bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human mast cells derived from fetal liver cells cultured with stem cell factor express a functional CD51/CD61 (alpha v beta 3) integrin
Authors: Shimizu Y , Irani AM , Brown EJ , Ashman LK , Schwartz LB 
Published: October 2019

Abstract
Human fetal livers contain progenitor cells that become mast cells after 4 weeks of culture with recombinant human stem cell factor. Expression of cell surface CD29 (beta 1), CD18 (beta 2), CD61 (beta 3), and beta 5 integrins was investigated on such cells by flow cytometry and adhesion measurements. High surface expression of CD49e, CD51, and CD61 along with kit was apparent by 4 weeks of culture, whereas expression of each at day 0 was low to undetectable. CD29 and CD49d were detected on cells from day 0 to 4 weeks of culture; CD49b, CD49c, CD49f, CD18, and CD54 expression was negligible. The fetal liver- derived mast cells spontaneously adhered to vitronectin. No evidence for degranulation was found during vitronectin-dependent adhesion. Adhesion occurred in part through the CD61/CD51 receptor. No evidence for adhesion to vitronectin through CD29 and beta 5 integrins was obtained. Almost all of the vitronectin-adherent cells expressed CD51, CD61, kit, and tryptase, and exhibited metachromasia with toluidine blue. Thus, among the fetal liver-derived cells, developing mast cells were selectively adherent to vitronectin. These mast cells and the other cell types present also adhere spontaneously to fibronectin and to laminin, this adhesion being partially inhibited by antibodies against CD61 and CD29 integrins. In conclusion, human mast cells acquire functional vitronectin receptors as they develop from fetal liver progenitors under the influence of rhSCF. This may be important for the recruitment, localization, and retention of developing mast cells.
Transforming growth factor beta (TGF-beta), a potent inhibitor of erythropoiesis: neutralizing TGF-beta antibodies show erythropoietin as a potent stimulator of murine burst-forming unit erythroid colony formation in the absence of a burst-promoting activity
Authors: Dybedal I , Jacobsen SE 
Published: October 2019

Abstract
Transforming growth factor beta (TGF-beta) is a bifunctional regulator of the growth of myeloid progenitors and is here demonstrated to directly inhibit the growth of primitive erythroid progenitors by 95% to 100% regardless of the cytokines stimulating growth. Autocrine TGF- beta production of primitive hematopoietic progenitors has previously been reported. In the present study, a neutralizing TGF-beta antibody (anti-TGF-beta) added to serum-containing cultures, resulted in a 3-, 4- , and 25-fold increase in burst-forming unit erythroid (BFU-E) colony formation in response to interleukin-4 (IL-4) plus erythropoietin (Epo), SCF plus Epo, and IL-11 plus Epo, respectively. The growth of BFU-E progenitors has been suggested to require a burst-promoting activity in addition to Epo. Accordingly, we observed no BFU-E colony formation in serum-containing cultures in response to Epo alone. In contrast, 50 BFU-E colonies were formed when anti-TGF-beta was included in the culture. In serum-free cultures, Epo also stimulated BFU-E colony formation in the absence of other cytokines, whereas anti-TGF- beta had no effect on the number of colonies formed. Quantitation of TGF-beta 1 in serum by an enzyme-linked immunosorbent assay method showed predominantly the presence of precursor (latent) TGF-beta 1, but also showed active TGF-beta 1 at a concentration sufficient to potently inhibit erythroid colony formation. Thus, neutralization of active TGF- beta 1 in serum shows that Epo alone is sufficient to stimulate the growth of murine BFU-E progenitors.
Megakaryocyte growth and development factor ameliorates carboplatin- induced thrombocytopenia in mice
Authors: Ulich TR , del Castillo J , Yin S , Swift S , Padilla D , Senaldi G , Bennett L , Shutter J , Bogenberger J , Sun D 
Published: October 2019

