bluuebunny/crossref_metadata_2025_split huggingface dataset:
Surreptitious ingestion of a long-acting vitamin K antagonist/rodenticide, brodifacoum: clinical and metabolic studies of three cases
Authors: Weitzel JN , Sadowski JA , Furie BC , Moroose R , Kim H , Mount ME , Murphy MJ , Furie B 
Published: October 2019

Abstract
The vitamin K metabolism of three patients with factitious purpura due to brodifacoum ingestion was studied. These patients, who presented with bleeding disorders due to deficiency of the vitamin K-dependent blood clotting proteins, were refractory to vitamin K1 at standard doses and required fresh frozen plasma to control bleeding until large doses of vitamin K1 were used. Metabolic studies demonstrated a blockade in vitamin K utilization, consistent with the presence of a vitamin K antagonist, but the patients denied use of anticoagulants. Warfarin assays were negative. We show that the factitious purpura in each patient was due to the surreptitious ingestion of brodifacoum, a potent second generation long-acting vitamin K antagonist used as a rodenticide. The coagulopathies responded to long-term therapy with large doses of vitamin K1. The serum elimination half-time for brodifacoum ranged from 16 to 36 days in these patients. The anticoagulant effect is of long duration, requiring chronic vitamin K treatment. With increasing availability of new rodenticides, factitious purpura due to surreptitious ingestion of these potent vitamin K antagonists is emerging as a new problem, previously associated with warfarin, with important implications for diagnosis and treatment.
Vampire bat salivary plasminogen activator is quiescent in human plasma in the absence of fibrin unlike human tissue plasminogen activator
Authors: Gardell SJ , Hare TR , Bergum PW , Cuca GC , O'Neill-Palladino L , Zavodny SM 
Published: October 2019

Abstract
The vampire bat salivary plasminogen activator (Bat-PA) is a potent PA that exhibits remarkable selectivity toward fibrin-bound plasminogen (Gardell et al, J Biol Chem 256: 3568, 1989). Herein, we describe the activity of recombinant DNA-derived Bat-PA (rBat-PA) in a human plasma milieu. rBat-PA and recombinant human single-chain tissue plasminogen activator (rt-PA) are similarly efficacious at lysing plasma clots. In stark contrast to rt-PA, the addition of 250 nmol/L rBat-PA to plasma in the absence of a clot failed to deplete plasminogen, alpha 2- antiplasmin and fibrinogen. The lytic activities exhibited by finger- domain minus Bat-PA (F- rBat-PA) and finger and epidermal growth factor- like domains minus Bat-PA (FG- rBat-PA) were less than rBat-PA, especially at low concentrations of PA; nevertheless, these truncated forms also possessed a strict requirement for a fibrin cofactor. The loss of PA activity following the addition of rBat-PA to plasma was slower than that observed when either rt-PA or two-chain rt-PA was added. The efficacy, fibrin selectivity, and decreased susceptibility to inactivation exhibited by rBat-PA in vitro in a human plasma milieu suggests that rBat-PA may be superior to rt-PA for the treatment of thrombotic complications.
Regulatory control of the terminal complement proteins at the surface of human endothelial cells: neutralization of a C5b-9 inhibitor by antibody to CD59
Authors: Hamilton KK , Ji Z , Rollins S , Stewart BH , Sims PJ 
Published: October 2019

Abstract
Functionally inhibitory antibody to the plasma membrane complement inhibitor CD59 has been used to investigate control of the terminal complement proteins at the endothelial cell surface. Antibodies against purified human erythrocyte CD59 (polyclonal anti-CD59 and monoclonal antibodies [MoAbs] 1F1 and 1F5) were found to bind specifically to monolayers of cultured human umbilical vein endothelial cells, and by Western blotting to recognize an 18- to 21-Kd endothelial protein. When bound to the endothelial monolayer, anti-CD59 (immunoglobulin G or Fab fragment) potentiated membrane pore formation induced upon C9 binding to C5b-8, and augmented the C5b-9-induced cellular responses, including stimulated secretion of von Willebrand factor and expression of catalytic surface for the prothrombinase enzyme complex. Although potentiating endothelial responses to the terminal complement proteins, anti-CD59 had no effect on the response of these cells to stimulation by histamine. Taken together, these data suggest that human endothelial cells express the CD59 cell surface inhibitor of the terminal complement proteins, which serves to protect these cells from pore- forming and cell-stimulatory effects of the C5b-9 complex. These data also suggest that the inactivation or deletion of this cell surface regulatory molecule would increase the likelihood for procoagulant changes in endothelium exposed to complement activation in plasma.
Molecular basis for alpha-thalassemia associated with the structural mutant hemoglobin Suan-Dok (alpha 2 109leu----arg) [published erratum appears in Blood 1991 Mar 15;77(6):1404]
Authors: Weiss I , Cash FE , Coleman MB , Pressley A , Adams JG , Sanguansermsri T , Liebhaber SA , Steinberg MH 
Published: October 2019

