bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bone marrow transplantation for patients with Philadelphia chromosome- positive acute lymphoblastic leukemia
Authors: Forman SJ , O'Donnell MR , Nademanee AP , Snyder DS , Bierman PJ , Schmidt GM , Fahey JL , Stein AS , Parker PM , Blume KG 
Published: October 2019

Abstract
We report the treatment outcome of allogeneic bone marrow transplantation in ten patients with Philadelphia chromosome-positive acute lymphoblastic leukemia. Six patients are alive and well for 6 to 30 months (median 19 months) after transplantation. Four patients died with transplant related complications. In view of the poor prognosis associated with this disease, marrow ablation followed by allogeneic or syngeneic marrow grafting may be the preferred treatment modality if a suitable marrow donor is available.
Analysis of CD1 molecules on thymus cells and leukemic T lymphoblasts identifies discrete phenotypes and reveals that CD1 intermolecular complexes are observed only on normal cells
Authors: Amiot M , Dastot H , Schmid M , Bernard A , Boumsell L 
Published: October 2019

Abstract
We looked at the surface expression of the three distinct human thymic cell surface differentiation antigens, CD1a, CD1b, and CD1c, that presently define the first cluster of differentiation (CD) on the cells from 34 patients with acute T cell malignancies. We also studied the expression of other T cell-restricted molecules, including the T cell receptors, on these cells. Our results confirm the extensive phenotypic heterogeneity of the cells from acute T cell malignancies, which contrast with the more limited phenotypic diversity of subacute or chronic T cell malignancies. Our study of normal children and fetal thymus cells shows that the extensive phenotypic heterogeneity of the malignant cells reflects the heterogeneity of the thymic subpopulations and shows that most of the phenotypes observed on malignant T cells have a normal counterpart, particularly in the fetal thymus. Moreover, we demonstrate that the CD1a molecules, which can form three different types of noncovalent intermolecular complexes on the surface of normal thymus cells, do not form any noncovalent intermolecular complexes on the surface of leukemic cells. We also show that CD1a molecules can form covalent intermolecular complexes with CD8 molecules on some but not all malignant cells.
Antiidiotypic IgG crossreactive with Rh alloantibodies in red cell autoimmunity
Authors: Masouredis SP , Branks MJ , Victoria EJ 
Published: October 2019

Abstract
IgG autoantibodies eluted from RBCs of antiglobulin positive normal blood donors contained at least two antibody populations, an IgG autoantibody (Ab 1), and an IgG population (Ab 2) that agglutinated RBCs coated with some Rh(D) alloantibodies. Eight of 24 autoantibody eluates tested agglutinated 3 of 10 anti-Rh(D) sensitized RBCs. The agglutinating activity was inhibited specifically by preincubation of the autoantibody eluate with the reactive anti-D. The reaction did not require the Fc domain of the anti-Rh(D), since autoantibody eluates agglutinated RBCs coated with F(ab')2 prepared from the reactive anti-D sera. These findings indicate that the RBCs of some antiglobulin- positive blood donors contain an immunoglobulin auto-antiidiotype (Ab 2) against the RBC autoantibody (Ab 1) which is demonstrable through its cross-reactivity with selected Rh(D) alloantibodies. Identification of auto-antiidiotypes in RBC autoimmunity lends support to the idiotype- antiidiotype network hypothesis of immune regulation and is consistent with the bizarre and complex serology of autoimmune hemolytic anemia. The absence of clinical hemolysis in antiglobulin-positive normal blood donors suggests that immunoglobulin idiotype-antiidiotype interactions may play a role in modulating the effects of RBC autoimmunity.
Analysis of hemoglobin F production in Saudi Arabian families with sickle cell anemia
Authors: Miller BA , Salameh M , Ahmed M , Olivieri N , Antognetti G , Orkin SH , Huisman TH , Nathan DG 
Published: October 2019

