bluuebunny/crossref_metadata_2025_split huggingface dataset:
An inhibitory monoclonal antibody to factor X that blocks prothrombin activation but not prothrombinase enzyme assembly
Authors: Church WR , Messier TL , Tucker MM , Mann KG 
Published: October 2019

Abstract
A monoclonal antibody (designated alpha BFX-2b) prepared against bovine factor X inhibited factor X activity in human, bovine, porcine, rabbit, and canine plasma. In assays using purified prothrombinase components, factor Xa, factor Va, phospholipid vesicles, and calcium ion with the fluorescent active site thrombin inhibitor dansylarginyl-N-(3-ethyl-1,5- pentanediyl)amide, the antibody inhibited the conversion of prothrombin to thrombin. Antibody alpha BFX-2b also blocked prothrombinase cleavage of the macromolecular substrates prethrombin 1 and prethrombin 2 but did not inhibit factor Xa hydrolysis of the synthetic substrate benzoyl- Ile-Glu-Gly-Arg-p-nitroanilide. The antibody also prevented the inactivation of factor Xa by antithrombin III but did not prevent the inactivation by soybean trypsin inhibitor. Antibody alpha BFX-2b bound factor Xa with a stoichiometry of 1:1 and an apparent dissociation constant of 9.0 x 10(-11) mol/L as estimated from its inhibition of prothrombinase activity. Antibody alpha BFX-2b did not prevent binding of factor Xa to factor Va-phospholipid as measured by using fluorescence polarization or high-pressure liquid gel chromatography with the fluorescent Factor Xa analogue dansyl-glutamyl-glycyl-arginyl- Xa. Immunoblotting of factor X following electrophoresis on sodium dodecyl sulphate-polyacrylamide gels and transfer to nitrocellulose indicated that the antigenic determinant recognized by antibody alpha BFX-2b was found on the heavy chain of factors X and Xa. From these observations it can be concluded that antibody alpha BFX-2b recognizes a highly conserved epitope on the factor X heavy chain that is remote from the topographic sites required for prothrombinase complex assembly and substrate hydrolysis but may be located at or near a portion of the macromolecular substrate binding site.
HLA-identical marrow transplantation during accelerated-phase chronic myelogenous leukemia: analysis of survival and remission duration
Authors: Martin PJ , Clift RA , Fisher LD , Buckner CD , Hansen JA , Appelbaum FR , Doney KC , Sullivan KM , Witherspoon RP , Storb R 
Published: October 2019

Abstract
Results of HLA-identical allogeneic marrow transplantation were analyzed for 66 patients with accelerated-phase chronic myelogenous leukemia (CML). Multivariate proportional hazards regression models were used to determine disease-related and transplant-related factors associated with posttransplant mortality and relapse. The projected 5- year survival rate was estimated at 18% by the product-limit method. The major causes of death were interstitial pneumonia, infection, and relapse. Splenomegaly at initial diagnosis and longer time interval from diagnosis to transplant were associated with decreased overall survival and event-free survival. Sixteen patients have relapsed between 17 and 1,569 days (median, 486) posttransplant. The use of T- cell-depleted marrow and older age of the donor or recipient were associated with an increased probability of leukemic relapse. Ten of the 16 relapses occurred among the 15 patients who received T-cell- depleted marrow. The actuarial relapse risk 2.5 years posttransplant was 100% in patients administered T-cell-depleted marrow as compared with 25% in patients administered unmodified marrow. The data in this report emphasize the increased risks and relatively poor results that occur when marrow transplantation is deferred until after signs of acceleration appear. When compared with results for patients who received transplants during chronic phase, the poor results seen here in patients administered unmodified marrow stem primarily from increased transplant-related mortality rather than increased relapse risk. The strikingly increased relapse rate associated with the use of T-cell depletion would discourage its use for graft-v-host disease prevention in patients who receive transplants for CML.
Failure of recombinant human granulocyte-macrophage colony-stimulating factor therapy in aplastic anemia patients with very severe neutropenia
Authors: Nissen C , Tichelli A , Gratwohl A , Speck B , Milne A , Gordon-Smith EC , Schaedelin J 
Published: October 2019

