bluuebunny/crossref_metadata_2025_split huggingface dataset:
B cell growth factor-induced proliferation of hairy cell lymphocytes and inhibition by type I interferon in vitro
Authors: Paganelli KA , Evans SS , Han T , Ozer H 
Published: October 2019

Abstract
Malignant B cells from hairy cell leukemia (HCL) patients are unable to proliferate when stimulated with standard B cell mitogens. Using chromatographically purified B cell growth factor (BCGF), HCL can be stimulated to proliferate as assessed by incorporation of tritiated thymidine [3HTdR] into DNA. Proliferation was found to be time dependent, with no detectable 3H-TdR incorporation in up to three days of culture, and significant stimulation evident at days 6 and 10. The presence of 10% BCGF in culture was an absolute requirement for HCL proliferation; however, this BCGF-induced DNA synthesis could be further augmented by the addition of anti-immunoglobulin heavy chain antibodies. BCGF-induced proliferation was abrogated in six of six patients by addition of 1,000 U/mL of recombinant alpha 2-interferon (IFN) at day 0, although 1,000 U/mL of recombinant gamma-IFN had no inhibitory effect in five of six patients studied. Specific cellular receptors for type I IFN were demonstrated in HCL by inhibition of binding of 125I-alpha 2-IFN by a 40-fold excess of unlabeled alpha 2 or beta IFN with no inhibition by unlabeled gamma-IFN. These data demonstrate that malignant HCL lymphoblasts express specific type I IFN receptors and that type I, but not type II IFN, can inhibit growth factor-induced DNA synthesis by hairy cells in vitro. They further suggest a direct antiproliferative mechanism of action for IFN in HCL and predict equivalent clinical activity by either alpha or beta, but not gamma IFN in this malignancy.
An explanation for nonimmunologic adsorption of proteins onto red blood cells: Schiff's base reactions
Authors: Jamin D , Demers J , Shulman I , Lam HT , Momparler R 
Published: October 2019

Abstract
During a phase I evaluation of diglycoaldehyde (INOX), an intravenous chemotherapeutic agent used to treat children with malignancies, all of eight patients tested developed a positive direct antiglobulin test (DAT) in vivo. The DAT became positive within one to seven days after the first administration of the drug and remained positive for up to 12 days following the last dose. The indirect antiglobulin tests were negative. None of the patients showed clinical or laboratory evidence of hemolysis at the time the DAT became positive or during follow-up. Eluates made from the red cells of two of the eight patients were both negative by indirect antihuman globulin testing. In vitro studies with INOX and glutaraldehyde, both dialdehyde compounds, showed nonimmunologic adsorption of protein onto red cells, probably by the condensation of aldehyde groups of these compounds to form Schiff's bases with amino acids of serum proteins and red cell membrane proteins. This reaction provides an explanation for the globulin detected on the red cells of patients treated with INOX.
The Dpg gene: an intracorpuscular modifier of red cell metabolism
Authors: Noble NA , Rothstein G 
Published: October 2019

Abstract
The genetic locus designated Dpg has two alleles in outbred Long-Evans rats. Genotype at this locus affects quantities of red cell 2,3- diphosphoglycerate (DPG) and adenosine triphosphate, as well as activities of two important glycolytic enzymes: phosphofructokinase and pyruvate kinase. Intravascular red cell survival is shortened in low- DPG animals. In order to get closer to the specific action of this locus, we addressed the question of whether the Dpg gene acts through intracorpuscular or extracorpuscular factors. Bone marrow transplantation after total body irradiation and 51Cr red cell survival after cross transfusion were the methods used. Because the animals that were used differed in hemoglobin phenotype, donor and recipient cells could be quantified in cross-transplanted animals. Phenotypic markers of Dpg genotype were measured in animals 40 to 50 days after transplantation. Values for these markers correlated highly with the percentage of donor and recipient cells present. In vivo survival of low-DPG red cells was significantly shorter than that of high-DPG cells (P less than .05), regardless of the genotype of the recipient. From the present studies, we conclude that the action of the Dpg gene is exerted by an intracorpuscular factor.
A chromosomal breakage syndrome with profound immunodeficiency
Authors: Conley ME , Spinner NB , Emanuel BS , Nowell PC , Nichols WW 
Published: October 2019

