bluuebunny/crossref_metadata_2025_split huggingface dataset:
IgM antibody response in acute hepatitis C viral infection
Authors: Clemens JM , Taskar S , Chau K , Vallari D , Shih JW , Alter HJ , Schleicher JB , Mimms LT 
Published: October 2019

Abstract
IgM antibody against hepatitis C virus (IgM anti-HCV) was measured in serial samples from 15 transfusion recipients in whom posttransfusion chronic non-A, non-B hepatitis (NANBH) developed and three plasmapheresis donors during acute HCV infection using recombinant proteins derived from three immunodominant regions: core, NS-3, and NS- 4 (c100). IgM anti-HCV core was detected in 13 of 15 posttransfusion patients. Nine of these patients had transient, acute-phase IgM anti- HCV core detected coincidentally or earlier than active IgG anti-HCV core response. The average duration of IgM anti-HCV core reactivity was 8.1 +/- 3.7 weeks. One patient lacking an IgM anti-HCV core response had detectable IgM anti-HCV NS-3 during the acute phase. Passive transfer of IgM anti-HCV was not observed in these posttransfusion cases, in contrast to the high frequency observed for IgG anti-HCV. Late IgM anti-HCV was detectable against core, c100, and NS-3 in three, two, and one posttransfusion patients, respectively. These data indicate that IgM anti-HCV core is a useful acute-phase marker in HCV infection.
Factor-dependent erythroid cell lines derived from mice transplanted with hematopoietic cells expressing the v-src oncogene
Authors: Kennedy M , Beug H , Wagner EF , Keller G 
Published: October 2019

Abstract
Transplantation of spleen cells from primary reconstituted mice expressing the v-src oncogene to secondary and tertiary irradiated recipients resulted in the emergence of erythroid precursors with a transformed phenotype. When cultured in methyl cellulose, these precursors generated colonies of undifferentiated cells that could be expanded into continuously growing factor-dependent cell lines in liquid culture. All lines tested had a similar phenotype and expressed the v-src oncogene. In addition they responded to factors that regulate normal erythroid development, namely erythropoietin (Epo), interleukin- 3 (IL-3), and mast cell growth factor (MGF), the ligand to the c-kit encoded receptor. When cells from one of the lines were maintained in the absence of factor, a “factor independent” subpopulation emerged that appeared to grow in an autocrine fashion. Conditioned medium from these cells stimulated their own growth as well as the growth of broad spectrum of normal precursors. Studies with neutralizing antibodies indicated that the predominant colony-stimulating factor produced by these cells is IL-3.
Mean corpuscular volume of heterozygotes for beta-thalassemia correlates with the severity of mutations
Authors: Rund D , Filon D , Strauss N , Rachmilewitz EA , Oppenheim A 
Published: October 2019

Abstract
The relationship between the degree of microcytosis and the type of mutation carried by beta-thalassemia heterozygotes was investigated. In 113 individuals, 18 different mutations were identified, correlated with mean corpuscular volume (MCV) values, and analyzed statistically. Overall, there was a wide range of MCV (56.3–87.3 fL). In almost all cases, carriers of beta(0) mutations had an MCV below 67 fL, whereas all but a few beta(+) heterozygotes had MCVs above this cutpoint. Mean MCV of beta(0) carriers was statistically significantly lower than those of beta(+) heterozygotes. The various beta(+) mutations were associated with significant differences in mean MCV values. In contrast, all the beta(0) (null) mutations had virtually identical ranges of MCV. The results indicate that degree of reduction in MCV is directly related to the severity of the mutation. Deviations, in four cases, were associated with concurrent alpha gene rearrangements, whereas in three other cases, the MCV was not significantly affected by concurrent alpha rearrangements. The MCV of beta-thalassemia heterozygotes is a valuable parameter in planning strategies for rapid identification of mutations in populations with great mutational diversity. Its use can be particularly advantageous in the setting of prenatal diagnosis. The pattern of mean corpuscular hemoglobin (MCH) values was similar to the MCV pattern. However, our results suggest that MCH may be preferred for carrier detection in population screening.
Absence of abnormalities of c-kit or its ligand in two patients with Diamond-Blackfan anemia
Authors: Abkowitz JL , Broudy VC , Bennett LG , Zsebo KM , Martin FH 
Published: October 2019

