bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hepatitis C virus serum markers and liver disease in children with leukemia during and after chemotherapy
Authors: Locasciulli A , Cavalletto D , Pontisso P , Cavalletto L , Scovena E , Uderzo C , Masera G , Alberti A 
Published: October 2019

Abstract
The pattern of hepatitis C virus (HCV) serum markers and liver disease was investigated in 11 leukemic children showing anti-HCV reactivity at least once during long-term observation to define the role of HCV infection and the behavior of HCV serologic markers in this patient cohort. Antibodies to HCV by first- and second-generation enzyme-linked immunosorbent assay (ELISA) and by second-generation (four antigens) recombinant immunoblotting assay (RIBA) and HCV-RNA by nested polymerase chain reaction (PCR) were serially examined in serum. Liver disease was defined according to transaminase levels. Seven of 11 patients were found HCV-RNA positive during chemotherapy and after blood transfusion, 3 of 11 became viremic during follow-up, and 1 of 11 was always HCV-RNA negative. Seroconversion to anti-HCV positivity by second-generation ELISA occurred in all the HCV-RNA positive children either during or after chemotherapy. Alanine aminotransferase (ALT) levels were elevated in all the HCV-RNA positive patients during antileukemic treatment and normalized in seven of them after therapy withdrawal, despite persisting viremia. These results indicate that HCV- RNA testing by polymerase chain reaction is required to correctly identify HCV infection in patients with leukemia while on chemotherapy. Viremia did not correlate with ALT levels and anti-HCV patterns.
Human pre-B cells differentiate into Ig-secreting plasma cells in the presence of interleukin-4 and activated CD4+ T cells or their membranes
Authors: Punnonen J , Aversa G , de Vries JE 
Published: October 2019

Abstract
Studies on human B-cell development have been hampered by the lack of reproducible culture techniques to induce pre-B cells to differentiate into Ig-secreting plasma cells. Here, we describe that highly purified surface (s) mu-, cytoplasmic (c) mu+, CD10+, CD19+ human pre-B cells derived from fetal bone marrow (BM) differentiate with high frequencies into Ig-secreting plasma cells, when cocultured with activated, cloned CD4+ T cells and with interleukin-4 (IL-4). Production of IgM, total IgG, IgG4, and IgE in pre-B-cell cultures was detected, indicating that the cells also underwent Ig isotype switching. Pre-B-cell differentiation occurred in the absence of BM stromal cells, IL-7, and stem cell factor (SCF). However, IL-7 significantly enhanced the levels of Ig produced, whereas SCF was ineffective. Neutralizing anti-IL-4 monoclonal antibodies (MoAbs) completely inhibited pre-B-cell differentiation showing the specificity of the reaction. Intact CD4+ T- cell clones could be replaced by membrane preparations of these cells, indicating that the costimulatory signals provided by the activated CD4+ T cells are contact-mediated. In contrast, anti-CD40 MoAbs failed to provide the costimulatory signal required for pre-B-cell differentiation, which may be related to the very low expression of CD40 on fetal BM B cells. Activated CD4+ T cells and IL-4 also induced s mu expression and Ig synthesis in cultures initiated with pre-B cells that had been preincubated in medium for 2 days, and from which spontaneously emerging s mu+ B cells were removed by using a fluorescence-activated cell sorter. These results support the notion that the Ig synthesis observed in pre-B-cell cultures was not caused by outgrowth and differentiation of cells that spontaneously matured into s mu+ B cells. In addition, IL-4 and CD4+ T cells strongly enhanced CD40 and HLA-DR expression on the majority of cultured pre-B cells, further indicating that CD4+ T cells and IL-4 activate bona fide pre-B cells. Taken together, these data indicate that activated CD4+ T cells and IL-4 can provide all the necessary signals required for human pre-B cells to differentiate into Ig-secreting plasma cells.
Differentiation state and responses to hematopoietic growth factors of murine myeloid cells transformed by myb
Authors: Gonda TJ , Macmillan EM , Townsend PV , Hapel AJ 
Published: October 2019