Abstract
Four patients with very severe aplastic anemia refractory to antilymphocyte globulin were administered recombinant human granulocyte- macrophage--colony stimulating factor (GM-CSF). One patient with minimal residual myelopoiesis responded transiently to two separate courses of GM-CSF at 4 and 8 micrograms/kg/d administered intravenously and another course at 4 micrograms/kg/d administered subcutaneously. Septicemia and bilateral pneumonia that had been resistant to conventional therapy resolved. Three patients with no evidence of residual myelopoiesis did not respond to GM-CSF. In one patient, the dose was increased to 32 micrograms/kg/d with no effect on hematopoiesis. Immediate side effects were minimal at GM-CSF doses up to 16 micrograms/kg/d. GM-CSF may, however, have been involved in the pathophysiology of thrombosis of the inferior vena cava in the patient administered 32 micrograms/kg/d. We conclude that GM-CSF does not induce hematopoiesis in long-standing, severe, treatment-resistant aplastic anemia with complete myelopoietic failure. However, in patients with minimal residual myelopoiesis, GM-CSF could be a promising adjuvant therapy for severe infection.
Detection of the molecular abnormality in chronic myeloid leukemia by use of the polymerase chain reaction
Authors: Dobrovic A , Trainor KJ , Morley AA 
Published: October 2019

Abstract
The bcr-abl translocation characteristic of chronic myeloid leukemia (CML) was detected by the polymerase chain reaction (PCR) modified to use mRNA as the starting material. Amplification of a sequence spanning the bcr-abl junction was obtained by using peripheral blood cells from all of 20 patients with classic CML, one patient with acute lymphoblastic leukemia probably secondary to CML, and two cell lines derived from patients with CML. The presence of bcr exon 3 in the mRNA was determined from the size of the amplified sequence; it was present in 14 and absent in seven patients. One leukemic cell per 1,000 nonleukemic cells could be readily detected, thus indicating the great sensitivity of the method. This technique is of routine value in CML both for diagnosis and for following the course of treatment.
The myeloid blood cell differentiation-inducing protein MGI-2A is interleukin-6
Authors: Shabo Y , Lotem J , Rubinstein M , Revel M , Clark SC , Wolf SF , Kamen R , Sachs L 
Published: October 2019

Abstract
The mouse myeloid blood cell differentiation-inducing protein, macrophage and granulocyte inducer, type 2A (MGI-2A), was purified, and the amino acid sequence of a CNBr cleavage peptide (22 residues) was determined. This amino acid sequence is identical to the sequence found in positions 73 to 94 of mouse interleukin-6 (IL-6). Recombinant mouse IL-6 protein induces differentiation of mouse myeloid leukemic cells that are induced to differentiation by MGI-2, and monoclonal antimouse- MGI-2 antibody, which neutralizes MGI-2, also completely neutralizes this IL-6-induced differentiation. These results show that the major type of mouse myeloid differentiation-inducing protein (MGI-2A) and IL- 6 are very similar and most likely identical proteins. Recombinant human IL-6 (also called interferon-beta 2 or B-cell differentiation factor), which shows only a 41% similarity to mouse IL-6, has 11 identical amino acid residues out of the 22 in the mouse MGI-2A peptide and also induces differentiation of the same myeloid leukemic cells.
In situ hybridization histochemistry localization of interleukin-3 mRNA in mouse brain
Authors: Farrar WL , Vinocour M , Hill JM 
Published: October 2019

Abstract
The hematopoietic growth factor interleukin-3 (IL-3) promotes the proliferation and maturation of pluripotent myeloid progenitor cells. In the immune system, IL-3 is synthesized by mitogen or antigen- stimulated T lymphocytes. We demonstrate the expression of IL-3 mRNA in mouse brain by in situ hybridization histochemistry and Northern blot analysis. The IL-3 mRNA is localized in discrete areas of the brain and can be found in neuronal cell body and astrocytes. Northern analysis of cerebellar RNA, compared with mRNA extracted from WEHI-3 cells, showed a single hybridization band, approximately 1.2 kb, suggesting similar processing between brain and myeloid cells. The molecular evidence and previous observations of IL-3-like biologic activity found in the brain suggest a potential role for IL-3 in the neurobiology of the CNS.
Alpha-tocopherol, an effective inhibitor of platelet adhesion
Authors: Jandak J , Steiner M , Richardson PD 
Published: October 2019