Abstract
As Diamond-Blackfan anemia shares clinical features with W and Steel defects in mice, we investigated the possibility that this human disorder might result from an abnormality of the c-kit receptor or its ligand, stem cell factor (SCF). For these studies, full nucleotide sequences for coding regions of c-kit and SCF were generated for two Diamond-Blackfan anemia patients and were normal. Similarly, the kds of SCF receptors on their marrow cells (31 pmol/L, 43 pmol/L) were comparable with those found in three normal controls (50 pmol/L, 55 pmol/L, 27 pmol/L). Serum SCF concentrations were 6.9 ng/mL in patient A, 14.6 ng/mL in patient B, who has been in hematologic remission since adolescence, and 2.7 ng/mL in the 3-year-old daughter of patient B, who also has Diamond-Blackfan anemia but is transfusion-dependent. It is possible that the SCF level in patient B increased with puberty, leading to her remission. These data provide evidence that Diamond- Blackfan anemia does not result from structural abnormalities of c-kit or SCF.
A unique factor XIII inhibitor to a fibrin-binding site on factor XIIIA
Authors: Fukue H , Anderson K , McPhedran P , Clyne L , McDonagh J 
Published: October 2019

Abstract
An 81-year-old woman, who presented with sudden episodes of spontaneous bleeding, was found to have a specific inhibitor of factor XIII. Her fibrin clots had approximately 70% gamma-gamma and no alpha polymer formation, under conditions where normal fibrin was fully cross-linked; the patient's clots were soluble in urea or monochloroacetic acid. Factor XIII activity in her plasma was 24%, measured by the dansylcadaverine incorporation assay. When mixed with normal plasma, the patient's plasma inhibited fibrin cross-linking; however, in mixtures of patient and normal plasma, there was no inhibition of factor XIII activity when assayed by the incorporation of dansylcadaverine into casein. Thus, this inhibitor was active against fibrin cross-linking but not against ligation of small molecules to casein. Consequently, gel electrophoresis of reduced, sodium dodecyl sulfate-solubilized fibrin clots was a simple, quantitative method that was used to measure inhibitor activity. This inhibitor is unique and has been designated inhibitor New Haven. It was neutralized by anti-IgG and anti-kappa. It did not inhibit the activation of factor XIII but did inhibit fibrin cross-linking. There was complex formation between the inhibitor and activated factor XIII (A′, A*) but not between A2 or fibrinogen. Only A′, A* and the 56-Kd fragment bound to affinity columns made with this IgG. The inhibitor significantly decreased the binding of A′, A* to fibrin clots. These data indicate that the epitope for this inhibitor is in a fibrin binding site. It is hidden in the zymogen and expressed on A′ and A*, indicating that the conformational change occurring with the cleavage of the activation peptide is sufficient to expose the fibrin binding site.
Differential roles of stromal cells, interleukin-7, and kit-ligand in the regulation of B lymphopoiesis
Authors: Billips LG , Petitte D , Dorshkind K , Narayanan R , Chiu CP , Landreth KS 
Published: October 2019

Abstract
Newly formed B lymphocytes are a population of rapidly renewed cells in the bone marrow of mammals and their steady state production presumably depends on a cascade of regulatory cells and cytokines. Although considerable information has been forthcoming about the role of interleukin-7 (IL-7) in potentiating pre-B-cell proliferation, few studies have addressed the possibility that multiple cytokines are involved in the progression of early events in cellular differentiation and proliferation in this hematopoietic lineage. Our laboratory previously described pre-B-cell differentiation mediated by the bone marrow stromal cell line S17. In this study, we further delineate the role of stromal cells in differentiation and proliferation of pre-B cells. These experiments show that the stromal cell line S17 potentiates the proliferative effect of IL-7 on B-lineage cells and that this S17-derived potentiator can be replaced with recombinant kit- ligand (KL). Our results further show that pre-B-cell formation from B220-, Ig- progenitor cells and expression of mu heavy chain of immunoglobulin is uniquely dependent on the presence of S17 stromal cells and cannot be reproduced with IL-7, KL, or costimulation with both IL-7 and KL. These data contribute to a rapidly evolving model of stromal cell regulation of B-cell production in the marrow and suggest unique roles for IL-7, KL, and as yet uncharacterized stromal cell- derived lymphokines in this process.
A gamma delta+ T-cell leukemia bearing a novel t(8;14)(q24;q11) translocation demonstrates spontaneous in vitro natural killer-like activity
Authors: Maziarz RT , Arceci RJ , Bernstein SC , Frazier L , Smith BR , Kasai M , Tantravahi R , Strominger JL 
Published: October 2019