Abstract
Murine hematopoietic cells can be transformed in vitro by recombinant retroviruses that express the myb oncogene, and hematopoietic growth factor (HGF)-dependent myeloid cell lines can be derived from these transformed primary cells. In this study, the differentiation state and responses of myb-transformed hematopoietic cells (MTHCs) have been investigated. We find that MTHCs exhibit properties of early myeloid progenitors including synergistic responses to combinations of HGFs and expression of certain surface markers. As reported previously, MTHCs respond well to granulocyte-macrophage colony-stimulating factor (GM- CSF) but can also respond to interleukin-3 (IL-3); the response to the latter factor depends on the mouse strain from which the cells are derived. Although these single factors stimulate MTHCs, combinations of these factors with colony-stimulating factor-1 (CSF-1 or M-CSF) or Steel factor (SLF or SCF) act synergistically to promote colony formation. The surface markers expressed by MTHCs include both granulocyte-macrophage lineage specific antigens Gr-1, 7/4, F4/80, and Mac-1, as well as two antigens found on early progenitors and stem cells--Thy-1 and Sca-1 (Ly6E). Expression of the latter markers is often heterogeneous and can be modulated by the growth factors to which the cells are exposed. Finally, we show that monocytic differentiation of MTHCs can be induced by exposure to tumor necrosis factor (TNF alpha). Taken together, these results suggest that MTHCs will be a useful model for studying HGF/cytokine responses in both proliferation and differentiation.
Interleukin-6 (IL-6) as an anti-inflammatory cytokine: induction of circulating IL-1 receptor antagonist and soluble tumor necrosis factor receptor p55
Authors: Tilg H , Trehu E , Atkins MB , Dinarello CA , Mier JW 
Published: October 2019

Abstract
The aim of this study was to investigate whether interleukin (IL)-6 induces the production of IL-1 and tumor necrosis factor (TNF) antagonists. Serial plasma samples were obtained from cancer patients participating in phase I and II trials of recombinant IL-6 administered as a 120-hour continuous intravenous (IV) infusion. Plasma IL-1 receptor antagonist (IL-1Ra) and soluble TNF receptor p55 (TNFsRp55) levels were measured by specific radioimmunoassays (RIAs). IL-1Ra levels increased rapidly, reaching peak values (9.6 +/- 1.7 ng/mL) within 2 to 4 hours of beginning treatment. Thereafter, levels promptly declined, reaching near baseline within 24 hours despite continuation of IL-6. TNFsRp55 plasma levels increased within 4 to 8 hours after initiating treatment and increased progressively throughout the duration of therapy. IL-1 beta and TNF-alpha plasma levels were below the detection limit in all samples tested. Peripheral blood mononuclear cells (PBMC) exposed to IL-6 produced only small amounts (1.56 +/- 0.3 ng/mL) of IL-1Ra, even in the presence of exogenous soluble IL-6 receptor (gp80). TNFsRp55 levels measured in the supernatants of IL-6- stimulated PBMC were below the detection limit of the assay. Macrophages generated by culturing monocytes in granulocyte-macrophage colony-stimulating factor (GM-CSF) were much more responsive to IL-6 than freshly isolated unfractionated or adherent PBMC and synthesized almost as much IL-1Ra when stimulated with IL-6 as with endotoxin. These results suggest that the antinflammatory properties of IL-6 may be due; in part, to the induction of IL-1Ra synthesis and the release of soluble TNF receptors. Our findings also suggest that tissue macrophages may be an important source of IL-6-induced IL-1Ra.
Attenuation of graft-versus-host disease and graft rejection by ex vivo immunotoxin elimination of alloreactive T cells in an H-2 haplotype disparate mouse combination
Authors: Cavazzana-Calvo M , Stephan JL , Sarnacki S , Chevret S , Fromont C , de Coene C , Le Deist F , Guy-Grand D , Fischer A 
Published: October 2019

