bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abnormal peroxidase-positive granules in “specific granule” deficiency
Authors: Parmley RT , Gilbert CS , Boxer LA 
Published: October 2019

Abstract
“Specific granule” deficiency (SGD) has been previously associated with lactoferrin deficiency. The antimicrobial peptides termed defensins, comprising 30% of normal primary granule proteins, have also been shown to be markedly deficient in SGD. The present study was undertaken to correlate these findings with ultrastructural morphometric analysis and peroxidase cytochemistry. Peroxidase-positive, rim-stained, large, defensin-rich dense granules, previously described as a subpopulation of azurophil or primary granules in normal neutrophils, were markedly decreased in a patient with SGD. Morphometric studies of peroxidase- positive granules indicated an average peroxidase-positive granule area (all profiles) in the patient of 0.019 +/- 0.017 micron 2 (mean +/- SD, n = 941) compared to control values from normal neutrophils of two volunteers of 0.049 +/- 0.033 micron 2 (n = 896) and 0.050 +/- 0.039 micron 2 (n = 873) (P less than 0.001 between patient and control samples). Granule histograms showed a single peak of small peroxidase- positive granules, whereas control samples contained more prominent subpopulations of larger peroxidase-positive granules. The total number of peroxidase-positive granules per 100 micron 2 of cytoplasm in the patient was 255 +/- 124 (mean +/- SD, n = 15 cell profiles), which was similar to control values of 266 +/- 63 and 212 +/- 109. Thus, the defensin deficiency in SGD is associated with a decrease in size rather than number of peroxidase-positive granules; suggesting that defensins contribute to normal peroxidase-positive granule size and that SGD is a more global granule deficiency than originally thought.(ABSTRACT TRUNCATED AT 250 WORDS)
In vivo administration of recombinant human granulocyte/macrophage colony-stimulating factor in acute lymphoblastic leukemia patients receiving purged autografts [see comments]
Authors: Blazar BR , Kersey JH , McGlave PB , Vallera DA , Lasky LC , Haake RJ , Bostrom B , Weisdorf DR , Epstein C , Ramsay NK 
Published: October 2019

Abstract
Based on the recent reports that recombinant human granulocyte/macrophage colony-stimulating factor (rhGM-CSF) accelerates the rate of engraftment in a variety of autologous bone marrow transplantation settings, we have investigated its effects on hematopoietic recovery of patients with acute lymphoblastic leukemia (ALL) undergoing autologous bone marrow transplantation. Our studies, which involved 25 autologous ALL recipients who received rhGM-CSF and 27 controls similar for disease status (remission or relapse) and disease type (B- or T-lineage) differed from previous studies in one important aspect: the bone marrows were purged with 4- hydroperoxcyclophosphamide (4HC) and anti-T or anti-B-cell lineage- specific antibodies before transplantation. Such treatments frequently lead to a reduction in the CFU-GM content of the transplanted marrow. Eighteen of 25 patients completed the entire course of rhGM-CSF. Of the 16 patients who received greater than or equal to 64 micrograms/M2/d for at least eight days, there were five patients who had an apparent rhGM-CSF response and 11 patients who did not respond. Of the parameters analyzed, only the number of CFU-GM progenitor cells infused per kilogram was significantly associated with an rhGM-CSF response. All patients receiving greater than or equal to 1.2 x 10(4) CFU-GM progenitors per kilogram achieved an absolute neutrophil count (ANC) greater than or equal to 1,000/microL by day 21 and had a greater than 50% decrement in ANC within 48 to 72 hours of discontinuing rhGM-CSF, as contrasted to none of the patients receiving less than or equal to 7.2 x 10(3) CFU-GM progenitors per kilogram.(ABSTRACT TRUNCATED AT 250 WORDS)
Nonhematopoietic tumor cells express functional GM-CSF receptors
Authors: Baldwin GC , Gasson JC , Kaufman SE , Quan SG , Williams RE , Avalos BR , Gazdar AF , Golde DW , DiPersio JF 
Published: October 2019

