bluuebunny/crossref_metadata_2025_split huggingface dataset:
The immunologic detection of minimal residual disease in acute leukemia [published erratum appears in Blood 1990 Nov 1;76(7):1901]
Authors: Campana D , Coustan-Smith E , Janossy G 
Published: October 2019

Abstract
Certain combinations of differentiation antigens are expressed on leukemia blasts and are absent or extremely rare among normal progenitors in the fetal liver and fetal and regenerating bone marrow. These combinations include cCD3/TdT, a thymic feature retained on thymic-acute lymphoblastic leukemia (T-ALL) blasts outside the thymus, and the coexpression of TdT and myeloid markers (CD13, CD33) on a proportion of ALL and acute myeloid leukemia (AML). Thus, double marker immunofluorescence assays are operationally leukemia-specific and can be applied in 35% of acute leukemias for detecting minimal disease at a less than 10(-4) level; only rare cases, 2 of 35 in our study, switch these relevant features during relapse. The sensitivity and specificity of these assays was tested as follows. First, bone marrow samples taken from patients who had originally presented with blasts expressing the leukemia-associated combinations but were in full morphologic remission were studied, and varying numbers (less than 0.01% to 10% of the mononuclear fraction) of cells with aberrant features were identified in 11.6% of the cases. Second, the outcome of 19 patients with minimal disease identified immunologically while in complete morphologic remission was investigated: all 19 patients have developed systemic relapse within 4 to 25 (median 14.5) weeks. In contrast, 17 of 25 patients also morphologically in complete remission and without residual disease identifiable immunologically after repeated testing are still in morphologic and immunologic remission (follow-up 17 to 114 weeks, median 28 weeks). Only eight patients in this group have relapsed so far: in two patients the relapse was localized in the cerebrospinal fluid, while in six patients a systemic relapse was observed 6 to 51 (median 21.5) weeks after the last negative immunologic bone marrow examination. In conclusion, no false-positive results were detected with these sensitive assays, and the introduction of appropriately planned prospective studies, including the immunologic detection of residual leukemia, is justified on the basis of these observations.
The gene for the human erythropoietin receptor: analysis of the coding sequence and assignment to chromosome 19p
Authors: Winkelmann JC , Penny LA , Deaven LL , Forget BG , Jenkins RB 
Published: October 2019

Abstract
The full-length coding sequence of the human erythropoietin receptor has been assembled from cDNA and genomic DNA. The derived 508 amino acid sequence is 82% identical to the murine erythropoietin (Epo) receptor with one single residue gap in alignment. There is no major structural difference between the human and murine receptor molecules. Nucleotide sequence homology is, as expected, very high within the coding domain. Unexpectedly, there are two distinct, short stretches of 3′ untranslated sequence homology between human and murine cDNAs. The functional significance of this sequence conservation is unknown. The human Epo receptor gene is localized to human chromosome 19p by in situ hybridization. This chromosome assignment is confirmed by hybridization to a panel of sorted human chromosomes.
Use of recombinant human granulocyte-macrophage colony-stimulating factor in graft failure after bone marrow transplantation
Authors: Nemunaitis J , Singer JW , Buckner CD , Durnam D , Epstein C , Hill R , Storb R , Thomas ED , Appelbaum FR 
Published: October 2019

Abstract
The effect of recombinant human granulocyte-macrophage colony- stimulating factor (rhGM-CSF) was evaluated in 37 patients with marrow graft failure after allogeneic (n = 15), autologous (n = 21), or syngeneic (n = 1) bone marrow transplantation. rhGM-CSF was administered by 2-hour infusion at doses between 60 and 1,000 micrograms/m2/d for 14 or 21 days. At doses of less than 500 micrograms/m2, rhGM-CSF was well-tolerated and did not exacerbate graft- versus-host disease in allogeneic transplant recipients. No patient with myelogenous leukemia relapsed while receiving rhGM-CSF. Twenty-one patients reached an absolute neutrophil count (ANC) greater than or equal to 0.5 x 10(9)/L within 2 weeks of starting therapy while 16 did not. None of seven patients who received chemically purged autologous marrow grafts responded to rhGM-CSF. The survival rates of GM-CSF- treated patients were significantly better than those of a historical control group.
Human erythropoietin receptor: cloning, expression, and biologic characterization
Authors: Jones SS , D'Andrea AD , Haines LL , Wong GG 
Published: October 2019