Abstract
Erythrocytes and progenitor-derived erythroblasts of sickle cell anemia patients from the Eastern Province of Saudi Arabia contain increased fetal hemoglobin and G gamma globin. A distinctive DNA polymorphism haplotype in the beta globin gene cluster (++- +-), tightly coupled to a C----T substitution at position -158 5′ to the cap site of the G gamma globin gene, is strongly associated with sickle cell disease in this region. To determine whether the increased fetal hemoglobin production and/or elevated G gamma globin content are tightly linked to this haplotype, we studied 55 members of five Saudi families in which sickle cell disease is present. The results did not suggest a tight linkage of the haplotype to increased fetal hemoglobin production. On the other hand, several sickle trait family members heterozygous for the haplotype had normal fetal hemoglobin production in culture but elevated G gamma to A gamma ratios in peripheral blood. This observation suggests that in this genetic background increased expression of the G gamma globin gene may occur without a measurable increase in total fetal hemoglobin production. The family studies also clearly demonstrate that increased fetal hemoglobin production by erythroid progenitors is dependent on zygosity for the sickle gene in this population. These findings strongly suggest that other factors, such as the products of genes stimulated by hemolytic stress or other genetic determinants associated with the Saudi beta S chromosome, may interact with the -158 C----T substitution and influence gamma globin gene expression in this population.
Extracellular matrix of cultured bovine aortic endothelial cells contains functionally active type 1 plasminogen activator inhibitor
Authors: Mimuro J , Schleef RR , Loskutoff DJ 
Published: October 2019

Abstract
The extracellular matrix (ECM) of cultured bovine aortic endothelial cells (BAEs) was analyzed by immunoblotting and reverse fibrin autography and shown to contain type 1 plasminogen activator inhibitor (PAI-1). Most PAI-1 in the ECM formed complexes with exogenously added tissue-type plasminogen activator (tPA), demonstrating that this PAI-1 was functionally active. The resulting tPA/PAI-1 complexes were recovered in the reaction solution, indicating that the PAI-1 in such complexes no longer bound to ECM. The PAI-1 could not be removed by incubating ECM in high salt (2 mol/L NaCl), sugars (1 mol/L galactose, 1 mol/L mannose), glycosaminoglycans (10 mmol/L heparin, 10 mmol/L dermatan sulfate), or epsilon-aminocaproic acid (0.1 mol/L). However, PAI-1 could be extracted from ECM by treatment with either arginine (0.5 mol/L) or potassium thiocyanate (2 mol/L), or by incubation under acidic conditions (pH 2.5). ECM depleted of PAI-1 by acid extraction was able to bind both the active and latent forms of PAI-1. In this instance, most of the bound PAI-1 did not form complexes with tPA, indicating that the latent form was not activated as a consequence of binding to ECM. Although the PAI-1 activity in conditioned medium decayed with a half-life (t 1/2) of less than 3 hours, the t 1/2 of ECM- associated PAI-1 was greater than 24 hours. These data suggest that PAI- 1 is produced by cultured BAEs in an active form and is then either released into the medium where it is rapidly inactivated or into the subendothelium where it binds to ECM. The specific binding of PAI-1 to ECM protects it from this inactivation.
Molecular determinants of clinical expression of hereditary elliptocytosis and pyropoikilocytosis
Authors: Coetzer T , Lawler J , Prchal JT , Palek J 
Published: October 2019

Abstract
The clinical severity of common hereditary elliptocytosis (HE) is highly variable, ranging from an asymptomatic carrier state to a severe hemolytic anemia. To elucidate the molecular basis of this variable clinical expression, we evaluated 56 subjects from 24 HE kindred, who carry alpha spectrin mutants characterized by a spectrin dimer (SpD) self-association defect related to a structural abnormality of the alpha I domain of spectrin. Twenty-nine subjects had common HE, 13 subjects have a closely related disorder, hereditary pyropoikilocytosis (HPP), and 14 are asymptomatic carriers. We compared the severity of hemolysis with the following biochemical parameters: (a) spectrin heterodimer self-association, as manifested by the percentage of SpD in the 4 degrees C low ionic strength spectrin extract; (b) spectrin structure, as examined by limited tryptic digestion of spectrin; and (c) spectrin content of the RBC membrane. Our analysis indicates that the severity of hemolysis may be correlated with quantitative differences in the percentage of SpD in the 4 degrees C spectrin extract, as well as the total spectrin content of the membrane. Thus, HPP subjects, who have the most severe hemolytic anemia, have the highest percentage of SpD as well as a decreased spectrin content. HE subjects and asymptomatic carriers, respectively, have a lower percentage of SpD and a normal spectrin content. Factors influencing these two determinants include functional differences between the individual spectrin mutants, the relative amounts of mutant spectrin present in the cells, the stability of mutant spectrin, and the possibility of a superimposed genetic defect involving spectrin synthesis.
Long lasting IgG subclass and antibacterial polysaccharide antibody deficiency after allogeneic bone marrow transplantation
Authors: Aucouturier P , Barra A , Intrator L , Cordonnier C , Schulz D , Duarte F , Vernant JP , Preud'homme JL 
Published: October 2019

