bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chloroquine attenuates hemorrhagic shock-induced suppression of Kupffer cell antigen presentation and major histocompatibility complex class II antigen expression through blockade of tumor necrosis factor and prostaglandin release
Authors: Ertel W , Morrison MH , Ayala A , Chaudry IH 
Published: October 2019

Abstract
Hemorrhagic shock suppresses the ability of Kupffer cells (KC) to present antigen and express the major histocompatibility complex class II (Ia) antigen. These alterations are concomitant with an enhanced release of cytokines (tumor necrosis factor [TNF], interleukin-1 [IL- 1], IL-6) and prostaglandin E2 (PGE2) by KC after hemorrhagic shock. The aim of this study was to determine whether chloroquine (CQ) administration in vivo before or after hemorrhage affects the altered cytokine and PGE2 release by KC as well as the capacity of KC to present antigen and express Ia. To study this, C3H/HeN mice were bled to and maintained at a mean arterial blood pressure of 35 mm Hg for 60 minutes, followed by fluid resuscitation. Chloroquine (10 mg/kg body weight) was injected intramuscularly 2 hours before or during resuscitation following shock. The administration of CQ led to a significant reduction in the hemorrhage-induced elevation of TNF, IL-6, and PGE2 release by KC; however, IL-1 secretion was not affected by CQ. In addition, CQ treatment abolished the hemorrhage-induced increase in circulating TNF and IL-6. These changes in cytokine and PGE2 release following CQ administration correlated with a significant enhancement of the antigen-presenting capacity of KC. No differences were observed between pretreatment and posttreatment with CQ. Our data indicate that CQ selectively inhibits the release of TNF, IL-6, and PGE2 by KC, while IL-1 secretion was unaffected. Because the reduction of these inflammatory mediators was concomitant with a significant improvement of KC capacity to present antigen and express Ia, we propose that TNF, IL-6, and PGE2 play a pivotal role in the induction of posthemorrhage immunosuppression. Furthermore, the data suggest that the suppression of KC functions occurs during or after resuscitation, because posttreatment with CQ was as effective as pretreatment. Additional studies indicated that the survival of animals after hemorrhage and sepsis was significantly increased by posttreatment of hemorrhaged mice with CQ. Thus, CQ, because of its unique ability to selectively inhibit the release of inflammatory cytokines and prostaglandins, represents a potent immunomodulating agent in the treatment of conditions associated with increased cytokine release and for decreasing the mortality from sepsis after hemorrhage.
Clonal granulocytes and bone marrow cells in the cellular phase of agnogenic myeloid metaplasia
Authors: Kreipe H , Jaquet K , Felgner J , Radzun HJ , Parwaresch MR 
Published: October 2019

Abstract
Myelofibrosis with myeloid metaplasia (MMM) belongs to the group of myeloproliferative syndromes. It is characterized by a sustained proliferation of megakaryocytes and increased medullary reticulin fibers. Until now the cellular phase at onset of the disease has not been analyzed for clonality of the hematopoietic cells. In this study we used X-linked restriction length polymorphism (RFLP) analysis to investigate the clonality of granulocytes and bone marrow cells from the cellular phase and advanced stages of the disease. In each of 12 heterozygous females, monoclonality of granulocytes or total bone marrow cells could be demonstrated. These results show that the cellular phase represents a monoclonal, and hence a probably neoplastic, proliferation of a pluripotent stem cell. The monoclonality of granulocytes present at the onset of disease should allow analysis of DNA of these easily accessible peripheral cells for the detection of specific clonal aberrations.
Late failure of autologous marrow grafts in lethally irradiated dogs given anti-class II monoclonal antibody
Authors: Greinix HT , Ladiges WC , Graham TC , Maslan S , Raff RF , Sandmaier BM , Appelbaum FR , Schuening FG , Deeg HJ , Storb R 
Published: October 2019

