bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of in vivo administration of interleukin-2 (IL-2) and IL-4, alone and in combination, on ex vivo human basophil histamine release
Authors: White MV , Igarashi Y , Emery BE , Lotze MT , Kaliner MA 
Published: October 2019

Abstract
Human basophils possess receptors for interleukin-2 (IL-2) and IL-4. The effect of 3 days of intravenous administration of IL-2 and/or IL-4 on basophil histamine release was examined in three groups of patients receiving IL-2, IL-4, or the combination of agents as part of a protocol to treat malignant melanoma or renal cell carcinoma. Because all patients received ranitidine for control of side effects, a control group of patients receiving ranitidine for Zollinger-Ellison's syndrome was also studied. IL-4 significantly inhibited IgE-mediated histamine release, while there was a trend for enhancement of IgE-mediated histamine release by IL-2. Administration of the combination of IL-2 and IL-4 did not alter IgE-mediated basophil histamine release. Both IL- 2 and IL-4, alone and in combination, enhanced basophil histamine release induced by histamine releasing factors in human nasal washings. The effect of IL-2 alone was significantly greater than that of IL-4 alone or the combination of IL-2 plus IL-4. Taken together, the data suggest that when coadministered, IL-4 may inhibit the effects of IL-2 on basophils. Neither cytokine exerted any effect on basophil histamine release induced by the calcium ionophore A23187, nor did ranitidine cause any effects on histamine release induced by any of the stimulants. Thus, human basophil reactivity can be affected by IL-2 and by IL-4. The role that these two cytokines play in basophil function in vivo is likely to be complex.
Chromosomal loss and deletion are the most common mechanisms for loss of heterozygosity from chromosomes 5 and 7 in malignant myeloid disorders
Authors: Neuman WL , Rubin CM , Rios RB , Larson RA , Le Beau MM , Rowley JD , Vardiman JW , Schwartz JL , Farber RA 
Published: October 2019

Abstract
We have examined a population of patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) for loss of heterozygosity of polymorphic markers on chromosomes 5 and 7. The rationale for this study was the observation that the majority of patients with therapy- related leukemia (t-AML or t-MDS), resulting from cytotoxic treatment for prior malignancies, have loss of chromosome 5 and/or 7 or deletions involving the long arms of one or both of these chromosomes. This cytogenetic finding suggested that tumor-suppressor genes, important in the development of AML, may be located in these chromosomal regions. We analyzed a total of 60 patients, 43 with primary MDS/AML de novo and 17 with t-MDS/t-AML. Leukemia cells were evaluated for restriction fragment length polymorphisms (RFLPs). Leukemia cell genotypes were compared with lymphoblastoid cell genotypes from the same patients. Two cases of loss of heterozygosity were identified from chromosomes lacking visible deletions: one involving chromosome 5 in a patient with AML de novo who had a visible deletion of 5q at a later stage of the disease, and one involving chromosome 7 in a patient with t-AML. We conclude that allele loss from loci on chromosomes 5 and 7 in MDS/AML, when it occurs, usually results from major deletion or simple chromosome loss, rather than from mitotic recombination or chromosome loss with duplication of the remaining homologue.
Rapid priming of human monocytes by human hematopoietic growth factors: granulocyte-macrophage colony-stimulating factor (CSF), macrophage-CSF, and interleukin-3 selectively enhance superoxide release triggered by receptor-mediated agonists
Authors: Yuo A , Kitagawa S , Motoyoshi K , Azuma E , Saito M , Takaku F 
Published: October 2019

