bluuebunny/crossref_metadata_2025_split huggingface dataset:
Loss of myeloid differentiation antigens precedes blastic transformation in chronic myelogenous leukemia
Authors: Todd MB , Waldron JA , Jennings TA , Rome LS , Markowitz SD , Holford TR , Gardner JP , Wolak JP , Malech HL 
Published: October 2019

Abstract
In order to determine whether antigenic patterns alter with disease progression and are thereby suggestive of impending blast crisis in chronic myelogenous leukemia, 50 bone marrow biopsy specimens from 32 patients were examined retrospectively using indirect immunoperoxidase labeling with three monoclonal antibodies that detect myeloid antigens. Monoclonal antibodies PMN13F6, PMN7C3, and PMN8C7 detect human neutrophil antigens that first appear at the myeloblast, promyelocyte, and metamyelocyte stages of differentiation, respectively, and persist throughout later differentiation. Percentages of antigen-positive bone marrow cells during the chronic phase were compared with percentages of antigen-positive cells at blast transformation, and time from bone marrow biopsy until blast crisis was correlated with the percentage of bone marrow cells expressing these antigens. Bone marrow biopsy samples from patients in the chronic phase who continue to remain clinically stable 4 to 106 months after biopsy expressed PMN13F6 antigen on 82% +/- 9% (mean +/- SD) of cells, PMN7C3 antigen on 62% +/- 14% of cells, and PMN8C7 on 68% +/- 14% of cells. Bone marrow biopsy specimens obtained from patients 1 or more years prior to blast transformation expressed PMN13F6 antigen on 81% +/- 12%, PMN7C3 antigen on 71% +/- 16%, and PMN8C7 on 64% +/- 16% of cells. Bone marrow biopsy samples obtained between 2 months and 1 year prior to blast crisis expressed PMN13F6 antigen on 68% +/- 15%, PMN7C3 on 51% +/- 17%, and PMN8C7 antigen on 46% +/- 18% of cells. Bone marrow biopsy specimens taken at the time of blast transformation expressed PMN13F6 antigen on 20% +/- 25%, PMN7C3 antigen on 19% +/- 25%, and PMN8C7 antigen on 13% +/- 25% of cells. The difference between the mean of antigen-positive cells from bone marrow biopsy samples obtained at the time of blast crisis was significant compared with the mean of positive cells from biopsy specimens obtained at all other phases of the disease (P less than .001 for all three antibodies). There was a positive correlation between loss of myeloid antigens and disease progression as determined by simple regression of log time and correlation analysis (PMN13F6, r = .6533, P less than .005; PMN7C8, r = .6304, P less than .005; PMN8C7, r = .5215, P less than .05). There was a negative correlation between percentage of immature cells and time to blastic crisis (r = -.6206, P less than .005).(ABSTRACT TRUNCATED AT 250 WORDS)
Clonal immunoglobulin gene rearrangements in tissues involved by Hodgkin's disease
Authors: Brinker MG , Poppema S , Buys CH , Timens W , Osinga J , Visser L 
Published: October 2019

Abstract
The nature of Reed-Sternberg cells, the abnormal cells of Hodgkin's disease, is controversial. Morphological and immunologic marker studies suggested different cells of origin. To investigate a possible B or T cell origin, immunoglobulin and T cell receptor gene analyses were performed on tissues from 11 patients in early and late stages of Hodgkin's disease. In addition, the immunologic marker patterns of the Reed-Sternberg cells were determined. Rearrangements of immunoglobulin heavy- and light-chain genes were detected in tissues from five patients, particularly in late stages of the disease when lymphocyte depletion had occurred. No rearrangements of T cell receptor genes were found. The results indicate that clonal immunoglobulin gene rearrangements can be detected in tissues involved by Hodgkin's disease.
Lactoferrin binding by leukemia cell lines
Authors: Yamada Y , Amagasaki T , Jacobsen DW , Green R 
Published: October 2019

