bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expression of Proteins Controlling Transbilayer Movement of Plasma Membrane Phospholipids in the B Lymphocytes From a Patient With Scott Syndrome
Authors: Zhou Quansheng , Sims Peter J. , Wiedmer Therese 
Published: October 2019

AbstractScott syndrome is a rare inherited bleeding disorder in which platelets and other blood cells fail to promote normal assembly of the membrane-stabilized proteases of the plasma coagulation system. The defect in Scott blood cells is known to reflect inability to mobilize phosphatidylserine from inner plasma membrane leaflet to the cell surface in response to an elevation of Ca2+ at the endofacial surface. To gain insight into the molecular basis of this membrane defect, we examined the expression in Scott cells of plasma membrane proteins that have been implicated to participate in the accelerated transbilayer movement of plasma membrane PL. By both reverse transcriptase-polymerase chain reaction (RT-PCR) and functional assay, the level of expression of the multidrug resistance (MDR)1 and MDR3 P-glycoproteins in immortalized B-lymphoblast cell lines from the patient with Scott syndrome were indistinguishable from matched cell lines derived from normal controls. Whereas the plasma membrane of Scott cells are insensitive to activation of the plasma membrane PL scramblase pathway, it had been shown that PL scramblase protein isolated from detergent-solubilized Scott erythrocytes exhibits normal function when incorporated into proteoliposomes (Stout JG, Basse F, Luhm RA, Weiss HJ, Wiedmer T, Sims PJ: J Clin Invest 99:2232, 1997). Consistent with this finding in Scott erythrocytes, we found that Scott lymphoblasts expressed normal levels of PL scramblase mRNA and protein, and that the deduced sequence of PL scramblase in Scott cells is identical to that of normal controls. These data suggest that the defect in Scott syndrome is related either to aberrant posttranslational processing of the PL scramblase polypeptide or to a defect or deficiency in an unknown cofactor that is required for normal expression of plasma membrane PL scramblase function in situ, or alternatively, reflects the presence of a detergent-dissociable inhibitor of this pathway.© 1998 by The American Society of Hematology.
Anemia in Children With Cancer Is Associated With Decreased Erythropoietic Activity and Not With Inadequate Erythropoietin Production
Authors: Corazza Francis , Beguin Yves , Bergmann Pierre , André Marie , Ferster Alina , Devalck Christine , Fondu Pierre , Buyse Marc , Sariban Eric 
Published: October 2019

AbstractA defect in erythropoietin (EPO) production has been advocated as being the main cause of anemia presented at time of diagnosis or during treatment by adults with solid tumors. On the basis of this defect, anemic cancer patients, both adults and children, have been treated with recombinant human EPO (rHuEPO). To further elucidate the pathophysiology of anemia in children with cancer, we measured serum soluble transferrin receptor (sTfR), a quantitative marker of erythropoiesis, and serum EPO at time of diagnosis and during chemotherapy in children suffering from solid tumor or leukemia. We determined serum EPO in 111 children (55 leukemia, 56 solid tumors) at time of diagnosis. In the last 44 patients (23 leukemia and 21 solid tumors), sTfR levels were also measured. Serum EPO together with sTfR levels were also determined in 60 children receiving chemotherapy (29 leukemia, 31 solid tumors). These results were compared with those obtained from appropriate control groups. In all patients, we found a highly significant correlation between the logarithm of EPO (log[EPO]) and the hemoglobin (Hb) level. In all subsets of patients, sTfR levels were inappropriately low for the degree of anemia. Neither leukemic nor solid tumor groups showed a significant inverse relationship between log(sTfR) and the Hb level as would be expected in anemic patients with appropriate marrow response. Thus, in children with cancer, anemia is associated with a decreased total bone marrow erythropoietic activity which, in contrast to what has been reported in anemic cancer adults, is not related to defective EPO production.© 1998 by The American Society of Hematology.
Impaired Expression of Integrin -4 Subunit in Cultured Mast Cells Derived From Mutant Mice of mi/mi Genotype
Authors: Kim Dae-Ki , Morii Eiichi , Ogihara Hideki , Hashimoto Koji , Oritani Kenji , Lee Young-Mi , Jippo Tomoko , Adachi Shiro , Kanakura Yuzuru , Kitamura Yukihiko 
Published: October 2019