Abstract
The chromosomal breakage syndromes--ataxia-telangiectasia, Fanconi's anemia, and Bloom's syndrome--are associated with growth failure, neurologic abnormalities, immunodeficiency, and an increased incidence of malignancy. The relationship between these features is unknown. We recently evaluated a 21-year-old female with more severe chromosomal breakage, immunodeficiency, and growth failure than in any of the mentioned disorders. As of November 1985, the patient remains clinically free of malignancy. At age 18, the patient's weight was 22.6 kg (50th percentile for seven years), height was 129 cm (50th percentile for eight years), and head circumference was 42 cm (50th percentile for six months). Laboratory studies demonstrated a marked decrease in both B and T cell number and function. The peripheral blood contained 400 to 900 lymphocytes/microL with 32% T11 cells, 17% T4 cells, and 21% T8 cells. The proliferative responses to phytohemagglutinin (PHA), pokeweed mitogen, and concanavalin A were less than 10% of control. There were 1% surface IgM positive cells, and serum IgG was 185 mg/dL, IgM 7 mg/dL, IgA 5 mg/dL. In lymphocyte cultures stimulated with the T cell mitogens PHA, phorbol ester, and interleukin 2, 55% of the banded metaphases demonstrated breaks or rearrangements. The majority of the breaks involved four fragile sites on chromosomes 7 and 14, 7p13, 7q35, 14q11, and 14q32. These are the sites of the genes for the T cell-antigen receptor and the immunoglobulin heavy chain and are sites of gene rearrangement in lymphocyte differentiation. Epstein-Barr virus stimulated B cells and fibroblast cultures also demonstrated a high incidence of breaks, but the sites were less selective. These findings suggest that the sites of chromosomal fragility in the chromosomal breakage syndromes may be informative and that factors other than the severity of the immunodeficiency or the high incidence of chromosomal damage may contribute to the occurrence of malignancy in the chromosomal breakage syndromes.
Human macrophage maturation and heterogeneity: analysis with a newly generated set of monoclonal antibodies to differentiation antigens
Authors: Andreesen R , Bross KJ , Osterholz J , Emmrich F 
Published: October 2019

Abstract
We have analyzed the expression of late differentiation antigens during terminal in vitro maturation of human macrophages (M phi) from blood monocytes (MO) in comparison to their distribution among mature M phi residing in various tissue sites. By immunizing mice with M phi derived from blood MO by culture on hydrophobic Teflon foils, monoclonal antibodies (mAbs) were developed (MAX.1, MAX.2, MAX.3, MAX.11) that reacted with lineage-restricted differentiation antigens. These antigens were expressed exclusively on M phi or were markedly increased after in vitro differentiation. The only overlap to another hemopoietic cell lineage was observed with MAX.3, which is shared by platelets and megakaryocytes. In the course of M phi maturation in vitro, the MAX.1 and MAX.3 antigens are detected within the cytoplasm two days before they appear on the cell surface. In contrast, the MAX.11 antigen is expressed simultaneously in the cytoplasm and at the cell surface, is found in varying degrees on a minor portion of blood MO and U937 cells, and is expressed rapidly at high density during early M phi differentiation in vitro. Among conventional mAbs that do not react with MO we found those against the transferrin (TF)-receptor, the BA-2, and the PCA1 antigen to label M phi. M phi matured in vivo and isolated from body fluids were positive with some but not all MAX mAbs. Distinctive patterns were observed with pulmonary M phi, exudate M phi from pleural and peritoneal effusions, synovial fluids, and early lactation milk. M phi from the alveolar space, for example, constantly expressed the MAX.2 antigen but not the MAX.3 antigen. Pleural effusion M phi, however, did not react with the MAX.1 mAb, but in most cases, it did react with the MAX.3 mAb. The detection of novel differentiation antigens, all expressed on monocyte-derived M phi but differently expressed on site-specific M phi in situ, underlines the remarkable heterogeneity among human M phi. The expression of these antigens is flexible because those MAX antigens that were not expressed in situ could be induced if cells from distinct tissue sites were cultured in vitro for several days. MAX mAbs may be of potential value to study both the sequential stages of maturation within the M phi lineage as well as differential developments induced by various culture conditions in parallel to environmental factors in vivo.
Proteoglycans in human long-term bone marrow cultures: biochemical and ultrastructural analyses
Authors: Wight TN , Kinsella MG , Keating A , Singer JW 
Published: October 2019