Abstract
Monocytes and macrophages have receptors for the iron-binding protein lactoferrin. Lactoferrin acts as a potent inhibitor of granulocyte- macrophage colony stimulating factor production when it binds to these cells. Using a rosette assay and immunofluorescence, we have shown that cultured leukemia cells, including the human erythroid leukemia cell line K562, also have lactoferrin binding sites. The number of binding sites on K562 cells was estimated using soluble 59Fe-lactoferrin. Inhibition studies demonstrate that lactoferrin binding sites are distinct and unrelated to receptors for transferrin or the Fc portion of IgG, which are present on K562 cells. However, electrostatic forces may be important for lactoferrin binding, since other polycationic proteins (eg, protamine) inhibit lactoferrin binding. Prior treatment of K562 cells with trypsin nearly abolishes lactoferrin binding. However, these cells recover their ability to bind lactoferrin when trypsin is removed. Unlike transferrin receptors, the expression of lactoferrin binding sites is not regulated by cellular iron status. Cytosine arabinoside arrests the proliferation of K562 cells and simultaneously leads to a reduction in lactoferrin surface binding, suggesting that lactoferrin binding may be dependent on cell proliferation.
Clinical significance of low levels of myeloperoxidase positivity in childhood acute nonlymphoblastic leukemia
Authors: Pui CH , Behm FG , Kalwinsky DK , Murphy SB , Butler DL , Dahl GV , Mirro J 
Published: October 2019

Abstract
The clinical significance of a low percentage of myeloperoxidase- positive blast cells in childhood acute nonlymphoblastic leukemia was determined. Of 155 consecutive cases studied by cytochemical staining methods, 14 were characterized by 4% to 15% (median 6%) myeloperoxidase- positive blasts. All 14 cases showed reactivity to Sudan black B stain, and 7 had Auer rods. The morphological subtypes of leukemia were M1 (8 cases), M2 (3), M4 (1), and M5 (2). Immunological marker studies disclosed the lymphoid-associated T11 antigen on cells from 8 of the 11 cases tested. Other lymphoid-related findings in these 8 cases included the T3 antigen and E rosette formation in 1 case each. Among cases that were prospectively studied for the expression of lymphoid-associated markers, 6 of 8 with low levels of myeloperoxidase positivity compared with only 1 of 44 with higher levels (greater than 15%) possessed such features (P less than 0.001). We conclude that low levels of myeloperoxidase reactivity distinguish cases of acute leukemia in which the blast cells coexpress lymphoid (T11 antigen) and myeloid markers.
Characterization of the chemotactic defect in polymorphonuclear leukocytes exposed to influenza virus in vitro
Authors: Moore DL , Mills EL 
Published: October 2019

Abstract
The mechanism by which influenza virus interferes with polymorphonuclear leukocyte (PMN) chemotaxis was investigated. Incubation of human PMN with influenza A virus in vitro for 30 minutes significantly decreased PMN migration under agarose in response to N- formyl-methionyl-leucyl-phenylalanine (FMLP) or zymosan-activated serum. Virus-treated PMN tended to aggregate in the under-agarose assay. Aggregation was avoided by using a more dilute PMN suspension in filter assays. Virus treatment significantly decreased migration through 100-micron thick cellulose nitrate filters but had no effect on migration through 10-micron thick polycarbonate filters or on PMN bipolar shape change. Virus was not chemotactic in the polycarbonate filter assay and did not induce shape change in purified PMN. It was concluded that influenza virus did not interfere with the ability of PMN to recognize a chemoattractant, undergo shape change, and move a short distance but did limit the extent of migration. Inhibition could not be explained by chemotactic deactivation, since the virus was not chemotactic.
Eosinophils do respond to fMLP
Authors: Yazdanbakhsh M , Eckmann CM , Koenderman L , Verhoeven AJ , Roos D 
Published: October 2019

