bluuebunny/crossref_metadata_2025_split huggingface dataset:
Establishment of a new Epstein-Barr virus-immortalized cell line from chronic lymphocytic leukemia with trisomy of chromosome 12 that produces monoclonal IgM against a sheep RBC antigen
Authors: Crescenzi M , Napolitano M , Carbonari M , Antonelli A , Petrinelli P , Gaetano C , Fiorilli M 
Published: October 2019

Abstract
Leukemia cells from a patient with chronic lymphocytic leukemia (CLL) were found to bind sheep RBC (SRBC) through their monoclonal surface IgM. A lymphoblastoid cell line was obtained by immortalization of leukemic cells with Epstein-Barr virus (EBV). Cultured leukemic cells were found to have a supernumerary chromosome 12, an abnormality typical of CLL of the B cell type. To our knowledge, this is the first EBV-immortalized cell line from B-CLL cells of known SRBC specificity and the third reported CLL cell line carrying trisomy of chromosome 12.
Elevation of IgE-binding factors in serum of patients with B cell- derived chronic lymphocytic leukemia
Authors: Sarfati M , Bron D , Lagneaux L , Fonteyn C , Frost H , Delespesse G 
Published: October 2019

Abstract
One hundred nineteen sera from patients with various lymphoproliferative diseases and normal sera were tested by a solid- phase radioimmunoassay (RIA) for their content in IgE-binding factor (IgE-BF), a soluble glycoprotein binding to IgE and derived from low- affinity IgE receptors (Fc epsilon R). Fc epsilon R, recently identified as CD23, are known to be expressed on the surface of B cells at the intermediate stage of differentiation. The results indicate that in all cases of chronic lymphocytic leukemia (CLL) tested (n = 40), IgE- BF levels (45 to 8,656 U/mL) were 3-fold to 500-fold higher than in 24 controls (15.5 +/- 2 U/mL). With a few exceptions, serum IgE-BF levels could differentiate patients with CLL from those with other leukemias or lymphomas. In vitro studies indicated that B lymphocytes isolated from CLL patients produced 8 to 50 times more IgE-BF than did normal B cells (P less than 0.001). IgE-BF level was correlated with the Rai stage of the disease (P = 0.002) and the lymphocyte count (P = 0.041). IgE-BF was purified to homogeneity from one CLL serum sample by a combination of affinity chromatography and reverse-phase high- performance liquid chromatography (HPLC). this IgE-BF proved identical to IgE-BF isolated from the culture supernatant of RPMI 8866 cells, a B lymphoblastoid cell line bearing Fc epsilon R and secreting IgE-BF. Indeed, the two molecules had the same mol wt (25 to 27 kd), the same isoelectric point, and the same tryptic map. We suggest that determination of serum IgE-BF might prove useful for clinical monitoring of CLL.
Lineage- and stage-specific adhesion of human hematopoietic progenitor cells to extracellular matrices from marrow fibroblasts
Authors: Coulombel L , Vuillet MH , Leroy C , Tchernia G 
Published: October 2019

Abstract
Local regulation of hematopoietic differentiation in the marrow requires close interactions with components of the microenvironment. In this study, we explored the capacity of human marrow hematopoietic progenitor cells to adhere in vitro to the extracellular matrix (ECM) secreted by human marrow fibroblasts. When marrow mononuclear cells were incubated on ECM-coated dishes, all types of progenitors adhered to this substrate through an active process requiring divalent cations and serum factors. The proportion of erythropoietic progenitors attached to ECM in two hours was at least twofold higher than that of granulopoietic progenitors. Moreover, in the erythroid lineage, the capacity to adhere to ECM increased with the degree of differentiation of the progenitor: 28% of CFU-E adhered to ECM as compared with 13% of immature BFU-E. Thus, ECM-mediated adherence varied both with the cell lineage and the maturation stage of the progenitor. Purified fibronectin could substitute for ECM in the adhesion assay, and ECM- mediated adhesion of CFU-E and BFU-E was partially inhibited by a polyclonal antifibronectin antibody, which implies that fibronectin may be one ECM component involved in progenitor cell adhesion. Incomplete inhibition of progenitor adhesion to ECM by the antifibronectin antibody, however, as well as the lower proportion of precursors attaching to purified fibronectin as compared with ECM suggest that other matrix molecules may also mediate erythroid progenitors attachment to ECM. These observations support the idea that hematopoietic progenitor cells may regulate their differentiation in part through the modulation of adhesive interactions with a number of constituents of the microenvironment.
The natural history of factor VIII:C inhibitors in patients with hemophilia A: a national cooperative study. II. Observations on the initial development of factor VIII:C inhibitors
Authors: McMillan CW , Shapiro SS , Whitehurst D , Hoyer LW , Rao AV , Lazerson J 
Published: October 2019