AbstractThe mi locus encodes a member of the basic-helix-loop-helix-leucine zipper protein family of transcription factors (hereafter called MITF). We have reported that expression of several genes was impaired in cultured mast cells (CMCs) ofmi/mi mice due to a defective transactivation ability of mutant MITF (mi-MITF). Because attachment of mi/mi CMCs to fibroblasts is impaired, we examined the expression of integrin genes in mi/mi CMCs in the present study. Among the integrin genes examined, the expression of integrin 4 subunit was barely detectable in mi/mi CMCs, and the 4 protein was not detected by flow cytometry either. The specific adhesion to vascular cell adhesion molecule-1 (VCAM-1), the ligand for 4 subunit, was observed in +/+ CMCs but not in mi/mi CMCs, indicating that the expression of integrin 4 subunit at a functional level did not occur in mi/mi CMCs. In the promoter region of the 4 subunit gene, there was a CACTTG motif to which normal MITF (+- MITF) bound. The coexpression of +-MITF but not of mi-MITF transactivated the promoter of the 4 subunit gene. The deletion or mutation of the CACTTG motif abolished the transactivation by +-MITF, suggesting that +-MITF directly transactivated the gene encoding 4 subunit of integrin.© 1998 by The American Society of Hematology.
Lysis of Plasma Clots by Urokinase-Soluble Urokinase Receptor Complexes
Authors: Higazi Abd Al-Roof , Bdeir Khalil , Hiss Edna , Arad Shira , Kuo Alice , Barghouti Iyad , Cines Douglas B. 
Published: October 2019

AbstractSingle-chain urokinase plasminogen activator (scuPA), the unique form secreted by cells, expresses little intrinsic plasminogen activator activity. scuPA can be activated by proteolytic cleavage to form a two-chain enzyme (tcuPA), which is susceptible to inhibition by plasminogen activator inhibitor type I (PAI-1). scuPA is also activated when it binds to its cellular receptor (uPAR), in which case the protein remains as a single chain molecule with less susceptibility to PAIs. Fibrin clots are invested with PAI-1 derived from plasma and from activated platelets. Therefore, we compared the fibrinolytic activity of complexes between scuPA and recombinant soluble uPAR (suPAR) to that of scuPA, tcuPA, and tcuPA/suPAR complexes. scuPA/suPAR complexes mediated the lysis of plasma-derived fibrin clots 14-fold more extensively than did equimolar concentrations of scuPA and threefold more extensively than did tcuPA or tcuPA/suPAR, respectively. The enhanced catalytic activity of scuPA/suPAR required that all three domains of the receptor be present, correlated with its PAI-1 resistance, was not dependent on fibrin alone, and required a plasma cofactor that was identified as IgG. Human IgG bound specifically to suPAR and scuPA/suPAR as determined by using affinity chromatography and immunoprecipitation. Plasma depleted of IgG lost most of its capacity to promote the fibrinolytic activity of scuPA/suPAR, and the activity of the complex was restored by adding plasma concentrations of purified IgG. These studies indicate that scuPA/suPAR can function as a plasminogen activator in a physiological milieu.© 1998 by The American Society of Hematology.
Is Hemoglobin Instability Important in the Interaction Between Hemoglobin E and β Thalassemia?
Authors: Rees D.C. , Clegg J.B. , Weatherall D.J. 
Published: October 2019

Abstract
Hemoglobin E (HbE; 2β226glu-lys), globally the commonest hemoglobin variant, is synthesized at a slightly reduced rate and has a homozygous phenotype similar to heterozygous β thalassemia. Yet, when it is inherited together with a β thalassemia allele, the resulting condition, HbE/β thalassemia, is sometimes characterized by a severe, transfusion-dependent thalassemia major. The severity of this interaction has not been explained. We have explored the possibility that it may reflect the instability of HbE consequent upon globin chain imbalance imposed by the β thalassemia allele. Time-course and pulse-chase globin chain synthesis studies at 37°C on peripheral blood and bone marrow suggest that hemoglobin instability is not significant in steady-state HbE/β thalassemia; this is confirmed by density-gradient centrifugation studies that show no decrease in HbE levels relative to HbA as HbE/β+ thalassemia red blood cells age. Globin binding to membranes was assessed and only  globin chains were found, in contrast to other unstable hemoglobins in which both  and β chains were present. However, in experiments performed on blood from HbE/β thalassemics in the temperature range 39°C to 41°C, there was evidence of instability of HbE, a finding that was also observed in homozygous HbE. These findings suggest that the phenotype of HbE/β thalassemia is primarily the result of the interaction of two β thalassemia alleles; however, hemoglobin instability may be important during febrile episodes, contributing to worsening anemia.
© 1998 by The American Society of Hematology.
Arg89Cys Substitution Results in Very Low Membrane Expression of the Duffy Antigen/Receptor for Chemokines in Fyx Individuals
Authors: Tournamille Christophe , Le Van Kim Caroline , Gane Pierre , Le Pennec Pierre Yves , Roubinet Francis , Babinet Jérôme , Cartron Jean Pierre , Colin Yves 
Published: October 2019