Abstract
Human granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulates the colony growth of myeloid progenitors in semisolid media, and enhances the function of mature effector cells, including neutrophils, monocytes, and eosinophils. Small cell carcinoma lines (SCCL) have properties of amine precursor uptake and decarboxylation (APUD) cells and express high levels of the enzyme, L-aromatic amino acid decarboxylase. We looked for possible expression of GM-CSF receptors on nonhematopoietic cells and found specific high-affinity binding of human GM-CSF to SCCL and to the SV40-transformed African green monkey kidney cell line, COS. The small cell carcinoma lines responded to GM-CSF with enhanced proliferation, and both small cells and COS cells were found to express authentic 84,000 dalton GM-CSF receptor protein. These findings indicate that nonhematopoietic cells can bind and respond to GM-CSF, suggesting additional biological activities as well as the possibility of tumor responses when GM-CSF is used therapeutically in humans. Since preliminary clinical trials using CSFs as adjunctive treatment in patients with solid tumors are underway, it will be important to consider the possible responsiveness of nonhematopoietic tumor cells to CSFs.
Candidacidal activity of the neutrophil myeloperoxidase system can be protected from excess hydrogen peroxide by the presence of ammonium ion
Authors: Beilke MA , Collins-Lech C , Sohnle PG 
Published: October 2019

Abstract
Excessive concentrations of hydrogen peroxide inhibit the neutrophil myeloperoxidase system, presumably by inactivating the hypochlorous acid produced by this system. Ammonium ion generated by neutrophils and other cells can react with hypochlorous acid to produce monochloramine, an oxidant with good microbicidal activity, but relative resistance to inactivation by other compounds. In an assay based on the oxidation of 5-thio-2-nitrobenzoic acid, hydrogen peroxide reacted more readily with sodium hypochlorite (used as a source of hypochlorous acid) than with monochloramine. Also, in this assay Candida albicans yeast inactivated the oxidant activity of hypochlorous acid more completely than they did that of monochloramine. The killing of Candida by sodium hypochlorite, as determined in a standard colony count microbicidal assay, was inhibited by equimolar and greater concentrations of hydrogen peroxide; killing of this organism by monochloramine was not affected by a tenfold excess concentration of hydrogen peroxide. In microbicidal assays using 4 mU of myeloperoxidase and optimal or excessive concentrations of hydrogen peroxide or glucose and glucose oxidase to generate hydrogen peroxide, the excessive concentrations inhibited killing of Candida, but not Staphylococcus aureus. The inhibition of Candida killing could be reversed by addition of ammonium ion to convert hypochlorous acid to monochloramine. These results indicate that for certain organisms such as C albicans, conversion of hypochlorous acid to monochloramine by reactions with ammonium ion may extend the range of hydrogen peroxide concentrations under which killing by the myeloperoxidase system can occur by protecting the necessary microbicidal oxidants from inactivation by excess hydrogen peroxide.
Studies on the myeloid synergistic factor from 5637: comparison with interleukin-1 alpha
Authors: McNiece IK , Kriegler AB , Quesenberry PJ 
Published: October 2019

Abstract
A synergistic factor that is produced by the human bladder carcinoma cell line 5637 (SF-1) stimulates primitive bone marrow progenitor cells, termed high proliferative-potential colony-forming cells (HPP- CFC), in the presence of an optimal dose of macrophage colony stimulating factor (CSF-1). Recent reports have demonstrated that interleukin-1 alpha (IL-1) is identical to hemopoietin 1 and have suggested that IL-1 is the synergistic factor present in 5637 conditioned medium (cm). We have compared the ability of recombinant human IL-1 alpha and partially purified preparations of SF-1 to synergize with optimal doses of CSF-1 to stimulate HPP-CFC. In all experiments performed the numbers of HPP-CFC colonies formed with IL-1 were significantly less than with SF-1. Replating experiments demonstrated that SF-1 plus CSF-1 generated HPP-CFC (responsive to IL-3 plus CSF-1); however, IL-1 plus CSF-1 resulted in no generation of HPP- CFC. Multiple factor combinations of IL-1 and SF-1 with G-CSF, GM-CSF, and CSF-1 also resulted in less HPP-CFC colony formation in cultures containing IL-1 compared with SF-1. Incubation of SF-1 with an antibody to IL-6 had no effect on HPP-CFC colony formation and IL-6 did not synergize with IL-1 plus CSF-1 or SF-1 plus CSF-1. These data suggest the presence of a factor in 5637 cm, which is distinct from G-CSF, GM- CSF, and IL-6, which synergizes with IL-1 to produce the SF-1 effect.
Characterization of the potentiation effect of activin on human erythroid colony formation in vitro
Authors: Yu J , Shao L , Vaughan J , Vale W , Yu AL 
Published: October 2019