Abstract
During a 4-year multicenter cooperative study of acquired factor VIII inhibitors in persons with hemophilia A, new inhibitors were detected in 31 of 1,306 patients who entered the study without an inhibitor or the history of an inhibitor. The incidence of new inhibitors was eight per 1,000 patient-years of observation. The factor VIII:C level before inhibitor development was less than or equal to 0.03 U/mL in 29 individuals and 0.06 U/mL and 0.07 U/mL in the remaining two. Factor VIII:Ag levels were measured in 27 individuals and were less than 0.03 U/mL in 23 and 0.05 to 0.11 U/mL in the remaining four. Maximum inhibitor levels ranged from 1.0 to 9,044 Bethesda U/mL. In seven patients under the age of 20, relatively weak inhibitors (none higher than 4.3 Bethesda U/mL) were detected on only a single occasion despite continued factor VIII challenge. In the other 24 patients with inhibitors detected on multiple occasions, 50% had appeared by age 20 and 71% by age 30. Seventeen of the 31 inhibitors, including 12 of 15 with maximum values greater than 10 Bethesda U/mL, developed within 75 exposure days to factor VIII.
Protein C deficiency resulting from possible double heterozygosity and its response to danazol
Authors: Gruppo RA , Leimer P , Francis RB , Marlar RA , Silberstein E 
Published: October 2019

Abstract
A unique family with protein C (PC) deficiency is described. The proband had a history of renal vein thrombosis as a newborn and iliofemoral thrombosis at the age of 6 years. After 6 months of heparin treatment, discontinuation of anticoagulation therapy was accompanied by persistent hypofibrinogenemia with increased fibrinogen consumption. With continuous infusion of heparin, fibrinogen turnover normalized, and the child has remained free of thrombosis. Both the immunologic level of PC and the functional activity measured by amidolytic assay were moderately reduced (47% and 34%, respectively). Functional activity of PC measured by its anticoagulant activity was disproportionately lower (14%). A 3-year-old asymptomatic sibling had a similar disproportionate reduction of PC anticoagulant activity compared with the amidolytic activity or immunologic level. The mother demonstrated type I PC deficiency with a proportionate reduction in immunologic protein levels (59%), anticoagulant activity (52%), and amidolytic activity (46%), whereas the father had type II PC deficiency with normal immunologic protein levels (102%), normal amidolytic function (98%), but a low anticoagulant function (50%). An abnormal PC molecule was detected by two-dimensional immunoelectrophoresis in the father and two children. These data are consistent with the hypothesis that the children are doubly heterozygous for two different types of PC deficiency inherited from each of the parents. A 14-day trial of danazol in the proband resulted in a rise in the PC antigen concentration from 66% to 98% but no change in PC anticoagulant function.
Plasmids in bacteria exposed to activated neutrophils mediate mutagenesis when transferred to new hosts
Authors: De Togni P , Fox HB , Morrissey S , Tansey LR , Levy SB , Babior BM 
Published: October 2019