Abstract
The effects of hematopoietic growth factors on human monocyte superoxide (O2-) release were investigated by using purified human monocytes in suspension. Among growth factors studied, granulocyte- macrophage colony-stimulating factor (GM-CSF), macrophage-CSF (M-CSF), and interleukin-3 (IL-3) primed human monocytes and enhanced O2- release stimulated by the receptor-mediated agonists, N-formyl- methionyl-leucyl-phenylalanine (FMLP) and concanavalin A (Con A), but not by phorbol myristate acetate, which bypasses the receptors to stimulate the cells. The optimal priming was obtained by pretreatment of cells with 1 to 5 ng/mL (0.07 to 0.34 nmol/L) GM-CSF, 50 to 100 ng/mL (0.5 to 1.1 nmol/L) M-CSF, or 10 to 20 ng/mL (0.6 to 1.3 nmol/L) IL-3 for 10 minutes at 37 degrees C. Potency of the maximal priming effects on FMLP- or Con A-induced O2- release was GM-CSF greater than M- CSF = IL-3. The combination of the optimal concentrations of any two CSFs resulted in the effect of more potent priming agent alone. Enhancement of O2- release by GM-CSF was observed over the complete range of effective concentrations of FMLP (10(-8) to 10(-6) mol/L). The pretreatment of monocytes with granulocyte-CSF (50 ng/mL), interferon- gamma (1,000 U/mL), or IL-4 (20 ng/mL) for 10 minutes at 37 degrees C had no effect on O2- release stimulated by FMLP or Con A. These findings show that GM-CSF, M-CSF, and IL-3 selectively enhance O2- release in human monocytes triggered by receptor-mediated agonists after short-term preincubation.
Subcellular distribution of the Rap1A protein in human neutrophils: colocalization and cotranslocation with cytochrome b559
Authors: Quinn MT , Mullen ML , Jesaitis AJ , Linner JG 
Published: October 2019

Abstract
Rap1A, a low molecular weight guanosine triphosphate-binding protein (LMWG), has been shown previously by us to be associated with purified cytochrome b from stimulated human neutrophils. In the present studies, we show that Rap1A is also associated with affinity-purified cytochrome b from unstimulated neutrophils and use specific anti-Rap1 peptide antibodies to biochemically and immunocytochemically determine the subcellular distribution of Rap1A in resting and activated human neutrophils. Analysis of the subcellular fractionation of unstimulated cells by Western blotting of isopycnic sucrose density gradient fractions with anti-Rap1 peptide antibodies indicated that Rap1A colocalized with cytochrome b in the plasma membrane as well as in the specific granule membranes and that it was translocated, along with cytochrome b, to the plasma membrane when the cells were stimulated with phorbol myristate acetate (PMA). No evidence for a cytosolic localization of Rap1A was found in our studies; however, if the cells were disrupted by sonication, rather than N2 cavitation, a fraction of the Rap1A was released from the membrane. Electron microscopy of thin sections of cryofixed, molecular-distillation dried neutrophils labeled with anti-Rap1 antibody alone or double-labeled with anti-Rap1 and anti- cytochrome b peptide antibodies confirmed our biochemical localization, and quantitation showed that more than half of the specific granule- associated Rap1A was translocated to the plasma membrane in PMA- stimulated cells. Ultrastructural analysis of neutrophils phagocytosing Staphylococcus aureus also demonstrated the translocation of Rap1A with cytochrome b. Approximately 70% of the total Rap1A labeling was associated with the phagolysosomal membrane, the site of assembly of the superoxide-generating system. The colocalization and cotranslocation of Rap1A with cytochrome b in resting and activated neutrophils is consistent with a functional association of these two molecules in the intact cell and provides further evidence for a role of this LMWG in the structure or function of the neutrophil superoxide- generating system.
Effect of recombinant human macrophage colony-stimulating factor in irradiated murine recipients of T-cell-depleted allogeneic or non- depleted syngeneic bone marrow transplants
Authors: Blazar BR , Aukerman SL , Vallera DA 
Published: October 2019