AbstractThe Duffy (FY) blood group antigens are carried by the DARC glycoprotein, a widely expressed chemokine receptor. The molecular basis of the Fya/Fyb and Fy(a-b-) polymorphisms has been clarified, but little is known about the Fyxantigen and the FY*X allele associated with weak expression of Fyb, Fy3, Fy5, and Fy6 antigens. We analyzed here the structure and expression of the FY gene in 4 Fy(a-bweak) individuals. As compared with Fy(a-b+) controls, the Fy(a-bweak) red blood cell membranes contained residual amount of DARC polypeptide and these cells were poorly bound by anti-Fy antibodies and chemokines. The FY gene from Fy(a-b+) and Fy(a-bweak) individuals differed by one substitution, C286T. The resulting Arg89Cys amino acid change reduced the binding of anti-Fy antibodies and chemokines to DARC transfectants. We concluded that the Fybweak donors carried theFY*X allele at the FY locus and that the Fyxantigen corresponds to highly reduced expression of a grossly normal Fyb polypeptide caused by the Arg89Cys substitution. Because FY is a single copy gene, this defect should also affect DARC expression in nonerythroid cells. Because the Fyx phenotype is not associated with apparent clinical consequences, we discussed these findings in the light of the putative roles of DARC in various tissues. Finally, we developed a Fyx DNA typing assay that should be useful for genetic studies and clinical transfusion medicine.© 1998 by The American Society of Hematology.
A Novel Mutation in the Coding Sequence of the FY*B Allele of the Duffy Chemokine Receptor Gene Is Associated With an Altered Erythrocyte Phenotype
Authors: Parasol Niva , Reid Marion , Rios Maria , Castilho Lilian , Harari Ilana , Kosower Nechama S. 
Published: October 2019

Abstract
The Duffy blood group system is of clinical and biological significance. Antibodies to Duffy antigens are responsible for some cases of transfusion incompatibility and newborn hemolytic disease. The Duffy protein is a receptor for the Plasmodium vivaxerythrocyte-binding protein and is also a receptor for various chemokines (thus renamed Duffy Antigen Receptor for Chemokines [DARC]). The two Duffy polymorphic antigens, Fya and Fyb (coded by the FY*A and FY*B alleles), are present on erythrocyte membranes. The Fy(a−b−) phenotype is the predominant one in populations of black people and also occurs in other populations, including some non-Ashkenazi Jewish groups. The Fy(a−b−) phenotype has been associated with a mutation in the FY*B promoter at the GATA box that abolishes the expression of erythrocyte Duffy protein. We describe here a novel mutation, present in the FY*B coding sequence (271C → T), that is associated with some Fy(b−) phenotypes among non-Ashkenazi Jews and among Brazilian blacks. The mutation is present in Fy(b−) individuals, who have wild-type FY*B GATA and carry the previously described 304G → A substitution. The 271C → T and 304G → A can be identified by restriction enzyme–generated restriction fragment length polymorphisms. The 271C → T substitution represents a considerable change in chemical nature (Arg91 → Cys), one which may affect the antigenic determinants of DARC, and thus be of clinical significance. The mutation may have implications for some physiological roles of DARC and be of interest in malaria research and in studies of population genetics.
MCP-1, not MIP-1α, Is the Endogenous Chemokine That Cooperates With TGF-β to Inhibit the Cycling of Primitive Normal but not Leukemic (CML) Progenitors in Long-Term Human Marrow Cultures
Authors: Cashman J.D. , Eaves C.J. , Sarris A.H. , Eaves A.C. 
Published: October 2019