Abstract
The plasmid pUC18 contains a lacZ alpha-complementation gene that codes for a small peptide that can complement the delta M15 mutation of the Escherichia coli lacZ (beta-galactosidase) gene, converting bacteria carrying that mutated gene from the lacZ- to the lacZ+ phenotype. This plasmid was used in experiments designed to study mutagenesis by human neutrophils. E coli carrying pUC18 were incubated with neutrophils under conditions in which little ingestion of the bacteria took place; the plasmid was then isolated and transformed into an E coli strain (BOZO) that carries the lacZ delta M15 mutation. Of these transformants, 11 of 205,000 were lacZ, suggesting that in these 11, alpha-complementation had been lost through a mutation. No lac- colonies were detected among several hundred thousand BOZO transformed with plasmid isolated from incubations in which phagocytosis could take place, nor from incubations from which neutrophils were omitted. Despite the lac- phenotype of these 11 transformants, plasmids reisolated from nine of them showed normal alpha-complementing ability when transformed into fresh BOZO. These findings indicated that in these nine, the mutations were located in the chromosomes of the transformed BOZO. It thus appears that on exposure to activated neutrophils, a plasmid may acquire a lesion (? mutation) that can somehow be transferred to the genome of a recipient microorganism, resulting in repair of the damaged plasmid accompanied by mutation of the recipient's chromosome. Restriction mapping of the DNA from four of these nine chromosomal mutants suggested that the mutations did not represent major insertions or deletions in the portion of the bacterial chromosome corresponding to the pUC18 lac operon insert, nor in the remainder of the lacZ delta M15 gene. These results confirm previous work showing that exposure to activated neutrophils can induce mutations in biological systems, and provides an experimental model in which the mechanism of neutrophil-mediated mutagenesis may be examined.
Evidence for posttranslational control of Hb C synthesis in an individual with Hb C trait and alpha-thalassemia
Authors: Liebhaber SA , Cash FE , Cornfield DB 
Published: October 2019

Abstract
The level of Hb C in the erythrocytes of individuals with Hb C trait decreases significantly in the presence of coexisting alpha- thalassemia. This relationship may result from the higher affinity of beta A than beta C for limiting amounts of alpha-globin during hemoglobin assembly. This mechanism would predict that the beta A and beta C synthetic capacity in alpha-thalassemic individuals with Hb C trait should be balanced despite the low levels of Hb C in their circulating erythrocytes. To directly test this prediction, we have measured the beta A and beta C synthetic capacity of reticulocyte RNA isolated from two individuals with Hb C trait, one with a normal alpha- globin genotype and one with alpha-thalassemia. The balanced expression of beta A and beta C in both cases supports the proposed posttranslational control over Hb C expression.
Detection of carriers of the autosomal form of chronic granulomatous disease
Authors: Verhoeven AJ , van Schaik ML , Roos D , Weening RS 
Published: October 2019

Abstract
The NADPH:O2 oxidoreductase catalyzing the respiratory burst in activated phagocytes from healthy individuals is not operative in phagocytes from patients with chronic granulomatous disease (CGD). In a microscopic slide test using the dye nitroblue tetrazolium (NBT), carriers of X-linked CGD can be recognized by a mosaic pattern of NBT- positive and NBT-negative cells, governed by the expression of an unaffected or an affected X chromosome, respectively. Until now, it has not been possible to detect carriers of the autosomal form of CGD (other than by family studies) because all cells of these carriers stain positive in the NBT test. We have investigated whether neutrophils from carriers of autosomal CGD can be recognized by measurement of the rate of oxygen uptake upon stimulation of the cells. It was found that with the phorbol ester PMA as a stimulus, the respiratory burst is significantly lower in autosomal CGD carriers. With serum-treated zymosan as a stimulus, no difference between controls and carriers was observed. The addition of f-Met-Leu-Phe (1 microM) to PMA-activated neutrophils of control donors caused a transient increase in oxygen consumption of about 40%. Under these conditions, an increase of more than 100% was observed in neutrophils from carriers of autosomal CGD. These findings provide a simple method for the detection of carriers of the autosomal form of CGD.
Assessment of proliferation during maturation of the B lymphoid lineage in normal human bone marrow
Authors: Hollander Z , Shah VO , Civin CI , Loken MR 
Published: October 2019

Abstract
Different stages of B lymphoid maturation were identified in normal bone marrow using multiple cell surface markers. The proliferation status of each of these maturational stages was determined by simultaneous quantitative DNA analysis on a flow cytometer. The technique used to quantify these parameters preserved the cell surface immunofluorescence, the light scattering properties and the stoichiometric binding to DNA. The proliferating cells were confined to a distinct population of cells expressing CD10. The number of proliferating cells in these populations was relatively constant among 12 separate bone marrow samples. The data suggest that the timing and rate of proliferation of cells within a single lineage may be a preprogrammed aspect of normal maturation.
Low total protein S antigen but high protein S activity due to decreased C4b-binding protein in neonates
Authors: Schwarz HP , Muntean W , Watzke H , Richter B , Griffin JH 
Published: October 2019