Abstract
Platelet adhesiveness was tested ex vivo in a group of six normal individuals receiving varying doses of alpha-tocopherol. Adhesion to glass slides coated with fibronectin, collagen, fibrinogen, or plasma proteins was studied by perfusing platelet-rich plasma through a flow chamber that allowed time- and space-resolved observations of platelet adhesion. Platelet adherence was measured in an area of parallel flow lines and low shear rate under standardized conditions before and after dietary supplementation with vitamin E at doses of 200 and 400 IU/d. Platelet adherence differed in magnitude depending on the adhesive surface. There was a distinct preference of platelets to adhere to sites that had been previously occupied. A remarkable decrease in platelet adherence was observed after vitamin E supplementation. The average decrease in adhesion after 2 weeks of 200 IU vitamin E was 75%. After 2 weeks of 400 IU vitamin E, platelet adhesion was reduced by 82%. The inhibitory activity of alpha-tocopherol was dose dependent and correlated well with the increase in alpha-tocopherol concentration in platelets after supplementation. Scanning electron microscopy revealed a striking decrease of pseudopodium formation in alpha-tocopherol- enriched platelets. Our results suggest that vitamin E may also be an effective antiadhesive agent in vivo.
Heparin binds to human monocytes and modulates their procoagulant activities and secretory phenotypes. Effects of histidine-rich glycoprotein
Authors: Leung L , Saigo K , Grant D 
Published: October 2019

Abstract
The binding of heparin to human monocytes and the monocytoid cell line U937 was characterized. Heparin binding was rapid, specific, saturable, and reversible. There was a single class of heparin binding sites, with an apparent dissociation constant of 0.19 mumol/L and 1.9 x 10(6) sites per cell. The binding was not dependent on the anticoagulant property of heparin. Analysis of surface-iodinated cell lysates by heparin affinity chromatography revealed a major 120 Kd cell surface heparin- binding protein. Histidine-rich glycoprotein, a potent heparin antagonist found in human plasma and platelets, decreased the affinity of heparin for cell binding. Cell surface bound heparin was functionally active and markedly accelerated the inactivation of thrombin by antithrombin III. Heparin induced the release of two monocyte secretory proteins of 160 and 17 Kd. Our study supports the thesis that heparin and related glycosaminoglycans interact with monocytes and macrophages, as well as endothelial cells and smooth muscle cells, and play an important and complex role in blood vessel wall biology.
Human T-lymphotropic virus I-infected T cells constitutively express lymphotoxin in vitro
Authors: Tschachler E , Robert-Guroff M , Gallo RC , Reitz MS Jr 
Published: October 2019

Abstract
We have studied the pattern of expression of the lymphokines tumor necrosis factor (TNF alpha) and lymphotoxin (TNF beta) in T-cell lines established by transformation with human T-lymphotropic virus, type I (HTLV-I), the etiologic agent of adult T-cell leukemia (ATL). We report here that nine of nine HTLV-I-infected T-cell lines, established by in vitro infection with HTLV-I, including those with CD4+ or CD8+ as well as CD4-/CD8- phenotypes, constitutively produce high levels of TNF alpha and -beta mRNA and secrete biologically active TNF beta into the culture medium. Similar patterns of expression are seen in six of six HTLV-I-infected T-cell lines directly established from ATL patients. In contrast, several T-cell lines, either uninfected or infected with human immunodeficiency virus I, did not produce comparable levels of the TNF beta. Comparisons of a normal functional T-cell clone before and after infection with HTLV-I show that expression of TNF beta mRNA is induced in the infected cells. The high level expression in HTLV-I- infected cell lines dose not seem to involve perturbation of the TNF alpha/beta genetic loci by proviral integration. A cell line (81–66/45) nonproductively transformed with HTLV-I that produces tat-1 in the absence of viral structural proteins, produces both TNF alpha and -beta mRNA. This suggests that expression of these cytokines could be mediated in trans by the tat-1 gene product.
Immunophenotype-karyotype associations in human acute lymphoblastic leukemia
Authors: Uckun FM , Gajl-Peczalska KJ , Provisor AJ , Heerema NA 
Published: October 2019

Abstract
The present study is a detailed analysis of the cytogenetic features of leukemic cells from 104 immunologically classified acute lymphoblastic leukemia (ALL) (78 B lineage and 26 T lineage) cases. Clonal chromosomal abnormalities were found in marrow blasts from 77 of 104 (74%) cases. Hyperdiploidy was much more frequent in B-lineage ALL cases, whereas normal diploidy was more common in T-lineage ALL cases. Fifty-nine of 104 cases (46 of 78 B-lineage ALL and 13 of 26 T-lineage ALL cases) had structural chromosomal abnormalities. Structural abnormalities involving 2p11, 7p13, 7p22, proximal q arm of 7 (7q11 or 7q22), 11q23–24, and translocations involving 12p11–13 appeared to be B- lineage specific. By comparison, structural abnormalities involving 7p15, 7q32, and 14q11 displayed T-lineage specificity. Structural abnormalities involving 9p22-p23 or 14q32, del (6)(q21-q23), del (12)(p11-p13), and the Philadelphia chromosome were found in B-lineage as well as T-lineage ALL cases. This study expands the current knowledge about immunophenotype-karyotype associations in ALL.
Analysis of N-RAS exon-1 mutations in myelodysplastic syndromes by polymerase chain reaction and direct sequencing
Authors: Bar-Eli M , Ahuja H , Gonzalez-Cadavid N , Foti A , Cline MJ 
Published: October 2019