Abstract
Megakaryocyte growth and development factor (MGDF) administered intraperitoneally (IP) to mice causes a dose-dependent thrombocytosis accompanied by a decrease in mean platelet volume. MGDF increases the number of megakaryocytes in the bone marrow and spleen. MGDF does not affect the circulating number of leukocytes. Carboplatin, a chemotherapeutic agent that causes thrombocytopenia in humans, administered to mice as a single IP injection at a nonlethal dose causes a significant, but reversible thrombocytopenia. The carboplatin- induced thrombocytopenia is accompanied by an increase in circulating endogenous MGDF that precedes the return of circulating platelets to a normal level. MGDF mRNA is constitutively present in the liver. After carboplatin treatment, hepatic MGDF mRNA does not increase in concordance with circulating MGDF. Circulating soluble MGDF receptor levels (c-mpl) do not change significantly during the course of carboplatin-induced thrombocytopenia. MGDF injected IP once daily beginning 1 day after injection of carboplatin reverses carboplatin- induced thrombocytopenia in a dose-dependent fashion. The normalization of circulating platelet numbers in carboplatin plus MGDF-treated mice is accompanied by a normalization of megakaryocyte numbers in the bone marrow. In conclusion, MGDF, by increasing the number of marrow megakaryocytes and circulating platelets is an effective therapy for carboplatin-induced thrombocytopenia in mice.
Mitochondrial dysfunctions in circulating T lymphocytes from human immunodeficiency virus-1 carriers [see comments]
Authors: Macho A , Castedo M , Marchetti P , Aguilar JJ , Decaudin D , Zamzami N , Girard PM , Uriel J , Kroemer G 
Published: October 2019

Abstract
In several models of lymphocyte apoptosis, two alterations of mitochondrial function precede advanced DNA fragmentation: (1) a reduction of mitochondrial transmembrane potential (delta psi m) and (2) an increase in mitochondrial generation of superoxide anion. Here we show that two fluorochromes allow for the identification of analogous mitochondrial perturbations in circulating T lymphocytes from human immunodeficiency virus (HIV)-1+ donors. The first among these fluorochromes, the cationic lipophilic dye DiOC6(3), measures delta psi m; the second marker, hydroethidine (HE), is nonfluorescent, unless it is oxidized by superoxide anions to the product ethidium (Eth). CD4+ or CD8+ cells from clinically asymptomatic HIV-1 carriers contain a significantly elevated percentage of cells endowed with enhanced HE --> Eth conversion and/or reduced DiOC6(3) uptake as compared with normal controls. Phenotypic characterization of (HE --> Eth)high cells from HIV+ donors shows that these cells possess a low delta psi m, thus demonstrating a functional alteration of mitochondria. In addition, (HE --> Eth)high cells display a reduced incorporation of the cardiolipin-specific dye nonyl-acridine orange (NAO), showing a structural defect of the cardiolipin-containing inner mitochondrial membrane. Control experiments involving rotenone, an inhibitor of the respiratory chain complex I, indicate that the reactive oxygen species responsible for HE --> Eth conversion is generated during mitochondrial electron transport. In synthesis, it appears that mitochondrial alterations occur in a significant percentage of circulating T lymphocytes from HIV-1 carriers. The extent of delta psi m reduction, as determined ex vivo, correlates with the frequency of cells undergoing DNA fragmentation after overnight in vitro culture. These observations may be important for the understanding and for the direct ex vivo quantitation of HIV-triggered lymphocyte destruction.
Role of free protein S and C4b binding protein in regulating the coagulant response to Escherichia coli
Authors: Taylor FB Jr , Dahlback B , Chang AC , Lockhart MS , Hatanaka K , Peer G , Esmon CT 
Published: October 2019

Abstract
Previous studies showed that infusion of C4b-binding protein with sublethal Escherichia coli (E. coli) in the primate produced a consumptive coagulopathy followed by microvascular thrombosis and renal failure. The first objective of this study was to characterize the pathophysiology and mechanism of this phenomena following infusion of both these agents with emphasis on defining the role of free protein S. The second objective was to examine the relevance of this model to the hemolytic uremic syndrome. Infusion of C4b-binding protein alone reduced free protein S and decreased platelet concentration to 20% of baseline, whereas infusion of the C4b-binding protein/protein S complex did not. There was no activation of other inflammatory or coagulant factors. Infusion of sublethal E coli alone produced a transient inflammatory response with no reduction of free protein S. However, coinfusion of C4b-binding protein with sublethal E coli reduced free protein S and produced a thrombocytopenia, anemia, and a microvascular thrombotic response, whereas infusion of the C4b-binding protein/protein S complex with sublethal E coli did not. Studies comparing the effects of neutralizing (S-163) and nonneutralizing (S-145) antibodies with protein S coinfused with sublethal E coli produced similar contrasting results. Therefore, we concluded that neutralization of free protein S, and not some other property of C4b-binding protein influenced by protein S, accounted for this microvascular thrombotic response. This response is similar to the hemolytic uremic syndrome characterized by thrombocytopenia, anemia, shistocytosis, and renal glomerular thrombosis with uremia. Comparison of the respective renal histopathologic appearance supports this conclusion. This raises the possibility that inhibition of protein S activity (possibly by one of the forms of C4b-binding proteins) might be one of the factors contributing to microvascular thrombotic disorder, such as the hemolytic uremic syndrome.
Synergistic inhibition of the intrinsic factor X activation by protein S and C4b-binding protein
Authors: Koppelman SJ , van't Veer C , Sixma JJ , Bouma BN 
Published: October 2019