Abstract
We have isolated the human homologue of the murine erythropoietin receptor (mEPO-R) from an erythroleukemia line, OCIM1, and from fetal liver. Both the cDNA and protein sequence of the human receptor were 82% homologous to the mEPO-R. Heterologous expression of the human cDNA in COS cells yielded a protein of about 66 Kd. The protein could be specifically immunoprecipitated with either an antibody raised against the amino terminus of mEPO-R or by a monoclonal antibody that bound EPO bound to its receptor. Cross-linking of radioiodinated EPO to COS cells expressing the human EPO-R gave apparent molecular weights of 66 and 100 Kd for the receptor. The murine interleukin-3-dependent pre-B- lymphocyte cell line, Ba/F3, was made EPO-dependent by transfection of the human cDNA into the cells and selecting for growth in EPO- containing media.
Tissue factor: identification and characterization of cell types in human placentae
Authors: Faulk WP , Labarrere CA , Carson SD 
Published: October 2019

Abstract
This is an immunohistologic study of tissue factor (TF) in snap frozen, unfixed, human normal-term placentae. Antibodies to TF were a monoclonal to human brain TF purified on a factor VII-agarose affinity column, and a polyclonal to a synthetic polypeptide representing the carboxyl-terminal nine amino acids of human TF. The results detail the localization and distribution of TF and characterize the cells in which it is found. TF was not observed in trophoblast, trophoblastic basement membranes, or noncellular components of connective tissue. TF was identified in some but not all macrophages, most fibroblast-like cells, and occasionally in perivascular cells and endothelium. The most consistent and intense reactions were obtained with vimentin-positive fibroblast-like cells in loose connective tissue. TF usually was not identified in fetal stem vessel endothelial cells, but TF reactivity was found in some of these cells in chorionic villi with histologic evidence of chronic inflammation. Such areas are uncommonly found in normal-term placentae. The vast majority of TF-reactive cells did not react with antibody to factor VII and were not in contact with blood. The biologic purpose of producing relatively great amounts of TF in areas remote from circulating factor VII is not known.
Binding and internalization of biotinylated interleukin-2 in human lymphocytes
Authors: Peters DK , Norback DH 
Published: October 2019

Abstract
The binding, internalization, and fate of interleukin-2 (IL-2) were studied in phytohemagglutinin (PHA)-activated human lymphocytes using biotinylated recombinant IL-2 (rIL-2). Streptavidin adsorbed to 18-nm colloidal gold beads (Au18-streptavidin) and streptavidin covalently bound to horseradish peroxidase (HRP-streptavidin) were used to follow the movement of biotinylated rIL-2 within cells over a 4-hour period. Results obtained from either probe were similar. Biotinylated rIL-2 was taken up in coated pits, transferred to a series of small uncoated vesicles and tubules in the peripheral cytoplasm of the cell, then concentrated and sequestered in uncoated vesicles, multivesicular bodies (MVB), and dense bodies (DB) in the peripheral and juxtanuclear cytoplasm of the cell. Occasionally, MVB containing Au18-streptavidin, or HRP-streptavidin, appear to have fused with the plasma membrane of the cell. No labeling of the Golgi cisternae, nuclear envelope, or nucleus was observed. Results from a competitive receptor binding assay and a cell proliferation assay indicate that both the affinity of rIL-2 for high affinity rIL-2 receptors and the proliferative activity of rIL- 2 were negligibly affected by the biotinylation procedure. These studies suggest that in activated lymphocytes, IL-2 is bound to receptors on the cell surface, gathered in coated pits, internalized by receptor-mediated endocytosis, concentrated in the endosomal compartments, and delivered to lysosomes for degradation.
Inhibition of interleukin-2-induced tumor necrosis factor release by dexamethasone: prevention of an acquired neutrophil chemotaxis defect and differential suppression of interleukin-2-associated side effects [see comments]
Authors: Mier JW , Vachino G , Klempner MS , Aronson FR , Noring R , Smith S , Brandon EP , Laird W , Atkins MB 
Published: October 2019