Abstract
We established a model of canine marrow autografts after 9.2 Gy total body irradiation (TBI) to study the role of class II antigens in hematopoietic stem cell growth and differentiation. Twenty dogs were given 9.2 Gy TBI, marrow, and intravenous (IV) murine anti-class II monoclonal antibody (MoAb). Infusion of 0.6 mg/kg/d of MoAb H81.98.21, an IgG2a reactive with HLA-DR, on days 0 to 4 after TBI did not prevent initial engraftment, but dogs died with late graft failure. MoAb B1F6, an IgG2a reactive with HLA-DR + DP, had no adverse effect on engraftment, although both MoAbs detect antigens on stem cells. The critical time for the effect of MoAbs is the first 4 days after transplantation. Our findings argue against several pathogenetic mechanisms, including removal of MoAb-coated stem cells by the reticuloendothelial system (RES), canine complement-mediated cytotoxic effects on stem cells, antibody-dependent cellular cytotoxicity, and inactivation of MoAb-coated cells by dog anti-mouse antibody. To distinguish between MoAb-induced damage to microenvironment (ME)/accessory cells (AC) and late graft failure from a lack of pluripotent stem cells, three dogs were given TBI, a marrow autograft, and MoAb H81.98.21 on days 0 to 4; one, given thoracic duct cells on day 6, developed graft failure; the other two, given marrow depleted of AC by L-leucyl L-leucine o-methyl ester (Leu-Leu-OMe), had sustained grafts. Findings support the notion that originally transplanted pluripotent stem cells are no longer present on day 6 and that the ME is functional and able to support newly injected stem cells.
Detection of human monocyte-reactive alloantibodies by flow cytometry after selective downmodulation of the Fc receptor I
Authors: Kuijpers RW , Dooren MC , von dem Borne AE , Ouwehand WH 
Published: October 2019

Abstract
Monocyte-reactive human alloantibodies may be of importance in situations such as transfusion reactions and bone marrow and kidney transplantation. So far, only complement-binding monocyte-reactive antibodies can be detected with a cytotoxicity assay. No antiglobulin assays are yet available that also detect noncomplement-fixing monocyte- reactive antibodies. The binding of monomeric IgG with high affinity to the Fc receptor I (FcRI) on monocytes has severely hampered the development of such an assay until now. We report on the selective removal of the FcRI from monocytes to test human sera in a flow cytofluorometry assay for the presence of monocyte-reactive IgG alloantibodies. Selective downmodulation of FcRI was accomplished by incubating the cells with murine monoclonal antibodies against FcRI followed by a second incubation with goat-antimouse IgG polyclonal antibodies. With such modified cells, human complement-binding and noncomplement-binding IgG and IgM alloantibodies against polymorphic determinants of the HLA class I and II glycoproteins, the human monocyte antigen system and polymorphic antigenic determinants of the LFA complex, can be detected in a sensitive and reproducible manner.
Characteristics of red blood cell populations fractionated with a combination of counterflow centrifugation and Percoll separation
Authors: Bosch FH , Werre JM , Roerdinkholder-Stoelwinder B , Huls TH , Willekens FL , Halie MR 
Published: October 2019

Abstract
Red blood cell (RBC) fractions were studied after separation of whole blood by means of counterflow centrifugation, Percoll column (Pharmacia, Uppsala, Sweden), and a combination of both separation techniques. Mean corpuscular volume (MCV), mean corpuscular hemoglobin concentration (MCHC), mean corpuscular hemoglobin (MCH), and hemoglobin A1c (HbA1c) were measured in each fraction. From the results it was obvious that the combination of both techniques was the best separation technique of these three. MCV had a good correlation with cell age as measured with HbA1c concentration gradient; MCH and MCHC less so. MCV and MCH decreased in parallel to an increase in HbA1c. MCHC increased with increasing HbA1c. From these data it is concluded that there is a steadily ongoing loss of cellular hemoglobin and proportionally more cellular water during the life of the RBC.
Recombinant rat stem cell factor stimulates the amplification and differentiation of fractionated mouse stem cell populations
Authors: Williams N , Bertoncello I , Kavnoudias H , Zsebo K , McNiece I 
Published: October 2019