Abstract
Recombinant macrophage colony-stimulating factor (rM-CSF), which reacts exclusively with cells of monocyte lineage, was evaluated in the murine bone marrow (BM) transplant setting for in vivo effects on recipient survival, hematologic recovery, and engraftment. Two types of fully allogeneic donors were selected based on the expression (BALB/c), or lack of expression (DBA/1), of hybrid hematopoietic histocompatibility (Hh1) antigens. These antigens are established targets for monocyte and/or natural killer (NK) cell-mediated graft rejection. Irradiated C57BL/6 mice were used as recipients for all experiments. Recipients of T-cell-depleted (TCD) BALB/c BM and a 14-day continuous subcutaneous infusion of 16.8 micrograms/d rM-CSF (n = 30) showed a significant decrease in donor cell engraftment as compared with recipients of donor BM administered pumps delivering saline. These mice administered rM-CSF also displayed significantly reduced levels of circulating leukocytes (predominantly lymphocytes) on day 14 posttransplant (compared with saline controls). Neither engraftment effects nor leukocyte effects were observed when C57BL/6 recipients were administered Hh1 nonexpressing TCD DBA/1 BM cells (n = 30), suggesting that the monocyte/macrophage population is important in long-term alloengraftment in certain donor-recipient strain combinations in which donor Hh1 antigens can serve as target antigens for host effector cells, but are not important in strain combinations in which they are not recognized. Circulating tumor necrosis factor alpha (TNF alpha) levels measured at two time periods during rM-CSF infusion were not elevated. Thus, the reduction in alloengraftment is not likely to be directly related to TNF alpha. However, in vivo elimination of NK cells in the BALB/c into C57BL/6 model prevented the impairment of engraftment mediated by rM-CSF. Thus, rM-CSF-mediated inhibition of alloengraftment is contingent on the presence of host NK cells with antidonor reactivity. Survival was unaffected when rM-CSF was administered in either allogeneic BM transplant model, but was significantly reduced when rM-CSF was administered to C57BL/6 recipients of syngeneic BM transplants. These data are the first analyzing the effects of rM-CSF in murine allogeneic BM transplantation and extend our previous studies using the BALB/c into C57BL/6 model in which in vivo infusions of recombinant granulocyte-macrophage CSF, but not recombinant granulocyte-CSF, lead to decreases in alloengraftment. These data show that rM-CSF-induced stimulation of monocytes may increase BM graft rejection in instances in which NK cells are involved in the rejection process. These data may have future clinical implications for the use of rM-CSF in allogeneic BM transplantation.
Detection of minimal residual disease by polymerase chain reaction in Philadelphia chromosome-positive chronic myelogenous leukemia following interferon therapy
Authors: Lee MS , Kantarjian H , Talpaz M , Freireich EJ , Deisseroth A , Trujillo JM , Stass SA 
Published: October 2019

Abstract
The significance of the polymerase chain reaction (PCR) in the detection of minimal residual disease in Philadelphia chromosome (Ph′)- positive chronic myelogenous leukemia (CML) following interferon therapy was investigated. Forty remission blood samples obtained at various remission time points from 29 patients in complete cytogenetic remission were analyzed. All 40 samples showed minimal residual Ph′- positive cells by PCR: 22 in remission for less than 12 months, 12 in remission for 12 to 24 months, four in remission for 25 to 60 months, and two in remission for more than 60 months. Of these 29 patients, seven relapsed at 4, 6, 9, 14, 17, 19, and 50 months after their first PCR-positivity during remission. One developed extramedullary myelopoiesis at 49 months after PCR-positivity. The remaining 21 patients remained in complete hematologic and cytogenetic remission with median follow-up of 13 months (range, 4 to 36 months) after PCR analysis. These findings indicate that PCR-positivity is not associated with immediate disease recurrence. Long-term follow-up is essential to determine the relevance of PCR-positivity, since late recurrence is observed in our study.
Multilineage phenotypes of interleukin-3-dependent progenitor cells
Authors: Ford AM , Healy LE , Bennett CA , Navarro E , Spooncer E , Greaves MF 
Published: October 2019

Abstract
Interleukin-3 (IL-3)-dependent murine FDCP-mix cells have multilineage differentiation capacity; they are nonleukemic, have a normal karyotype, and are nonimmortalized. These cells coexpress on their cell surface the “early” B-lineage marker B220/CD45R and the myeloid marker Mac-1/iC3b receptor (CR3), transcribe germline T-cell receptor gamma genes, and express the macrophage lineage growth factor receptor gene c- fms as a predominant 8.4-kb transcript. They do not detectably express at the stable mRNA or protein level other lymphoid precursor cell genes including CD2, TdT, lambda 5, and BP1. Induction of granulocyte/macrophage differentiation in these cells closes down expression of the lymphoid genes and activates stable expression of genes specific to the myeloid lineage, including myeloperoxidase. Expression of the c-fms gene at the mRNA level is upregulated and the dominant stable transcript is now in the 4.1-kb form typical of the macrophage lineage. These data provide a plausible explanation for the coexpression of lymphoid and myeloid lineage markers on human leukemic cells of stem cell or progenitor cell origin and have implications for the programming of lineage potential in normal multipotential hematopoiteic progenitor cells.
Impaired fetal erythrocytes' filterability: relationship with cell size, membrane fluidity, and membrane lipid composition
Authors: Colin FC , Gallois Y , Rapin D , Meskar A , Chabaud JJ , Vicariot M , Menez JF 
Published: October 2019

