bluuebunny/crossref_metadata_2025_split huggingface dataset:
Myeloid growth factor(s) regulation of ornithine decarboxylase: effects of antiproliferative signals interferon-gamma and cAMP
Authors: Farrar WL , Harel-Bellan A 
Published: October 2019

Abstract
Colony-stimulating factors (CSFs) stimulate the activation and steady- state mRNA accumulation of an important regulatory enzyme for macromolecular synthesis, ornithine decarboxylase (ODC). Cloned murine CSF-dependent cell lines exhibited a rapid activation of ODC enzyme activity, detectable within ten minutes of stimulations with either interleukin-3 (IL-3), GM-CSF, or G-CSF. This early phase of enzyme activation did not require early protein or mRNA synthesis. The subsequent protracted rise in ODC activity occurring four to six hours after CSF treatment was dependent on increases in steady-state ODC mRNA accumulation and de novo protein synthesis. CSF, therefore, modulates both posttranslational activation of preexisting ODC and stabilization and accumulation of ODC mRNA. Antiproliferative signals, such as cAMP or interferon-gamma (IFN-gamma), effectively inhibited the CSF-directed increase in steady-state ODC mRNA. Cotreatment of the murine NSF 60.8 cell line with IFN-gamma and GM-CSF decreased steady-state ODC mRNA greater than 80% as compared with GM-CSF-treated cells alone. IFN treatment did not cause any appreciable destabilization of mature ODC mRNA, suggesting that its major effect may be at the level of ODC mRNA transcription or posttranscriptional processing. These data indicate that the ODC gene-protein system is an important molecular locus of the effects of myeloid proliferative and antiproliferation signals.
Biogenesis of the vitronectin receptor in human endothelial cell: evidence that the vitronectin receptor and GPIIb-IIIa are synthesized by a common mechanism
Authors: Polack B , Duperray A , Troesch A , Berthier R , Marguerie G 
Published: October 2019

Abstract
Human endothelial cells express a membrane glycoprotein alpha beta heterodimer similar to the human platelet glycoprotein IIb-IIIa complex (GPIIb-IIIa). This noncovalently associated complex is the vitronectin receptor (VNR). These two receptors belong to the cytoadhesin family and share the same beta subunit. They express different recognition specificities: platelet GPIIb-IIIa is a receptor for fibrinogen, fibronectin, and von Willebrand factor (vWF), whereas VNR is a receptor for vitronectin, and is possibly a receptor for fibrinogen and vWF. We analyzed the biosynthesis of the endothelial cell VNR. Our data show that VNR alpha is a two-chain protein which is biosynthesized as a single-chain precursor: the pro-VNR alpha. Pro-VNR alpha forms a complex with VNR beta, and this association occurs prior to the Golgi- mediated processing of the oligosaccharide side chains. Mature VNR beta is glycosylated by not fully processed oligosaccharide side chains because it remains endoglycosidase H (endo H) sensitive, even when the complex is expressed on the cell surface. This characteristic appears as a common feature for the members of the cytoadhesin family. These results indicate that although VNR and GPIIb-IIIa are biosynthesized in different cells, their expression is controlled by similar mechanisms, providing further support for the concept that the cytoadhesin family constitutes a distinct group of adhesion receptors.
High pp60c-src level in human platelet dense bodies
Authors: Rendu F , Lebret M , Danielian S , Fagard R , Levy-Toledano S , Fischer S 
Published: October 2019