Abstract
The role of recombinant rat stem cell factor (rrSCF) was studied on defined primitive bone marrow cell populations. In agar culture of 500 lineage-negative/Sca-1-positive (Lin-/Sca-1+) cells, rrSCF alone stimulates small colonies of predominantly granulocytic cells. The combinations of rrSCF plus interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF), or macrophage CSF (CSF-1) stimulated primitive progenitor cells defined as high proliferative potential colony-forming cells (HPP-CFC). Synergistic increases in total colony numbers were obtained with rrSCF plus GM-CSF, granulocyte CSF (G-CSF), CSF-1, or IL-6, but not IL-1 or IL-3. Lin-/Sca-1+ cells were incubated in liquid culture at 3,000 cells/mL for 6 days in the presence of rrSCF alone or in combination with other growth factors. The total number of cells was increased twofold in the presence of rrSCF, with the progeny primarily myeloid in nature. The greatest increase in cell number was obtained with rrSCF plus IL-3, where the cell number increased 40-fold. These factors also stimulated an increase in HPP-CFC (10-fold) and GM-CFC (500-fold). To determine if these interactions were direct, single Lin-/Sca-1+ cells were sorted into microtiter wells and the cell proliferation scored 6 days later. RrSCF synergized with IL-3, IL-6, and G-CSF to stimulate the proliferation of single cells. The cells in positive wells were subcultured into colony-forming assays and up to 400 CFC per well were obtained after 14 days incubation of the secondary cultures. These data demonstrate that rrSCF acts in combination with various growth factors to directly stimulate the amplification potential of hematopoietic primitive precursors, resulting in differentiation of these precursors.
Patterns of Epstein-Barr virus infection in non-neoplastic lymphoid tissue
Authors: Niedobitek G , Herbst H , Young LS , Brooks L , Masucci MG , Crocker J , Rickinson AB , Stein H 
Published: October 2019

Abstract
Taking advantage of the abundant expression of the small Epstein-Barr virus (EBV)-encoded RNAs (EBERs) in latently infected cells, we have analyzed 72 normal and hyperplastic lymph nodes and three tonsils of acute infectious mononucleosis (IM) for the presence and distribution of EBV+ cells using EBER-specific in situ hybridization, in some cases combined with immunohistologic demonstration of cell type- characteristic antigens. In IM, large numbers of EBV+ lymphoid B blasts were detectable in extrafollicular areas, whereas germinal centers were generally free of EBV+ cells. In reactive lymph nodes, the frequency of EBV+ cells varied with the degree of lymphoid hyperplasia and underlying immune status. The lowest numbers of EBV+ cells were detected in nonactivated lymph nodes and highest in human immunodeficiency virus-associated lymphadenopathy. If present in these lymph nodes, EBV+ cells were almost exclusively localized to extrafollicular areas, as also observed in IM. However, in contrast to IM, these cells were mainly small lymphocytes. Furthermore, in some instances, occasional scattered EBV+ cells were seen within germinal centers, and in two cases diffuse expansions of EBV+ cells occurred within a single germinal center each, indicating that under certain circumstances EBV+ B lymphocytes may participate in physiologic germinal center reactions. These findings reflect the interference of EBV with physiologic lymphoid differentiation pathways and provide a link to EBV-associated malignant lymphomas with a postulated origin from germinal center cells.
Phase I trial of an interleukin-2 (IL-2) fusion toxin (DAB486IL-2) in hematologic malignancies expressing the IL-2 receptor
Authors: LeMaistre CF , Meneghetti C , Rosenblum M , Reuben J , Parker K , Shaw J , Deisseroth A , Woodworth T , Parkinson DR 
Published: October 2019

Abstract
DAB486IL-2 is a recombinant fusion toxin in which the native receptor binding domain of diphtheria toxin has been replaced with human interleukin-2 (IL-2). It selectively binds and intoxicates only cells that bear the high-affinity receptor for IL-2. In the first clinical trial of a genetically engineered ligand fusion-toxin, we have treated 18 patients with chemotherapy-resistant IL-2 receptor expressing hematologic malignancies with escalating doses of DAB486IL-2. The maximal tolerated dose of a daily intravenous bolus of DAB486IL-2 was 0.1 mg/kg per day for 10 doses, established by asymptomatic, reversible elevations of hepatic transaminases without changes in other tests of liver function. Other mild reversible side effects noted were rash, nausea, elevated creatinine, chest tightness, and fever. Pharmacokinetic analysis showed a monophasic clearance of 5.8 +/- 0.7 minutes with peak levels of 3,549 +/- 1,041 mg/mL at the 0.1 mg/kg dose. Approximately 50% of patients developed an antibody response to diphtheria toxin or DAB486IL-2. The presence of such antibodies did not preclude patients from experiencing an antitumor response as four of the six patients with antitumor effect had detectable antibody titers. Although this was a phase I trial designed to define the safety of DAB486IL-2, remissions were observed in three patients lasting from 5 to over 18 months. The ability to achieve significant tumor reductions in this group of heavily treated patients is encouraging and suggests additional trials are warranted in hematologic malignancies.
Hydroxyurea: effects on hemoglobin F production in patients with sickle cell anemia [see comments]
Authors: Charache S , Dover GJ , Moore RD , Eckert S , Ballas SK , Koshy M , Milner PF , Orringer EP , Phillips G Jr , Platt OS 
Published: October 2019