AbstractThe long-term culture (LTC) system has been useful for analyzing mechanisms by which stromal cells regulate the proliferative activity of primitive normal, but not chronic myeloid leukemia (CML), hematopoietic progenitor cells. In previous studies, we identified two endogenous inhibitors in this system. One is transforming growth factor-β (TGF-β), which is equally active on primitive normal and CML progenitors. The other we now show to be monocyte chemoattractant protein-1 (MCP-1). Thus, MCP-1, when added to LTC, blocked the activation of primitive normal progenitors but did not arrest the cycling of primitive CML progenitors. Moreover, the endogenous inhibitory activity of LTC stromal layers could be overcome by the addition of neutralizing antibodies to MCP-1, but not to macrophage inflammatory protein-1α (MIP-1α). However, neither of these antibodies antagonized the inhibitory activity of NAc-Ser-Asp-Lys-Pro (AcSDKP) on primitive normal but not CML progenitor cycling in this system. Moreover, none of six other -C-C- or -C-X-C- chemokines, previously shown to inhibit primitive normal human CFC proliferation in semisolid assays, were found to act as negative regulators when added to normal LTC. These results provide further support for the concept that primitive CML progenitor cell proliferation is deregulated when these cells are exposed to limiting concentrations of multiple inhibitors, only some of which have differential actions on normal and Ph+/BCR-ABL+ cells.
The Sialomucin CD164 (MGC-24v) Is an Adhesive Glycoprotein Expressed by Human Hematopoietic Progenitors and Bone Marrow Stromal Cells That Serves as a Potent Negative Regulator of Hematopoiesis
Authors: Zannettino Andrew C.W. , Bühring Hans-Jörg , Niutta Silvana , Watt Suzanne M. , Benton M. Ann , Simmons Paul J. 
Published: October 2019

AbstractMucin-like molecules represent an emerging family of cell surface glycoproteins expressed by cells of the hematopoietic system. We report the isolation of a cDNA clone that encodes a novel transmembrane isoform of the mucin-like glycoprotein MGC-24, expressed by both hematopoietic progenitor cells and elements of the bone marrow (BM) stroma. This molecule was clustered as CD164 at the recent workshop on human leukocyte differentiation antigens. CD164 was identified using a retroviral expression cloning strategy and two novel monoclonal antibody (MoAb) reagents, 103B2/9E10 and 105.A5. Both antibodies detected CD164/MGC-24v protein expression by BM stroma and subpopulations of the CD34+ cells, which include the majority of clonogenic myeloid (colony-forming unit–granulocyte-macrophage [CFU-GM]) and erythroid (blast-forming unit-erythroid [BFU-E]) progenitors and the hierarchically more primitive precursors (pre-CFU). Biochemical and functional characterization of CD164 showed that this protein represents a homodimeric molecule of approximately 160 kD. Functional studies demonstrate a role for CD164 in the adhesion of hematopoietic progenitor cells to BM stromal cells in vitro. Moreover, antibody ligation of CD164 on primitive hematopoietic progenitor cells characterized by the cell surface phenotype CD34BRIGHTCD38− results in the decreased recruitment of these cells into cell cycle, suggesting that CD164 represents a potent signaling molecule with the capacity to suppress hematopoietic cell proliferation.© 1998 by The American Society of Hematology.
The Cryptic inv(2)(p23q35) Defines a New Molecular Genetic Subtype of ALK-Positive Anaplastic Large-Cell Lymphoma
Authors: Wlodarska Iwona , De Wolf-Peeters Chris , Falini Brunangelo , Verhoef Gregor , Morris Stephan W. , Hagemeijer Anne , Van denBerghe Herman 
Published: October 2019

Abstract
Recently, a distinctive entity characterized by expression of the anaplastic lymphoma kinase (ALK) protein [most frequently due to the t(2;5)(p23;q35)-associated NPM-ALK fusion] has emerged within the heterogenous group of non-Hodgkin’s lymphomas (NHL) classified as anaplastic large-cell lymphoma (ALCL). Sporadic variant 2p23/ALK abnormalities identified in ALK-positive ALCL indicate that genes other than NPM may also be involved in the deregulation of ALK and lymphomagenesis. We report here three cases with an inv(2)(p23q35) detected by fluorescence in situ hybridization (FISH) in young male patients with ALK-positive ALCL. In contrast to ALCL cases with the classical t(2;5)(p23;q35) that usually show both cytoplasmic and nuclear or predominantly nuclear alone localization of the NPM-ALK chimeric product, in all three cases with an inv(2)(p23q35) the ALK protein accumulated in the cytoplasm only, supporting the previous assumption that the oncogenic potential of ALK may not be dependent on its nuclear localization. As the first step to identify theALK partner gene involved in the inv(2)(p23q35), we performed extensive FISH studies and demonstrated that the 2q35 breakpoint occurred within the 1,750-kb region contained within the 914E7 YAC. Moreover, a striking association of the inv(2)(p23q35) with a secondary chromosomal change, viz, ider(2)(q10)inv(2)(p23q35), carrying two additional copies of the putative ALK-related fusion gene, was found in all three patients, suggesting that, in contrast to the standard t(2;5)/NPM-ALK fusion, multiple copies of the putative 2q35-ALK chimeric gene may be required for efficient tumor development. In summary, we demonstrate that the inv(2)(p23q35), a variant of the t(2;5)(p23;q35), is a recurrent chromosomal abnormality in ALK-positive ALCL, the further characterization of which should provide new insight into the pathogenesis of these lymphomas.
© 1998 by The American Society of Hematology.
The Val34Leu Polymorphism in the A Subunit of Coagulation Factor XIII Contributes to the Large Normal Range in Activity and Demonstrates That the Activation Peptide Plays a Role in Catalytic Activity
Authors: Kangsadalampai S. , Board P.G. 
Published: October 2019