Abstract
Hemoglobin (Hb) Suan-Dok (alpha 109Arg) is a rare alpha-globin structural mutation that is linked to an alpha-thalassemia (alpha-thal) determinant. When inherited in trans to an alpha-thal-1 mutation (-), it results in Hb H disease associated with low levels (9%) of the Suan- Dok Hb. The nature of the thalassemic defect associated with the alpha SD mutation has been investigated by structural and functional studies. Sequence analysis of the cloned Suan-Dok allele showed a missense mutation (T----G) at codon 109 in an otherwise normal alpha 2-globin gene. When the alpha 2SD-globin gene was introduced into mouse erythroleukemia cells, the steady state alpha-globin messenger RNA (mRNA) level was equivalent to the alpha A-globin gene control. Although in vitro translation of a synthetic alpha 2SD-globin mRNA generated levels of alpha globin equivalent to alpha 2A-globin mRNA at early time points, the ratio of alpha SD to alpha A globin decreased markedly at later time points. These data suggest that the thalassemic defect associated with the Suan-Dok mutation results from a significant instability of the alpha SD globin.
Expression of platelet glycoprotein Ib by cultured human megakaryocytes: ultrastructural localization and biosynthesis
Authors: Debili N , Kieffer N , Nakazawa M , Guichard J , Titeux M , Cramer E , Breton- Gorius J , Vainchenker W 
Published: October 2019

Abstract
Glycoprotein Ib (GPIb), the receptor for von Willebrand factor, is a two-chain member constituent of the platelet/megakaryocytic lineage. Studies on its expression have been hampered by the difficulties in obtaining purified megakaryocytes in a sufficient number. We report a suspension liquid culture procedure that allowed isolation of more than 1 x 10(6) megakaryocytes with a purity ranging from 3% to 88% from the blood of patients with chronic myeloid leukemia, from fetal liver or from normal human bone marrow. GPIb was detected on the plasma membrane of all maturing megakaryocytes and also of promegakaryoblasts devoid of demarcation membranes. GPIb was detected on demarcation membranes of maturing megakaryocytes but was absent from all other organelles, including alpha granules. Biosynthesis of 35S-methionine labeled megakaryocytes showed that GPIb with similar electrophoretic mobility to the platelet molecule was synthesized and that it was also composed of two chains, since its molecular weight shifted in reducing conditions from 170 Kd to 145 Kd. The beta chain remained undetectable after methionine metabolic labeling, but it was immunoprecipitated after 3H-leucine metabolic labeling, confirming that this subunit is devoid of methionine. GPIb was associated with GPIX, as it is in platelets, since anti-GPIb antibodies coprecipitated a 17 Kd polypeptide.
Plasma cells in multiple myeloma express a natural killer cell- associated antigen: CD56 (NKH-1; Leu-19)
Authors: Van Camp B , Durie BG , Spier C , De Waele M , Van Riet I , Vela E , Frutiger Y , Richter L , Grogan TM 
Published: October 2019

Abstract
Bone marrow samples from 55 patients with multiple myeloma (MM) and 23 patients with monoclonal gammopathy of undertermined significance (MGUS) were evaluated with a broad panel of monoclonal antibodies. Plasma cells from 78% (43/55) of patients with MM strongly expressed the natural killer cell antigen CD56 (NKH-1, Leu-19). Of the 23 patients with MGUS, none showed strong CD56 reactivity, although three had weak reactivity in less than 20% of plasma cells. Myeloma cells expressing CD56 did not coexpress the CD57 or CD16 antigens. Patients with CD56-positive plasma cells had both indolent and aggressive disease. However, the 12 CD56-negative patients had predominantly aggressive disease with an unexpected preponderance of kappa Bence Jones only myeloma (5/10[50%] evaluable patients). Polyclonal plasma cells from non-neoplastic tissue sites (normal bone marrows, lymph nodes, tonsillar biopsies, and gut-mucosa biopsies) showed a near absence of CD56. We conclude that isolated, strong CD56 expression is common in MM, but not in MGUS or reactive plasma cells. The potential biologic importance of CD56 positivity in myeloma is reviewed.
Bone marrow stromal cells modulate both kappa light chain and Ly1 antigen expression on Ly1+ pre-B cell lines in vitro
Authors: Kruger MG , Riley RL , Riley EA , Elia JM 
Published: October 2019