Abstract
Phosphoproteins phosphorylated in vivo were examined in resting and thrombin-activated human blood platelets. Thrombin-stimulation resulted in an overall increase in labeled proteins containing phosphotyrosine. The most prominent was a protein of 60 Kd. By electroblotting, the 60 Kd protein was identified as the pp60c-src, the normal cellular homolog of the transforming protein of Rous sarcoma virus. We have examined the intracellular distribution of the pp60c-src within platelets. Use of immunoprecipitation and electrotransfer to study isolated membranes, alpha-granules, lysosomes, and dense granules (also termed dense bodies) revealed that pp60c-src was highly enriched in dense bodies. In view of the prominent role of these granules in platelet function, We postulate that protein phosphorylation by activated pp60c-src is involved in early steps of platelet activation.
Interleukin-1 beta rather than lymphotoxin as the major bone resorbing activity in human multiple myeloma
Authors: Kawano M , Yamamoto I , Iwato K , Tanaka H , Asaoku H , Tanabe O , Ishikawa H , Nobuyoshi M , Ohmoto Y , Hirai Y 
Published: October 2019

Abstract
Human myeloma cells were purified from bone marrow aspirates from four patients having advanced myeloma, including one with common acute lymphoblastic leukemia antigen-positive myeloma. All of these myelomas had marked bone lytic lesions. From the culture supernatants of these purified myeloma cells, bone-resorbing activities were significantly revealed by 45Ca-release bone resorption assay, and IL-1 activities were also detected by IL-1 bioassay (mouse thymocyte comitogenic assay). Sandwich enzyme immunoassay for IL-1 alpha or IL-1 beta revealed that IL-1 beta was responsible for IL-1 activity of these culture supernatants. Furthermore, the bone resorbing activities of these culture supernatants were completely neutralized by pretreatment of anti-IL-1 beta, but not anti-IL-1 alpha antibody. By Northern blot analysis, IL-1 beta mRNA was identified from these myeloma cells. Therefore, it is concluded that myeloma cells produce IL-1 beta, which acts as bone-resorbing activity in multiple myeloma.
Hematopoietic bone marrow recovery after radiation therapy: MRI evaluation
Authors: Casamassima F , Ruggiero C , Caramella D , Tinacci E , Villari N , Ruggiero M 
Published: October 2019

Abstract
Magnetic resonance imaging (MRI) is able to detect the increase of adipocytes in the hematopoietic bone marrow that occurs as a consequence of radiotherapy and is indicative of the loss of myeloid tissue. By monitoring this process, it is also possible to determine the recovery of the bone marrow. The amount of viable hematopoietic tissue plays a fundamental role in determining whether the patient is able to undergo further antineoplastic therapy, particularly chemotherapy. We examined 35 patients who had been treated with radiotherapy for Hodgkin's lymphoma (12), uterine cervix carcinoma (nine), ovarian dysgerminoma (six), testicular seminoma (four), and non- Hodgkin's lymphoma (four). We observed that radiation-induced modifications of the MRI pattern in the bone marrow are tightly linked to two parameters; the administered radiation dose and the length of time passed after the treatment. Bone marrow recovery was observed only when patients were treated with doses lower than 50 Gy. The earlier radiation-induced modifications of the bone marrow MRI pattern occurred 6 to 12 months after irradiation, and they were most evident 5 to 6 years after the treatment. From 2 to 9 years after radiotherapy, we observed partial recovery. Complete recovery, when it occurred, was observed only 10 to 23 years after the treatment. Our results indicate that MRI studies are likely to be useful in the assessment of radiation- induced injuries.
Heparin cofactor II-proteinase reaction products exhibit neutrophil chemoattractant activity
Authors: Hoffman M , Pratt CW , Brown RL , Church FC 
Published: October 2019

Abstract
The physiologic function of the plasma glycoprotein heparin cofactor II (HCII) is not well understood. An in vivo role for thrombin (IIa) inhibition by HCII in the presence of certain glycosaminoglycans (dermatan sulfate and heparin) can be proposed. Many proteins, such as complement components, can be proteolyzed to generate secondary bioactive molecules. HCII is a substrate for the human neutrophil (PMN) proteinases cathepsin G (CG) and elastase (LE). We found that degradation of HCII by CG or LE generated products with potent PMN chemotactic activity, which did not stimulate the PMN oxidative burst. Our results suggest that HCII may be a physiologic regulator of the acute inflammatory response.
Characterization of two monoclonal antibodies against cytochrome b558 of human neutrophils
Authors: Verhoeven AJ , Bolscher BG , Meerhof LJ , van Zwieten R , Keijer J , Weening RS , Roos D 
Published: October 2019