Abstract
High concentrations of tumor necrosis factor (TNF) alpha have been detected in the plasma of patients undergoing immunotherapy with interleukin 2 (IL-2), suggesting that this cytokine may play a role in the fever and shocklike state induced by the administration of high- dose IL-2. Dexamethasone has been shown to inhibit the synthesis of TNF by monocytes activated in vitro by endotoxin. To determine if dexamethasone can exert a similar suppressive effect on IL-2-induced TNF synthesis in vivo, the concentration of TNF alpha was measured in plasma samples serially obtained (a) from cancer patients participating in a phase I dose escalation clinical trial with high-dose IL-2 administered in conjunction with dexamethasone (IL-2/Dex) and (b) from patients participating in concurrent studies with IL-2 alone. In contrast to the high plasma levels of TNF alpha detected in patients receiving IL-2 alone, TNF levels in most of the IL-2/Dex patients remained below the threshold of detectability of our TNF radioimmunoassay. The concurrent administration of dexamethasone also prevented the IL-2-induced increase in serum levels of C-reactive protein, a hepatic acute phase reactant whose synthesis is regulated by proinflammatory cytokines such as TNF. The steroid-treated patients also failed to develop the neutrophil chemotactic defect characteristic of IL-2 recipients. The concomitant administration of dexamethasone increased the maximum tolerated dose of IL-2 approximately threefold and markedly reduced the hypotension and organ dysfunction ordinarily observed in these patients. These results demonstrate that dexamethasone inhibits the release of TNF into the circulation of patients undergoing immunotherapy with IL-2. They further suggest that the altered spectrum and reduced severity of IL-2 side effects observed in patients receiving dexamethasone may be attributable in part to the suppressive effect of steroids on IL-2-induced TNF synthesis.
Kidney cell lysates contain an activity that stimulates mature erythroid burst-forming-unit (mBFU-E) proliferation
Authors: Royet J , Mouchiroud G , Arnaud S , Oddos T , Galland S , Blanchet JP 
Published: October 2019

Abstract
This study reports the detection of an activity that stimulates the development of a subclass of burst-forming unit-erythroid (BFU-E) progenitors giving rise to small bursts in semi-solid cultures established in the presence of saturating concentrations of erythropoietin. These progenitors are considered to be mature BFU-E. The activity is found in extracts from kidney cells and appears to be physiologically regulated as it was respectively enhanced and decreased in kidneys from anemic and polycythemic mice. The disappearance of activity in kidney-cell extracts during long-term polycythemia correlated with an accumulation of mature BFU-E in the spleen and bone marrow of polycythemic mice. Using specific neutralizing antibodies and in vitro tests, we also show that this activity is different from hemopoietins known to share burst promoting activity (Interleukin-3 [IL- 3], granulocyte-macrophage colony-stimulating factor [GM-CSF], Interleukin-4 [IL-4], erythropoietin [EPO], human interleukin for DA cells [HILDA]) and that it can stimulate erythroid differentiation in long term bone marrow cell cultures.
Interleukin-6 (IL-6) is an intermediate in IL-1-induced proliferation of leukemic human megakaryoblasts
Authors: Brach MA , Lowenberg B , Mantovani L , Schwulera U , Mertelsmann R , Herrmann F 
Published: October 2019

Abstract
We have examined the in vitro effects of recombinant human (rh) interleukin-1 (IL-1) on the growth of purified megakaryoblasts obtained from patients with acute megakaryoblastic leukemia. We demonstrate that both IL-1 alpha and IL-1 beta treatment of these cells led to stimulation of DNA synthesis (as shown by increase of 3H-thymidine incorporation up to 35-fold) and also resulted in colony formation of leukemic megakaryoblasts. However, the stimulatory effect of IL-1 was dependent on endogenous production of IL-6, because addition of neutralizing monoclonal antibody (MoAb) to IL-6 abrogated the stimulatory activity of IL-1. In contrast, neutralizing MoAbs to granulocyte (G)-colony stimulating factor (CSF), granulocyte-macrophage (GM)-CSF, and macrophage (M)-CSF failed to counteract the growth- enhancing effects of IL-1. Leukemic megakaryoblasts accumulated IL-6 mRNA and released IL-6 protein into their culture supernatant when exposed to rh IL-1 but failed to disclose transcripts for G-, GM-, and M-CSF under these conditions. Analysis of IL-6 receptor (IL-6R) transcript levels demonstrated that megakaryoblasts constitutively expressed IL-6R mRNA and that these transcripts are down-regulated to undetectable levels upon exposure to IL-1 and IL-6. Increase of 3H- thymidine incorporation by megakaryoblasts could be duplicated by exogenous IL-6 that could be blocked by neutralizing MoAb to IL-6. In conclusion, our results suggest that leukemic megakaryoblasts could produce and secrete IL-6, and express IL-6R, and that the growth- enhancing effect of IL-1 on these cells is indirect, via production of IL-6 by leukemic cells.
Parvovirus B19-induced perturbation of human megakaryocytopoiesis in vitro
Authors: Srivastava A , Bruno E , Briddell R , Cooper R , Srivastava C , van Besien K , Hoffman R 
Published: October 2019

