bluuebunny/crossref_metadata_2025_split huggingface dataset:
Use of a monoclonal antibody (GA3) to demonstrate lineage restricted O- glycosylation on leukosialin during terminal erythroid differentiation
Authors: Bettaieb A , Farace F , Mitjavila MT , Mishal Z , Dokhelar MC , Tursz T , Breton- Gorius J , Vainchenker W , Kieffer N 
Published: October 2019

Abstract
A murine monoclonal antibody (GA3) obtained by immunizing mice with cells of the human erythroleukemic cell line K562 is shown to define a 105 kilodalton (kd) membrane antigen on K562 cells that is restricted within the hematopoietic system to the erythroid lineage and to a minor population of CD3, CD4 positive T lymphocytes. Cocapping studies and immunoprecipitation experiments performed with GA3 and L10, an anti- sialophorin monoclonal antibody reacting with leukosialin (Gp 105) on K562 cells, demonstrate that the antigen detected by GA3 on K562 cells is identical to leukosialin. Neuraminidase treatment but not tunicamycin treatment of K562 cells abolishes the expression of the GA3- epitope without affecting the L10-epitope thus providing evidence that terminal sialic acid present on O-linked oligosaccharide chains on Gp 105 is essential for the expression of the GA3-epitope. Further analysis by flow cytometry and immune panning experiments performed on bone marrow cells with GA3 or L10 demonstrate that, in contrast to L10, which reacts with all types of hematopoietic progenitors, the epitope recognized by GA3 is restricted to the erythroid lineage, and appears during erythroid differentiation before glycophorin A on the earliest morphologically recognizable erythroid precursor, the proerythroblast. Our results therefore suggest that O-linked oligosaccharides on leukosialin express lineage restricted and even maturation restricted antigenic structures that might serve as cell lineage specific markers.
Bone marrow transplantation for the treatment of acute nonlymphoblastic leukemia in children aged less than 2 years
Authors: Johnson FL , Sanders JE , Ruggiero M , Chard RL Jr , Thomas ED 
Published: October 2019

Abstract
Eleven children with acute nonlymphoblastic leukemia in first remission who were less than 2 years of age at diagnosis were treated with 120 mg/kg of cyclophosphamide, 12-Gy fractionated total-body irradiation, and marrow transplantation. Seven patients remain in complete remission from 3.5 to 13.8 years posttransplant, four for more than 6.75 years. The immediate posttransplant course was relatively uncomplicated in surviving patients. No child developed severe graft-v-host disease. The major long-term side effect has been a slowing in growth. Although the prognosis for such children with conventional chemotherapy remains poor, intensive cytotoxic therapy and marrow transplantation offers an alternative therapy with a chance for cure.
Identification and characterization of a differentiation antigen in human neutrophils and monocytes
Authors: Nozawa R , Kato H , Ito T , Yokota T 
Published: October 2019

Abstract
Human promyelocytic leukemia (HL-60) cells were induced to differentiate into macrophage-like cells by treatment with 10(-7) mol/L 1,25-dihydroxyvitamin D3 (VD3). A monoclonal antibody (MoAb, 60B8), reactive with the particulate of the differentiated cells but not of the untreated cells, was isolated. The antigen recognized by the MoAb became apparent two days after VD3 treatment, and its concentration increased and peaked on day 6. Human neutrophils, followed by monocytes and differentiated HL-60 cells, showed the greatest abundance of the antigen. Monocytes cultured for eight days in vitro lost the antigen. No 60B8 antigen was seen in other blood cells. The MoAb precipitated two polypeptides with an apparent molecular weight (mol wt) of 15,000 (15 k) and 13 k in the detergent-solubilized, 35S-methionine-labeled lysate of the differentiated HL-60 cells. Double-sandwich type enzyme- linked immunosorbent assay (ELISA) devised for the quantitative assay of 60B8 antigen indicated that some 2% to 5% of neutrophil protein was 60B8 antigen. This antigen was not exposed on the neutrophil cell surface, since the cells were not stained immunofluorescently with either mono- or polyclonal antibody, unless they had become permeable. The neutrophil membrane and the granules were separated on the Percoll density gradient, and the antigen was found localized in the plasma membrane-rich fraction. These findings suggested that 60B8 antigen is a novel differentiation antigen for phagocytic cells.
Recombinant alpha 2-interferon in the treatment of B chronic lymphocytic leukemia in early stages
Authors: Rozman C , Montserrat E , Vinolas N , Urbano-Ispizua A , Ribera JM , Gallart T , Compernolle C 
Published: October 2019