Abstract
Mutations in codons 12 or 13 of the first exon of the N-RAS gene have been reported in myelodysplastic syndromes (MDS) in frequencies that vary between 9% and 40% depending on the techniques used in analysis. Gene amplification and direct sequencing provides the only unambiguous method of detecting those mutations that induce amino acid alterations. Using this technique, we analyzed 21 MDS patients for mutations in exon- 1 of N-RAS. Codon 12 mutations substituting aspartic acid (GAT) for glycine (GGT) were found in four cases, and a codon 13 mutation substituting alanine (GCT) for glycine (GGT) was detected in one patient. We conclude that N-RAS exon-1 mutations in one patient. We conclude that N-RAS exon-1 mutations producing amino acid changes occur in about 20% to 25% of MDS cases.
Monocyte antigen CD14 is a phospholipid anchored membrane protein
Authors: Simmons DL , Tan S , Tenen DG , Nicholson-Weller A , Seed B 
Published: October 2019

Abstract
A cDNA clone encoding the human monocyte antigen CD14 was isolated by transient expression in COS cells of a cDNA library prepared from phorbol diester-treated HL60 cells. RNA blot analysis showed abundant expression of a single mRNA species in mature monocytes and an increased expression of the mRNA following induction of differentiation in leukemic cell lines. The DNA blot hybridization pattern was consistent with a single-copy gene. The predicted amino acid sequence lacks the characteristic transmembrane domain and stop transfer motif of conventionally anchored membrane proteins. COS cells transfected with the CD14 cDNA released virtually all CD14 protein in soluble form following treatment with glycosyl phosphatidylinositol-specific phospholipase C, and CD14 immunoreactivity was absent from the affected monocytes of a patient with paroxysmal nocturnal hemoglobinuria (PNH). The data show that, to the limit of experimental sensitivity, all monocyte CD14 is joined to the plasma membrane by a phosphatidylinositol phospholipid.
Respiratory burst in adherent human neutrophils: triggering by colony- stimulating factors CSF-GM and CSF-G
Authors: Nathan CF 
Published: October 2019

Abstract
Human neutrophils adherent to proteins derived from serum or plasma, or to the basement membrane protein laminin, underwent a delayed but massive respiratory burst in response to recombinant human CSF-GM or CSF-G. No such response was elicited from neutrophils in suspension. On a molar basis, CSF-GM (EC50 approximately 126 pmol/L) and CSF-G (EC50 approximately 585 pmol/L) were about as potent as TNF alpha and TNF beta in their elicitation of H2O2 release and orders of magnitude more potent than previously studied formylated peptides or C5a. CSF-GM and CSF-G prime suspended neutrophils for a respiratory burst in response to soluble agonists, such as formylated peptides. Compared to the CSF- primed respiratory burst of nonadherent neutrophils, the CSF-triggered response of adherent neutrophils is markedly more delayed in onset (73 to 95 minutes), prolonged in duration (150 to 180 minutes), and greater in extent (approximately 60 to 100 nmol H2O2 released/10(6) neutrophils). Neither CSF-M, interleukin-3 (IL-3), nor bacterial lipopolysaccharide triggered the respiratory burst in adherent neutrophils, nor did CSF-GM or CSF-G trigger a respiratory burst in adherent monocytes. Release of CSF-GM and CSF-G in response to antigens, bacterial products, or cytokines may give mononuclear cells control over the respiratory burst of noncirculating neutrophils during inflammatory and immune responses.
Antihuman plasma glutathione peroxidase antibodies: immunologic investigations to determine plasma glutathione peroxidase protein and selenium content in plasma
Authors: Avissar N , Whitin JC , Allen PZ , Palmer IS , Cohen HJ 
Published: October 2019