Abstract
Murine Ly1+ pre-B cell lines, including 70Z/3 and three pre-B cell lines derived from long-term bone marrow cultures, exhibited selective adherence to bone marrow stromal cells. In contrast, splenic B cells, the A20 B-cell lymphoma, and four Ly1- B cell lines derived from long- term bone marrow cultures failed to adhere substiantially to bone marrow cultures failed to adhere substiantially to bone marrow stroma. Ly1+ pre-B cell lines were induced to express kappa light chains by exposure to either lipopolysaccharide (LPS), recombinant interleukin-1 (IL-1), or stromal cells. However, induction of kappa light chains failed to prevent pre-B cell adherence to stromal cells. Supernatants derived from primary bone marrow stromal cells decreased Ly1 expression on the Ly1+ pre-B cell lines. These experiments suggest that (1) expression of immunoglobulin light chains by developing Ly1+ pre-B cells is mediated by bone marrow stromal cells; (2) loss of specific adherence to stroma is progressive and occurs post-light chain induction; and (3) soluble products of stromal cells may downregulate expression of surface Ly1 on otherwise Ly1+ pre-B cells. The importance of these observations to the development of both the Ly1- and Ly1+ B cell lineages in the mouse is discussed.
Production of tumor necrosis factor-alpha by B-cell chronic lymphocytic leukemia cells: a possible regulatory role of TNF in the progression of the disease
Authors: Foa R , Massaia M , Cardona S , Tos AG , Bianchi A , Attisano C , Guarini A , di Celle PF , Fierro MT 
Published: October 2019

Abstract
Tumor necrosis factor-alpha (TNF) is a cytokine that displays a pleomorphic array of effects on different cell populations. Evidence is presented that TNF may be constitutively produced by B-cell chronic lymphocytic leukemia (B-CLL) and hairy cell leukemia (HCL) cells and that it may play a relevant role in these diseases. These conclusions are based on the presence of circulating levels of TNF in the serum of 20 of the 24 patients tested (83.3%), while undetectable values were found in normal sera. The suggestion that the increased serum levels were due to the leukemic cell population is strengthened by the evidence that purified B-CLL and HCL cells may constitutively release variable degrees of TNF. These levels markedly increase after incubation with interferon gamma or phytohemagglutinin (PHA) plus phorbol myristate acetate (PMA). The cellular release of TNF by primary B-CLL cells was significantly (P less than .001) higher in B-CLL stage O-I patients compared with stage II-III patients. The demonstration that, in B-cell chronic lymphoproliferative disorders, the pathologic cells may release TNF was further confirmed by the presence of the mRNA for this cytokine in primary and/or in pre-activated cells. Recombinant TNF was capable of inducing a proliferative signal only in a minority of cases (4/24); in most cases it was ineffective, and, in a few, it reduced the degree of proliferation. Furthermore, in costimulatory experiments with interleukin-2 and PHA plus PMA, TNF was ineffective. On the other hand, when primary B-CLL cells were incubated in the presence of an anti-TNF antibody, in 8 of 12 independent experiments a 2- to 15-fold increase in thymidine uptake was documented. Taken together, these results suggest that TNF may play a regulatory role in the progression of the neoplastic clone in B-cell chronic lymphoproliferative disorders and may be implicated in some of the side effects associated with these diseases.
High frequency of human T-cell leukemia-lymphoma virus type II infection in New Mexico blood donors: determination by sequence- specific oligonucleotide hybridization
Authors: Hjelle B , Scalf R , Swenson S 
Published: October 2019