Abstract
Proteoglycans within the extracellular matrix of human bone marrow have been implicated in the process of hematopoiesis, but little is known about the structure and composition of these macromolecules in this tissue. Hematopoietically active human long-term bone marrow cultures were incubated with medium containing 35S-sulfate and 3H-glucosamine as labeling precursors. Proteoglycans present in the medium and cell layer were extracted with 4 mol/L guanidine HCI and purified by diethylaminoethyl (DEAE)-Sephacel ion exchange and molecular sieve chromatography. Both culture compartments contain a large chondroitin sulfate proteoglycan (MI, CI) that eluted in the void volume of a Sepharose CL-4B column and contained glycosaminoglycan chains of molecular weight (mol wt) approximately 38,000. A second population of sulfate-labeled material was identified as a broad heterogenous peak (MII, CII) that was included on Sepharose CL-4B at Kav = 0.31. This material when chromatographed on Sepharose CL-6B could be further separated into a void peak (MIIa, CIIa) and an included peak eluting at Kav = 0.39 (MIIb, CIIb). The void peaks (MIIa, CIIa) were susceptible to chondroitinase ABC digestion (99%) but slightly less susceptible to chondroitinase AC digestion (90%). Papain digestion of these peaks revealed them to be proteoglycans with glycosaminoglycan chains of mol wt approximately 38,000. The included peaks on Sepharose CL-6B (MIIb, CIIb) from both medium and cell layer compartments resisted digestion with papain, indicating the presence of glycosaminoglycan chains of mol wt approximately 38,000 either free or attached to a small peptide. Although this material was susceptible to chondroitinase ABC (98%), it was considerably less susceptible to chondrotinase AC (approximately 60%), indicating that it contained dermatan sulfate. A small amount of heparan sulfate proteoglycan was also identified but constituted only approximately 10% of the total sulfated proteoglycan extracted from these cultures. Additionally, approximately 40% of the incorporated 3H- activity radioactivity was present as hyaluronic acid. Electron microscopy revealed a layer of adherent cells covered by a mat containing ruthenium red-positive granules that were connected by thin filaments. The extracellular matrix layer above the adherent cells contained a mixture of hematopoietic cells. Chondroitinase ABC treatment of the cultures completely removed the ruthenium red-positive granules overlying the cells and resulted in a loss of approximately 70% of the 35S-sulfate-labeled material from the cell layer.(ABSTRACT TRUNCATED AT 400 WORDS)
Analysis of natural killer cells in patients with aplastic anemia
Authors: Gascon P , Zoumbos N , Young N 
Published: October 2019

Abstract
We have analyzed natural killer (NK) cells in 43 patients with severe aplastic anemia, using cytotoxicity assays and microfluorometry with monoclonal antibodies, prior to and after treatment with antithymocyte globulin (ATG). Before treatment, natural killer cell activity (NKa) in both peripheral blood and bone marrow was markedly decreased in 76% of patients as compared with normal controls. Although we have measured low NKa in patients receiving large numbers of blood transfusions (means = 150 U of RBCs), six aplastic patients had low NKa in the absence of transfusions, and the average number of transfusions in the total population was low (means = 24). Purification of larger granular lymphocytes (LGLs) from peripheral blood of aplastic anemia patients failed to recover significant NKa. Most of these large granular lymphocytes showed few azurophilic granules. NKa was appropriately enhanced in these patients samples by exposure of mononuclear cells to either interleukin 2 (IL-2) or interferon (IFN). Analysis of peripheral blood phenotypic markers showed that cells bearing Leu 7 antigen were in the normal range in aplastic anemia (means = 12% +/- 2%; normal = 16% +/- 2%), but there was a deficiency of Leu 11+ cells (means = 8% +/- 2%; normal = 15% +/- 2%). The number of Leu 11+ cells was well correlated with NKa. In 13 of 22 patients treated with ATG, NKa returned to the normal range, and recovery of NKa was correlated to hematopoietic recovery. Our results suggest that deficient NKa is an intrinsic feature of aplastic anemia, and that the circulating cells in this disease are of the pre-NK cell stage.
Mapping of distinct von Willebrand factor domains interacting with platelet GPIb and GPIIb/IIIa and with collagen using monoclonal antibodies
Authors: Girma JP , Kalafatis M , Pietu G , Lavergne JM , Chopek MW , Edgington TS , Meyer D 
Published: October 2019

