bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of the megakaryocyte secretory response: studies of continuously monitored release of endogenous ATP
Authors: Miller JL 
Published: October 2019

Abstract
Megakaryocytes share a number of structural and chemical properties with their progeny, blood platelets. With the availability of highly purified preparations of megakaryocytes isolated from guinea pig bone marrow, it is now also possible to study functional aspects of these cells. The present work reports the first study of the release of endogenously stored materials in megakaryocytes. Guinea pig megakaryocytes isolated to 75%-90% purity were exposed to thrombin or calcium ionophore (A23187) and the release of ATP was continuously monitored with the luciferin-luciferase reaction. Both maximal extent and initial rate of release were studied. Thrombin-induced release was half-maximal at thrombin concentrations of 0.2–0.5 NIH U/ml. At 4 U/ml thrombin, maximal release was 538 +/- 147 nmole ATP/10(9) megakaryocytes. A23187 induced half-maximal responses at concentrations of 7–8 microM. ATP release by ionophore showed a nearly absolute requirement for extracellular calcium, with release by thrombin showing only a partial calcium dependence. Following overnight culture, the response to thrombin was unchanged, whereas ATP release in response to ionophore was consistently increased (p less than 0.01). By comparison of maximally releasable ATP with total cellular ATP content, the storage pool of ATP in megakaryocytes was determined to comprise only 2%-6% of total megakaryocyte ATP, in contrast to an ATP storage pool of 20%-30% in guinea pig platelets. This difference may reflect further entry of ATP into the storage pool compartment or an enhanced ability of the cell to recognize and respond fully to platelet stimuli as the megakaryocyte reaches full maturity.
Flow cytometry of reticulocytes applied to clinical hematology
Authors: Tanke HJ , Rothbarth PH , Vossen JM , Koper GJ , Ploem JS 
Published: October 2019

Abstract
Reticulocytes in fixed human blood samples were stained for RNA with the fluorescent dye pyronin Y and measured by flow cytometry. The resulting relative frequency distributions of the RNA fluorescence intensities concurred with the different stages in maturation from early reticulocytes to mature red cells. A computer program was written to calculate from these frequency distributions the relative number of reticulocytes, their relative RNA content, and the median of the reticulocyte population (RNA index). This method was applied to 30 healthy blood bank donors (control group), as well as to patients with various hematologic disorders showing abnormal erythropoietic activity. The measured percentage of reticulocytes, RNA content, and RNA index were found to correlate well with the various hematologic disorders. Changes in erythropoiesis could be clearly followed, as was demonstrated by analyzing blood samples from children with aplastic anemia or acute myeloid leukemia, who were treated with allogeneic bone marrow transplantation. Measurements on blood samples from healthy blood bank donors showed that with this method, small changes in the reticulocyte population, such as the appearance of polychromatic erythrocytes in the peripheral blood 5–8 hr after donation, can be detected. The statistical reliability and the information provided on the maturation stage of the entire reticulocyte population make flow cytometry of peripheral blood reticulocytes a more informative method for the study of hematologic abnormalities than conventional methods for reticulocyte counting and classification.
Persistent epstein-barr virus infection mimicking juvenile chronic myelogenous leukemia: immunologic and hematologic studies
Authors: Herrod HG , Dow LW , Sullivan JL 
Published: October 2019

Abstract
Epstein-Barr virus (EBV) infections may induce a diverse clinical picture, ranging from the well characterized infectious mononucleosis (IM) syndrome to the rare X-linked lymphoproliferative syndrome. We describe two unrelated children, a 21-mo-old white boy and a 15-mo-old black girl, who presented with the clinical and laboratory findings characteristically seen in juvenile chronic myelogenous leukemia (JCML). Results of periodic serodiagnostic tests indicated that they likely have persistent infection with EBV. Both had elevated IgG antibody to viral capsid antigen (greater than or equal to 1:320) and antibody to early antigen (1:20–1:40) that have persisted for 3 yr of more. Both patients had EBV-specific suppressor cell activity, decreased natural killer cell activity, and diminished antibody- dependent cell-mediated cytotoxicity (ADCC) activity. These changes suggest an underlying defect in the immunoregulatory network controlling EBV infection. The patients have shown clinical improvement without treatment. It appears that EBV infections are capable of inducing symptoms similar to those seen in JCML. Careful evaluation for evidence of EBV infection in patients presenting with symptoms compatible with JCML seems warranted.
Differences in myeloperoxidase activity from neutrophilic polymorphonuclear leukocytes of differing density: relationship to selective exocytosis of distinct forms of the enzyme
Authors: Pember SO , Kinkade JM Jr 
Published: October 2019

