bluuebunny/crossref_metadata_2025_split huggingface dataset:
Recombinant human granulocyte-macrophage colony-stimulating factor in patients with myelodysplastic syndromes--a phase I/II trial
Authors: Ganser A , Volkers B , Greher J , Ottmann OG , Walther F , Becher R , Bergmann L , Schulz G , Hoelzer D 
Published: October 2019

Abstract
In a phase I/II study, 11 patients with myelodysplastic syndromes (MDS) and severe transfusion-dependent cytopenia were treated with recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) to investigate the effects of rhGM-CSF on normal hematopoiesis and leukemic cells. The treatment schedule included dose escalation from 15 micrograms/m2 to 150 micrograms/m2 administered by continuous intravenous (IV) infusion for seven to 14 days and was repeated after a two-week treatment-free interval. The blood leukocyte counts increased dose dependently by 130% to 1,800% in ten patients; a rise of monocytes and eosinophils occurred in seven and six patients, respectively. No sustained increase in reticulocytes or platelets was observed. Lymphocyte counts increased in all patients affecting both T- helper and T-suppressor cells; however, the lymphocytes were not activated as analyzed by the expression of the interleukin-2 receptor. In four of the patients, all with greater than 14% blast cells in the bone marrow, the percentage of bone marrow blast cells increased during treatment with rhGM-CSF. Cytogenetic data indicated induction of both proliferation and differentiation of the leukemic clones by rhGM-CSF. Toxic side effects were minor with slight fever, phlebitis at the infusion site, and bone pain in the minority of patients. In conclusion, rhGM-CSF effectively stimulates hematopoiesis in vivo in patients with myelodysplastic syndromes. However, as the leukemic cell population can be stimulated in patients with a higher initial blast cell count, the combination of rhGM-CSF with other differentiation- inducing or cytotoxic agents has to be considered.
Successful treatment of refractory Hodgkin's disease by high-dose combination chemotherapy and autologous bone marrow transplantation
Authors: Gribben JG , Linch DC , Singer CR , McMillan AK , Jarrett M , Goldstone AH 
Published: October 2019

Abstract
Forty-four patients with refractory Hodgkin's disease were treated with high-dose combination chemotherapy followed by autologous bone marrow rescue. Twenty-two patients (50%) entered complete remission within 6 months of the procedure and four other patients are free of disease progression. Only two patients have subsequently relapsed from complete remission (CR). Bone marrow suppression was the predictable major toxicity of this procedure, and two patients (4.5%) died of sepsis during the aplastic phase. High-dose therapy with autologous bone marrow transplantation (ABMT) appears to be an effective salvage regimen for patients with refractory Hodgkin's disease.
Various human hematopoietic growth factors (interleukin-3, GM-CSF, G- CSF) stimulate clonal growth of nonhematopoietic tumor cells [see comments]
Authors: Berdel WE , Danhauser-Riedl S , Steinhauser G , Winton EF 
Published: October 2019

Abstract
We have studied the effect of recombinant human hematopoietic growth factors (interleukin-3 [rhIL-3], granulocyte-macrophage colony- stimulating factor [rhGM-CSF], and granulocyte CSF [rhG-CSF]) on the clonal growth of human colon adenocarcinoma cell lines HTB-38, CCL 187, and WiDr (CCL 218). The factors stimulated clonal growth of HTB-38 and CCL 187 in a capillary modification of the human tumor clonogenic assay in agar up to twofold. There were dose-response correlations over a range of 1 to 10,000 U/mL for rhIL-3, rhGM-CSF, and rhG-CSF. Incubation with neutralizing monoclonal antibodies abolished the stimulation of clonal growth by rhGM-CSF. The WiDr cell line was nonresponsive to rhIL- 3 and rhGM-CSF. These results represent the first evidence that a variety of hematopoietic growth factors can stimulate the growth of clonogenic cells of some nonhematopoietic malignant cell lines in vitro.
The secretory release reaction initiated by complement proteins C5b-9 occurs without platelet aggregation through glycoprotein IIb-IIIa
Authors: Ando B , Wiedmer T , Sims PJ 
Published: October 2019