Abstract
A highly malignant human T-cell leukemia was identified by cell surface analysis as a member of the T-cell receptor (TCR) gamma delta lineage. Cytogenetic and molecular analysis showed a novel t(8;14)(q24;q11) rearrangement involving the J delta 1 gene segment on chromosome 14 and the distal end of chromosome 8 near the c-myc proto-oncogene locus. The gamma delta TCR of the leukemia blasts was functionally intact and could be activated to generate intracellular calcium flux and to target Fc receptor-mediated redirected tumor cell lysis. In addition, non- major histocompatibility complex restricted lysis of a limited target cell panel was shown by fresh leukemic blasts and by the in vitro- maintained leukemia cells that was comparable to known T-cell lines with natural killer-like activity. These data suggest that the T-cell leukemia potentially had in vivo functional cytolytic activity. However, whether this activity did contribute to the patient's clinical condition could not be determined.
Isolation of cDNA coding for an ubiquitous membrane protein deficient in high Na+, low K+ stomatocytic erythrocytes
Authors: Stewart GW , Hepworth-Jones BE , Keen JN , Dash BC , Argent AC , Casimir CM 
Published: October 2019

Abstract
Human red blood cells (RBCs) that are deficient in an integral membrane- associated protein (“stomatin“) of apparent molecular mass 31 Kd show a catastrophic increase in passive membrane permeability to the univalent cations Na+ and K+ and are stomatocytic in shape. We have purified this protein from normal RBC membranes and isolated a cDNA clone coding for it. The deduced protein sequence is unrelated to that of any known ion- transport-related protein. Selective solubilization studies using detergents show that while the protein is strongly associated with the phospholipid bilayer, it also binds to the cytoskeleton. The predicted polypeptide has a single trans-membranous hydrophobic segment near the N-terminus, which would locate it in the membrane; the large C-terminal domain is hydrophilic and cytoplasmic in orientation and is presumed to be responsible for the attachment to the cytoskeleton. By inference, the protein has the function of closing a latent ion channel. The messenger RNA encoding this protein is ubiquitously distributed in different human cell types and tissues and is thus presumably a widely distributed regulator of transmembrane cation fluxes. As a membrane- bound inhibitor protein of Na+ and K+ transport, it is unique among the known components of membrane-transport proteins.
Acute- and chronic-phase chronic myelogenous leukemia colony-forming units are highly sensitive to the growth inhibitory effects of c-myb antisense oligodeoxynucleotides
Authors: Ratajczak MZ , Hijiya N , Catani L , DeRiel K , Luger SM , McGlave P , Gewirtz AM 
Published: October 2019

Abstract
We have previously demonstrated that malignant hematopoietic colony- forming units (CFUs) may be purged from normal CFU by exposure to c-myb antisense oligodeoxynucleotides (oligomers). This novel strategy appeared particularly promising for patients with chronic myelogenous leukemia (CML) in blast crisis, since in some cases complete elimination of bcr-abl-expressing cells was accomplished. We have examined 11 additional patients, including seven in chronic phase, in order to extend these initial observations. We sought in particular to determine if elimination of bcr-abl-expressing clones was a usual event. Exposure of CML cells to c-myb antisense oligomers resulted in inhibition of CFU-granulocyte, macrophage (CFU-GM)-derived colony formation in eight of 11 (73%) cases evaluated. Inhibition was antisense sequence-specific, dose-dependent, ranged between 58% and 93%, and was statistically significant (P less than or equal to .03) in seven of the eight cases. In two cases, CFU-granulocyte, erythrocyte, monocyte, megakaryocyte (CFU-GEMM)-derived colony formation was also examined and found to be inhibited by the c-myb antisense oligomers in a sequence-specific manner. To determine whether CML CFU had been reduced or eliminated after exposure to the antisense oligomers, we examined cells in the residual colonies for bcr-abl mRNA expression using a reverse transcription-polymerase chain reaction detection technique (RT-PCR). Eight cases were evaluated and in each case where antisense myb inhibited growth, bcr-abl expression as detected by RT- PCR was either greatly decreased or nondetectable. No residual leukemic CFU were demonstrable on replating of treated cells. These results suggest that c-myb antisense oligomers substantially inhibit the growth and survival of CML CFU in both chronic and blast phase of disease. They may therefore prove useful for both ex vivo and in vivo treatment of CML.
Propagation of human blastic myeloid leukemias in the SCID mouse
Authors: Sawyers CL , Gishizky ML , Quan S , Golde DW , Witte ON 
Published: October 2019