Abstract
Serum IgG subclasses were measured by a competitive indirect immunoassay with monoclonal antibodies in 31 leukemic patients before and after bone marrow transplantation. Antibodies to Hemophilus influenzae type b (Hib) capsular polysaccharide were determined in 28 cases. Abnormally low or borderline subclass (mostly IgG2 and IgG4) levels were found late after transplant in 23 infected and noninfected patients. These levels persisted for as long as 25 months, in association with low or borderline IgA levels in 78% of the cases. IgG2, IgG4, and IgA often showed a parallel evolution, whereas IgG1, IgG3, and IgM often varied together in the opposite way. Class but not subclass deficiencies were more frequent in patients with graft-v-host disease (GVHD). Subclass abnormalities predominated in infected patients, with mean levels correlating with the severity of infections; however, the abnormalities are not clearly predictive of infections in individual cases. Most patients with Hib pneumonia showed virtually no IgG antibody response to Hib, and one-half of the patients had a moderate IgM and IgA response. In the whole series, many sera collected greater than 1 year after graft contained very low or undetectable antibodies. Correlation between anti-Hib antibody and IgG2 levels was significant but weak because of discrepancies that were only partially explained by the subclass distribution of the antibodies.
Serum immunoreactive erythropoietin in children with cyanotic and acyanotic congenital heart disease
Authors: Haga P , Cotes PM , Till JA , Minty BD , Shinebourne EA 
Published: October 2019

Abstract
Serum immunoreactive erythropoietin (siEp) was measured in 27 cyanotic and 21 acyanotic children with congenital heart disease, age 4 months to 10 years. The geometric mean value was 9 mIU/mL for each group with 95% range from 3 to 26 mIU/mL and 4 to 22 mIU/mL for the cyanotic and acyanotic subjects, respectively. The levels are similar to those found in normal adults using the same assay system. Three cyanotic subjects showed increased siEp values. One was anemic relative to his hypoxemia, and the other two showed signs of increasing hypoxia. There was a significant negative correlation between siEp and arterial oxygen content. However, siEp did not correlate significantly with hemoglobin, hematocrit, PaO2, or SaO2. Despite normal siEp levels, the cyanotic children showed compensatory erythropoiesis with significantly elevated hemoglobin and hematocrit levels, which did correlate inversely with PaO2 and SaO2. Arterial oxygen content was also significantly higher in the cyanotic subjects (p less than 0.02). The cyanotic children seemed to display the same pattern as observed in man and animals exposed to prolonged hypobaric hypoxia, where after an initial rise in erythropoietin values the levels fall to normal, while increased erythropoiesis is sustained.
High-dose chemoradiotherapy and autologous bone marrow transplantation for resistant multiple myeloma
Authors: Barlogie B , Alexanian R , Dicke KA , Zagars G , Spitzer G , Jagannath S , Horwitz L 
Published: October 2019

Abstract
Seven patients with advanced multiple myeloma, refractory to therapy with alkylating agent-VAD (vincristine-adriamycin-dexamethasone), received a regimen combining high-dose melphalan with total body irradiation supported by autologous bone marrow transplantation. Very rapid, usually greater than 90% tumor mass reduction was achieved in six patients, regardless of prior chemotherapy responsiveness and marrow plasmacytosis up to 30%. Despite signs of early relapse in three patients (median remission duration of all patients, 15 months), five remain alive and well without further cytotoxic therapy from 2 to 21 months (median, 9+ months). Two patients died, one from surgical complications after transplantation and a second due to persistent neutropenia with fatal pneumonia. This treatment provides meaningful disease control for selected patients with resistant myeloma and a poor prognosis.
Asialo-von Willebrand factor inhibits platelet adherence to human arterial subendothelium: discrepancy between ristocetin cofactor activity and primary hemostatic function
Authors: Lawrence JB , Gralnick HR 
Published: October 2019