Abstract
The secretory and aggregation responses of stirred platelets exposed to complement proteins C5b-9 was investigated. C5b-9 assembly on the platelet surface resulted in the release of dense granule adenosine triphosphate (ATP) accompanied by a decrease in sample turbidity, but no detectable cell lysis. Inhibition of cellular protein kinase C completely blocked the C5b-9 initiated release of ATP, confirming the secretory nature of this response. Addition of fibrinogen (up to 1 mg/mL) had no effect on either the release of ATP or the decreased turbidity observed for C5b-9 cells. Addition of the peptides Arg-Gly- Asp-Ser (RGDS) and fibrinogen gamma-chain carboxyl-terminal (gamma 397- 411) at concentrations sufficient to completely block fibrinogen binding to GP IIb-IIIa had no effect on either C5b-9 induced dense granule secretion or the associated turbidity change. Microscopic examination and electronic particle counting of the stirred platelet suspensions confirmed that no aggregation of C5b-9 platelets occurred even when these cells were stirred in the presence of fibrinogen. The capacity of the C5b-9 proteins to initiate platelet secretion without activation of cell surface glycoprotein (GP) IIb-IIIa suggests a mechanism for intravascular dissemination of activated platelets during complement activation in vivo.
Inhibition of platelet adhesion to fibronectin, fibrinogen, and von Willebrand factor substrates by complex gangliosides
Authors: Santoro SA 
Published: October 2019

Abstract
Gangliosides, which are complex glycosphingolipids containing sialic acid, are found in cell membranes and have been implicated in a variety of cell surface events including cellular adhesion. Complex gangliosides were observed to inhibit the adhesion of thrombin- activated platelets to substrates of fibronectin, von Willebrand factor, and fibrinogen. This adhesion, which is mediated by the glycoprotein IIb-IIIa complex, was differentially inhibited by gangliosides depending on the number of sialic acid residues present within the ganglioside. The observed order of effectiveness was GT1b greater than GD1a greater than GM1 greater than asialo-GM1. Another structurally related glycosphingolipid, globoside, exhibited little inhibitory activity. In contrast to the inhibition of platelet adhesion to von Willebrand factor mediated by the glycoprotein IIb-IIIa complex, gangliosides had no detectable effect on the ristocetin-dependent adhesion of platelets to von Willebrand factor mediated by glycoprotein Ib. These results suggest that the function of the glycoprotein IIb- IIIa complex may be modulated by gangliosides in a manner similar to that previously described for the closely related vitronectin receptor.
Paracrine rather than autocrine regulation of myeloma-cell growth and differentiation by interleukin-6
Authors: Klein B , Zhang XG , Jourdan M , Content J , Houssiau F , Aarden L , Piechaczyk M , Bataille R 
Published: October 2019

Abstract
To explore the mechanisms involved in the pathogenesis of human multiple myeloma (MM), we investigated the potential role of interleukin-6 (IL-6), a B-cell differentiation factor in humans, and a growth factor for rat/mouse heterohybridomas and murine plasmacytomas. Using a heterohybridoma assay, we found that two well-documented human myeloma cell lines, RPMI 8226 and U266, did not secrete IL-6 and did not express RNA messengers for IL-6. Neutralizing antibodies to IL-6 did not inhibit their proliferation, and recombinant IL-6 did not stimulate it. Taken together, these data show that IL-6 is not the autocrine growth factor of these human myeloma cell lines. A high production of IL-6 was found in the bone marrows of patients with fulminating MM, compared with patients with inactive or slightly active MM, or to healthy donors. This IL-6 production was assigned to adherent cells of the bone-marrow environment but not to myeloma cells. A spontaneous proliferation of myeloma cells freshly isolated from patients was observed in short-term cultures. Recombinant IL-6 was able to amplify it two- to threefold. The spontaneous proliferation of the myeloma cells was inhibited by anti-IL-6 antibodies and reinduced by recombinant IL-6. After 2 to 3 weeks of culture, the myeloma-cell proliferation progressively declined and no IL-6-dependent myeloma cell lines could be obtained despite repeated additions of fresh IL-6 and costimulation with other cytokines such as tumor necrosis factor (TNF)beta, or IL-1 beta. These data demonstrated a paracrine but not autocrine regulation of the growth and differentiation of myeloma cells by IL-6.
Phenotypic analysis of human myeloma cell lines
Authors: Duperray C , Klein B , Durie BG , Zhang X , Jourdan M , Poncelet P , Favier F , Vincent C , Brochier J , Lenoir G 
Published: October 2019