Abstract
We have used monoclonal antibodies (M Abs) and proteolytic fragmentation to localize structurally the functional sites of human von Willebrand factor (vWF) responsible for interaction with membrane glycoproteins GPIb, GPIIb/IIIa, and with collagen. SpII (215 kd) and SpIII (320 kd), the S aureus V-8 protease homodimeric fragments representing the carboxy-terminal and amino-terminal segments of the vWF subunit, competitively inhibited the binding of multimeric vWF to thrombin-stimulated or ristocetin-stimulated platelets, respectively. Specific saturable binding of each fragment was observed to stimulate platelets appropriately and was inhibited only by selected M Abs that both bound to the specific fragment and inhibited the corresponding function. M Ab 9, which blocks thrombin-induced binding of vWF to platelets, inhibited binding of SpII to platelets and bound to SpII as well as to a dimeric, 86-kd thermolysin fragment composed of 42-kd and 23-kd subunits, each possessing the epitope. Binding of SpII was also inhibited by a M Ab to GPIIb/IIIa. Thus, it appears that a portion of the carboxy-terminal end of vWF contains the ligand site for the GPIIb/IIIa receptor. In contrast, M Ab H9, which blocks ristocetin- induced binding of vWF to platelets, inhibited binding of SpIII to platelets and bound to SpIII as well as to monomeric 33-kd and 28-kd subtilisin fragments. Binding of SpIII to platelets was also inhibited by a M Ab to GPIb. Thus, it appears that a small segment of the amino- terminal part of vWF contains the ligand for the platelet GPIb receptor. The collagen binding site of vWF was localized with M Ab B203, which inhibits vWF interaction with collagen. This M Ab also bound to SpIII as well as to monomeric 26-kd and 23-kd subtilisin fragments. Thus, the third functional site responsible for collagen binding appears to be localized on the amino-terminal portion of vWF, in a linear sequence different from those responsible for interaction with either of the platelet receptors. These assignments of functional sites should facilitate the localization of structural defects of vWF in the various forms of vWD and support the role of vWF as an adhesive protein with multiple interactive sites.
Quinidine purpura: evidence that glycoprotein V is a target platelet antigen
Authors: Stricker RB , Shuman MA 
Published: October 2019

Abstract
Quinidine-induced thrombocytopenia has been associated with both immune complex and autoantibody binding to platelets. In the present study, serum antibody from six of six patients with quindine purpura was shown by immunoblotting to bind to a single platelet membrane protein of mol wt 80,000. This target protein was absent from Bernard-Soulier (BSS) platelets. F(ab)2 prepared from one patient's serum also bound to this protein, indicating autoantibody rather than immune complex binding to the target antigen. Antibody binding to the 80-kd protein was preserved after treatment of platelets with concentrations of trypsin or chymotrypsin that completely removed glycoprotein Ib (GPIb). Preincubation of platelet proteins with one patient's serum blocked binding of a polyclonal rabbit antibody against glycoprotein V (GPV), indicating that these antibodies recognize the same antigen. By wheat germ affinity chromatography, GPV was shown to copurify with GPIb. Quinidine-induced antibody bound to the wheat germ-purified GPV but not to GPIb. We conclude that quinidine purpura is associated with autoantibody directed against platelet GPV.
Juvenile chronic myelogenous leukemia: characterization of the disease using cell cultures
Authors: Estrov Z , Grunberger T , Chan HS , Freedman MH 
Published: October 2019

Abstract
To characterize juvenile chronic myelogenous leukemia (JCML), the proliferative properties of bone marrow (BM) and peripheral blood (PB) cells from nine patients were studied using assays for CFU-C and CFU- GEMM and liquid cultures. All specimens showed two reproducible abnormalities: impaired growth of normal hematopoietic progenitors and excessive proliferation of monocyte-macrophage colonies in the absence of exogenous colony-stimulating activity (CSA). Cytogenetic studies in one patient indicated that the CFU-C were malignant because BM cells at diagnosis and monocyte-macrophage colonies showed an abnormal karyotype, whereas PB lymphocytes did not. In contrast to JCML, PB from six adults with Philadelphia (Ph1) chromosome-positive chronic myelogenous leukemia (Ph1 + CML) yielded CSA-dependent CFU-C colonies which were composed of granulocytes, macrophages, or both, as well as exuberant growth of BFU-E colonies. Co-cultures of JCML BM adherent or nonadherent cells with normal BM resulted in suppression of normal hematopoietic colony formation. Supernatant from JCML adherent cells in liquid culture or plasma from newly diagnosed untreated JCML patients also suppressed control BM colony growth in a dose-dependent manner. These findings confirm that JCML is a malignant disorder of monocytic lineage and suggest that the mechanism of hematopoietic failure in JCML is mediated by an inhibitory monokine secreted by malignant JCML cells.
Human parvovirus B19-induced epidemic acute red cell aplasia in patients with hereditary hemolytic anemia
Authors: Saarinen UM , Chorba TL , Tattersall P , Young NS , Anderson LJ , Palmer E , Coccia PF 
Published: October 2019