Abstract
Activin, also named FSH-releasing protein, was previously shown to induce hemoglobin accumulation in K562 cells and potentiate the proliferation and differentiation of CFU-E in human bone marrow cultures. Present studies indicate that the potentiation effect of activin is lineage specific. In addition to CFU-E, activin caused an increase in the colony formation of BFU-E from either bone marrow or peripheral blood. It had little effect on the colony formation of CFU- GM and the mixed colonies from CFU-GEMM. In serum-depleted culture, the effect of activin was shown to be dose-dependent with doses effective at picomolar concentrations. The potentiation effect of activin was exerted indirectly through mediation of both monocytes and T lymphocytes. Activin was also found to increase specifically the proportion of DNA-synthesizing erythroid progenitors from both bone marrow and peripheral blood. It had little effect on DNA synthesis in CFU-GM and in mitogen-stimulated lymphocytes. Addition of the monocytes or T lymphocytes to their respective depleted subpopulations of mononuclear cells reconstituted the enhancing effect of activin on the colony formation and DNA synthesis of erythroid progenitors. These results strongly suggest a specific role of activin in potentiating the proliferation and differentiation of erythroid progenitors in vitro.
Role of von Willebrand factor in mediating platelet-vessel wall interaction at low shear rate; the importance of perfusion conditions
Authors: Badimon L , Badimon JJ , Turitto VT , Fuster V 
Published: October 2019

Abstract
We have previously observed that von Willebrand factor (vWF) plays an important role in platelet deposition on subendothelium at low values of wall shear rate (200 to 400 seconds-1). In the present study, we have investigated the mechanism responsible for such a defect in platelet deposition at low shear rates in the absence of vWF. Blood from both normal and von Willebrand's disease (vWD) animals was exposed to de-endothelialized aorta from normal pigs for a range of shear rates (200 to 3,000 seconds-1) and exposure times (three to 30 minutes) in a tubular perfusion chamber. Variations in the method of inhibiting coagulation (none, heparin, citrate, hirudin, and EDTA) and of perfusing blood (in vitro v ex vivo) were compared by determining the influence of wall shear rate and vWF on the deposition of 111In-labeled platelets on subendothelium. Whereas platelet deposition was reduced in the absence of vWF for all experimental variations at high shear rates (greater than 850 seconds-1), a defect was observed at low shear rates only when heparinized blood was exposed by means of an ex vivo perfusion system. Maximum sensitivity of the measurement occurs under ex vivo perfusion conditions due to the reduced ability of platelets to deposit in normal blood when recirculated in vitro. Our results indicate that vWF mediates platelet-vessel wall interaction even at low shear rates and that such effect can only be observed in systems where platelet function is minimally affected by the experimental conditions.
Thrombospondin interaction with plasminogen. Evidence for binding to a specific region of the kringle structure of plasminogen
Authors: DePoli P , Bacon-Baguley T , Kendra-Franczak S , Cederholm MT , Walz DA 
Published: October 2019

Abstract
Platelet thrombospondin interacts with plasminogen in a specific and saturable manner. Thrombospondin was found to specifically bind to plasminogen and the nonenzyme chain of plasmin. Preincubation of 125I- labeled thrombospondin with 30 mmol/L lysine was without effect in the binding of thrombospondin to immobilized plasminogen; preincubation of 125I-labeled plasminogen with 30 mmol/L lysine, on the other hand, significantly reduced the binding of plasminogen to immobilized thrombospondin, suggesting that the interaction of thrombospondin with plasminogen is not the direct result of the lysine binding sites of plasminogen. Arginine and benzamidine, ligands known to specifically bind to the kringle 5 domain of plasminogen, blocked the binding of thrombospondin to plasminogen. Limited elastase proteolysis of plasminogen and plasmin resulted in the generation of two distinct thrombospondin binding domains, one of which was retained on lysine- agarose. The isolation and amino-terminal analysis of these domains following elastase proteolysis of plasminogen identified them, respectively, as a domain containing kringle structures 4 and 5 and plasmin and the other domain consisting of kringle 5-plasmin. A 16- residue synthetic peptide, which represents the amino acids linking kringle 4 to kringle 5 (residues 435–450 of native plasminogen), was without effect in either binding to thrombospondin or blocking the binding of thrombospondin to plasminogen. Plasminogen, therefore, possesses a single thrombospondin interactive site that is independent of, but influenced by, the lysine binding site containing kringle structures and most likely is located within the kringle 5 domain.
Plasminogen activators in dextran sulfate-activated euglobulin fractions: a molecular analysis of factor XII- and prekallikrein- dependent fibrinolysis
Authors: Hauert J , Nicoloso G , Schleuning WD , Bachmann F , Schapira M 
Published: October 2019