Abstract
Eosinophils were isolated from normal human blood by separation over Percoll gradients, which resulted in eosinophil suspensions of a purity higher than 95% and recoveries of about 65%. Normal human eosinophils were found to respond to formyl-methionyl-leucyl-phenylalanine (fMLP) at concentrations greater than 10(-7) mol/L with an increase in the concentration of intracellular free calcium, oxygen consumption, nitroblue tetrazolium reduction, and chemiluminescence. The maximal response of eosinophils to fMLP was lower than that of neutrophils isolated from the same blood samples and required at least ten times as much fMLP as was needed for neutrophils. Low fMLP concentrations (approximately 10(-8) mol/L), which in themselves did not stimulate O2 consumption by either eosinophils or neutrophils, primed these cells to respond to a suboptimal concentration of another stimulus. Purification of eosinophils after treatment of whole blood with fMLP showed that these eosinophils had lost their ability to respond to fMLP. We conclude that normal eosinophils do respond to fMLP and that therefore fMLP should not be used to isolate eosinophils.
Homosexual men with thrombocytopenia have impaired reticuloendothelial system Fc receptor-specific clearance
Authors: Bender BS , Quinn TC , Spivak JL 
Published: October 2019

Abstract
Classic immune thrombocytopenia purpura (ITP) occurs predominantly in women and is associated with either normal or impaired Fc receptor- mediated clearance of antibody-coated cells. Recently, an increasing incidence of thrombocytopenia has been observed in homosexual men, but whether Fc receptor-mediated clearance of antibody-coated cells is normal or impaired in these men is unknown. To study this question, we measured the in vivo clearance of anti-Rho(D) IgG antibody-sensitized 51Cr-labeled autologous red cells in five homosexual men with thrombocytopenia without an evident cause. All five had antibodies to human immunodeficiency virus, and four had circulating immune complexes as determined by a Clq-binding assay. Two of the men tested also had an increase in platelet-associated IgG. In the four homosexual men with platelet counts of 20,000/microL or less, the clearance half-time of IgG-sensitized red cells was prolonged (mean, 106 minutes; range, 72 to 140 minutes) as compared with the clearance of such cells in five hematologically normal men (mean, 39 minutes; range 30 to 50 minutes; P less than .005). One homosexual man with a platelet count of 81,000/microL had a normal clearance half-time (30 minutes). Three patients whose platelet counts increased after corticosteroid therapy were restudied. In all three, the clearance of antibody-coated cells was shortened and returned to normal in the one patient who had achieved a complete remission. No correlation was observed between the presence of platelet-associated IgG or circulating immune complexes and the clearance half-time. These data indicate that severe thrombocytopenia occurring in homosexual men as in some patients with classic ITP is associated with defective in vivo Fc receptor-mediated clearance of antibody-coated cells.
Recombinant human granulocyte colony-stimulating factor repairs the abnormalities of neutrophils in patients with myelodysplastic syndromes and chronic myelogenous leukemia
Authors: Yuo A , Kitagawa S , Okabe T , Urabe A , Komatsu Y , Itoh S , Takaku F 
Published: October 2019