Abstract
Existing in vitro culture technology does not permit the routine propagation of most human myeloid leukemias. Previous work has shown the usefulness of mice with severe combined immunodeficiency (SCID) for the growth of human lymphoblastic leukemia. We show here that human myeloid cell lines and bone marrow samples from patients with acute myeloid leukemia (AML) and blast crisis of chronic myeloid leukemia (CML) also grow in SCID mice. Human AML or CML cell lines (three of three lines tested) grew in the bone marrow and peripheral blood of the mice after intravenous (IV) inoculation in a pattern closely resembling human AML. To define the best conditions for the growth of primary human myeloid leukemia cells, samples were transplanted into mice at several alternative sites. Using flow cytometry and Southern analysis, mice were analyzed at defined intervals up to 36 weeks after transplantation for the presence of human cells in various tissues. For four of four patients with AML and two of two patients with blast crisis of CML, myeloblasts grew locally at the site of implantation and were detected in the murine hematopoietic tissues. In contrast, marrow implants from patients in the chronic phase of CML (six patients) showed infrequent and limited myeloid growth in the mice. These findings demonstrate that the SCID mouse is a reproducible system for the propagation of blastic human myeloid leukemias. The differential growth of early- versus late-phase CML suggests that the SCID mouse may be a useful assay for identifying biologically aggressive leukemias early in their clinical presentation.
Type 1 plasminogen activator inhibitor synthesis of endothelial cells is downregulated by smooth muscle cells
Authors: Christ G , Seiffert D , Hufnagl P , Gessl A , Wojta J , Binder BR 
Published: October 2019

Abstract
Plasminogen activator inhibitor type 1 (PAI-1), the physiologic inhibitor of both tissue-type plasminogen activator (tPA) and urokinase- type plasminogen activator (uPA), is a major biosynthetic product of endothelial cells in vitro; endothelial cells in vivo, in contrast, do not appear to produce significant amounts of PAI-1 as made evident by in situ-hybridization studies in normal mice. This suggests that the high rate of PAI-1 synthesis of endothelial cells in vitro might be a result of the culture conditions. When human umbilical vein endothelial cells (HUVEC) were grown on human amniotic membranes, resembling the natural growth support instead of coated plastic, their morphology was changed from the cobblestone-like appearance on plastic to an in vivo like flagstone pattern. However, this morphological change had no significant effect on the synthesis and secretion of PAI-1. When smooth muscle cell (SMC) conditioned media (CM) were added to HUVEC cultures, PAI-1 antigen secretion of HUVEC was reduced by 40% to 60% as measured by enzyme-linked immunosorbent assay (ELISA). Immunoprecipitation experiments using 36S-methionine metabolically labeled HUVEC and Northern blot analysis of HUVEC PAI-1 mRNA indicate that this reduction was attributable to decreased PAI-1 synthesis and reduced steady-state levels of both the 3.2 kb and 2.2 kb form of PAI-1 mRNA. This effect was dose-dependent and observed under serum-containing as well as serum- free conditions, in the absence or presence of endothelial cell growth supplement (ECGS, 0 to 100 micrograms/mL) and attributable to a nondialyzable factor. Our data suggest that the high level of PAI-1 biosynthesis of endothelial cells in vitro may be attributable to the lack of a soluble factor produced by SMC, which controls and suppresses PAI-1 biosynthesis of endothelial cells in vivo.
Basic fibroblast growth factor promotes the proliferation of human megakaryocyte progenitor cells
Authors: Bruno E , Cooper RJ , Wilson EL , Gabrilove JL , Hoffman R 
Published: October 2019