Abstract
The Albuquerque branch of the United Blood Services system was found to have an unusually high blood donor human T-cell leukemia/lymphoma virus (HTLV) seroprevalence (0.72 per 1,000). Many studies investigating HTLV seroprevalence and transmission have assumed that all seropositivity is due to HTLV type I (HTLV-I); recent data dispute this conclusion. We investigated the high prevalence of HTLV seropositivity in New Mexico by determining whether HTLV-I or HTLV-II is predominant in our donors. Using polymerase chain reaction (PCR) amplification of proviral DNA from peripheral blood, followed by sequence-specific hybridization with oligonucleotide probes to distinguish the two viruses, we demonstrate that 9 of 10 Western blot-confirmed HTLV-seropositive blood donors from New Mexico are infected with HTLV-II. Implications of this finding for donors and the safety of the blood supply are discussed.
A comparison of treatment of canine cyclic hematopoiesis with recombinant human granulocyte-macrophage colony-stimulating factor (GM- CSF), G-CSF interleukin-3, and canine G-CSF
Authors: Hammond WP , Boone TC , Donahue RE , Souza LM , Dale DC 
Published: October 2019

Abstract
Cyclic hematopoiesis in gray collie dogs is a stem cell disease in which abnormal regulation of cell production in the bone marrow causes cyclic fluctuations of blood cell counts. In vitro studies demonstrated that recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-3 (IL-3), and granulocyte colony stimulating factor (G-CSF) all stimulated increases in colony formation by canine bone marrow progenitor cells. Based on these results, gray collie dogs were then treated with recombinant human (rh) GM-CSF, IL-3, or G-CSF subcutaneously to test the hypothesis that pharmacologic doses of one of these hematopoietic growth factors could alter cyclic production of cells. When recombinant canine G-CSF became available, it was tested over a range of doses. In vivo rhIL-3 had no effect on the recurrent neutropenia but was associated with eosinophilia, rhGM-CSF caused neutrophilia and eosinophilia but cycling of hematopoiesis persisted. However, rhG-CSF caused neutrophilia, prevented the recurrent neutropenia and, in the two animals not developing antibodies to rhG- CSF, obliterated periodic fluctuation of monocyte, eosinophil, reticulocyte, and platelet counts. Recombinant canine G-CSF increased the nadir neutrophil counts and amplitude of fluctuations at low doses (1 micrograms/kg/d) and eliminated all cycling of cell counts at high doses (5 and 10 micrograms/kg/d). These data suggest significant differences in the actions of these growth factors and imply a critical role for G-CSF in the homeostatic regulation of hematopoiesis.
Transforming growth factor beta inhibits endomitosis in the Dami human megakaryocytic cell line
Authors: Greenberg SM , Chandrasekhar C , Golan DE , Handin RI 
Published: October 2019

Abstract
Megakaryocyte development is a carefully controlled process that is at least partially regulated by cytokines. Previous investigations of megakaryocyte development have focused primarily on defining growth factors that induce or enhance differentiation. In this study we demonstrate that a specific cytokine, transforming growth factor beta 1 (TGF beta 1), inhibits the phorbol myristate acetate (PMA)-induced differentiation of the Dami human megakaryocytic cell line. The addition of purified platelet TGF beta 1 inhibits PMA-induced endomitosis in a dose-dependent manner. Inhibition of endomitosis occurs with as little as 0.4 pmol/L TGF beta 1, is half-maximal at 6.4 pmol/L, and is maximal between 40 and 200 pmol/L TGF beta 1. Inhibition does not require other growth factors or nonmegakaryocytic cells. Removal of TGF beta 1 from the cultures decreases inhibition, suggesting that the continuous presence of TGF beta 1 is required and that its effects are reversible. This effect occurs even though the Dami cells constitutively express TGF beta 1 messenger RNA (mRNA) and the TGF beta 1 mRNA levels are increased by PMA. TGF beta 1 also has been shown to inhibit endomitosis during short-term culture of primary human megakaryocytes. These results suggest a model in which negative as well as positive regulatory factors modulate a critical stage of megakaryocyte development.
Evidence that chronic lymphocytic leukemia B lymphocytes are frequently committed to production of natural autoantibodies
Authors: Borche L , Lim A , Binet JL , Dighiero G 
Published: October 2019