AbstractThere is a wide normal range of coagulation factor XIII activity that has never been adequately explained. A polymorphism substituting leucine for valine at position 34 in the activation peptide of the A subunit of factor XIII has recently been discovered in nondeficient individuals, and the present studies indicate that the leucine substitution results in a significant increase in transglutaminase activity. The frequency of the Leu34 allele in the Australian Caucasian population is 0.27, which is high enough to suggest that the inheritance of either the Val34 or Leu34 alleles may contribute to the wide normal range of activity. Although there has been structural evidence indicating that the activation peptide does not dissociate from the enzyme after thrombin cleavage, the discovery of elevated activity resulting from the Leu34 substitution is the first direct evidence that the activation peptide plays a continuing role in the function of factor XIII.© 1998 by The American Society of Hematology.
Polymorphisms of Platelet Membrane Glycoprotein Ib Associated With Arterial Thrombotic Disease
Authors: Gonzalez-Conejero Rocio , Lozano Maria L. , Rivera Jose , Corral Javier , Iniesta Juan A. , Moraleda Jose M. , Vicente Vicente 
Published: October 2019

AbstractPlatelet membrane glycoprotein Ib (GPIb) is a major receptor for von Willebrand factor and thrombin, which plays a key role in the initial development of thrombi. Two polymorphisms (HPA-2 and VNTR) that affect phenotype have been described in GPIb. The relevance of these polymorphisms to thrombotic disease was investigated by genotypic identification in three case-control studies: 104 case patients with acute cerebrovascular disease (CVD), 101 case patients with acute coronary heart disease (CHD), 95 patients with deep venous thrombosis (DVT), and one control age-, sex-, and race-matched for each case patient. Results show that the C/B genotype of the VNTR and the HPA-2b polymorphisms of GPIb are strongly associated with increased risk of coronary heart disease and cerebral vascular disease but not with deep vein thrombosis. These two polymorphisms of GPIb may represent newly identified risk factors for arterial thrombotic disease, but not for venous thrombosis.© 1998 by The American Society of Hematology.
Fas/APO-1 (CD95)–Mediated Apoptosis Is Activated by Interferon-γ and Interferon- in Interleukin-6 (IL-6)–Dependent and IL-6–Independent Multiple Myeloma Cell Lines
Authors: Spets Helena , Georgii-Hemming Patrik , Siljason Jan , Nilsson Kenneth , Jernberg-Wiklund Helena 
Published: October 2019

AbstractA poor response to Fas-induced apoptosis is evident in some multiple myeloma (MM) cell lines and primary cells. In this study, we have examined the possibility to increase the sensitivity to Fas-induced apoptosis by pretreatment of MM cells with interferon-γ (IFN-γ) or interferon- (IFN-). Both IFN-γ and IFN- markedly increased the Fas-induced apoptosis in all cell lines tested (U-266-1970, U-266-1984, and U-1958). In the U-266-1970 and U-1958 cell lines, pretreatment with either IFN-γ or IFN- also inhibited proliferation in a dose-dependent manner. In contrast, IFN-γ activation of the Fas death pathway in the U-266-1984 cells was not accompanied by growth inhibition. Incubation with the IFNs increased the Fas antigen expression in one of three cell lines but did not alter the expression of Bcl-2 or Bax. The IFNs are important regulators of growth and survival in MM cells. Our results suggest that activation of Fas-mediated apoptosis is a novel mechanism by which the IFNs exert inhibitory effects on MM cells.© 1998 by The American Society of Hematology.