Abstract
We examined the in vitro effect of recombinant human granulocyte colony- stimulating factor (rhG-CSF) on neutrophil anomalies in 20 patients with myelodysplastic syndromes (MDS) and eight patients with chronic myelogenous leukemia (CML). Neutrophil alkaline phosphatase (NAP) activity was determined in nine MDS patients and eight CML patients by a scoring method. NAP scores were decreased in six of the nine patients with MDS and in all of the patients with CML. In all patients with these diseases, NAP scores increased by incubating the blood with rhG- CSF. An increase in NAP scores by rhG-CSF was observed even at a concentration of 1 U/mL in patients with MDS but was observed only at higher concentrations (1,000 to 10,000 U/mL) in patients with CML. Significant increases in NAP scores occurred at 12 hours' incubation in patients with MDS, whereas the increase was more gradual in patients with CML. This time course difference was thought to be due mainly to the difference in cell populations of circulating myeloid cells between MDS patients and CML patients. Induction of NAP activity by rhG-CSF in patients with both these diseases was suppressed by the addition of inhibitors of RNA or protein synthesis. Neutrophil superoxide anion (O2- ) production induced by N-formyl-methionyl-leucyl-phenylalanine (fMLP) was determined in the other 11 patients with MDS. This neutrophil function was decreased in seven of the 11 patients with MDS, normal in two patients, and increased in two patients. Preincubation with rhG-CSF caused a significant increase in fMLP-induced O2- production in nine of the 11 patients with MDS. rhG-CSF enhanced this neutrophil function in a time- and dose-dependent manner, and maximal stimulation was observed at 2,000 to 4,000 U/mL of rhG-CSF and at five to ten minutes' incubation. The present results show that rhG-CSF is able to repair at least in part the neutrophil anomalies in these patients, and our data, especially for patients with MDS, suggest the clinical usefulness of rhG-CSF for this preleukemic disorder.
Photoradiation models for the clinical ex vivo treatment of autologous bone marrow grafts
Authors: Atzpodien J , Gulati SC , Strife A , Clarkson BD 
Published: October 2019

Abstract
To assess the potential of photoradiation therapy for the in vitro purging of residual tumor cells from autologous bone marrow (BM) transplants, we studied normal marrow and tumor cell clonogenicity in response to different light-activated compounds by using the fluorescent dyes dihematoporphyrin ether (DHE) and merocyanine-540 (MC- 540). After photoradiation of cells with white light, both DHE and MC- 540 showed high cytocidal activity toward lymphoid and myeloid neoplastic cells but had a significantly lesser effect on normal granulocyte-macrophage (CFU-GM), erythroid (BFU-E), and mixed colony- forming (CFU-GEMM) progenitor cells. Acute promyelocytic leukemia (HL- 60), non-B, non-T, CALLA-positive acute lymphoblastic leukemia (Reh), and diffuse histocytic B cell lymphoma (SK-DHL-2) cell lines were exposed to different drug concentrations in combination with white light at a constant illumination rate of 50,000 lux. With DHE doses varying from 2.0 to 2.5 micrograms/mL and MC-540 concentrations of 15 to 20 micrograms/mL, clonogenic tumor cells could be reduced by more than 4 logs when treated alone or in mixtures with normal irradiated human marrow cells. However, preferential cytotoxicity towards neoplastic cells was highly dependent on the mode of light activation. MC-540 had no substantial effect on malignant lymphoid (SK-DHL-2) and myeloid (HL-60) cells and on normal marrow myeloid (CFU-GM) precursors when drug incubation was performed in the dark and followed by light exposure of washed cells. Equal doses of MC-540 (15 to 20 micrograms/mL) could preferentially eliminate tumor cells under conditions of simultaneous light and drug treatment (30 minutes at 37 degrees C). When using DHE (2.5 micrograms/mL), 29.3%, 46.8%, and 27.5% of normal marrow CFU-GM, BFU-E, and CFU-GEMM, respectively, were spared after sequential drug and light exposure of cells, whereas simultaneous treatment reduced both normal (CFU-GM) and neoplastic cells below the limits of detection. In summary, our results indicate the usefulness of various photoradiation models for the ex vivo treatment of leukemic and lymphomatous bone marrow autografts.
ADP causes subsecond changes in protein phosphorylation of platelets
Authors: Carty DJ , Freas DL , Gear AR 
Published: October 2019