Abstract
CD5+ B lymphocytes have been postulated to be primarily involved in autoantibody production. To investigate whether CD5 B lymphocytes from chronic lymphocytic leukemia (CLL) patients display the same function, we fused B lymphocytes from 23 CD5+ B-CLL with nonsecreting murine myeloma X-63 cells. Hybrids were derived from 18 of the 23 patients, but only hybrids from 13 patients were found to secrete immunoglobulin (Ig) (IgM kappa 4, IgM lambda 8, and only kappa light chain 1). Supernatants of these hybrids were tested against an extensive panel of antigens by enzyme-linked immunosorbent assay, indirect immunofluorescence, and hemagglutination. At the same time, peripheral blood mononuclear cells (PBMC) from 15 of these patients, including most patients from whom secreting hybrids had not been obtained, were stimulated with phorbol myristate acetate (PMA). Our results indicated that secreting heterohybrids from CLL B lymphocytes are frequently obtained; however, this is highly dependent on the light chain phenotype, since 8 of 9 lambda-expressing CLL produced hybrids secreting complete Igs, as compared with 4 of 12 kappa-expressing CLL. In addition, B lymphocytes of most patients from whom we failed to derive secreting hybrids also failed to secrete Ig on PMA stimulation. Secondly, CD5+ B-CLL lymphocytes were frequently committed to the production of natural autoantibodies, since in 8 of 15 cases (including hybrids and PMA stimulation) anti-Fc activity was found; three of these also displayed a multispecific binding pattern.
Abnormal FcRIII expression by neutrophils from very preterm neonates
Authors: Carr R , Davies JM 
Published: October 2019

Abstract
To further investigate the neutrophil dysfunction of newborn infants, we have measured expression of the neutrophil Fc gamma receptors FcRIII and FcRII in extremely immature preterm neonates born at 24 to 32 weeks of gestation. Fc receptor expression was measured by FACS analysis of cells stained with monoclonal antibody Leu11b for FcRIII and IV-3 for FcRII. “Well” preterm neonates displayed reduced FcRIII, 51.05 +/- 2.0 (mean fluorescence channel +/- SE) when compared with term neonates, 69.24 +/- 5.5 and adult controls, 71.83 +/- 3.0. “Stressed” preterm neonates with severe respiratory distress syndrome or septicemia had a further downregulation of FcRIII, 32.67 +/- 3.0 and 35.75 +/- 1.8, respectively, associated with grossly abnormal cellular fluorescence distribution. In well preterm neonates, expression of FcRIII improved to adult levels during the first two postnatal weeks, suggesting a postnatal maturation of function. Stressed neonates had signs of partial neutrophil activation (increased Mac-1 expression and chemotactic ability), leading us to propose that the further downregulation of FcRIII may be due to receptor shedding in vivo by partially activated cells. FcRII expression was found to be equivalent to adult levels in both well preterm and stressed neonates. Reduced neutrophil FcRIII expression may provide some explanation for the reported abnormalities of phagocytosis and bacterial killing in preterm neonates.
An antibody that facilitates hematopoietic engraftment recognizes CD44
Authors: Sandmaier BM , Storb R , Appelbaum FR , Gallatin WM 
Published: October 2019

Abstract
Pretreatment of recipients with the monoclonal antibody (MoAb) S5 facilitates engraftment of bone marrow from mismatched, unrelated donors in the canine transplantation model. In the direct comparisons reported here, the S5 glycoprotein (gp) was found to have structural homology to CD44 that in humans has been implicated in adhesive interactions of one type of effector cell, the lymphocyte. The S5 antigen and gp90Hermes-1 exhibited codistribution on canine peripheral blood cells. Both S5 and Hermes-1 (anti-CD44) MoAbs recognized 90-Kd species in radioimmune precipitations of 125I surface-labeled canine peripheral blood lymphocytes and bone marrow cells. Competitive antibody binding experiments showed that the epitope detected by S5 was distinct from that bound by Hermes-1 but overlapped with those defined by two other known anti-CD44 reagents, IM7 and Hutch-1. Sequential immunoprecipitation with S5 and Hermes-1 indicated that the two antibodies recognize the same or overlapping subsets of membrane gps. Tryptic digestion of S5 and anti-CD44 immunoprecipitates generated two major iodinated peptides of 27 and 35 Kd in both cases, a further indication of structural homology. Similarly, after N-glycanase digestion, S5 and CD44 immunoprecipitates were resolved to a single 68- Kd species. These findings suggest that CD44-mediated adhesive events may affect the fate of transplanted hematopoietic cells. The previous implications of this gp in T-lymphocyte activation and lymphocyte adhesion to endothelium thus provide useful paradigms to analyze its function in the bone marrow transplant setting.