Abstract
Platelet adherence at high wall shear rates requires plasma von Willebrand factor (vWF). Clinically, the ristocetin cofactor (RCof) activity is the only widely available assay for vWF function. When purified vWF is treated with neuraminidase to yield asialo-vWF (AS- vWF), its RCof activity is increased by 20% to 40%. AS-vWF binds to normal human platelets independently of ristocetin and induces platelet aggregation in the presence of fibrinogen. To determine whether AS-vWF also shows an enhanced capacity to support platelet adherence to subendothelium, we used the Baumgartner technique. Intact vWF, AS-vWF, or AS-vWF treated with beta-galactosidase (asialo, agalacto-vWF; AS,AG- vWF) was added to normal citrated whole blood before perfusion over human umbilical artery segments (wall shear rate, 2,600 sec-1). Four micrograms per milliliter AS-vWF caused a 69% reduction in total platelet adherence compared with citrated whole blood (P less than .001), and 4 micrograms/mL AS,AG-vWF led to a 48% reduction (P less than .005). With 4 micrograms/mL intact vWF, the platelet adherence values were not significantly different from the controls. No significant differences in subendothelial platelet thrombi or postperfusion platelet counts were evident among any of the groups. In reconstituted afibrinogenemic perfusates, 4 micrograms/mL AS-vWF caused a 42% reduction in platelet adherence (P less than .05). Thus, AS-vWF is a potent inhibitor of platelet adherence, despite its enhanced RCof specific activity. Abnormalities in vWF carbohydrate may play a role in impaired primary hemostasis in some patients with von Willebrand's disease.
Evidence that microenvironmental factors account for the age-related decline in neutrophil function
Authors: Lipschitz DA , Udupa KB , Boxer LA 
Published: October 2019

Abstract
We measured the function of neutrophils harvested from the supernatant of long-term marrow cultures in which stromal cell cultures derived from young mice were recharged with hematopoietic cells from old mice and vice versa. The functions measured were superoxide generation and enzyme secretion (lysozyme and glucuronidase), following cell activation by either phorbol myristate acetate (PMA) or Formyl- methionyl-leucyl-phenylalanine (FMLP). In addition we measured cytosolic calcium concentration and its increase following activation by FMLP. In all culture combinations recharge resulted in the recovery of greater than 2 X 10(6) cells/flask (95% neutrophils, 98% viable). Histologic studies of cytoplasmic markers indicated that recovered neutrophils were derived from the stem cell population employed for recharge. For each neutrophil parameter measured, function was markedly improved when old hematopoietic stem cells were recharged onto a young stroma and was significantly diminished when young stem cells were recharged onto an old stroma. This applied to superoxide generation, basal and stimulated enzyme levels, and to basal cytosolic calcium concentration and its increase following activation by FMLP. These results indicate that when old hematopoietic stem cells proliferate in a young microenvironment, neutrophil function returns virtually to normal. Conversely, function diminishes when young stem cells proliferate in an old stroma. These findings demonstrate, for the first time, that neutrophil function is modulated by microenvironmental factors, hormonal, cellular, or matrix, which are decreased in the elderly. That an age-related decline in function is extrinsic to the cell and is reversible has significance for the study of neutrophil function and of cellular aging and has potential therapeutic implications.
Histone H1 degrees is synthesized by human lymphocytic leukemia cells but not by normal lymphocytes
Authors: Mannironi C , Rossi V , Biondi A , Ubezio P , Masera G , Barbui T , D'Incalci M 
Published: October 2019