Abstract
Monoclonal antibodies (MoAbs) were raised against cytochrome b558, a membrane-bound component of the NADPH:O2 oxidoreductase in human neutrophils. This cytochrome consists of a low-molecular-weight (low- mol-wt) subunit of 22 to 23 Kd, probably encoded by an autosomal gene, and a high-mol-wt subunit of 75 to 90 Kd, encoded on the X-chromosome. MoAb 449 reacts with the low-mol-wt subunit and MoAb 48 with the high- mol-wt subunit on Western blots of purified cytochrome b558 and on blots of whole neutrophil extracts. In extracts of neutrophils from patients with chronic granulomatous disease (CGD) in which cytochrome b558 is not detectable by spectrophotometric methods, the low-mol-wt subunit is present, albeit in a much smaller amount. The high-mol-wt subunit is not detected by MoAb 48 in neutrophils of patients with X- linked CGD and in neutrophils of patients with the autosomal, cytochrome-b558-negative form of the disease. These results can be explained by a marked instability of these subunits when the synthesis of either of the two is disturbed. In differentiated HL-60 cells, the high-mol-wt subunit appears to be present in a different form. Cloning of the low-mol-wt subunit with the help of MoAb 449 suggests the presence of a heme-binding site on this subunit. By comparison of the binding characteristics of MoAb 449 to intact and permeabilized neutrophils with those of MoAb 7D5, recently isolated by Nakamura et al (Blood 69:1404, 1987), the low-mol-wt subunit was established as a transmembrane protein.
Influence of acute and chronic graft-versus-host disease on relapse and survival after bone marrow transplantation from HLA-identical siblings as treatment of acute and chronic leukemia [published erratum appears in Blood 1989 Aug 15;74(3):1180]
Authors: Sullivan KM , Weiden PL , Storb R , Witherspoon RP , Fefer A , Fisher L , Buckner CD , Anasetti C , Appelbaum FR , Badger C 
Published: October 2019

Abstract
To assess the influence of graft-versus-host disease (GVHD) on recurrent leukemia and survival after allogeneic marrow transplantation, we studied 1,202 patients with acute nonlymphocytic leukemia (ANL), acute lymphocytic leukemia (ALL), and chronic myelogenous leukemia (CML) given unmodified marrow grafts from HLA- identical siblings. Proportional hazards regression models using acute GVHD and chronic GVHD as time-dependent covariates demonstrated a significant association of GVHD with a decreased relative risk (RR, 0.33 to 0.42) of relapse in patients with ANL, ALL, and CML transplanted in advanced disease. Among patients developing either acute or chronic GVHD, treatment failure (that is, mortality or relapse) was decreased in patients with ALL transplanted in relapse (RR = 0.70, P less than .033) and CML in blast crisis (RR = 0.37, P less than .009). This effect was independent of age, sex, preparative regimen, GVHD prophylaxis, or length of follow-up. Five-year actuarial estimates were derived for the subset of 657 patients who survived in remission 150 days after transplant and were at risk for development of chronic GVHD. Among patients with ANL in first remission or CML in chronic phase, GVHD had an adverse effect on survival and no apparent influence on relapse. Among patients with ANL and ALL transplanted in relapse, the probability of relapse after day 150 was 74% without [corrected] GVHD, 45% with acute and chronic GVHD, 35% with [corrected] only acute GVHD, and 34% with only chronic GVHD (P less than .001). Actuarial survival in these four GVHD groups was 25%, 34%, 59%, and 62%, respectively (P less than .009). Among patients with CML in acceleration or blast crisis, the probability of relapse after day 150 was 65% without GVHD and 36% with acute and/or chronic GVHD (P less than .017). We conclude that acute and chronic GVHD were associated with a durable antileukemic effect and improved survival in patients transplanted in advanced stages of ALL and CML.
Methotrexate and cyclosporine versus cyclosporine alone for prophylaxis of graft-versus-host disease in patients given HLA-identical marrow grafts for leukemia: long-term follow-up of a controlled trial
Authors: Storb R , Deeg HJ , Pepe M , Appelbaum F , Anasetti C , Beatty P , Bensinger W , Berenson R , Buckner CD , Clift R 
Published: October 2019