Abstract
Elicited murine neutrophilic polymorphonuclear leukocytes (PMN) were fractionated by Percoll density gradient centrifugation into high density (HD) and intermediate density (ID) populations. As described in the accompanying article HD- and ID-PMN appear to represent “resting” and “activated” cell populations, respectively. Consistent with this possibility, histochemical and biochemical evidence suggested that ID- PMN were degranulated compared to HD-PMN. Myeloperoxidase (MPO) in the ID-PMN population showed increased sensitivity to inhibition by 3-amino- 1,2,4-triazole, and HD-PMN exhibited a 2–3-fold increase in chloride and iodide oxidation per unit of MPO activity compared to ID-PMN. When HD-PMN were induced to degranulate in vitro, the remaining cell- associated MPO displayed enzymatic properties characteristic of the activity associated with ID-PMN. The mechanism of this phenomenon was also investigated in vitro using purified human peripheral blood PMN and the synthetic chemotactic peptide N-formyl-methionyl-leucyl- phenylalanine. Differences in cell-associated MPO activity were shown to be related to selective exocytosis of enzymatically and chromatographically distinct forms of the enzyme. These data indicate that, in addition to the well known selective exocytosis of specific and azurophilic granules induced by various agents, selectivity may also occur at the level of enzymatically distinct forms of a particular granule enzyme. Moreover, our observations provide further evidence that density differences may be utilized to fractionate and study the generation of functionally distinct subpopulations of PMN that arise in vivo as well as in vitro following exposure to various stimuli.
Four cases of t(4;11) acute leukemia and its myelomonocytic nature in infants
Authors: Nagasaka M , Maeda S , Maeda H , Chen HL , Kita K , Mabuchi O , Misu H , Matsuo T , Sugiyama T 
Published: October 2019

Abstract
Four cases of acute infantile leukemia with translocation (4;11) (q21;q23) are reported. Although leukemia with this chromosomal abnormality has been classified as L2 acute lymphoblastic leukemia by the FAB classification, two of our cases appeared to be of myelomonocyte origin as demonstrated by cytochemical, immunologic, and electron microscopic studies and differentiation induction by 12- tetradecanoyl-phorbol-13-acetate and methylformamide. This chromosomal change is associated with poor prognosis.
Markedly elevated serum IgE levels following allogeneic and syngeneic bone marrow transplantation
Authors: Ringden O , Persson U , Johansson SG , Wilczek H , Gahrton G , Groth CG , Lundgren G , Lonnqvist B , Moller E 
Published: October 2019

Abstract
Serum IgE levels were studied in 25 bone marrow transplant recipients (in 12 patients twice weekly and in 13 patients, at random). A 2–748- fold increase in serum IgE was recorded in 20 of the 25 patients after transplantation, the highest IgE value observed being 8,000 kU/liter. The IgE elevation appeared concomitantly with acute graft-versus-host disease (GVHD) in 14 patients. Both events occurred on day 24 +/- 2 (mean +/- SE). When the acute GVHD was diagnosed, there was a significant increase in serum IgE as compared to the first posttransplantation value. In one patient in whom GVHD recurred, a second IgE peak was seen, and in another patient with flaring GVHD, IgE levels increased on several occasions. In 6 patients without clinical signs of GVHD, a rise in IgE occurred on day 35 +/- 12. One of these patients was grafted with marrow from her identical twin. The rise in IgE did not correlate with an elevated proportion of eosinophil granulocytes. In the majority of the patients, no correspondent increases in serum IgG, IgA, or IgM were seen during the period with increased IgE after transplantation.
Effect of heparin on the in vivo release and clearance of human platelet factor 4
Authors: Rao AK , Niewiarowski S , James P , Holt JC , Harris M , Elfenbein B , Bastl C 
Published: October 2019