Abstract
Patients with sickle cell anemia were treated with daily doses of hydroxyurea, to assess pharmacokinetics, toxicity, and increase in fetal hemoglobin (Hb) production in response to the drug. Plasma hydroxyurea clearances were not a useful guide to maximum tolerated doses of the drug. The mean daily single oral dose that could be maintained for at least 16 weeks was 21 mg/kg (range, 10 to 35 mg/kg). Among 32 patients, last HbF levels were 1.9% to 26.3% (mean, 14.9%) with increases in HbF over initial values of 1.4% to 20.2% (mean, 11.2%). The most significant predictors of last HbF were last plasma hydroxyurea level, initial white blood count and initial HbF concentration. Last HbF was not related to beta globin haplotype or alpha globin gene number. No serious toxicity was encountered. Clinically significant bone marrow depression was avoided, and chromosome abnormalities after 2 years of treatment were no greater than those observed before treatment. The period of observation has been too short to evaluate the risk of carcinogenesis. Patient's red cells developed striking macrocytosis. Median red cell Hb concentrations did not change. Hb concentrations increased, on average 1.2 g/dL, but serum erythropoietin levels increased. Patients' body weights increased, and some returned to work or school, but no conclusions regarding therapeutic efficacy could be drawn from this uncontrolled open-label study.
Allogeneic bone marrow transplantation for acute myeloid leukemia in first remission: a randomized trial of a busulfan-Cytoxan versus Cytoxan-total body irradiation as preparative regimen: a report from the Group d'Etudes de la Greffe de Moelle Osseuse [see comments]
Authors: Blaise D , Maraninchi D , Archimbaud E , Reiffers J , Devergie A , Jouet JP , Milpied N , Attal M , Michallet M , Ifrah N 
Published: October 2019

Abstract
From October 1987 to December 1990, 101 patients with acute myeloid leukemia (AML) were randomized to be transplanted in first complete remission (CR1). Preparative regimen including Cytoxan (120 mg/kg) with total body irradiation (CYTBI) (N = 50) or busulfan (16 mg/kg) (BUSCY) (N = 51) was followed by allogeneic bone marrow transplantation (BMT) from an HLA-identical sibling. Mean time between diagnosis and BMT was 119 days. The outcome for CYTBI at 2 years is better for probability of disease-free survival (DFS) (72% v 47%) (P less than .01), survival (75% v 51%) (P less than .02), relapse (14% v 34%) (P less than .04), and transplant mortality (8% v 27%) (P less than .06). In multivariable analysis, higher relapse and decreased survival and DFS were associated with BUSCY regimen, while chronic graft-versus-host disease also influenced independently the probability of relapse. This demonstrates the present limitation of busulfan use in this setting, possibly due to probable individual variations in biodisponibility. Furthermore, besides the anti-leukemic effect of preparative regimens, this trial points out the progress accomplished in BMT management (transplant mortality = 8% in CYTBI) over the last 20 years as well as the effectiveness of transplant in early first CR after CYTBI (DFS = 72% at 2 years).
Decreased expression of eosinophil peroxidase and major basic protein messenger RNAs during eosinophil maturation
Authors: Gruart V , Truong MJ , Plumas J , Zandecki M , Kusnierz JP , Prin L , Vinatier D , Capron A , Capron M 
Published: October 2019