Abstract
We developed a general quenched-flow approach to study platelet function as early as 0.3 seconds after stimulation. Phosphorylation of 20- and 47-kiloDalton (kD) proteins was analyzed during the first 5 seconds of platelet response to ADP from 0.5 to 10.0 mumol/L and compared with the progress of aggregation. The onset time for aggregation and phosphorylation of both proteins was less than 1 second; 20-K phosphorylation was increased greater than 200% and 47-K phosphorylation was increased 50%. The ADP sensitivity of 20-K phosphorylation was greater than that of 47-K phosphorylation (P less than .025), and of that of aggregation (P less than .01), with Ka values of 0.7, 1.0, and 1.2 mumol/L of ADP, respectively. The cyclooxygenase inhibitor indomethacin had no effect on aggregation, but inhibited both phosphorylations. Its inhibition of 20-K phosphorylation was greater than that of 47-K phosphorylation. Platelet activation by ADP thus induced biochemical changes well before 1 second. The quenched- flow approach may help to reveal relationships between phospholipase activation, calcium fluxes, and protein phosphorylation during these early periods of platelet activation.
Hemophilia A: carrier detection and prenatal diagnosis by DNA analysis
Authors: Pecorara M , Casarino L , Mori PG , Morfini M , Mancuso G , Scrivano AM , Boeri E , Molinari AC , De Biasi R , Ciavarella N 
Published: October 2019

Abstract
In this study, we used DNA polymorphisms for carrier detection and prenatal diagnosis of hemophilia A in a large group of Italian families. The restriction fragment length polymorphisms (RFLPs) investigated were the intragenic polymorphic Bc/I site within the factor VIII gene; the extragenic multiallelic Taq I system at the St14 locus; and the extragenic Bg/II site at the DX13 locus. The factor VIII probe was informative in 30%, St14 in 82%, and DX13 in 60% of obligate carriers. The combination of factor VIII-Bc/I and St14-Taq I showed that 91% of obligate carriers were heterozygotes for one or both; with all three probes, only 4% of obligate carriers were noninformative. In families clearly segregating for hemophilia A, RFLP analysis allowed us to define the carrier status for the hemophilia A gene in all 27 women tested. RFLP analysis allowed us to exclude the carrier status in 39 of 45 female relatives of sporadic patients. The combination of RFLP analysis and biological assay of factor VIII allowed us to identify a de novo mutation in the maternal grandfather in 7 of 12 of the families with sporadic cases, for which members of three generations were available for study. Nine of 10 couples requesting prenatal diagnosis provided informative RFLP DNA pattern. Carrier status was excluded in two women, two fetuses were shown to be female, and prenatal diagnosis was carried out in five pregnancies by DNA analysis. Prenatal testing was successful in three instances and failed in two because a sufficient amount of chorionic villous DNA was not obtained for the analysis.
Blood cells participate in the fibrinolytic response to tissue-type plasminogen activator
Authors: Hammouda MW , Moroz LA 
Published: October 2019

Abstract
Exercise and venous occlusion stimulate fibrinolysis. In addition to increased concentrations of tissue-type plasminogen activator (tPA) and increased plasmin-mediated fibrinolysis in plasma, these stimuli produce additional cellular-phase activity in blood that is of the same magnitude as the plasma response. To determine whether tPA alone, rather than other consequences of these stimuli, is responsible for the cellular response, the in vitro effects of tPA on whole blood, plasma, and calculated cellular-phase (whole blood minus plasma) activities were determined by solid-phase radiofibrin assay on venous blood from ten normal subjects (seven men, three women). At tPA concentrations encompassing physiological and therapeutic levels (5 to 100 ng/mL; 0.7 to 14 IU/mL), increments in whole blood were consistently in excess of those in companion plasma and represented increased cellular-phase activity equivalent in magnitude to the well-known increase in plasma activity. Fibrinolytic activity produced by 10 to 20 ng tPA/mL (1.4 to 2.8 IU/mL) was consistently detected in whole blood and plasma by 60 minutes, with higher concentrations (100 ng or 14 IU tPA/mL) detectable after a five-minute assay in all subjects. Thus, tPA alone, without invoking fibrinolytic factors extraneous to blood or other effects of exercise or venous occlusion, accounts for both cellular and plasma responses to these stimuli. The considerable cellular response, the mechanism of which remains to be elucidated, may constitute a determinant of individual therapeutic responsiveness to tPA.
Deoxycytidine preferentially protects normal versus leukemic myeloid progenitor cells from cytosine arabinoside-mediated cytotoxicity
Authors: Bhalla K , MacLaughlin W , Cole J , Arlin Z , Baker M , Graham G , Grant S 
Published: October 2019