Abstract
A mouse anti-interleukin-2 receptor A-chain-specific PC61-immunotoxin (PC61-IT) strongly inhibited a primary mixed lymphocyte culture and major histocompatibility complex (MHC)-restricted cytotoxicity. The allodepleted T cells retained their proliferative and cytotoxic capacities in response to third-party stimulation, showing that PC61-IT specifically deleted recipient antigen-specific T-cell clones from the donor mouse. The ability of this specific allodepletion to prevent graft-versus-host disease (GVHD) and graft rejection was investigated in vivo. IT-depleted, activated parental T lymphocytes (C3H/eB) were intravenously injected into lethally irradiated CDF1 mice. GVHD was evaluated after 6 days on the severity of gut lesions. PC61-IT-treated cells significantly reduced both donor T-cell infiltration and acceleration of epithelial renewal (a sensitive index of gut damage) as compared with those for the corresponding untreated controls. The effect of selective allo-depletion on prevention of GVHD and graft rejection was further studied after MHC-haploincompatible bone marrow (BM) transplantation. A significant increase in survival was observed in mice receiving 2 x 10(6) T-cell-depleted BM cells and 0.5 x 10(6) PC61-IT-treated T cells, because one-third were alive without GVHD (and with stable full or partial engraftment) after 100 days, whereas all the mice infused with BM and sham-treated T cells died within 80 days from GVHD, and all the mice infused with BM cells alone rejected grafts. Furthermore, specific tolerance in chimeras towards donor cells could be shown. These results as observed in an experimental in vivo model corroborate previous results obtained in vitro in humans and lead us to consider the use of this selective allodepletion in human BM transplant from donors other than identical familial siblings.
Effects of stem cell factor (kit-ligand) and interleukin-3 on the growth and serine proteinase expression of rat bone-marrow-derived or serosal mast cells
Authors: Haig DM , Huntley JF , MacKellar A , Newlands GF , Inglis L , Sangha R , Cohen D , Hapel A , Galli SJ , Miller HR 
Published: October 2019

Abstract
The effects of rat stem-cell factor (SCF) and interleukin-3 (IL-3), alone or in combination, on the in vitro growth and serine proteinase expression of rat serosal/connective-tissue mast cells (CTMC) or bone marrow-derived mast cells (BMMC) were examined. Rat SCF stimulated the growth of both CTMC and BMMC. IL-3 stimulated BMMC growth to a lesser extent than did SCF, whereas CTMC numbers did not increase in IL-3. However, SCF and IL-3 had synergistic effects on the growth of both BMMC and CTMC. SCF favoured the maintenance of rat mast cell proteinase- I (RMCP-I) in CTMC, but did not induce detectable production of RMCP-I in BMMC. In contrast, when IL-3 or lymph node-conditioned medium (LNCM) was added to SCF, a subpopulation of CTMC expressed and stored the soluble proteinase RMCP-II. In BMMC, the RMCP-II content of cells maintained in SCF was significantly less than that of cells maintained in IL-3 or LNCM. RMCP-II also appeared in the supernatants of BMMC, especially when BMMC numbers were increasing rapidly in SCF with or without IL-3 or LNCM. Thus, SCF and IL-3 can regulate the growth of rat BMMC and CTMC, as well as influence their production and release of proteinases.
Blood coagulation factor Va abnormality associated with resistance to activated protein C in venous thrombophilia
Authors: Sun X , Evatt B , Griffin JH 
Published: October 2019