Abstract
Protein S, a vitamin K-dependent cofactor for activated protein C, exists in normal adult plasma in a free anticoagulantly active form and in an inactive form complexed to C4b-binding protein. Immunologic and functional levels of protein S and C4b-binding protein in plasma were determined for 20 newborn infants and compared with adult normal pooled plasma. Total protein S antigen levels averaged 23%, similar to other vitamin K-dependent plasma proteins. However, the protein S anticoagulant activity was 74% of that of adult normal plasma. This apparent discrepancy of activity to antigen was shown to be due to low or undetectable levels of C4b-binding protein, which results in the presence of most if not all of protein S in its free and active form. The relatively high level of anticoagulantly active protein S in infants may enhance the potential of the protein C pathway, thereby minimizing risks of venous thrombosis in this group.
Polyspecific natural antibodies and autoantibodies secreted by human lymphocytes immortalized with Epstein-Barr virus
Authors: Seigneurin JM , Guilbert B , Bourgeat MJ , Avrameas S 
Published: October 2019

Abstract
Recent studies have shown that autoreactive B cells and autoantibodies are present in pathological as well as in normal situations. In the present study, we immortalized human B cell lines from normal individuals and from patients with malignant or benign dysglobulinemia with Epstein-Barr virus and examined, after cloning, the autoantibody reactivities of the immunoglobulins secreted by these cells. Forty-two supernatants were analyzed by enzyme-immunoassay on a panel of 13 self and non-self antigens: trinitrobenzenesulfonic acid (TNP), DNA, L- glutamine, L-alanine, L-tyrosine (GAT), actin, myosin, tubulin, albumin, renin, spectrin, transferrin, thyroglobulin, myoglobin, peroxidase, and by immunofluorescence in tissue sections. Fourteen (33%) of the immunoglobulin-secreting cell lines were found to have an autoantibody function; seven secreted IgM, six IgA, and one IgG. The light chains were of the kappa type in 11 cases. The vast majority of these clones reacted with more than five antigens of the panel and all of them reacted with TNP. No correlation was found between a given isotype and an antibody specificity. More than half of these antibodies also reacted with cellular antigens present in tissue sections. None of the four cell lines secreting monoclonal antiviral antibodies reacted with any of the antigens of the panel. The results indicate that immunoglobulins secreted by human monoclonal lymphoid cell lines can have polyspecific autoantibody functions, similar to those found in normal human polyclonal antibodies, in human monoclonal paraproteins and in natural monoclonal antibodies synthesized by murine or rat clones obtained from physiologically normal animals.
Is there a role for selective vasodilation in the management of sickle cell disease?
Authors: Rodgers GP , Roy MS , Noguchi CT , Schechter AN 
Published: October 2019

Abstract
To test the hypothesis that microvascular obstruction to blood flow at the level of the arteriole may be significant in individuals with sickle cell anemia, the ophthalmologic effects of orally administered nifedipine were monitored in 11 steady-state patients. Three patients with evidence of acute peripheral retinal arteriolar occlusion displayed a prompt reperfusion of the involved segment. Two other patients showed fading of retroequatorial red retinal lesions. Color vision performance was improved in six of the nine patients tested. The majority of patients also demonstrated a significant decrease in the amount of blanching of the conjunctiva which reflects improved blood flow to this frequently involved area. Such improvements were not observable in a control group of untreated stable sickle cell subjects. These findings support the hypothesis that inappropriate vasoconstriction or frank vasospasm may be a significant factor in the pathogenesis of the microvascular lesions of sickle cell disease and, further, that selective microvascular entrapment inhibition may offer an additional strategy to the management of this disorder. We believe a larger, placebo-controlled study with nifedipine and similar agents is warranted.
Synergistic effect of granulocyte-macrophage colony-stimulating factor and 1,25-dihydroxyvitamin D3 on the differentiation of the human monocytic cell line U937
Authors: Zuckerman SH , Surprenant YM , Tang J 
Published: October 2019