Abstract
Using a two-dimensional gel electrophoresis system (sodium dodecyl sulphate/acetic acid-urea-hexadecyltrimethylammonium bromide) coupled with fluorography, we investigated the synthesis of H1 isoproteins in leukemic cells obtained from peripheral blood of eight children suffering from acute lymphoblastic leukemia (ALL) (four T-ALL, three common ALL, and one B-ALL) and in normal peripheral lymphocytes. H1 degrees was synthesized in leukemic cells but not in normal lymphocytes. Inhibition of DNA synthesis with hydroxyurea and 1-beta-D- arabinofuranosylcytosine induced an increase of relative synthesis of H1 degrees in leukemic cells but did not induce any detectable synthesis of H1 degrees in normal lymphocytes. H1 degrees synthesis was also undetectable in peripheral lymphocytes of leukemic children in complete remission after chemotherapy and in lymphocytes of a homozygotic twin of a leukemic patient. H1 degrees may be a marker of malignant transformation of lymphocytes and as such could be of use for early detection of relapse in patients with acute lymphocytic leukemia in apparent complete remission.
Secretion of interleukin-1 by acute myeloblastic leukemia cells in vitro induces endothelial cells to secrete colony stimulating factors
Authors: Griffin JD , Rambaldi A , Vellenga E , Young DC , Ostapovicz D , Cannistra SA 
Published: October 2019

Abstract
The interaction of acute myeloblastic leukemia (AML) cells with stromal cells was investigated by adding AML-conditioned media to cultures of human endothelial cells. This conditioned media contained factors that induced expression of both the granulocyte macrophage colony- stimulating factor (GM-CSF) and granulocyte CSF (G-CSF) genes and release of colony stimulating activity from endothelial cells. The conditioned media contained interleukin-1 (IL-1) bioactivity and the endothelial cell stimulatory activity was partially neutralized by anti- IL-1 antiserum. Constitutive expression of the IL-1-beta gene was detected in ten of 17 AML cases analyzed. These results suggest that the unregulated secretion of IL-1 by AML cells can induce stromal cells in vitro to overproduce CSFs. This could contribute to the unrestricted growth of AML cells.
Acquisition of formyl peptide receptors during normal human myeloid differentiation
Authors: Sullivan R , Griffin JD , Malech HL 
Published: October 2019

Abstract
By using a newly developed immune rosetting technique to isolate highly purified populations of myeloid precursor cells from normal human bone marrow and then inducing their differentiation with granulocyte and macrophage colony-stimulating factors (G/M-CSFs) in vitro, we studied the surface expression of chemotactic peptide receptors as the cells matured from the stage of the myeloblast to that of the mature, segmented neutrophil. We used ethylene glycol bis(succinimidyl succinate) to link N-formyl-Nle-Leu-Phe-Nle-[125I]iodo-Tyr-Lys to chemotactic peptide receptors on the surface of myeloid cells at sequential stages of maturation and then determined the density of receptor-radioligand complexes by autoradiography after sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). Specific, saturable formyl peptide receptors were not detectable at the level of the myeloblast but gradually emerged through progressive stages of neutrophil maturation. The specific receptors for formyl peptide that appeared during cellular maturation had a mol wt of 55 to 70 kiloDalton (kD), corresponding to those present on the surface of peripheral blood neutrophils, and binding of the radioligand was highly specific in that it was completely inhibited by a 1,000-fold excess of F-Met Leu Phe. These data correlate with and provide insight into our recent observation that F-Met Leu Phe-induced membrane depolarization and transient increases in cytosolic free calcium are gradually acquired as neutrophils mature. This report represents to our knowledge the first description of the maturational development of chemotactic peptide receptor expression in normal human myeloid cells.
Radiogenic leukemia revisited
Authors: Moloney WC 
Published: October 2019

Abstract
Radiation-induced leukemia is considered to be similar to the de novo disease. However, following an analysis of clinical and hematological findings in leukemia occurring in irradiated cervical cancer patients, adult Japanese atomic-bomb survivors, and spondylitics treated with x- ray, striking differences were noted. Acute leukemias in cervical cancer patients and Japanese survivors were similar in type to acute de novo leukemias in adults. Cell types among spondylitics were very dissimilar; rare forms, eg, acute erythromyelocytic leukemia (AEL) and acute megakaryocytic leukemia, were increased. Pancytopenia occurred in 25 of 35 cases and erythromyelodysplastic disorders were noted in seven of 35 acute cases. The leukemias and myelodysplastic disorders closely resembled those occurring in patients treated with alkylating agents. This similarity suggests a common pathogenesis involving marrow stem cell injury and extra-medullary mediators of hematopoiesis. Investigation of early acute leukemias and myelodysplastic disorders with newer techniques may provide valuable insights into the pathogenesis of leukemia in humans.