Abstract
A coagulation test abnormality, termed activated protein C (APC) resistance, involving poor anticoagulant response to APC is currently the most common laboratory finding among venous thrombophilic patients. Because the anticoagulant activity of APC involves inactivation of factors Va and VIIIa, studies were made to assess the presence of abnormal factors V or VIII. Diluted aliquots of plasma from two unrelated patients with APC resistance and thrombosis were added to either factor VIII-deficient or factor V-deficient plasma and APC resistance assays were performed. The results suggested that patients' factor V but not factor VIII rendered the substrate plasma APC resistant. When factor V that had been partially purified from normal or APC resistant patients' plasmas using immunoaffinity chromatography was added to factor V-deficient plasma, APC resistance assays showed that patients' factor V or factor Va, but not normal factor V, rendered the substrate plasma resistant to APC. Studies of the inactivation of each partially purified thrombin-activated factor Va by APC suggested that half of the patients' factor Va was resistant to APC. These results support the hypothesis that the APC resistance of some venous thrombophilic plasmas is caused by abnormal factor Va.
Total marrow failure induced by pegylated stem-cell factor administered before 5-fluorouracil
Authors: Molineux G , Migdalska A , Haley J , Evans GS , Dexter TM 
Published: October 2019

Abstract
To examine the potential role of stem-cell factor (SCF) in cancer chemotherapy, we have administered it to mice either before or after 5- fluorouracil (5-FU). When polyethylene glycolated (PEG-ylated) SCF was administered to mice before 5-FU, it had a significant sensitizing effect on primitive bone marrow cells. Examination of the hematopoietic status of these mice showed that the damage caused by 5-FU to both bone marrow and spleen hematopoiesis was exaggerated when it was preceded by SCF. SCF given before each of two 5-FU treatments at 7-day intervals resulted in the death of all treated mice. The time of death and hematopoietic status of these animals are compatible with the onset of hypoplastic marrow failure leading to pancytopenia and death. SCF given after 5-FU had little impact either on the initial degree of hematopoietic damage or subsequent recovery. Gut populations were similarly sensitized to 5-FU by prior treatment with SCF, and the damage caused to intestinal populations was greater than that resulting from 5-FU alone. This indicates that the different tissues may be similarly sensitized by SCF. The sensitizing effect of SCF was reversed by concurrent administration of transforming growth factor (TGF)-beta 3, and survival of the majority of the mice was ensured. Examination of hematopoiesis in mice treated concurrently with SCF and TGF-beta 3 showed that the degree of marrow and spleen damage had reverted to that caused by 5-FU alone. In further experiments, 100% survival and normal hematopoiesis could be attained by transplantation of 1 million syngeneic bone marrow cells 24 hours after 5-FU treatment following SCF sensitization. These data indicate that PEG-ylated SCF can sensitize normally resistant hematopoietic and gut stem cells to the effects of 5- FU. This sensitization resulted in effective eradication of hematopoiesis in SCF-pretreated/5-FU-treated animals and their subsequent death from marrow failure. These findings imply that SCF pretreatment may represent a novel method of increasing the effectiveness of conventional chemotherapy, making marrow ablation more effective without drug dose escalation and perhaps sensitizing some tumor cells to the effects of therapy.
C-kit gene is expressed by skin mast cells in embryos but not in puppies of Wsh/Wsh mice: age-dependent abolishment of c-kit gene expression
Authors: Yamazaki M , Tsujimura T , Morii E , Isozaki K , Onoue H , Nomura S , Kitamura Y 
Published: October 2019