Abstract
Ten previously untreated patients with early B cell chronic lymphocytic leukemia (B-CLL) (seven in Rai's stage 0, three in stage I) were given recombinant alpha 2-interferon (alpha 2IF) (2 X 10(6) U/m2 intramuscularly three times a week for a minimum of 14 weeks) to assess its effectiveness. All patients were evaluable for response to therapy and toxicity. No complete response was achieved. In all cases a definite, although transient reduction in the absolute number of peripheral blood lymphocytes was observed. In eight patients an increase in the absolute number of granulocytes was detected. None of the patients experienced severe hematologic toxicity. Fatigue, malaise, and fever were the more common side effects, but all patients were able to finish their treatment as planned. The results of this pilot study suggest that low doses of recombinant alpha 2-IF have some activity in early and previously untreated B-CLL and that further studies of IF effectiveness in B-CLL seem warranted.
Clonal rearrangement of the T cell receptor beta gene in the circulating lymphocytes of erythrodermic follicular mucinosis
Authors: LeBoit PE , Abel EA , Cleary ML , Hoppe RT , Williams ML , Wood GS , Parslow TG 
Published: October 2019

Abstract
Follicular mucinosis is a condition characterized by the abnormal accumulation of acidic mucopolysaccharides in hair follicles. It is classically described as occurring idiopathically in young persons and within the infiltrates of mycosis fungoides in older individuals. We report a 12-year-old girl who had erythrodermic follicular mucinosis, hypereosinophilia, circulating Sezary cells, and both immunophenotypic and genotypic evidence of T cell neoplasia. Erythrodermic follicular mucinosis may represent an unusual variant of the Sezary syndrome, which to date has not been described in children or adolescents.
Shear-induced platelet aggregation can be mediated by vWF released from platelets, as well as by exogenous large or unusually large vWF multimers, requires adenosine diphosphate, and is resistant to aspirin
Authors: Moake JL , Turner NA , Stathopoulos NA , Nolasco L , Hellums JD 
Published: October 2019

Abstract
Fluid shear stress in arteries and arterioles partially obstructed by atherosclerosis or spasm may exceed the normal time-average level of 20 dyne/cm2. In vitro, at fluid shear stresses of 30 to 60 dyne/cm2 applied for 30 seconds, platelet aggregation occurs. At these shear stresses, either large or unusually large von Willebrand factor (vWF) multimers in the suspending fluid exogenous to the platelets mediates aggregation. Adenosine diphosphate (ADP) is also required and, in these experiments, was released from the platelets subjected to shear stress. At 120 dyne/cm2, the release of endogenous platelet vWF multimers can substitute for exogenous large or unusually large vWF forms in mediating aggregation. Endogenous released platelet vWF forms, as well as exogenous large or unusually large vWF multimers, must bind to both glycoproteins Ib and the IIb/IIIa complex to produce aggregation. Shear- induced aggregation is the result of shear stress alteration of platelet surfaces, rather than of shear effects on vWF multimers. It is mediated by either large plasma-type vWF multimers, endogenous released platelet vWF forms, or unusually large vWF multimers derived from endothelial cells, requires ADP, and is not inhibited significantly by aspirin. This type of aggregation may be important in platelet thrombus formation within narrowed arterial vessels, and may explain the limited therapeutic utility of aspirin in arterial thrombosis.
Allogeneic marrow grafting with partially mismatched, unrelated marrow donors
Authors: Gingrich RD , Ginder GD , Goeken NE , Howe CW , Wen BC , Hussey DH , Fyfe MA 
Published: October 2019

Abstract
Forty patients with advanced hematologic malignancies or severe aplastic anemia received marrow grafts from partially mismatched, unrelated marrow donors. All patients were administered conventional prophylaxis for acute graft-v-host disease (GVHD) consisting of methotrexate and low-dose glucocorticoids. All but two patients who survived at least 30 days showed durable engraftment. Six patients survive 17+ to 36+ months following transplantation. Severe acute GVHD was seen in 47% of the patients; however, no direct correlation between GVHD and the degree of mismatching could be determined. Fatal infections were seen in 29 patients, and in the majority the infection occurred after the granulocyte count had risen to greater than 500 cells/microL. We conclude that the problems encountered in this pilot study can potentially be solved, and that further studies with this type of marrow grafting are warranted.
B19 parvovirus replicates in circulating cells of acutely infected patients
Authors: Kurtzman GJ , Gascon P , Caras M , Cohen B , Young NS 
Published: October 2019