Abstract
We examined the ability of high concentrations of the naturally occurring nucleoside deoxycytidine (dCyd) to reverse the cytotoxicity of high (eg, greater than or equal to 10(-5) mol/L) concentrations of 1- B-D arabinofuranosylcytosine (Ara-C) toward normal (CFU-GM) and leukemic myeloid progenitor cells (L-CFU). Leukemic myeloblasts from patients with acute nonlymphocytic leukemia (ANLL) and normal human bone marrow mononuclear cells were cultured in soft agar in the continuous presence of 10(-5) to 5 X 10(-5) mol/L of Ara-C together with dCyd (10(-4) to 5 X 10(-3) mol/L). Administration of 10(-5) mol/L of Ara-C alone eradicated colony formation in all samples tested. Coadministration of 10(-3) mol/L of dCyd restored 72.2% of control colony formation for CFU-GM, but only 10.9% for L-CFU. When higher concentrations of Ara-C (eg, 5 X 10(-5) mol/L) were administered, dCyd- mediated protection toward CFU-GM decreased, but remained significantly greater than that observed for L-CFU. Incubation with 10(-3) mol/L of dCyd reduced the 4-hour intracellular accumulation of the triphosphate derivative of Ara-C (Ara-CTP) in both normal and leukemic cells by greater than 98%; under identical conditions, a significant expansion of the intracellular of the triphosphate derivative of dCyd (dCTP) pools was observed in normal bone marrow mononuclear cells but not in leukemic blasts. This finding was associated with a greater reduction in Ara-C DNA incorporation in normal elements. These in vitro studies suggest that dCyd may preferentially protect normal v leukemic myeloid progenitor cells from the lethal actions of high-dose Ara-C.
Bipotential cell differentiation of KU-812: evidence of a hybrid cell line that differentiates into basophils and macrophage-like cells
Authors: Fukuda T , Kishi K , Ohnishi Y , Shibata A 
Published: October 2019

Abstract
KU-812-F is a subclone of KU-812, which has cytological features similar to the parent clone, and which carries the Philadelphia chromosome. We studied the effects of various chemical agents and serum- free culture (SF-C) condition on its differentiation. The KU-812-F subclone differentiated into macrophage-like cells with phorbol myristate acetate (PMA), but not with other agents. Unexpectedly, under SF-C, KU-812-F cells differentiated into mature basophil-like cells, and the histamine content of cell lysates increased in proportion to maturation. The addition of the condensed supernatant of SF-C promoted the cloning efficiency of KU-812-F cells in semisolid SF-C, whereas the cloning efficiency was reduced in SF-C alone. KU-812-F cells expressed myelomonocytic antigens. Additionally, My4 was induced with PMA and SF- C, but less often. HLA-DR was not expressed in any culture conditions, despite blastic morphology of KU-812-F cells or macrophage-like cells induced with PMA. The IgE receptor could not be demonstrated under any conditions. Correspondingly, immature and mature KU-812-F cells did not respond to anti-IgE or concanavalin A (con A), while histamine release was induced with PMA. In conclusion, KU-812-F belongs to the myeloid cell lineage and is at least a bipotential cell that can differentiate into basophils and macrophage-like cells. Although the functions appear to be dissimilar to those of normal basophils, the KU-812-F cell line may be a good model for basophil differentiation. Moreover, KU-812-F cells may provide new insights because they grow in semisolid culture by an autostimulating mechanism.