Abstract
The Wsh is a mutant allele at the W (c-kit) locus of mice, but no significant abnormalities are found at the coding region of the Wsh allele. Since cultured mast cells derived from the spleen of Wsh/Wsh mice do not express messenger RNA (mRNA) of c-kit, we studied the interrelation between the number of mast cells and the magnitude of c- kit mRNA expression in the skin of Wsh/Wsh mice of various ages. The number of mast cells in the skin of Wsh/Wsh embryos of 18 days postcoitum (pc) was approximately 40% that of normal control (+/+) embryos, but the number of mast cells decreased exponentially after birth; the number dropped to 0.6% that of +/+ mice at day 150 after birth. A weak but apparent signal of c-kit mRNA was detectable in the skin of 18-day pc Wsh/Wsh embryos by RNase protection assay but not in the skin of 5-day-old Wsh/Wsh mice. The number of c-kit protein- containing cells was significantly greater in the skin of 18-day pc Wsh/Wsh embryos than in the skin of 5-day-old Wsh/Wsh mice. The abolishment of c-kit mRNA expression appeared to be specific, because the expression of mast cell carboxypeptidase A mRNA but not of c-kit mRNA was detectable by in situ hybridization in skin mast cells of 5- day-old Wsh/Wsh mice. Taken together, the expression of c-kit mRNA was abolished first, then the content of c-kit protein dropped to undetectable levels, and then the disappearance of Wsh/Wsh mast cells themselves followed.
Reproducible obtaining of human myeloma cell lines as a model for tumor stem cell study in human multiple myeloma
Authors: Zhang XG , Gaillard JP , Robillard N , Lu ZY , Gu ZJ , Jourdan M , Boiron JM , Bataille R , Klein B 
Published: October 2019

Abstract
We report a novel, reproducible methodology which enabled 10 human myeloma cell lines (HMCL) to be obtained from each of 10 tumor samples harvested from 9 patients with extramedullary proliferation. Fresh samples were cultured with interleukin 6 (IL-6) and granulocyte macrophage-colony stimulating factor (GM-CSF) at a high cell density and resulting HMCL growth became progressively dependent on IL-6 alone, no longer requiring GM-CSF. These HMCL, which had the same immunoglobulin gene rearrangements as the patients' original myeloma cells, were designated XG-1 to XG-9. XG HMCL had a plasma cell morphology, expressed plasma cell antigen (Ag), namely cytoplasmic immunoglobulins, CD38, B-B4 Ag, and CD77, and lacked the usual B-cell Ag. They also expressed activation antigens such as CD28 with coexpression of CD28 and its ligand, B7 Ag, in four HMCL. Six HMCL expressed CD40, 4 CD23, and 5 its ligand, CD21. The XG HMCL bore adhesion molecules VLA-4 and CD44 (all 10 HMCL), VLA-5 (7 HMCL), and CD56 (4 HMCL). Finally, cytogenetic study of 8 HMCL indicated a 14q+ chromosome, and t(11,14) translocation was found in 6 of 8 and 5 of 8 HMCL, respectively. The possibility of obtaining malignant plasma cell lines reproducibly from each patient with extramedullary proliferation offers a unique tool for studying the phenotype and abnormalities of the still unidentified tumor stem cell in this disease.
Rearrangement of CCND1 (BCL1/PRAD1) 3' untranslated region in mantle- cell lymphomas and t(11q13)-associated leukemias
Authors: Rimokh R , Berger F , Bastard C , Klein B , French M , Archimbaud E , Rouault JP , Santa Lucia B , Duret L , Vuillaume M 
Published: October 2019

Abstract
Rearrangement and overexpression of CCND1 (BCL1/PRAD1), a member of the cyclin G1 gene family, are consistent features of t(11q13)-bearing B- lymphoid tumors (particularly mantle-cell lymphoma [MCL]). Its deregulation is thought to perturb the G1-S transition of the cell cycle and thereby to contribute to tumor development. As suggested by previously published studies, rearrangement of the 3′ untranslated region (3′ UTR) of CCND1 may contribute to its activation in some lymphoid tumors. To define further the prevalence of such rearrangements, we report here the result of the molecular study of 34 MCL and six t(11q13)-associated leukemias using a set of probes specific to the different parts of the CCND1 transcript. We also sequenced the entire cDNA of the overexpressed CCND1 transcripts in a t(11q13)-associated leukemia. DNA from four of these 40 patients showed rearrangement of the 3′ UTR of CCND1 coexisting with major translocation cluster (MTC) rearrangement. Southern blot and sequence analyses showed that, as a result of these rearrangements, the 3′ AU- rich region containing sequences involved in mRNA stability and in translational control is eliminated. Moreover, the finding that the CCND1 mRNA half-life was greater than 3 hours (normal tissues, 0.5 hours) in three t(11q13)-associated cell lines stresses the importance of posttranscriptional derangement in the activation of CCND1. Finally, we did not observe any mutation in the coding frame of the CCND1 cDNA analyzed.
Reductions in physiologic shear rates lead to CD11/CD18-dependent, selectin-independent leukocyte rolling in vivo
Authors: Gaboury JP , Kubes P 
Published: October 2019