Abstract
To elucidate the mechanism by which activation of the contact system of blood coagulation leads to expression of fibrinolytic activity, we have determined the molecular characteristics of the plasminogen activators present in dextran sulfate-treated euglobulin fractions by electrophoretic-zymographic analysis and specific immunoadsorption. In addition to free and protease inhibitor-bound tissue-type plasminogen activator (t-PA), dextran sulfate precipitates of euglobulins contained the complex formed between plasma kallikrein and C1-inhibitor, an indicator of prekallikrein activation. These precipitates also contained substantial fibrinolytic activity related to urinary-type plasminogen activator (u-PA). Autoradiographic analysis was then used to evaluate the cleavage of 125I-single-chain u-PA (prourokinase) in dextran sulfate euglobulins as well as after exposure to kallikrein or beta-factor XIIa. This analysis supported the conclusion that plasma kallikrein-mediated cleavage and activation of single-chain u-PA is the mechanism operative for the development of lytic activity in euglobulin precipitates following activation of the contact system.
Erythropoietin stimulates a rise in intracellular-free calcium concentration in single BFU-E derived erythroblasts at specific stages of differentiation
Authors: Miller BA , Cheung JY , Tillotson DL , Hope SM , Scaduto RC Jr 
Published: October 2019

Abstract
Human cord blood progenitor-derived erythroblasts have recently been shown to respond to erythropoietin (Epo) or granulocyte-macrophage colony-stimulating factor (GM-CSF) with a transient increase in intracellular free calcium concentration [Cac]. However, the importance of [Cac] changes in mediating cell proliferation and/or differentiation is undefined. In the present study, the response of erythroid precursors at different stages of differentiation to Epo was examined. Erythroblasts were derived from adult blood erythroid progenitors (BFU- E) at day 7 or day 10 of culture. [Cac] was measured in individual Fura- 2 loaded cells with fluorescence microscopy coupled digital video imaging. The dynamic range (Rmax/Rmin) of intracellular Fura-2 was similar to that measured in free solution, suggesting insignificant amounts of intracellular Ca insensitive forms of Fura-2. Baseline [Cac] of erythroid cells calculated with an in vitro calibration method was 44 +/- 4 nmol/L and with an in vivo method was 46 +/- 4 nmol/L. Treatment of day 7 BFU-E derived erythroblasts with Epo resulted in no significant increase in [Cac]. In contrast, in more mature erythroblasts (day 10 of culture), Epo stimulated a large increase in [Cac] from 49 +/- 11 nmol/L at baseline to 279 +/- 47 nmol/L. This [Cac] increase occurred in phosphate buffered saline (PBS) containing no added calcium. The increase in [Cac] persisted for 18 minutes and was dose dependent. Day 7 and day 10 control cells treated with either insulin or media showed no significant change in [Cac] during 18 minutes of observation. Our data demonstrate that early (day 7) and late (day 10) erythroblasts display different responses to Epo, at least in terms of intracellular Ca++ fluxes. The differential [Cac] response observed in early and late erythroid precursors to growth factor stimulation suggests that [Cac] may be an important signal in cell differentiation.
Combined and sequential effects of human IL-3 and GM-CSF on the proliferation of CD34+ hematopoietic cells from cord blood
Authors: Saeland S , Caux C , Favre C , Duvert V , Pebusque MJ , Mannoni P , deVries JE 
Published: October 2019