Abstract
The lipid composition of erythrocytes (red blood cells [RBCs]) plays a significant role in determining certain membrane biophysical properties. We have found that fetal RBCs showed a dramatically low filterability compared with adult RBCs and questioned whether this could be a consequence of their membrane lipid composition. We therefore studied fetal RBCs at two different gestational ages, neonatal RBCs and adult RBCs. Biophysical parameters were studied using two different techniques, filterability and membrane fluidity. The latter was measured by fluorescence polarization using three different probes. The membrane lipid composition was examined by measuring cholesterol and phospholipids. After extraction of the phospholipids, followed by high performance thin-layer chromatography, the fatty acids in the phospholipid subfractions were analyzed by gas-liquid chromatography. The fetal RBCs' filterability was found to be correlated with both the larger size and the higher hemoglobin content of the cells, but there was no correlation between RBC filterability and fluidity or membrane lipid composition. In adult RBCs, compared with neonatal RBCs, the slight increase of unsaturated fatty acids in phosphatidylcholine and phosphatidylethanolamine should have increased the membrane fluidity. However, in RBCs, no change was observed in the fluidity parameters measured by fluorescence polarization.
Red blood cell changes during the evolution of the sickle cell painful crisis
Authors: Ballas SK , Smith ED 
Published: October 2019

Abstract
A longitudinal study of the red blood cell (RBC) deformability, percent of dense erythrocytes, and hematologic parameters has been conducted during 117 painful crises affecting 36 patients with sickle cell anemia between January, 1985 and December, 1990. RBC deformability was determined by osmotic gradient ektacytometry and the percentage of dense cells was quantitated by centrifugation on a discontinuous Stractan density gradient. The data indicate that the painful crisis is a process that follows a bimodal form of evolution. The first phase of the painful crisis is characterized by increase in the severity of pain, increase in the number of dense cells, and a decrease in RBC deformability. In some patients the changes in dense cells and RBC deformability are evident 1 to 3 days before the onset of pain. In addition, the hemoglobin level decreases and the reticulocyte count increases during this initial phase. The second phase of the crisis is characterized by reduction in pain intensity, decrease in the number of dense cells, and increase in RBC deformability to values higher than those seen in the steady state. Moreover, the improvement in RBC deformability and the decrease in the number of dense cells at the end of a crisis seem to constitute new risk factors that may incite a recurrence of the crisis within 1 month in about 50% of painful episodes. The pathophysiologic events responsible for this bimodal behavior of RBCs during painful episodes may represent the appearance of factors that induce (1) preferential trapping of deformable cells in the microcirculation during the first phase of the crisis, followed by a decrease of dense cells and the appearance of new deformable RBCs released from the bone marrow during the second phase of the crisis; or (2) variable sickling of all circulating RBCs during the first phase followed by disappearance of dense RBCs and their replenishment by deformable cells during the second phase.
Regulatory effects of gallium on transferrin-independent iron uptake by human leukemic HL60 cells
Authors: Chitambar CR , Sax D 
Published: October 2019

Abstract
Gallium, a pharmacologically important metal, resembles iron with respect to transferrin (Tf) binding and Tf receptor-mediated cellular uptake. In the present study, we examined the effect of gallium on Tf- independent iron uptake by HL60 cells. In contrast to the inhibitory effect of Tf-gallium on Tf-iron uptake, gallium nitrate, in a time-, temperature-, and concentration-dependent manner, stimulated Tf- independent uptake of iron-nitrilotriacetic acid (Fe-NTA). Preexposure of cells to gallium followed by removal of gallium also resulted in sustained stimulation of iron uptake. The anti-Tf receptor monoclonal antibody 42/6 blocked Tf-iron uptake, but had no effect on gallium- induced stimulation of Tf-independent iron uptake. Gallium increased the number of cell membrane iron-binding sites, without a change in their affinity for iron. Ferric chloride stimulated Tf-independent gallium uptake. Although gallium nitrate inhibited cell growth in Tf- free medium, cellular proliferation was restored by Fe-NTA. Gallium and iron appear to share the same Tf-independent cellular uptake system in HL60 cells. Exposure of cells to gallium results in the activation of cell membrane non-Tf iron carriers that may play a role in overcoming the Tf-independent growth-inhibitory effects of gallium.
Use of alpha interferon for the treatment of relapse of chronic myelogenous leukemia in chronic phase after allogeneic bone marrow transplantation
Authors: Higano CS , Raskind WH , Singer JW 
Published: October 2019