Abstract
B19 parvovirus is the etiologic agent of fifth disease and transient aplastic crisis. In natural infections, B19 antigen and DNA have been detected in sera early in the course of aplastic crisis and only rarely in fifth disease. We have found B19 DNA in circulating cells of infected patients by DNA dot blot with a virus-specific probe: in four of four sickle cell patients with aplastic crisis, in one asymptomatic sibling, and in one normal adult with fifth disease. Only two of the sera showed B19 DNA. High-molecular weight intermediate forms were detected by Southern analysis of DNA extracted from cells, thus indicating active replication of virus in cells rather than passive adsorption to their surface membranes. Separation of cells into high- and low-density fractions resulted in a concentration of the virus DNA in the granulocytic fraction.
Fibrinogen-derived peptide B beta 1-42 is a multidomained neutrophil chemoattractant
Authors: Skogen WF , Senior RM , Griffin GL , Wilner GD 
Published: October 2019

Abstract
The formation and degradation of fibrin play a central role in hemostasis, but other activities have been associated with fibrin(ogen)- derived peptides, which suggests that products of fibrin(ogen) turnover may be involved in inflammation and wound healing. The present study was undertaken to determine whether the plasmic fibrinogen-derived peptide B beta 1–42 has effects on inflammatory cells and fibroblasts (FB). B beta 1–42 was found to be a potent chemotaxin for neutrophils (PMN) and FB, maximally stimulating PMN migration at 10(-9) mol/L peptide. Unlike the chemotactic factors f-Met-Leu-Phe and C5a, B beta 1– 42 did not induce the release of lysosomal hydrolases and superoxide anion from PMN, nor did it stimulate directed movement of monocytes (MN). These features of B beta 1–42 resemble the properties of human fibrinopeptide B (hFpB), the 14-reside, thrombin-cleaveable fragment that constitutes the amino terminus of B beta 1–42, and suggested that the chemotactic effects of B beta 1–42 are mediated through its hFpB domain. Against this conclusion, however, were observations that (a) desensitization of PMN with 10(-7) mol/L hFpB ablated chemotaxis to hFpB without affecting chemotaxis to B beta 1–42; (b) antiserum to hFpB, which recognizes the B beta 1–14 sequence both free and bound to larger fragments of the B beta chain, blocked hFpB chemotactic activity but did not affect B beta 1–42-mediated chemotaxis; (c) desensitization of PMN with equimolar amounts of hFpB and beta 15–42 (10(-7) mol/L), the isolated carboxyterminal sequence of B beta 1–42 remaining after the removal of hFpB, completely inhibited B beta 1–42-mediated chemotaxis; and (d) beta 15–42 itself was chemotactic for PMN. These data indicate that PMN recognize several independent domains within the amino terminal region of the human fibrinogen B beta chain and that these biologic effects extend to mesenchymal cells.
Molecular analysis of clonality and bcr rearrangements in Philadelphia chromosome-positive acute lymphoblastic leukemia
Authors: Turhan AG , Eaves CJ , Kalousek DK , Eaves AC , Humphries RK 
Published: October 2019

Abstract
Philadelphia chromosome (Ph1)-positive chronic myelogenous leukemia (CML) patients consistently show a rearrangement in a 5.8-kilobase length of chromosome 22, referred to as the breakpoint cluster region (bcr). In Ph1-positive acute lymphoblastic leukemia (ALL), the breakpoint in chromosome 22 is more heterogeneous and, in some instances, does not occur within this region. In such cases the cell of origin of the neoplastic clone and the relationship of the disease to CML has remained obscure. We have analyzed the bcr rearrangement in the malignant cells from three patients who presented with Ph1-positive ALL and who in cytogenetic studies had shown evidence of variable involvement of myeloid cells in the Ph1-positive clone. Rearrangements in bcr typical of most cases of CML were detected in purified granulocyte preparations from two of the ALL patients (nos. 1 and 2) and in the blasts from patient 3 at the time of her terminal relapse. In the same analysis the simultaneously obtained granulocytes from patient 3, however, did not show any evidence of bcr rearrangement. Patient 3 was also heterozygous for the BamHI polymorphism in the X- linked hypoxanthine phosphoribosyltransferase (HPRT) gene, thus permitting a different method of clonal analysis based on methylation differences in active and inactive alleles. When DNA from her granulocytes that had shown no bcr rearrangement was hybridized to an HPRT probe, a pattern typical of a polyclonal population was seen. A similar pattern was exhibited by her marrow fibroblasts. In marked contrast, her simultaneously isolated blasts showed an unambiguous monoclonal pattern. These findings demonstrate the origin of the disease in the first two patients in a cell with myelopoietic as well as lymphopoietic potential and confirm the restricted lymphoid cell origin of the neoplastic clone in the third Ph1-positive ALL patient. Furthermore, they indicate that different target cells for transformation within the hematopoietic system may be affected by very similar bcr rearrangements.
Anti-RH immunoglobulin therapy for human immunodeficiency virus-related immune thrombocytopenic purpura
Authors: Oksenhendler E , Bierling P , Brossard Y , Schenmetzler C , Girard PM , Seligmann M , Clauvel JP 
Published: October 2019