Abstract
Parvovirus B19 infection leads to transient aplastic crises in individuals with chronic hemolytic anemias or immunodeficiency states. An additional unexplained sequela of B19 infection is thrombocytopenia. Because B19 is known to have a remarkable tropism for human erythropoietic elements, and is not known to replicate in nonerythroid cells, the etiology of this thrombocytopenia is uncertain. We sought to define the pathobiology of B19-associated thrombocytopenia by examining the role of B19 on in vitro megakaryocytopoiesis. B19 infection of normal human bone marrow cells significantly suppressed megakaryocyte (MK) colony formation compared with mock-infected cells. No such inhibition was observed with a nonpathogenic human parvovirus, the adeno-associated virus 2 (AAV). The B19-MK cell interaction was also studied at the molecular level. Whereas low-density bone marrow cells containing erythroid precursor cells supported B19 DNA replication, no viral DNA replication was observed in B19-infected MK-enriched fractions as determined by the presence of viral DNA replicative intermediates on Southern blots. However, analysis of total cytoplasmic RNA isolated from B19-infected MK fractions showed a low-level expression of the B19 genome as detected by quantitative RNA dot blots as well as by Northern analysis. Furthermore, a frame-shift mutation in a recombinant AAV-B19 hybrid genome segment that encodes the viral nonstructural (NS1) protein significantly reduced the observed inhibition of MK colony formation. These studies indicate tissue- tropism of B19 beyond the erythroid progenitor cell, and lend support to the hypothesis that B19 genome expression may be toxic to cell populations that are nonpermissive for viral DNA replication.
Plasmin-induced redistribution of platelet glycoprotein Ib
Authors: Michelson AD , Barnard MR 
Published: October 2019

Abstract
Platelet membrane glycoprotein Ib (GPIb), a receptor for von Willebrand factor and thrombin, is present on the platelet surface membrane, in intraplatelet stores, and in plasma (as the proteolytic fragment glycocalicin). We examined the hypothesis that after plasmin-mediated cleavage of platelet surface GPIb, platelets can replenish their surface GPIb pool. Incubation of washed platelets with plasmin (1 hour, 22 degrees C) resulted in loss of platelet surface GPIb, but further incubation (3 hours, 37 degrees C) in autologous plasma resulted in restoration of platelet surface GPIb, as determined by ristocetin- induced platelet agglutination and a flow cytometric assay of platelet binding of three GPIb-specific monoclonal antibodies. Despite the restoration of platelet surface GPIb after the 3-hour incubation of plasmin-treated platelets in autologous plasma, the whole platelet GPIb content (measured by enzyme-linked immunosorbent assay [ELISA], sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and flow cytometry) remained reduced, quantitatively corresponding to an increase in plasma glycocalicin concentration (measured by ELISA). The loss and restoration of platelet surface GPIb occurred on all platelets and, as evidenced by lack of inhibition by prostaglandin E1, EDTA, and cytochalasins, was not mediated by cyclic AMP, extracellular Ca2+, or the platelet microfilament system. In summary, this study shows that after plasmin-mediated cleavage of platelet surface GPIb, platelets can replenish their surface GPIb pool by recruitment of GPIb molecules from the intraplatelet pool (or from a sequestered surface site).
Development of antibodies to thrombin and factor V with recurrent bleeding in a patient exposed to topical bovine thrombin
Authors: Zehnder JL , Leung LL 
Published: October 2019

Abstract
A 65 year old patient who was exposed to topical bovine thrombin during cardiac surgery developed markedly prolonged clotting times and a severe bleeding diathesis. Mixing studies with normal plasma failed to correct the clotting times. Platelet transfusions, immunosuppressive and immunomodulatory therapies were ineffective, but plasmapheresis was effective in decreasing clotting times and in the resolution of clinical bleeding events. The patient's purified IgG reacted with bovine thrombin by immunoblotting and enzyme-linked immunosorbent assay (ELISA). However, the IgG reacted minimally with human thrombin. In view of the severe bleeding, a coexisting inhibitor was sought. The patient's factor V activity was 1% of normal and was not corrected by mixing with normal plasma, demonstrating the presence of an inhibitor against factor V. The patient's IgG reacted with both bovine and human factor V. Immunoblotting localized the site of antibody binding to the light chain of activated bovine factor V. Detectable amounts of bovine factor V were found in commercial bovine thrombin preparations by ELISA. The data suggest that patients exposed to topical bovine thrombin may develop antibodies to thrombin and factor V. Anti-thrombin antibodies may mask coexisting factor V inhibitors responsible for clinical bleeding.
Plasma thrombomodulin in health and diseases
Authors: Takano S , Kimura S , Ohdama S , Aoki N 
Published: October 2019