Abstract
Patients with acute nonlymphoblastic leukemia (ANL) in first remission (n = 38) or chronic myelocytic leukemia (CML) (n = 55) were given cyclophosphamide and total body irradiation, followed by marrow infusion from HLA-identical siblings. To evaluate postgrafting prophylaxis for acute graft-versus-host disease (GVHD), the patients were randomized to receive either methotrexate and cyclosporine (n = 43) or cyclosporine alone (n = 50). Methotrexate/cyclosporine significantly reduced the incidence and severity of acute GVHD, and improved early survival. This report updates the results with a 3.0 to 4.5 year follow-up. Methotrexate/cyclosporine did not interfere with sustained hematopoietic engraftment, although granulocyte recovery to 1,000/microL was delayed by five days on the average. The incidence of chronic GVHD was identical in the two groups (26% v 24%). Disease-free 3-year survival was slightly better in the methotrexate/cyclosporine group (65% v 54%), but this benefit was restricted to patients with CML (73% v 54%), while no improvement was seen in patients with ANL (41% v 41%). In contrast to patients with CML (relapse rates 8% v 9%), the early survival benefit among patients with ANL given methotrexate/cyclosporine was offset by an increase in leukemic relapses (29% v 16%).
Interleukin-3 is a differentiation factor for human basophils
Authors: Valent P , Schmidt G , Besemer J , Mayer P , Zenke G , Liehl E , Hinterberger W , Lechner K , Maurer D , Bettelheim P 
Published: October 2019

Abstract
The effect of recombinant human (rh) cytokines, interleukin-1 alpha (IL- 1 alpha), interleukin-2 (IL-2), interleukin-3 (IL-3), interleukin-4 (IL- 4), granulocyte/macrophage colony stimulating factor (GM-CSF), granulocyte colony stimulating factor (G-CSF), monocyte/macrophage colony stimulating factor (M-CSF), interferon-alpha (IF-alpha), interferon-gamma (IF-gamma), and the tumor necrosis factor-alpha (TNF- alpha) on differentiation and function of metachromatic cells (MCS) was studied. Among all cytokines tested, rh interleukin-3 (rhIL-3) selectively induced a significant formation of MCS (IL-3: 1.1 +/- 0.6 x 10(5) v control: 0.02 +/- 0.15 x 10(5) MCS/mL suspension) and dose dependent increase in formation of intracellular histamine (IL-3, 100 U/mL: 95 +/- 23 ng/mL v control: 1.8 +/- 0.8 ng/mL) in a bone marrow suspension culture system (analyzed on day 14 of culture). Besides MCS, formation of eosinophils was observed in this culture system in the continuous presence of rhIL-3, whereas IL-3 pulse-stimulation for three hours and subsequent exposure to control medium induced growth of MCS but not of eosinophils. By combined immunofluorescence/toluidine blue staining, MCS were found to express a cell surface marker profile that corresponds to the immunological phenotype of peripheral blood basophils (MY-7(CD13)+, VIM12(CD11b)+, VIM2+, MAX1-, MAX24- and YB5B8- ). Furthermore, cultured MCS expressed surface membrane receptors for IgE and could be triggered for nontoxic histamine release by a monoclonal anti-IgE antibody. To evaluate a possible influence of IL-3 on basophil function, studies were extended to freshly obtained blood basophils (healthy volunteers, n = 3). However, like all other cytokines tested, rhIL-3 failed to induce basophil histamine release. Taken together, our studies demonstrate that IL-3 is a differentiation factor for human basophils.
The growth of Rauscher erythroleukemia cells is mediated by autocrine production of a factor with biological activity similar to interleukin- 3
Authors: Migliaccio G , Migliaccio AR , Ruscetti S , Adamson JW 
Published: October 2019