Abstract
The complement protein C4b-binding protein plays an important role in the regulation of the protein C anticoagulant pathway. C4b-binding protein can bind to protein S, thereby inhibiting the cofactor activity of protein S for activated protein C. In this report, we describe a new role for C4b-binding protein in coagulation. We observed inhibition of the intrinsic factor X activating reaction by the complex of C4b-binding protein and protein S. At the plasma concentration of protein S, the factor X activation was inhibited for 50% and addition of C4b-binding protein led to a potentiation of the inhibition to almost 90%. Because C4b-binding protein alone had no effect on the activation of factor X, we hypothesized that binding of C4b-binding protein to protein S was a prerequisite for optimal inhibition of factor X activation. C4b-binding protein lacking the beta-chain, which is unable to bind to protein S, did not potentiate the inhibitory effect of protein S. In an earlier study, we observed that C4b-binding protein increased the binding affinity of protein S for factor VIII. Therefore, a possible interaction of C4b-binding protein with factor VIII was investigated. C4b-binding protein bound to factor VIII and to thrombin activated factor VIII in a saturable and specific way. Also, factor VIII in complex with von Willebrand factor was able to bind C4b-binding protein. The beta-chain of C4b-binding protein was not required for the interaction with factor VIII because C4b-binding protein lacking the beta-chain also bound to factor VIII. Monoclonal antibodies directed against the alpha-chain of C4b-binding protein inhibited the binding to factor VIII, whereas monoclonal antibodies directed against the beta-chain had no effect on the binding to factor VIII. This finding indicates that the binding site for factor VIII on C4b-binding protein is localized on the alpha-chains of C4b-binding protein. The potentiation by C4b-binding protein of the inhibition of the factor X activation by protein S was blocked by a monoclonal antibody directed against the alpha-chain of C4b-binding protein. This finding indicates that the potentiation of the inhibitory effect of protein S was mediated via an interaction of C4b-binding protein with factor VIII. C4b-binding protein did not bind to factor V and was not able to potentiate the inhibitory effect of protein S on prothrombinase activity.(ABSTRACT TRUNCATED AT 400 WORDS)
In vitro establishment and characterization of two acquired immunodeficiency syndrome-related lymphoma cell lines (BC-1 and BC-2) containing Kaposi's sarcoma-associated herpesvirus-like (KSHV) DNA sequences
Authors: Cesarman E , Moore PS , Rao PH , Inghirami G , Knowles DM , Chang Y 
Published: October 2019

Abstract
Two unique DNA fragments were recently identified in over 90% of acquired immunodeficiency syndrome (AIDS)-related Kaposi's sarcoma tissues. Sequence analysis suggests that these fragments belong to a previously unidentified human herpesvirus, Kaposi's sarcoma-associated herpesvirus (KSHV). These fragments have also been identified in a subset of non-Hodgkin's lymphomas in human immunodeficiency virus-positive patients; specifically, in body cavity-based lymphomas (AIDS-BCBLs). We have established two cell lines derived from AIDS-BCBLs, BC-1 and BC-2, which retain the KSHV sequences, and have used them to further characterize this putative viral genome. In this report, we demonstrate that the KSHV sequences represent a portion of a much larger DNA molecule that is located predominantly in the nucleus of the infected cells. In situ hybridization of metaphase spreads made from both of these cell lines show these sequences in episomal structures. Their presence in the cells as large nuclear episomes supports previous sequence homology data suggesting that KSHV belongs to the herpesvirus family. These cell lines provide a continuous source of KSHV sequences. Thus, they represent an important tool for future studies of this recently described human herpesvirus that may be involved in the pathogenesis of Kaposi's sarcoma and some AIDS-related non-Hodgkin's lymphomas.
A novel antigen detected by the CBF.78 antibody further distinguishes anaplastic large cell lymphoma from Hodgkin's disease
Authors: al Saati T , Tkaczuk J , Krissansen G , Print C , Pileri S , Ralfkiaer E , Grogan TM , Meggetto F , Delsol G 
Published: October 2019

