cells but less adherent than SS RBC. AS RBC did not differ significantly in their adhesive properties from normal RBC. Less- dense RBC were more adherent to EC than dense cells for normal, SS, and high-reticulocyte control RBC. The number of cells adherent at a given time during washout was a very strong function of wall shear rate. In addition, at all shear rates studied, the average velocity of individual SS RBC in the region near the EC surface was approximately half that of AA RBC at the same bulk volumetric flow rate through the flow chamber. These findings suggest that the increased adhesion of sickle RBC is at least partially related to the increased numbers of less-dense RBC present. Increased adherence of the less-dense cells to the EC lining vessel walls could contribute to microvascular occlusion by lengthening vascular transit times of other sickle cells.
Proteolytic degradation of von Willebrand factor after DDAVP administration in normal individuals
Authors: Batlle J , Lopez-Fernandez MF , Lopez-Borrasca A , Lopez-Berges C , Dent JA , Berkowitz SD , Ruggeri ZM , Zimmerman TS 
Published: October 2019

Abstract
The infusion of 1-deamino-8-D-arginine vasopressin (DDAVP) in normal individuals is followed by an increase in factor VIII/von Willebrand factor (vWF) in plasma, by an increase in intensity of all sizes of multimers, and by the appearance of larger multimers of vWF than those seen in the resting state. Since the larger multimers are rapidly cleared and proteolysis is known to cause disaggregation of large multimers, we evaluated the degree of vWF proteolysis after DDAVP administration. DDAVP was infused into eight normal adult volunteers, and the relative proportions of the intact 225 kilodalton (kDa) subunit and the 189, 176, and 140 kDa vWF fragments were compared before and at different times after DDAVP infusion. The relative proportion of the 176 kDa fragment was increased, whereas that of the other species was decreased, thereby indicating that proteolytic fragmentation had occurred. However, plasmin did not appear to be responsible because the vWF fragments characteristically produced by this enzyme could not be detected. Concomitant analysis of vWF multimeric structure showed that these changes were accompanied by an increase in the relative proportion of the satellite bands, which suggests that they were proteolytically generated. Proteolysis may explain, at least in part, rapid clearance of larger vWF multimers released by DDAVP.
S-100 beta positive human T lymphocytes: their characteristics and behavior under normal and pathologic conditions
Authors: Takahashi K , Yoshino T , Hayashi K , Sonobe H , Ohtsuki Y 
Published: October 2019

Abstract
The characteristics of human S-100 beta-positive T lymphocytes (S-100 beta+ T cells) and their fluctuation in peripheral blood under normal and various pathologic conditions were investigated. S-100 beta+ T cells were small lymphocytes with no particular subcellular structures and showed a proliferative response to mitogens. They were present mainly in peripheral blood under normal conditions but accumulated in T zones of lymph nodes with nonspecific T-zone hyperplasia, where numerous interdigitating reticulum cells existed. In healthy adults approximately 1% to 4% (mean 3.4%) of peripheral blood mononuclear cells were S-100 beta+ T cells. The proportion of S-100 beta+ T cells in peripheral blood tended to significantly decrease (less than 0.5%) in patients with neoplastic diseases; this tendency was apparently related to tumor progression.
Pseudosickling of hemoglobin Setif
Authors: Charache S , Raik E , Holtzclaw D , Hathaway PJ , Powell E , Fleming P 
Published: October 2019

Abstract
Hemoglobin Setif produces pseudosickling of red cells in vitro; the nature of the process and the conditions that “trigger” it are unknown. Studies of red cells, hemolysates, purified hemoglobin solutions, and artificial mixtures of Hb A and Setif suggest that pseudosickling is produced by intracellular crystallization of insoluble hemoglobin. Increased tonicity of the suspending medium accentuates the process, probably by causing a rise in intracellular hemoglobin concentration. If precipitates from A/Setif mixtures are analyzed, they always contain Hb A, suggesting an unusual mechanism for the process. Despite the fact that osmolality in the renal medulla is similar to that which produces pseudosickling in vitro, carriers do not have renal dysfunction of the type found in patients with sickle cell disease.
CFU-GM content of bone marrow graft correlates with time to hematologic reconstitution following autologous bone marrow transplantation with 4- hydroperoxycyclophosphamide-purged bone marrow
Authors: Rowley SD , Zuehlsdorf M , Braine HG , Colvin OM , Davis J , Jones RJ , Saral R , Sensenbrenner LL , Yeager A , Santos GW 
Published: October 2019

Abstract
Autologous bone marrow transplants (BMTs) can repopulate the hematologic system of patients treated with marrow-ablative chemotherapy and/or radiotherapy. However, treatment of the bone marrow graft to eliminate residual tumor cells prior to reinfusion can delay the return of peripheral blood elements, presumably from damage to or loss of hematopoietic stem cells responsible for hematologic recovery. To develop a model predictive of hematologic recovery, we studied the progenitor cell contents of 4-hydroperoxycyclophosphamide (100 micrograms/mL)-purged bone marrow grafts of 40 consecutive patients undergoing autologous BMT at this center. Granulocyte-macrophage colonies (CFU-GM) were grown from all grafts after treatment with this chemotherapeutic agent, but erythroid (BFU-E) and mixed (CFU-GEMM) colonies were grown from only 44% and 33% of the grafts respectively. The recovery of CFU-GM after purging ranged from 0.07% to 23%. The logarithm of CFU-GM content of the treated grafts was linearly correlated with the time to recovery of peripheral blood leukocytes (r = -0.80), neutrophils (r = -0.79), reticulocytes (r = -0.60), and platelets (r = -0.66). The CFU-GM content of purged autologous bone marrow grafts may reflect the hematopoietic stem cell content of the grafts and thus predict the rate of hematologic recovery in patients undergoing autologous BMT.