Abstract
The potential hazards of steroids in human immunodeficiency virus (HIV)- infected patients led us to evaluate the effectiveness and safety of anti-D and anti-c Ig in 17 adults with severe HIV-related immune thrombocytopenic purpura (platelet count less than 20 x 10(9)/L). The 14 Rh+ patients received 12 to 25 micrograms/kg of anti-D IgG intravenously on two consecutive days. A significant platelet rise above 50 x 10(9)/L was obtained in nine patients. Repeated boosters were performed in six cases and were effective in all cases. The 3 Rh- patients had a good response after they were given 20 mL x 2 of plasma containing potent anti-c antibodies. Therapy was well tolerated, and only one patient had significant hemolysis. These data suggest that anti-Rh IgG can be effective and safe in HIV-related thrombocytopenic purpura and that a specific interaction between the RBC antigens and the anti-Rh antibodies is required.
Ambiguous phenotypes and genotypes in 16 children with acute leukemia as characterized by multiparameter analysis
Authors: Ludwig WD , Bartram CR , Ritter J , Raghavachar A , Hiddemann W , Heil G , Harbott J , Seibt-Jung H , Teichmann JV , Riehm H 
Published: October 2019

Abstract
Ambiguous phenotypes and genotypes were observed in 16 children with acute leukemia. Surface marker, cytogenetic, molecular genetic, and DNA flow cytometric analyses as well as standard morphologic and cytochemical studies were used to divide the patients into three groups. The first group comprised five children with acute leukemia whose blast cells were morphologically lymphoid, while immunophenotyping disclosed simultaneous expression of early pre-B cell and myeloid features. Molecular genetic studies showed evidence of heavy-chain immunoglobulin (Ig) gene rearrangements in all patients. Cytogenetic data, available in three of these children, revealed t(4;11). In five of the 16 patients, morphologic and surface marker analyses indicated the coexistence of two separate cell populations, one with myeloid and the other with early pre-B cell features. Further evidence of B cell commitment in these patients was provided by demonstration of Ig heavy-chain gene rearrangements in all five patients. Surprisingly, one of the five patients showed oligoclonal Ig heavy-chain as well as monoclonal gene rearrangement for the beta chain of the T cell receptor (beta-TCR). The last group consisted of four cases with otherwise typical acute lymphoblastic leukemia (ALL), early pre-B cell phenotype, and coexpression of myeloid or T cell-associated antigens, and two children with unequivocal acute myeloid leukemia (AML) and coexpression of T cell antigens. Gene rearrangement of Ig heavy-chain could be demonstrated in five of six patients, additional Ig light-chain gene rearrangement in two children with ALL, and bigenotypic features (Ig heavy-chain and beta-TCR gene rearrangement) in one patient. In none of the 16 patients did flow cytometry disclose clonal abnormalities of leukemic cell DNA content. Based on these findings, we suggest that malignant transformation in the first and second group of patients took place at a stage ontogenetically close to the pluripotent stem cell, whereas ambiguous phenotypes in the third group resulted from aberrant gene expression or insufficient reagent specificity.
Methylthioadenosine phosphorylase deficiency in acute leukemia: pathologic, cytogenetic, and clinical features
Authors: Traweek ST , Riscoe MK , Ferro AJ , Braziel RM , Magenis RE , Fitchen JH 
Published: October 2019