Abstract
A novel antigen detected by the CBF.78 monoclonal antibody (MoAb) is strongly expressed on cortical thymocytes and weakly expressed on resting peripheral T lymphocytes. Expression of the antigen is increased on phytohemagglutinin (PHA)- and anti-CD3-activated T lymphocytes and on Epstein-Barr virus-transformed B lymphocytes. The CBF.78 immunoprecipitated a protein of 116 kD from resting and PHA-activated peripheral blood mononuclear cells. CBF.78 MoAb did not inhibit T-cell proliferation induced by anti-CD3 antibody. This MoAb was effective for immunostaining on paraffin sections after microwave-oven heating of tissue sections. Among malignant lymphomas, the antigen recognized by CBF.78 MoAb was found to be mainly expressed by T-cell lymphomas (49+ of 74), particularly those of high-grade malignancy (31+ of 36), whereas only occasional B-cell lymphomas (4+ of 107) expressed the antigen. A distinctive pattern of reactivity was shown by 108 cases of anaplastic large cell lymphomas. Strong positivity for CBF.78 antibody was observed in 86+ of 108 cases, irrespective of B, T, or null phenotype. This multicenter study suggests that CBF.78 MoAb could be of diagnostic value in differentiating Hodgkin's-like anaplastic large cell lymphomas from cases of Hodgkin's disease rich in neoplastic cells. Only a few cases of Hodgkin's disease (13+ of 126) showed rare Reed-Sternberg cells that stained, In these few cases, staining was weak to moderate and confined to cytoplasm. CBF.78 MoAb was nonreactive with all nonhematopoietic neoplasms examined (0+ of 48). Further studies should delineate the function of this new antigen and its clinical utility.
Generation of CD4+ cytotoxic T-lymphocyte clones from a patient with severe graft-versus-host disease after allogeneic bone marrow transplantation: implications for graft-versus-leukemia reactivity
Authors: Faber LM , van Luxemburg-Heijs SA , Veenhof WF , Willemze R , Falkenburg JH 
Published: October 2019

Abstract
HLA-identical bone marrow transplantation (BMT) is associated with both graft-versus-host disease (GVHD) and graft-versus-leukemia (GVL) reactivity. Different T-cell subsets from the bone marrow (BM) graft may be responsible for GVHD and GVL reactivity after BMT. In the etiology of GVHD, not only CD8+ but also CD4+ donor T lymphocytes may play an important role. Here we report a patient with chronic myeloid leukemia (CML) who was transplanted with the BM from his HLA-genotypically identical sister. After BMT there was complete engraftment, but the patient died because of acute GVHD grade III-IV in complete remission. Cytotoxic T-lymphocyte (CTL) lines were generated after BMT using the irradiated leukemic cells from the patient as stimulator cells and the donor-originated peripheral blood mononuclear cells, procured from the patient after BMT, as responder cells. The generated CTL lines showed specific lysis of the recipient lymphocytes and leukemic cells in a 51Cr release assay. Two types of CTL clones could be established from these CTL lines, both phenotypically CD4+. Clone type I showed male-specific HLA-DQ5-restricted lysis of the recipient lymphocytes, but not of the circulating relatively mature leukemic cells from the patient. This may be explained by the low HLA-DQ5 expression of the more mature CML cells. Clone type II showed HLA-DR2-restricted minor histocompatibility antigen-specific lysis of the recipient lymphocytes and leukemic cells. Both types of CTL clones showed antigen-specific cell-mediated growth inhibition of the recipient clonogenic leukemic precursor cells. These CD4+ CTL clones produced several activating cytokines including tumor necrosis factor alpha, interferon gamma, granulocyte-macrophage colony-stimulating factor (GM-CSF), and macrophage CSF. Our results illustrate that these CD4+ CTL clones may have induced GVHD directly by cytolysis and indirectly by activating cytokines. Because both types of CTL clones recognized the recipient leukemic progenitor cells, they may also contribute to GVL reactivity after BMT.
Allogeneic blood stem cell transplantation: peripheralization and yield of donor-derived primitive hematopoietic progenitor cells (CD34+ Thy- 1dim) and lymphoid subsets, and possible predictors of engraftment and graft-versus-host disease
Authors: Korbling M , Huh YO , Durett A , Mirza N , Miller P , Engel H , Anderlini P , van Besien K , Andreeff M , Przepiorka D 
Published: October 2019