Abstract
Under serum-deprived and chemically defined culture conditions, the growth of Rauscher erythroleukemia cells is mediated by an autocrine mechanism. The growth-promoting activity is produced by fresh or irradiated cells and resembles the activity of interleukin-3 (IL-3) in its ability to sustain colony formation from three of four IL-3- dependent cell lines and to induce formation of granulocyte/macrophage (GM) colonies and, in the presence of erythropoietin (Ep), of erythroid bursts and mixed erythroid colonies. IL-3, IL-1, IL-4, IL-6, GM colony- stimulating factor (GM-CSF), G-CSF, M-CSF, Ep, and media conditioned by concanavalin A-stimulated mouse spleen cells or phytohemagglutinin- stimulated LBRM 33 cells were unable to induce proliferation of the Rauscher erythroleukemia cells. Northern analysis of total and polyA- selected RNA extracted from untreated Rauscher cells or from cells 24 hours after irradiation showed the presence of message for M-CSF but not for IL-3, IL-1, GM-CSF, or G-CSF. The production of IL-6 was excluded by a sensitive bioassay. These results indicate that the autocrine growth of the Rauscher cell line is mediated by a growth factor different from IL-3, but with similar biological activity. Activation of the expression of such a growth factor during viral infection may contribute to the generation of leukemic cells that have the property to grow in vitro and generate Rauscher erythroleukemia cell lines.
Mast cell typing: demonstration of a distinct hematopoietic cell type and evidence for immunophenotypic relationship to mononuclear phagocytes
Authors: Valent P , Ashman LK , Hinterberger W , Eckersberger F , Majdic O , Lechner K , Bettelheim P 
Published: October 2019

Abstract
The immunologic surface marker profile of human mast cells (MCs) was established using a combined toluidine/immunofluorescence staining procedure [49 monoclonal antibodies (MoAbs) tested]. Ascites (n = 9) MCs as well as enzymatically dispersed MCs from all organs tested (lung n = 11, skin n = 7, intestinum n = 10) exhibited an identical marker profile. MCs were recognized by MoAbs clustered as CD9 (anti-gp24), CD33 (anti-gp67), and CD45 (anti-gp220) as well as by MoAbs directed against membrane-bound IgE. MoAB YB5B8 (anti-gp145) selectively recognized MCs. Most significantly, however, MCs were stained by MoAbs MAX1 (anti-gp65), MAX3 (anti-gp68), MAX11 (anti-gp65), and MAX24 (anti- gp65). These antibodies bind to surface membrane antigens associated with a late stage of monocyte/macrophage differentiation. Thus, our results provide definite evidence that MCs share surface membrane markers with mononuclear phagocytes. In contrast, MCs are stained neither by lymphatic markers (CD1–8, 10, 19–24) nor by myelomonocytic markers (CD11–17). MCs also lack the interleukin-2 (IL-2) receptor (CD25), the T10 antigen (CD38), and most of the myelocytic markers expressed on peripheral blood (PB) basophils. Thus, MCs displayed a unique phenotype within the hematopoietic system. This new approach enabled us to enrich human lung MCs to a purity greater than 95% by means of negative selection with complement-mediated cell lysis. Purified MCs were subsequently stained with MoAbs and analyzed by flow cytometry, which confirmed the results obtained from the double- staining experiments. We next examined cultured metachromatic cells derived from bone marrow (BM) and peripheral blood colony-forming units (CFU). These metachromatic cells previously could not be classified by morphologic criteria alone and have therefore been termed basophil- like/MC-like cells. In this study, toluidine blue-positive cells obtained from either pooled multipotential colonies (day 14-CFU-GEM) or pooled myelocytic colonies (day 16/17-CFU-GM/G/M) were recognized by MoAbs MY7 (CD13), VIM12 (CD11b), and VIM2, as well as by an anti-IgE MoAb, after preincubation with IgE. In contrast, CFU-derived metachromatic cells were not stained by MoAb YB5B8. This marker profile corresponds to the immunologic phenotype of blood basophils and excluded a detectable formation of mature MCs in colonies derived from cultured hematopoietic stem cells.
Proteoglycan synthesis by hematopoietic progenitor cells
Authors: Minguell JJ , Tavassoli M 
Published: October 2019