Abstract
Blast cells from 100 cases of acute leukemia were evaluated for the presence of methylthioadenosine phosphorylase (MTAase), an enzyme important in polyamine metabolism. Ten cases (10%) had undetectable levels of MTAase activity. Of the 10, 5 had acute lymphoblastic leukemia (ALL), 3 had acute myeloblastic leukemia (AML) and 2 expressed mixed lineage markers as determined by immunophenotyping. A relatively high frequency (38%) of MTAase deficiency was seen in ALL of T-cell origin. Nonmalignant hematopoietic cells from three patients with MTAase-deficient leukemias had readily detectable enzyme activity. Chromosomal abnormalities were detected in four of the seven MTAase- deficient cases in which karyotypic analysis was performed. No consistent karyotypic defect was apparent, and only one case displayed changes in chromosome 9, the putative location of the MTAase structural gene. The clinical findings among the enzyme-deficient cases were unremarkable except that all patients were male (P less than .01). Only one patient had “lymphomatous” features. We conclude that MTAase deficiency occurs in a wide variety of acute leukemias, that the lack of enzyme activity is specific to the malignant cells, and that an increased incidence occurs in ALL of T-cell origin. Furthermore, no specific gross chromosomal abnormality is associated with the enzyme deficiency. The marked male predominance in patients with MTAase- deficient acute leukemias suggests involvement of the X chromosome in the loss of enzyme activity. The absence of MTAase in some leukemias may be therapeutically exploitable.
Activation and proliferation signals in murine macrophages: synergistic interactions between the hematopoietic growth factors and with phorbol ester for DNA synthesis
Authors: Hamilton JA , Vairo G , Nicola NA , Burgess A , Metcalf D , Lingelbach SR 
Published: October 2019

Abstract
There has been recent interest in the synergistic interactions between the growth factors involved in the in vitro control of hematopoiesis and other cell lineages. As a convenient model system, such interactions governing the DNA synthesis in murine bone marrow-derived macrophages (BMMs) were studied. By themselves, murine colony- stimulating factor-1 (CSF-1) and recombinant murine granulocyte- macrophage CSF (GM-CSF) were stimulators of DNA synthesis in quiescent or noncycling BMMs, whereas recombinant murine interleukin-3 (IL-3) and the phorbol ester, 12-O-tetradecanoyl-phorbol-13-acetate (TPA), were weak mitogens. On the other hand, murine granulocyte CSF (G-CSF), concanavalin A (Con A), and lipopolysaccharide (LPS) were inactive on their own. When the quiescent BMMs were exposed to combinations of the CSFs, there were striking synergistic effects for both GM-CSF and IL-3 with suboptimal doses of CSF-1, with a smaller effect for GM-CSF with IL-3 and little or no effect for CSF-1 with G-CSF. CSF-1, GM-CSF, and IL-3 could also synergize with TPA; CSF-1 cooperated with 1-oleoyl-2- acetylglycerol (OAG), both sets of results pointing to an interaction with protein kinase C. LPS completely abolished the CSF-1-mediated stimulation of DNA synthesis. We propose that BMMs are suitable normal cells in which to examine in depth the various mechanistic possibilities for these interactions.
The Wistar Furth rat: an animal model of hereditary macrothrombocytopenia
Authors: Jackson CW , Hutson NK , Steward SA , Ashmun RA , Davis DS , Edwards HH , Rehg JE , Dockter ME 
Published: October 2019

Abstract
The mechanisms that determine and regulate platelet size are unknown. By phase microscopy, we observed that Wistar Furth (WF) rats had macrothrombocytopenia. In this study, we have characterized and compared platelets and megakaryocytes of WF rats with those of Wistar, Long-Evans hooded (LE), and Sprague-Dawley rats. In addition, we have examined the mode of inheritance of this WF rat platelet abnormality. The average platelet count of WF rats was only one-third that of the other three rat strains. In contrast, the mean platelet volume (MPV) of adult WF rats was twice that of the other rat strains; however, the average megakaryocyte diameter and DNA content distribution of WF rats were not significantly different from those of LE rats. The average megakaryocyte concentration was 30% lower in the WF strain compared with that of LE rats. Mazelike membrane formations were observed in WF platelets and megakaryocytes by electron microscopy. Reciprocal crosses of WF and LE rats resulted in offspring with MPVs and platelet counts like those of LE rats, indicating that the macrothrombocytopenic trait is recessive in its inheritance. Reciprocal marrow transplants between the WF and LE strains resulted in MPVs like those of the donor strain, demonstrating that the macrothrombocytopenia is an intrinsic marrow abnormality of the WF strain. Splenectomy did not alter the MPV of WF rats. The response of WF megakaryocytes and platelets to severe, acute thrombocytopenia was similar to that of LE rats except that the shift to higher megakaryocyte DNA contents was muted and platelet recovery was slower in the WF rats. In summary, the WF rat has a hereditary macrothrombocytopenia that is recessive in nature and not due to differences in megakaryocyte size or DNA content. These results suggest that the macrothrombocytopenia of WF rats results from the formation of fewer platelets per megakaryocyte, possibly resulting from a qualitative or quantitative defect in some component necessary for proper subdivision of megakaryocyte cytoplasm into platelets.