Abstract
The proliferative effects of recombinant human interleukin-3 (IL-3) and granulocyte-macrophage colony-stimulating factor (GM-CSF) were investigated in semi-solid and liquid cultures of purified CD34+ hematopoietic cells obtained from umbilical cord blood. No important differences in overall cloning efficiencies in response to IL-3 or GM- CSF were observed in semi-solid medium in the presence of erythropoietin (Ep). However, GM-CSF was less effective for the development of erythroid bursts (BFU-E), and only IL-3 was observed to induce significant numbers of mixed-erythroid colonies (E-MIX). Both IL- 3 and GM-CSF also induced proliferation of CD34+ in liquid cultures. Proliferative responses to IL-3 were found to be more rapid and stronger than to GM-CSF, although the number of initial responsive cells as judged by autoradiography were comparable. Enhanced proliferation of CD34+ cells both in semi-solid and liquid cultures was obtained in the presence of combinations of IL-3 and GM-CSF. The responses observed were less than additive, with the exception of the development of eosinophil colonies and clusters, where IL-3 and GM-CSF were found to act synergistically. In secondary cultures, proliferative responses to GM-CSF were strongly enhanced by preculture of CD34+ cells in IL-3 for four to 11 days, and to a lesser extent by preculture in GM- CSF. Finally, responses to IL-3 were not affected by preculture of CD34+ cells in the presence of GM-CSF. Our results indicate that there is a wide overlap of cells capable of proliferating either in response to IL-3 or to GM-CSF within the cord blood CD34+ compartment. However, differences in primary proliferation kinetics and increased responsiveness to GM-CSF following preculture suggest the importance of a sequential action of IL-3 and GM-CSF in the expansion of CD34+ cells.
Susceptibility of monocytes to lymphokine-activated killer cell lysis: effect of granulocyte-macrophage colony-stimulating factor and interleukin-3
Authors: Djeu JY , Widen R , Blanchard DK 
Published: October 2019

Abstract
Cultured human monocytes have been shown to be susceptible to lysis by autologous lymphokine-activated killer (LAK) cells. To determine factors that might modulate the sensitivity of monocytes to lysis, we cultured adherent peripheral blood leukocytes (PBL) in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF) or interleukin-3 (IL-3) since these cytokines have been reported to affect both functional and physical characteristics of monocytes. Both recombinant human GM-CSF and IL-3 were found to significantly enhance the susceptibility of monocytes to lysis by LAK cells in a dose- dependent manner, with GM-CSF being slightly more effective. In a kinetics study, the lysability of monocytes increased after two days of incubation with either cytokine, with maximal susceptibility occurring after four to six days of culture. The effects of GM-CSF and IL-3 appeared to be specific for monocytes since culture of either nonadherent cells or granulocytes, which are normally resistant to LAK- mediated lysis, did not induce sensitivity. While the effects of GM-CSF and IL-3 have been shown to be synergistic in some cases, they did not act synergistically to induce monocyte susceptibility to LAK lysis. In cold target experiments cytokine-treated monocytes reciprocally blocked lysis, suggesting that similar target structures were modulated with either factor. FACS analysis and sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) demonstrated comparable modulation of surface antigens with either GM-CSF or IL-3. Thus, these cytokines can serve to augment susceptibility of monocytes to LAK cells, emphasizing the complex interactions that occur in the immune system.
T-cell nonmalignant clonal proliferation in ataxia telangiectasia: a cytological, immunological, and molecular characterization
Authors: Stern MH , Theodorou I , Aurias A , Maier-Redelsperger M , Debre M , Debre P , Griscelli C 
Published: October 2019

Abstract
Cytogenetically abnormal T-cell nonmalignant clones are a characteristic feature of ataxia telangiectasia (AT). Here, we study a t(14;14) clone from a patient with AT, and provide a cytological, immunological, and molecular characterization. This cellular population is clonal at the molecular level, but is phenotypically heterogeneous, with CD4+CD8+ and CD4-CD8+ cells. Although these cells do not divide in the peripheral blood, a majority of them are found in G1 phase and express the membrane antigen 4F2, a very early marker of activation. Many similarities are found between this nonmalignant AT clone and T- cell prolymphocytic leukemia at the morphologic, cytogenetic, and immunologic levels, despite the different clinical courses associated with these proliferations. We hypothesize that the t(14;14) translocation is linked to the abnormal morphology and immunophenotype of the AT clone cells, but that this translocation confers only a preactivated state to the cells. A complete malignant transformation would then be due to secondary events.