Abstract
Multiple myeloma (MM) is a B-cell malignancy characterized by the accumulation, primarily in bone marrow, of a clone of plasma cells. The nature of the stem cells feeding the tumoral compartment is still unknown. To investigate this special point, we have studied the phenotypes of nine well-known human myeloma cell lines (HMCLs) and compared them with those of normal lymphoblastoid cell lines (LCLs). Twenty-four clusters of differentiation involved in B lymphopoiesis were investigated using a panel of 65 monoclonal antibodies (MoAbs). For each cluster, the percentage of positive cells and the antigen density were determined, giving rise to a “quantitative phenotype”. We thus classified the HMCLs into two different groups: those with cytoplasmic mu chains (c mu+) and those without (c mu-). In the first (c mu+) group, comprising seven cell lines, the HMCLs had a phenotype of pre-B/B cells close to that of Burkitt's lymphoma cell lines. They expressed low densities of surface mu chains, without detectable cytoplasmic or surface light chains. Three of them were infected with the Epstein Barr virus (EBV). These c mu+ HMCLs bore most of the B-cell antigens except CD23. They expressed the CALLA antigen (CD10) and lacked the plasma-cell antigen PCA1. In contrast, LCLs expressed surface light chains, high densities of CD23, low densities of PCA1 antigen, and no CD10 antigen. The c mu- HMCLs had a plasma-cell phenotype, lacking most of the B-cell antigens and expressing high densities of PCA1 antigen.(ABSTRACT TRUNCATED AT 250 WORDS)
Involvement of guanine nucleotide binding proteins in neutrophil activation and priming by GM-CSF
Authors: McColl SR , Kreis C , DiPersio JF , Borgeat P , Naccache PH 
Published: October 2019

Abstract
Pre-incubation of human neutrophils with pertussis toxin significantly inhibited the neutrophil-directed biologic actions of granulocyte- macrophage colony-stimulating factor (GM-CSF) in three separate assays: the induction of c-fos mRNA, the enhancement of both platelet- activating factor-induced mobilization of intracellular calcium, and stimulation of leukotriene synthesis by the calcium ionophore A23187. Cholera toxin did not have an effect on the latter two assays. Pre- treatment of human neutrophils with pertussis toxin did not affect the binding of GM-CSF to its surface receptor. These results provide the first evidence that a pertussis toxin substrate plays an important mediatory role in the mechanism of action of GM-CSF.
Viscoelastic properties of red cell membrane in hereditary elliptocytosis
Authors: Chabanel A , Sung KL , Rapiejko J , Prchal JT , Palek J , Liu SC , Chien S 
Published: October 2019

Abstract
The viscoelastic properties of the RBC membrane are in part determined by a submembrane network of proteins consisting of spectrin alpha beta heterodimers (SpD) assembled head-to-head to form spectrin tetramers (SpT) and spectrin oligomers (SpO). SpT, in turn, are connected into a two-dimensional network by the linkage of distal ends of SpT to protein 4.1 and actin. With the micropipette technique, we determined the membrane viscoelastic properties of RBCs from a subset of patients with hereditary elliptocytosis (HE); these RBCs exhibit membrane skeletal instability, defective SpD self-association, and a molecular defect in the alpha I domain of spectrin, which is involved in the SpD-SpD contact (HE SpD alpha-SpD). The elastic modulus and viscosity of the membrane were significantly higher for the HE RBCs than for the control cells. Incubation of normal cells with N-ethyl-maleimide (NEM) produced a similar defective SpD self-association and a significant increase in the viscoelastic parameters of the membrane. The data provide evidence that the mode of assembly of membrane spectrin in the cytoskeletal protein network plays a major role in determining the rheologic behavior of erythrocyte membrane.
PADGEM protein in human erythroleukemia cells
Authors: Yeo E , Furie BC , Furie B 
Published: October 2019

Abstract
PADGEM protein, a platelet alpha granule membrane glycoprotein with a molecular weight of 140,000, is translocated to the plasma membrane during granule secretion and platelet activation. PADGEM protein is expressed on the surface of activated platelets but not on the surface of resting platelets. Human erythroleukemia (HEL) cells contain platelet alpha granule-like organelles, alpha granule proteins, and express platelet membrane glycoproteins GPIIb/IIIa and GPIb. We demonstrate that HEL cells express a protein that has a molecular weight identical to that of PADGEM and binds to anti-PADGEM antibodies. The exposure of HEL cells in culture to dimethylsulfoxide (DMSO) increased the number of cells expressing PADGEM. Fluorescence activated flow cytometric analysis demonstrated an increase in mean surface expression of PADGEM in DMSO-exposed cells compared to noninduced cells. Total cell content of PADGEM was increased 5.3-fold after DMSO exposure, as determined by radioimmunoassay. Direct binding experiments with the monoclonal anti-PADGEM antibody KC4 demonstrated specific, saturable, and time-dependent interaction of KC4 with HEL cells. A Kd of 7 nM was estimated. There were 14,000 surface binding sites per cell in noninduced cells and 24,000 surface binding sites per cell in DMSO- induced HEL cells. Surface expression of PADGEM protein on HEL cells was not increased with platelet agonists, including thrombin, epinephrine, ADP, nor cytokines, including IL-1, IL-2, tissue necrosis factor. The presence of PADGEM protein in HEL cells should facilitate the elucidation of the function of PADGEM protein.
Procoagulant activity of endotoxin-treated human endothelial cells exposed to native human flowing blood
Authors: Clozel M , Kuhn H , Baumgartner HR 
Published: October 2019