Abstract
Plasma glutathione peroxidase (GSHPx) (glutathione: H2O2 oxidoreductase) is a unique selenoglycoprotein. Treatment of this enzyme with glycopeptidase F partially deglycosylates it and establishes the presence of N-linked sugar moieties. Antibodies raised in a rabbit against the purified enzyme from plasma were found to be specific, noninhibitory, and capable of precipitating the enzymatic activity. The antibodies precipitated greater than 90% of the GSHPx activity of normal plasma, thus indicating that the selenoenzyme is the main if not the sole GSHPx activity of plasma. The antibodies did not precipitate RBC GSHPx. A slight cross-reactivity of the antibodies was found with rat plasma GSHPx. A GSHPx activity precipitation assay of normal plasma in the presence of selenium (Se)-deficient plasma indicates that no cross-reactive protein in the Se-deficient plasma interferes with the precipitation of the GSHPx activity from normal plasma. Thus, GSHPx protein as well as activity is deficient in plasma in the absence of Se. Antibodies against GSHPx either from RBCs or from plasma were used to specifically immunoprecipitate most of the GSHPx activity from RBCs or plasma, respectively, in healthy individuals to determine the amount of Se associated with the protein. GSHPx accounts for approximately 15% of the Se in RBCs and 12% of the Se in plasma. Thus, in normal individuals, these proteins account for only a fraction of plasma and RBC Se.
Inactivation of Friend erythroleukemia virus and Friend virus- transformed cells by merocyanine 540-mediated photosensitization
Authors: Sieber F , Krueger GJ , O'Brien JM , Schober SL , Sensenbrenner LL , Sharkis SJ 
Published: October 2019

Abstract
The Friend virus complex was used as a model to study the effects of merocyanine 540 (MC 540)-mediated photosensitization on enveloped viruses. Simultaneous exposure to the lipophilic dye MC 540 and white light inactivated cell-free virus, cell-associated virus, and virus- transformed cells. When used under experimental conditions that are known to preserve most mature blood cells, at least some coagulation factors, and a significant portion of the pluripotent hematopoietic stem cell compartment, MC 540-mediated photosensitization reduced virus titers by greater than or equal to 4 log and the concentration of in vitro clonogenic erythroleukemia cells by greater than or equal to 5 log. Animals that received a single intravenous injection of photosensitized virus were resistant to a subsequent challenge with live virus. High sensitivity to MC 540-mediated photosensitization appears to be a property that is shared by other enveloped viruses. Thus, photosensitization mediated by MC 540 may be of benefit in the sterilization of blood products (in particular, cellular products), the production of vaccines, and selected areas of antiviral therapy.
Suppressive effects in vivo of purified recombinant human H-subunit (acidic) ferritin on murine myelopoiesis
Authors: Broxmeyer HE , Williams DE , Geissler K , Hangoc G , Cooper S , Bicknell DC , Levi S , Arosio P 
Published: October 2019

Abstract
Purified recombinant human heavy-chain (acidic) ferritin (rHF) was assessed in vivo in mice for effects on the proliferation (percentage of cells in S-phase) and absolute numbers of granulocyte-macrophage (CFU-GM), erythroid (BFU-E), and multipotential (CFU-GEMM) progenitor cells in the femur and spleen and on the nucleated cells in the marrow, spleen, and blood. rHF significantly decreased cycling rates and absolute numbers of marrow and splenic hematopoietic progenitors and marrow and blood nucleated cellularity. These effects were apparent in BDF1, C3H/Hej and DBA/2 mice and were dose dependent, time related, and reversible. Suppressive effects were noted within three hours for progenitor cell cycling, within 24 hours for progenitor cell numbers, and within 48 hours for circulating neutrophils. Additionally, hematopoietic progenitor cells in DBA/2 mice infected with the polycythemia-inducing strain of the Friend virus complex (FVC-P) were insensitive to the in vivo administration of rHF. These studies demonstrate activity of rHF in vivo on myelopoiesis of normal but not FVC-P-infected mice. Since rHF suppresses hematopoietic progenitor cell proliferation from normal donors in vitro and from normal mice in vitro and in vivo but does not suppress progenitor cells from patients with leukemia in vitro or from mice with FVC-P-infection in vitro or in vivo, rHF may be useful as a candidate adjunct molecule for the protection of normal hematopoietic progenitor cells during chemotherapy.
Crossover study of immunoglobulin replacement therapy in patients with low-grade B-cell tumors
Authors: Griffiths H , Brennan V , Lea J , Bunch C , Lee M , Chapel H 
Published: October 2019

Abstract
A randomized crossover study of prophylactic immunoglobulin (IgG) therapy was performed in patients with chronic lymphocytic leukaemia (CLL) or non-Hodgkin's lymphoma (NHL). Twelve patients with hypogammaglobulinemia or a history of recurrent infections received infusions of IgG or placebo intravenously (IV) every 3 weeks for 1 year. They were then switched to the alternative preparation for another year. The number of serious bacterial infections was significantly less (P = .001; Mainland's cross-over method) in the months in which patients received IgG. Serious bacterial infections showed a trend to be associated with an IgG level less than 6.4 g/L (P = .046; Fisher's exact test).