Abstract
From March to August 1984, 26 patients with hereditary hemolytic anemia in northeastern Ohio developed acute, profound red cell aplasia. The patients included 14 males and 12 females 2 to 23 years old, with sickle cell anemia (20 cases), hemoglobin SC-disease (4 cases), sickle- beta-thalassemia (1 case), or hereditary spherocytosis (1 case). All had an acute onset of severe reticulocytopenia and anemia and prodromal symptoms of illness including fever, abdominal symptoms, headache, and arthralgias. Twenty-two received transfusions. Reticulocytosis occurred spontaneously within 2 to 14 days of presentation. In five acute-phase sera, 10(8) to 10(12) viral particles/mL were detected by electron microscopy. Human parvovirus B19 DNA was demonstrated in high concentration by hybridization in the same five acute-phase sera and in low concentration in sera of eight additional patients. The five highly viremic sera inhibited erythroid colony formation in vitro. B19- specific IgM was detected in sera of 24/26 patients, and B19-specific IgG in 21 of 22 patients tested. Our results indicate that human parvovirus B19 was the etiologic agent in this large epidemic of life- threatening acute red cell aplasia in patients with hereditary hemolytic anemia.
Effects of recombinant human GM-CSF on proliferation of clonogenic cells in acute myeloblastic leukemia
Authors: Griffin JD , Young D , Herrmann F , Wiper D , Wagner K , Sabbath KD 
Published: October 2019

Abstract
Proliferation of acute myeloblastic leukemia (AML) cells in vitro is limited in most cases to a small subset of blasts that have several properties of stem cells. These leukemic colony-forming cells (AML-CFU) generally require addition of exogenous growth factors for proliferation in agar or methylcellulose. These factors can be supplied by media conditioned by phytohemagglutinin-stimulated normal leukocytes or by CSF-secreting tumor cell lines. However, the exact factor or factors required for stimulation of AML-CFU growth have not been defined. We compared the AML-CFU stimulatory activity of a human recombinant GM-CSF with that of GCT-CM, Mo-CM, and the PHA-leukocyte feeder system in 15 cases of AML. In each of the 12 cases that required exogenous growth factors for maximum AML-CFU growth, recombinant GM-CSF could replace either GM-CSF or Mo-CM, and could partially replace the PHA-leukocyte feeder system. These results indicate that this GM-CSF is a growth promoter of AML-CFU in these culture systems.
In vitro release of physically separable factors from monocytes that exert opposing effects on erythropoiesis
Authors: Feldman L , Cohen CM , Dainiak N 
Published: October 2019

Abstract
In order to investigate the capacity of monocytes to release erythroid burst-promoting activity (BPA), we added media conditioned by homologous monocytes to both serum-free human and serum-restricted murine marrow culture. We found that soluble, membrane vesicle-free culture medium is a potent source of the growth factor. On the other hand, monocyte membranes or exfoliated plasma membrane vesicles elaborate a factor that inhibits erythroid burst formation by up to 100%. Inhibitory activity is expressed in a dose-dependent fashion over a wide range of concentrations (0.001 to 10 micrograms/mL) tested. Experiments with antilymphocyte plasma membrane IgG, which has been shown to neutralize both soluble and membrane-bound lymphocyte-derived BPA in human marrow culture, indicate that the expression of soluble BPA by monocytes is unaffected by these antibodies. Furthermore, while antimembrane IgG is capable of absorbing BPA from LCM supernatants, these antibodies are ineffective in removing BPA from MCM supernatants, suggesting that these two soluble growth factors may be antigenically distinct. Our findings indicate that while monocytes release soluble BPA, they are also a source of membrane-associated factors that exert inhibitory effects on erythropoiesis in vitro.