Abstract
Sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by immunoblot analysis of plasma thrombomodulin concentrate revealed that four degraded forms of thrombomodulin with different molecular weights are present in plasma. Plasma concentrations of thrombomodulin in patients with various diseases were measured by two methods of enzyme- linked immunosorbent assay using monoclonal antibodies. One method measures intact thrombomodulin and degraded forms of thrombomodulin; the other does not detect the two smaller degraded forms of thrombomodulin present in plasma. The results indicated that thrombomodulin was increased in the circulating blood of patients with disseminated intravascular coagulation syndrome, pulmonary thromboembolism, adult respiratory distress syndrome, chronic renal failure, or acute hepatic failure. The different values obtained by the two methods indicate that the increase of plasma thrombomodulin found in these patients was mainly due to an increase of the smaller fragments of degraded forms, suggesting that the release of thrombomodulin from endothelial cells was accelerated in various disease states by proteolytic activity generated on the surface of the endothelium and may be removed from the circulation mostly by the kidneys and liver.
Effect of hemoglobin oxidation products on the stability of red cell membrane skeletons and the associations of skeletal proteins: correlation with a release of hemin
Authors: Jarolim P , Lahav M , Liu SC , Palek J 
Published: October 2019

Abstract
Oxidative injury to hemoglobin (Hb) leads to formation of methemoglobin (MetHb), reversible hemichromes (rHCRs), and irreversible hemichromes (iHCRs). iHCRs precipitate and form Heinz bodies that attach to the red cell membrane causing injury that leads to hemolysis. The molecular mechanisms of this membrane damage have not been fully elucidated. We have studied the effect of Hb oxidation products on the mechanical stability of red cell membrane skeletons and the associations of membrane skeletal proteins. Hb and MetHb stabilized the isolated membrane skeletons, whereas further oxidation to rHCRs abolished this stabilizing effect. Crude iHCRs prepared by phenylhydrazine oxidation of Hb destabilized membrane skeletons by decreasing formation of the spectrin-protein 4.1-actin complex, the effect similar to that of pure hemin. Whereas virtually no hemin was released from Hb and MetHb, high concentrations of hemin were released from crude iHCR preparations. After removal of this hemin fraction by Dowex resin, the iHCRs lost their destabilizing effect. We conclude that as the oxidation of Hb proceeds, the stabilizing effect of Hb on the membrane skeleton is gradually lost and the deleterious effect increases. The destabilization of the red cell membrane skeleton in the presence of crude iHCR is caused by release of hemin, which lowers the stability of membrane skeleton by weakening the spectrin-protein 4.1-actin interaction.
Direct relationship between remission duration in acute myeloid leukemia and cell cycle kinetics: a leukemia intergroup study
Authors: Raza A , Preisler HD , Day R , Yasin Z , White M , Lykins J , Kukla C , Barcos M , Bennett J , Browman G 
Published: October 2019

Abstract
Cell cycle characteristics including labeling indices (LI), duration of S-phase (Ts), and total cell cycle time (Tc) were determined in 54 standard-risk, newly diagnosed patients with acute myeloid leukemia following an infusion of bromodeoxyuridine. Remission induction therapy consisting of cytosine arabinoside and daunomycin was then administered to all patients, followed by three courses of consolidation to those who achieved complete remissions (CR). Older patients appeared to have more rapidly cycling cells (P = .003). No unique cell cycle characteristics were identified for patients who achieved remission versus those who had resistant disease. However, the pretherapy cell cycle characteristics were a strong prognosticator for remission duration. CR patients were divided into those whose leukemic cell Tc were above median (A) and below median (B). Among 14 B patients, median duration of response was 211 days, and all relapsed by day 600. Among 18 A patients, the median has not as yet been reached, with nine patients in continuous complete remission (log rank P = .007, Wilcoxon P = .04). We conclude that cell cycle characteristics of leukemic cells play a role in determining remission duration, perhaps because the leukemic cells of the former patients regrow slowly between courses of chemotherapy.