Abstract
Basic fibroblast growth factor (bFGF), a multifunctional growth factor produced by bone marrow stromal cells, is known to be a potent modulator of hematopoiesis. Because bFGF is present in both human megakaryocytes (MKs) and platelets, we have hypothesized that this growth factor might affect human megakaryocytopoiesis. To test this hypothesis, either low density bone marrow (BM) cells (LDBM), a human BM subpopulation (CD34+ DR+) enriched for the colony-forming unit megakaryocyte (CFU-MK) or a BM subpopulation (CD34+ DR-) enriched for the more primitive burst-forming unit megakaryocyte (BFU-MK) were assayed in the presence of this growth factor. The effect of bFGF on MK colony formation differed according to the cell population assayed. bFGF alone had on MK colony-stimulating activity (MK-CSA) when either CD34+ DR+ or CD34+ DR- BM cells were cloned, but exhibited MK-CSA equivalent to that of interleukin-3 (IL-3) when LDBM cells were used as the target cell population. The MK-CSA of bFGF was inhibited by the addition of neutralizing antisera to either IL-3 and/or granulocyte- macrophage colony-stimulating factor (GM-CSF) but not IL-6. The addition of excess amounts of either IL-3 or GM-CSF to cultures containing bFGF plus anti-IL-3 or anti-GM-CSF reversed the inhibition by the corresponding antisera. The addition of bFGF and IL-3 to assays containing CD34+ DR+ or CD34+ DR- cells increased the size of both CFU- MK- and BFU-MK-derived colonies, respectively, when compared with assays containing IL-3 alone. This increase in MK colony size mediated by bFGF was not affected by addition of either an anti-GM-CSF or anti- IL-6 neutralizing antisera. When LDBM cells were assayed, bFGF alone increased CFU-MK-derived colony size when compared with control values. However, this potentiation of MK colony size by bFGF could be reversed by the addition of either anti-IL-3 or anti-GM-CSF but not anti-IL-6 antisera. In addition, the effects of bFGF and IL-3 on the size of MK colonies cloned from LDBM were not additive. These results suggest that bFGF affects human megakaryocytopoiesis by directly promoting MK progenitor cell proliferation and stimulating BM accessory cells to release growth factor(s) with MK-CSA, such as IL-3 and GM-CSF. We conclude that bFGF, likely produced by cellular components of the BM microenvironment, plays an important role in the control of human megakaryocytopoiesis.
Aspirin does not inhibit adenosine diphosphate-induced platelet alpha- granule release
Authors: Rinder CS , Student LA , Bonan JL , Rinder HM , Smith BR 
Published: October 2019

Abstract
The involvement of metabolites of arachidonic acid in platelet-dense granule secretion and secondary platelet-platelet interactions is well characterized. However, their role in heterotypic interactions dependent on alpha-granule secretion is less well understood. Using platelet-surface expression of P-selectin as a marker of alpha-granule secretion, we have shown that: (1) aspirin treatment of platelets at doses that block dense granule secretion does not inhibit alpha-granule secretion to adenosine diphosphate (ADP); (2) synergism between epinephrine and ADP in the induction of P-selectin expression is similarly unaffected by aspirin; and (3) the ability of P-selectin to mediate adhesion of activated platelets to monocytes and polymorphonuclear lymphocytes in whole blood is also unchanged by aspirin treatment. To further explore the mechanisms responsible for platelet alpha-granule secretion, we have shown that inhibition of Na+/H+ exchange by either acidification of the extracellular medium or amiloride treatment blocked ADP-induced P-selectin expression. In contrast, incubation with the platelet lipoxygenase inhibitor 5,8,11- eicosatrynoic acid, by itself and with aspirin, did not decrease ADP- induced P-selectin expression. We conclude that platelet alpha-granule secretion in response to ADP is dependent on intact Na+/H+ exchange but is independent of the lipoxygenase- and cyclooxygenase-dependent metabolites of arachidonic acid.