Abstract
In this study, we tested the hypothesis that reducing shear rates in postcapillary venules causes CD18-dependent, selectin-independent leukocyte rolling. Intravital microscopy was used to assess shear rate- dependent leukocyte rolling in 25- to 40-microns rat mesenteric venules. Pretreatment of animals with 25 mg/kg fucoidin, a carbohydrate moiety that binds to and inhibits selectin function, essentially abolished the number of spontaneously rolling leukocytes. When shear rates were reduced by 50% (from 438 +/- 36 s-1 to 222 +/- 19 s-1) in the presence of fucoidin, leukocyte rolling increased fourfold, suggesting a selectin-independent mechanism of leukocyte rolling. Administration of CL26, an anti-CD18 antibody, prevented the leukocyte rolling associated with reduced shear rates. A second objective was to determine if the integrin-mediated leukocyte rolling at reduced shear rates would lead to firm adhesion of leukocytes in the presence of a chemotactic stimulus. Animals were pretreated with fucoidin and 100 nmol/L platelet-activating factor (PAF) was superfused over the mesentery. Fucoidin prevented leukocyte rolling and subsequent PAF- induced adhesion at normal shear rates; however, when shear rates were reduced by 50%, a significant CD18-dependent increase in leukocyte rolling (10-fold) and adhesion (5-fold) was noted within 15 minutes. These data raise the possibility that, at lower shear rates, as is the case in various inflammatory conditions, selectin-independent, CD18- dependent leukocyte rolling and subsequent adhesion can occur in postcapillary venules.
Platelets inhibit fibrinolysis in vitro by both plasminogen activator inhibitor-1-dependent and -independent mechanisms
Authors: Fay WP , Eitzman DT , Shapiro AD , Madison EL , Ginsburg D 
Published: October 2019

Abstract
Platelet-rich thrombi are resistant to lysis by tissue-type plasminogen activator (t-PA). Although platelet alpha-granules contain plasminogen activator inhibitor-1 (PAI-1), a fast-acting inhibitor of t-PA, the contribution of PAI-1 to the antifibrinolytic effect of platelets has remained a subject of controversy. We recently reported a patient with a homozygous mutation within the PAI-1 gene that results in complete loss of PAI-1 expression. Platelets from this individual constitute a unique reagent with which to probe the role of platelet PAI-1 in the regulation of fibrinolysis. The effects of PAI-1-deficient platelets were compared with those of normal platelets in an in vitro clot lysis assay. Although the incorporation of PAI-1-deficient platelets into clots resulted in a moderate inhibition of t-PA-mediated fibrinolysis, normal platelets markedly inhibited clot lysis under the same conditions. However, no difference between PAI-1-deficient platelets and platelets with normal PAI-1 content was observed when streptokinase or a PAI-1-resistant t-PA mutant were used to initiate fibrinolysis. In addition, PAI-1-resistant t-PA was significantly more efficient in lysing clots containing normal platelets than wild-type t-PA. We conclude that platelets inhibit t-PA-mediated fibrinolysis by both PAI- 1-dependent and PAI-1-independent mechanisms. These results have important implications for the role of PAI-1 in the resistance of platelet-rich thrombi to lysis in vivo.