Abstract
We evaluated the levels of mRNAs encoding cationic proteins in peripheral blood eosinophils (PBE) purified from patients with eosinophilia and in eosinophils differentiated from cord blood cells (CBC) by culture with recombinant human interleukin-3 (rhIL-3), rhGM- CSF, and rhIL-5. Messenger RNAs encoding eosinophil peroxidase (EPO), major basic protein (MBP), eosinophil-derived neurotoxin (EDN), and eosinophil cationic protein (ECP) were detected by Northern blot hybridization with the respective specific oligonucleotide probes. In mature PBE, MBP mRNA appeared to be absent, whereas EPO mRNA was barely detectable in only 5 of the 19 patients. In contrast, EDN and ECP mRNAs were observed in the PBE of all patients. In CE, EPO, and MBP, mRNAs were abundant in immature eosinophils and their amounts decreased after differentiation toward eosinophils. ECP and EDN mRNAs followed the same patterns, but mRNAs were less abundant at all timepoints studied. Study of mRNA t1/2 during the time course of differentiation indicated that changes in the stability of the different mRNAs were not responsible for the variations observed in the steady-state levels. Together, these results suggest that regulation of expression differs among EPO, MBP, EDN, and ECP mRNAs during the time course of eosinophil differentiation.
In vivo efficacy of B43 (anti-CD19)-pokeweed antiviral protein immunotoxin against BCL-1 murine B-cell leukemia
Authors: Uckun FM , Chelstrom LM , Irvin JD , Finnegan D , Gunther R , Young J , Kuebelbeck V , Myers DE , Houston LL 
Published: October 2019

Abstract
We show that a highly aggressive subclone of murine BCL-1 B-lineage leukemia expresses a single 2.4-kb transcript hybridizing to the human CD19 cDNA probe and reacts strongly with the anti-human CD19 monoclonal antibodies (MoAb) B43, B4, Leu-12, and J3–119. In contrast to their strong reactivity with anti-human CD19 MoAb, BCL-1 cells show no reactivity with MoAb directed against human CD22, CD72, HLA-DR, IgD, or IgM. Western blot analysis of BCL-1 whole cell lysates with the anti- human CD19 MoAb J3–119 showed a single 69-Kd protein band, which was not detected by the negative control MoAb G19.4 (anti-CD3). In contrast to BCL-1 cells, normal BALB/c splenocytes or mouse splenocyte/myeloma hybridoma cell lines did not (1) express any transcripts that hybridized to the human CD19 cDNA probe, (2) react with B43/anti-CD19 MoAb, or (3) express the 69-Kd protein that reacts with the anti-human CD19 MoAb J3–119. Murine BCL-1 B-cell leukemia thus provides a unique model of disseminated B-lineage leukemia to evaluate the antileukemic efficacy of anti-CD19 immunotoxins. This model was subsequently used to evaluate the in vivo homing ability, pharmacokinetics, and antileukemic efficacy of B43 MoAb conjugated to the plant hemitoxin pokeweed antiviral protein (PAP). B43-PAP immunotoxin (1) showed strong and antigen-specific reactivity with BCL-1 cells, (2) promptly penetrated the spleens of leukemic mice, (3) rapidly reduced the BCL-1 leukemia burden of leukemic mice and, most importantly, (4) improved survival. Finally, B43-PAP immunotoxin was more effective against BCL-1 leukemia than 700 cGy (LD100/30) total body irradiation (TBI) followed by syngeneic bone marrow transplantation (BMT).
Effect of nerve growth factor on the release of inflammatory mediators by mature human basophils
Authors: Bischoff SC , Dahinden CA 
Published: October 2019

Abstract
Nerve growth factor (NGF) is a neurotrophic cytokine known to regulate the survival and function of peripheral and central neuronal cells. Recently, the spectrum of action could be extended to non-neuronal cell types such as rat mast cells and human B lymphocytes. The present study shows that NGF affects the function of mature human basophils isolated from the peripheral blood of healthy donors. Both murine NGF 7S and recombinant human NGF beta enhance histamine release and strongly modulate the formation of lipid mediators by basophils in response to various stimuli. This priming effect of NGF on basophils occurs rapidly within 10 to 15 minutes of preincubation, is dose-dependent, and requires similarly low concentrations (1 to 40 pmol/L) of human NGF beta as the induction of neurite outgrowth in ganglion cells. Cell fractionation studies indicate that NGF acts directly on human basophils without an involvement of other cell types, suggesting the presence of high-affinity NGF receptors on basophils. NGF by itself (up to 4 nmol/L of human NGF beta) does not induce the release of inflammatory mediators directly. The effect of human NGF on basophil mediator release is similar to that of the hematopoietic growth factors interleukin-3, interleukin-5, and granulocyte-macrophage colony- stimulating factor. The present study further demonstrates that NGF acts as a pleiotropic cytokine at the interface between the nervous and the immune system, and that NGF may be involved in inflammatory processes and hypersensitivity reactions.