Abstract
Eighteen patients with relapse of chronic myelogenous leukemia (CML) after allogeneic bone marrow transplantation (BMT) were treated with recombinant human alpha 2a interferon (IFN). Relapse was defined as greater than 90% metaphases containing the Philadelphia chromosome (Ph) and hematologic abnormalities consistent with chronic-phase (CP) CML. There were 11 males and seven females, with a median age of 38 years (range, 3 to 55). Three patients relapsed after second BMT. Only one patient had received T-cell-depleted marrow initially. The initial IFN dose of 3 x 10(6) U/m2/d was escalated to the maximum tolerated dose or to a maximum of 6 x 10(6) U/m2/d. IFN controlled the white blood cell (WBC) counts in 14 of 16 patients who had abnormal counts, and in all six patients with an elevated platelet count. Six patients (33%) have had a complete disappearance of the Ph and two have had a partial response (less than 35% Ph+ metaphases). One patient has a decrease in Ph+ metaphases after 9 months of IFN. Five patients had no significant cytogenetic response after 9 to 12 months, and four developed clinical accelerated phase or blast crisis after 3 to 6 months on therapy. Of four patients with a sex marker, the Ph- population was of donor origin in three and of host origin in one. Clonal cytogenetic abnormalities other than Ph were present in 13 patients and did not predict for lack of response to IFN. IFN is effective in suppressing the Ph clone in some patients who relapse with CML after allogeneic BMT and controls the blood counts in the majority.
Role of tumor necrosis factor-alpha and its specific 55-Kd and 75-Kd receptors in patients with lymphoproliferative disease of granular lymphocytes
Authors: Zambello R , Trentin L , Bulian P , Cassatella M , Raimondi R , Chisesi T , Agostini C , Semenzato G 
Published: October 2019

Abstract
The role of tumor necrosis factor-alpha (TNF-alpha) in the development of in vitro proliferative and cytotoxic abilities of granular lymphocytes (GL) in patients with lymphoproliferative disease of GL (LDGL) has been investigated. To this aim, taking advantage of the recent generation of specific monoclonal antibodies (MoAbs) reacting with the p55 and p75 TNF receptors (TNF-R) (htr-9 and utr-1 MoAb, respectively), we evaluated the expression and the functional role of each TNF-R in freshly isolated highly purified GL from a series of 10 LDGL patients (six CD3+ T-lineage GL and four CD3- natural killer [NK]- lineage GL). The expression of TNF-alpha transcripts and the release of TNF-alpha in the culture medium at resting conditions and following cell activation were also studied. Our data indicate that at resting conditions both CD3+ and CD3- GL express only the p75 TNF-R. Accordingly, a specific inhibition of phycoerythrin (PE)-conjugated TNF- alpha binding was demonstrated by the anti-p75 TNF-R utr-1 MoAb, but not by the anti-p55 htr-9 MoAb. Following activation with interleukin-2 (IL-2), anti-CD3, or anti-CD16 MoAbs, an increased expression of the p75 TNF-R and a slight induction of the p55 TNF-R was observed. Weak expression of specific TNF-alpha transcripts was detected at resting conditions and on unstimulated cells, whereas both IL-2 or anti-CD3 MoAb induced TNF-alpha mRNA. Under these in vitro conditions, detectable amounts of this cytokine were demonstrated in the culture supernatant of GL. The cytotoxic and proliferating activities mediated by IL-2 or anti-CD3 MoAb were dampened by anti-TNF-alpha antibody, suggesting a role for endogenous TNF-alpha in these functions. Both utr- 1 and htr-9 MoAbs showed a moderate inhibition of proliferative activity, whereas cytotoxicity was not reduced. Taken together, our results suggest that TNF-alpha plays a role in the mechanisms leading to CD3+ and CD3- GL in vitro activation in patients with LDGL.