Abstract
Apheresis-derived hematopoietic progenitor cells have recently been used for allogeneic transplantation. Forty-one normal donors were studied to assess the effects of recombinant human granulocyte colony-stimulating factor (rhG-CSF) (12 micrograms/kg/d) on the peripheralization of hematopoietic progenitor cells and lymphoid subsets. The white blood cell, polymorphonuclear cell (PMNC), and lymphocyte concentrations at the peak of rhG-CSF effect in the donor's peripheral blood (PB) exceeded baseline by 6.4-, 8.0-, and 2.2-fold, respectively. Corresponding concentrations of PB CD34+ cells and primitive subsets such as CD34+ Thy-1dim, and CD34+ Thy-1dim CD38- cells increased by 16.3-fold, 24.2-fold, and 23.2-fold, respectively in eight normal donors. The percentage of CD34+ Thy-1dim and CD34+ Thy- 1dim CD38- cells among CD34+ cells increased as well, suggesting an additional peripheralization effect of rhG-CSF on primitive CD34+ subsets. The preapheresis PB CD34+ and CD34+ Thy-1dim cell concentrations were predictive of their corresponding apheresis yield per liter of donor blood processed PB lymphoid subsets were not significantly affected by rhG-CSF treatment. The mean apheresis-derived yield of CD34+, CD34+ Thy-1dim, and CD34+ Thy-1dim CD38- cells per kilogram of recipient body weight and per liter of donor blood processed was 48.9 x 10(4) (n = 41), 27.2 x 10(4) (n = 10), and 1.9 x 10(4) (n = 10), respectively. As compared with 43 single bone marrow (BM) harvest, the CD34+ cell yield of peripheral blood progenitor cell allografts of 41 normal donors exceeded that of BM allografts by 3.7- fold and that of lymphoid subsets by 16.1-fold (CD3+), 13.3-fold (CD4+), 27.4-fold (CD8+), 11.0-fold (CD19+), and 19.4-fold (CD56+CD3-). All PBPC allografts were cryopreserved before transplantation. The mean recovery of CD34+ cells after freezing, thawing, and washing out dimethylsulfoxide was 86.6% (n = 31) and the recovery of lymphoid subsets was 115.5% (CD3+), 121.4% (CD4+), 105.6% (CD8+), 118.1% (CD19+), and 102.4% (CD56+CD3-). All donors were related to patients: 39 sibling-to-sibling, 1 parent-to-child, and 1 child-to-parent transplant. Thirty-eight transplants were HLA fully identical, two transplants differed in one and two antigens. Engraftment occurred in 38 recipients; two patients died too early to be evaluated, and one patient did not engraft. The lowest CD34+ cell dose transplanted and resulting in complete and sustained engraftment was 2.5 x 10(6)/kg of recipient body weight.(ABSTRACT TRUNCATED AT 400 WORDS)
p53 overexpression as a marker of poor prognosis in mantle cell lymphomas with t(11;14)(q13;q32)
Authors: Louie DC , Offit K , Jaslow R , Parsa NZ , Murty VV , Schluger A , Chaganti RS 
Published: October 2019

Abstract
The t(11;14)(q13;q32) translocation, which juxtaposes the BCL1 oncogene with the Ig heavy chain locus, has been associated with an uncommon subtype of non-Hodgkin's lymphoma (NHL) termed mantle cell lymphoma (MCL). To date, no molecular marker that serves as an indicator of tumor progression or clinical prognosis has been described for NHLs with this translocation. We examined a panel of NHLs with t(11;14) for overexpression of p53 and correlated the results with single-strand conformation polymorphism (SSCP) analysis, karyotypic features, and clinical course. NHLs with t(11;14) were identified from 30 patients. The diagnosis was MCL for 23 of 30, small lymphocytic lymphoma for 4 of 30, and diffuse large-cell lymphoma for 3 of 30 cases. The results of immunohistochemistry analysis using a monoclonal anti-p53 antibody on paraffin-embedded specimens were compared with the SSCP data, the tumor karyotypes, and clinical course of each patient. DNA sequencing of exons was performed on cases that showed conformational changes by SSCP analysis. NHLs from 5 of 23 patients with MCL were positive for p53 overexpression. Deletions of chromosome 17p were identified in 2 of 30 cases, both of which were MCLs showing p53 overexpression. Two of the five MCLs with p53 overexpression showed evidence for TP53 mutations. None of the 18 MCLs negative for p53 overexpression showed conformational changes by SSCP. For these 18 patients with MCLs that did not overexpress p53, the median survival was 63 months, compared with 12 months for the 5 patients with MCLs positive for p53 overexpression (P < .001). These results suggest that p53 overexpression in MCL with t(11;14)(q13;q32) may serve as a marker of poor prognosis.