Abstract
It has been reported that cultured endothelial cells become procoagulant when exposed to endotoxin. This prompted us to investigate whether human endothelial cells treated with endotoxin could promote the generation of fibrin when exposed to human flowing blood. For this purpose we used a parallel-plate perfusion chamber in which confluent cultured endothelial cells from human umbilical veins were exposed for five minutes to directly drawn human nonanticoagulated blood, at wall shear rates of 100, 650, and 2600 sec-1. Fibrin deposition was assessed by morphometry. No fibrin deposition occurred on normal endothelial cells. In contrast, cells incubated with endotoxin for 4 or 18 hours induced fibrin deposition, but only at a shear rate of 100 sec-1. Since some extracellular matrix was exposed between the cells, we investigated whether extracellular matrix played a role in fibrin formation. When the endothelial cells incubated or not with endotoxin were removed by EDTA, the exposed extracellular matrix perfused with blood at 100 sec-1 supported platelet and fibrin deposition in both cases. This suggests that the effect of endotoxin on endothelial cells was not due to extracellular matrix alteration but only to cellular activation or secretion of procoagulant substances. We conclude that human endothelial cells treated with endotoxin can trigger fibrin formation and deposition at their surface when exposed to flowing blood at low shear rate.
Involvement of bcl-2 gene in Japanese follicular lymphoma
Authors: Amakawa R , Fukuhara S , Ohno H , Doi S , Oguma S , Tanabe S , Yamabe H , Edamura S , Tomono N , Nasu K 
Published: October 2019

Abstract
A t(14;18) (q32;q21) chromosome translocation is closely associated with the follicular lymphoma, which is prevalent in the United States, and the t(14;18) causes the juxtaposition of a bcl-2 gene on chromosome 18 with an immunoglobulin heavy-chain gene locus on chromosome 14. Genomic DNAs from 30 Japanese patients with follicular lymphoma were examined for the molecular features by Southern blot hybridization. Using probe b for the major breakpoint cluster region of a bcl-2 gene, the rearrangements were detected in eight patients. Six of the eight patients had breakpoints located within the major breakpoint region, while two had breakpoints outside this cluster region but within the region of the 7.5-kb SstI fragment containing the probe b sequence. In two patients, pFL-2 probe detected the bcl-2 gene rearrangements that occurred near or within the minor breakpoint cluster region. These ten patients had a rearranged JH-containing fragment that migrated with the rearranged bcl-2 fragment. In the other 20 patients, these two chromosome 18-specific DNA probes did not detect the bcl-2 rearrangements. Compared with studies performed in the United States, the statistical analysis indicates a significant difference in frequency of the bcl-2 gene rearrangements near or within the major breakpoint cluster region (P = 0.0027) and the minor breakpoint cluster region (P = 0.029). However, the distribution difference of these events was not significant.
The enhancer-like sequence 3′ to the A gamma gene is polymorphic in human populations
Authors: Bouhassira EE , Krishnamoorthy R , Ragusa A , Driscoll C , Labie D , Nagel RL 
Published: October 2019

Abstract
Cloning and sequencing of the enhancer 3′ of the A gamma globin gene of a particularly low G gamma and HbF sickle cell anemia (SCA) patient unexpectedly revealed three base changes (T----C, C----A, and A----G at sites +2285, +2460, and +2676) previously associated with the Seattle- type HPFH, thus leading the authors to suspect that the three mutations were polymorphic. The determination of the incidence of the mutations among various ethnic groups allowed the authors to conclude that this is a widely spread polymorphism, thus excluding any role of these base changes in the determination of the hereditary persistence of fetal hemoglobin (HPFH) phenotype. The origin of these three mutations is not clear because they appear linked, and the same bases (C, A, G) are found in homologous position in the 3′ of the normal G gamma gene. As C, A, G at positions +2285, +2460, and +2676 are found with a 100% frequency in African SS patients and presumably among normal Africans (to explain the extremely high frequency among normal American blacks), it is likely that this was the sequence preceding the division of races. The presence of T, C, and A at the same positions apparently occurred after the divergence between blacks and the other races, that is, within the last 1 million years.
High-level secretion of tumor necrosis factor-alpha contributes to hematopoietic failure in hairy cell leukemia [see comments]
Authors: Lindemann A , Ludwig WD , Oster W , Mertelsmann R , Herrmann F 
Published: October 2019