Abstract
The synthesis of proteoglycans (PG) by hematopoietic stromal cells has been reported. But PG synthesis by hematopoietic progenitor cells has not been explored. We have studied synthesis, cellular distribution, and molecular characteristics of PG by a cloned interleukin-3 (IL-3)- dependent hematopoietic progenitor cell line, FDCP-1, which is cloned from murine long-term marrow cultures. Under appropriate conditions the cell can differentiate into granulocytes and macrophages, and therefore, can be considered CFU-GM equivalent. The pattern of PG synthesis was studied by 35SO4 labeling. FDCP-1 cells actively synthesize PG, which are distributed in the intracellular, membrane- associated (MP), and extracellular pools. After purification of the 35S- labeled material by ion-exchange and gel filtration techniques, a single chondroitin sulfate-PG (CIS-PG) was observed to be present in the three studied pools. By Sepharose CL-4B chromatography, this PG has a Kav of 0.47, which after alkaline treatment is shifted to a Kav of 0.67. This indicates the proteoglycan nature of the 35SO4-labeled material. The MP CIS-PG is not stable. It is released to the culture medium where it is subsequently processed. However, in the presence of hematopoietic stromal cells D2X, the stability of MP proteoglycan of FDCP-1 cells is enhanced, suggesting that the synthesis of PG by progenitor cells and its accumulation in the membrane may have a role in the interaction between progenitor and stromal cells.
Factor VIII:C concentrate purified from plasma using monoclonal antibodies: human studies
Authors: Brettler DB , Forsberg AD , Levine PH , Petillo J , Lamon K , Sullivan JL 
Published: October 2019

Abstract
Conventional clotting factor concentrates have, until recently, been “of intermediate purity,” containing less than 1% of the coagulation factor, and greater than 99% extraneous plasma proteins such as fibrinogen, fibronectin, gamma globulins, and traces of many others. We report here the results of a new factor VIII concentrate that is purified from human plasma using a mouse monoclonal antibody to factor VIII:vWF in an affinity chromatography system. The resultant concentrate has an activity of between 3,000 and 5,000 U/mg protein before albumin is added as a stabilizer. Seven patients with severe hemophilia A and no inhibitor who were positive for antibody to human immunodeficiency virus (HIV) have been treated solely with this concentrate for over 24 months. Factor usage in these patients has ranged from 611 U/kg/yr to 2,022 U/kg/yr. These patients have infused approximately once per week on the average, most often for joint hemorrhages. The efficacy of the concentrate is excellent. No allergic reactions have occurred and no factor VIII antibodies have developed. In these seven patients mean CD4 counts stabilized (856 +/- 619 at screen v 778 +/- 686 at 24 months) and there was reversal of skin test anergy. In a comparison group on conventional intermediate purity concentrate chosen retrospectively decreases in mean CD4 cell counts similarly did not occur. However, the number of the comparison patients who were anergic increased over the course of the study. These observations indicate the possibility that more highly purified concentrates may stabilize immune function in HIV seropositive patients.