Abstract
The human monoblastlike cell line U937 can be induced to differentiate by a variety of agents including gamma-interferon, phorbol esters, retinoic acid, and 1,25-dihydroxyvitamin D3 (VD3). Incubation of U937 with 1 to 1,000 units of recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) did not induce macrophage differentiation. A synergistic effect on macrophage differentiation was observed, however, when U937 was cocultured with 10(-8) mol/L VD3 plus 50 U/mL GM-CSF. GM-CSF-plus VD3-treated cells demonstrated significant increases in OKM1 antigen expression, increased chemokinesis and chemotaxis, and increased Fc receptor-mediated erythrophagocytosis. Human peripheral blood monocyte cultures also demonstrated increased OKM1 antigen expression and chemotaxis when incubated with 50 to 500 U/mL of GM-CSF for 48 to 72 hours. VD3, however, was not necessary for the increases in effector function observed for GM-CSF-stimulated monocyte cultures. In distinction to the synergistic effect of GM-CSF on VD3-induced differentiation of U937, recombinant human granulocyte colony-stimulating factor (G-CSF) at comparable concentrations had no augmenting effect over that observed for VD3 alone. These results suggest that GM-CSF, in the presence of other physiological stimuli, can induce significant phenotypic changes in GM-CSF-nonresponsive cells of the monocytic lineage and can increase the effector functions of GM- CSF-responsive peripheral blood monocyte cultures.
Proliferation of normal human promyelocytes and myelocytes after a single pulse stimulation by purified GM-CSF or G-CSF
Authors: Begley CG , Nicola NA , Metcalf D 
Published: October 2019

Abstract
Enriched populations of either normal human promyelocytes and myelocytes or blast cells were obtained by fluorescence-activated cell sorting with the monoclonal antibody WEM-G11. These populations were used to study the effect of pulse stimulation by purified recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) or cross-reacting purified murine granulocyte colony-stimulating factor (G- CSF). Maximal clone formation by promyelocytes and myelocytes was observed in 1-mL agar cultures stimulated continuously with 400 units of either CSF and in cultures of cells that were pulse stimulated by 3,200 units (or greater) of either CSF. Pulse stimulation by 800 units of GM-CSF or G-CSF generated 75% clone formation, and pulse stimulation by 200 units CSF gave 50% clone formation. The majority of clones formed by pulse-stimulated cells were only two cells in size; however, some clones were up to 15 cells in size after a single exposure to CSF. Clone formation was not observed in cultures of blast cell populations after a single pulse stimulation with GM-CSF or G-CSF.
Syngeneic leukocytes together with suramin failed to improve immunodeficiency in a case of transfusion-associated AIDS after syngeneic bone marrow transplantation
Authors: Verdonck LF , de Gast GC , Lange JM , Schuurman HJ , Dekker AW , Bast BJ 
Published: October 2019

Abstract
A 22-year-old man who underwent syngeneic bone marrow transplantation (BMT) for acute lymphoblastic leukemia acquired a human immunodeficiency virus (HIV) infection by transfusion of blood products from a donor at risk. The manifestations were acute encephalopathy together with immune thrombocytopenia in the early posttransplant period, and acquired immunodeficiency syndrome (AIDS) developed 20 months after BMT. Because he had a syngeneic donor, the possibility of reconstituting the immune system was investigated by repeated transfer of healthy syngeneic lymphocytes and by combining repeated transfer of syngeneic lymphocytes with the antiviral agent suramin to protect the infused leukocytes from being attacked by HIV. No improvement was observed clinically or in the patient's immune functions by these efforts.
Autologous peripheral hematopoietic stem cell transplantation restores hematopoietic function following marrow ablative therapy
Authors: Kessinger A , Armitage JO , Landmark JD , Smith DM , Weisenburger DD 
Published: October 2019

Abstract
From ten patients with advanced malignant disease involving the bone marrow, autologous hematopoietic stem cells were collected from the peripheral blood during eight four-hour pheresis procedures and cryopreserved. No manipulations to increase the number of stem cells circulating in the blood were used during the collections. Following marrow ablative chemotherapy or chemoradiotherapy, the autologous cells were thawed and infused intravenously (IV). WBCs reappeared in the circulation at a median of eight days (range seven to 11 days) after stem cell infusion. Two patients died early, whereas the other eight reached normal numbers of circulating granulocytes that have persisted for up to greater than 20 months. These eight patients became independent of RBC transfusions (hemoglobin concentration greater than 10 g/dL) at a median of 27 days (range 11 to 58 days) after transplantation. One patient received platelet transfusions for counts less than 50 x 109)/L, one patient developed a clinical picture of idiopathic thrombocytopenic purpura, and six patients maintained a platelet count greater than 20 x 10(9)/L at a median of 23 days (range 14 to 25 days) following stem cell infusion. This technique allows patients ineligible for autologous bone marrow transplantation due to unacceptable anesthetic risks, prior pelvic irradiation, or bone marrow metastases to receive marrow ablative therapy.