Abstract
Hairy cell leukemia (HCL) is frequently associated with severe pancytopenia. The authors detected high levels of tumor necrosis factor (TNF)-alpha in the bone marrow serum of patients with HCL and found anti-TNF-alpha neutralizing monoclonal antibodies (MoAbs) to be able to enhance hematopoiesis of HCL patients in in vitro colony assays. As potent producers of TNF-alpha, hairy cells could be identified, thus implicating the malignant population in the pathogenesis of hematopoietic failure due to inappropriate secretion of this cytokine.
Molecular characterization of a high A2 beta thalassemia by direct sequencing of single strand enriched amplified genomic DNA
Authors: Thein SL , Hesketh C , Brown JM , Anstey AV , Weatherall DJ 
Published: October 2019

Abstract
Two families, one of Anglo-Saxon-Dutch descent, and the other, West Indian black, have an atypical beta thalassemia characterized by an unusually high level of Hb A2 in the heterozygous state. Restriction endonuclease mapping showed a deletion of about 1.35 kilobase (kb) in the 5′ region of the beta globin gene. Direct sequencing of a specific region of genomic DNA amplified by a new modification of the polymerase chain reaction defined the deletion to be 1,393 base pairs (bp) and to be the same in both families. The deletion extends from 485 bp 5′ to the mRNA CAP site to the middle of the second intervening sequence. This deletion, together with three others previously described that remove the 5′ end of the beta gene but leave the delta gene intact, are all associated with unusually high levels of Hb A2 in the heterozygous state.
Interleukin-1 accelerates murine granulocyte recovery following treatment with cyclophosphamide
Authors: Stork L , Barczuk L , Kissinger M , Robinson W 
Published: October 2019

Abstract
This study investigated the effects of recombinant human interleukin-1 (rhIL-1 alpha) on granulocyte recovery following treatment of mice with cyclophosphamide (CPM). CF1 mice were injected with 0.5 microgram rhIL- 1 alpha or heat-inactivated rhIL-1 alpha according to five different regimens, before and/or following 200 mg/kg CPM. Significant neutrophilia initially developed in treatment mice of all five regimens and accelerated granulocyte recovery occurred in treatment mice of four IL-1 regimens. Significant elevations in serum colony stimulating activity (CSA) occurred in treatment mice at a number of time points studied. In addition, marked increases in the percentage of maturing granulocyte precursors and in the proportion of cells cycling in S and G2/M were observed in treatment marrow throughout the IL-1 regimen. Before granulocyte recovery, premature nuclear segmentation was noted in metamyelocytes of treatment marrow. Concomitant with granulocyte recovery, treatment marrow was significantly more cellular and contained more total CFU-GM, more CFU-GM in S phase, more cells in S and G2/M, and more mitotic figures than control marrow. Splenic myelopoiesis was also enhanced in treatment mice. These data suggest that IL-1 significantly hastens granulocyte recovery following treatment with CPM by enhancing both proliferation and maturation of myeloid precursors.
Expression of human interleukin-3 (multi-CSF) is restricted to human lymphocytes and T-cell tumor lines
Authors: Niemeyer CM , Sieff CA , Mathey-Prevot B , Wimperis JZ , Bierer BE , Clark SC , Nathan DG 
Published: October 2019

Abstract
While the cellular sources for granulocyte-macrophage colony- stimulating factor (GM-CSF) are known to be widely distributed among several cell types, interleukin-3 (IL-3) gene expression has been demonstrated in only certain T-cell clones and in blood mononuclear cells stimulated with phytohemagglutinin (PHA) and phorbol-myristate- acetate (PMA). To determine which blood cells were responsible for this expression, we fractionated PHA/PMA-stimulated mononuclear cells and identified T lymphocytes as the source of IL-3 mRNA. Low-level IL-3 expression was detected as well in several stimulated human T-cell lines. Hematopoietic stromal cells such as fibroblasts and endothelial cells could not be induced to express IL-3 mRNA. The kinetics of IL-3 mRNA induction in mononuclear cells and lymphocytes stimulated with PHA/PMA or anti-CD3 monoclonal antibody (MoAb) and interleukin-1 (IL-1) were similar to those observed for GM-CSF expression.