Abstract
Intravenous injection of heparin (100 U/kg) into normal volunteers resulted in an increase of platelet factor 4 (PF4) level in platelet- poor plasma from a mean value of 18.1 +/- 6.6 ng/ml before the injection to 257.9 +/- 68.3 ng/ml at 5 min after injection. PF4 antigen isolated from “postheparin plasma” by adsorption on heparin-agarose and elution with 2.0 M NaCl and “authentic PF4” isolated from human platelets showed identical patterns of migration as determined by sodium dodecylsulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Material released by washed human platelets was injected intravenously into rats. The clearance of PF4 followed a biphasic exponential pattern. The half-lives (T1/2) for the fast and slow components for control rats were 1.2 and 17.1 min. Heparin significantly extended the half-life of human PF4 in rat circulation. The clearance of PF4 injected together with heparin followed a single component model with a half-life of 27.6 min. Administration of heparin to rats that had been previously injected with human platelet releasate resulted in a 30-fold increase of plasma PF4 level in their circulation. The clearance of PF4 from the circulation of these rats (T1/2 = 45 min) fitted a single component model. We propose that PF4 is originally secreted by platelets into circulation and subsequently bound reversibly to vascular sites from which it can be released back into the circulation by heparin. The fast component of PF4 clearance that is abolished by heparin may reflect binding of this protein to the endothelial cells.
Specific translocations characterize Burkitt's-like lymphoma of homosexual men with the acquired immunodeficiency syndrome
Authors: Chaganti RS , Jhanwar SC , Koziner B , Arlin Z , Mertelsmann R , Clarkson BD 
Published: October 2019

Abstract
A Burkitt's-like B-cell lymphoma (BLL) has recently been shown to be associated with the acquired immunodeficiency syndrome (AIDS), which affects homosexual men. We report cytogenetic studies of two BLL tumors in homosexual men. Both tumors had chromosome translocations characteristic of Burkitt's lymphoma (BL), one the t(8;14) and the other the t(8;22). The pathway of lymphomagenesis in this disorder is discussed in the light of recent data on chromosome change and localization of immunoglobulin genes and oncogenes.
The entire beta-globin gene cluster is deleted in a form of gamma delta beta-thalassemia
Authors: Fearon ER , Kazazian HH Jr , Waber PG , Lee JI , Antonarakis SE , Orkin SH , Vanin EF , Henthorn PS , Grosveld FG , Scott AF , Buchanan GR 
Published: October 2019

Abstract
We have used restriction endonuclease mapping to study a deletion involving the beta-globin gene cluster in a Mexican-American family with gamma delta beta-thalassemia. Analysis of DNA polymorphisms demonstrated deletion of the beta-globin gene from the affected chromosome. Using a DNA fragment that maps greater than 40 kilobases (kb) 5′ to the epsilon-gene as a probe, reduced amounts of normal fragments were found in the DNA of affected family members. Similar analysis using radiolabeled DNA fragments located 3′ to the beta-globin cluster has shown that the deletion extends more than 17 kb 3′ to the beta-gene, but terminates before the 3′ endpoint of the Ghanian HPFH deletion. Hence, this gamma delta beta-thalassemia deletion eliminates over 105 kb of DNA and is the first report of a deletion of the entire beta-globin gene cluster.
Prognostic significance of receptors for the third component of complement an heavy chain phenotype in diffuse B-cell lymphomas
Authors: Gold EJ , Mertelsmann RH , Filippa DA , Szatrowski TH , Koziner B , Clarkson B 
Published: October 2019

Abstract
As part of a larger study to determine the prognostic significance of cell marker phenotype in diffuse lymphomas, 51 patients with monoclonal B-cell lymphoma were further characterized by receptors for C3 (EAC rosettes) as well as heavy and light chain phenotypes. Patients with greater than 10% EAC rosette-forming cells were found to have a statistically significant longer survival than those with less than 10% EAC rosettes (p = 0.005). A similar trend in survival duration was found for patients whose cells expressed mu heavy chain on their surfaces when compared to those with gamma heavy chain on their cell surfaces (p = 0.05). No difference was observed for light chain phenotype. No correlation was observed between these prognostic groups and any of the three most frequently used histologic classifications (i.e., Rappaport, Lukes, Kiel).
The effect of monocytes in the peripheral blood CFU-C assay system
Authors: To LB , Haylock DN , Juttner CA , Kimber RJ 
Published: October 2019

Abstract
The effect of cellular interactions in the in vitro assay of myeloid progenitor cells in peripheral blood (PB CFU-C) was investigated. Ficoll-Paque-separated peripheral blood mononuclear cells (PB MNC) from 7 healthy subjects were cultured at cell concentrations from 10 to 0.625 X 10(5) MNC/plate in doubling dilutions. The number of colonies per 10(6) lymphocytes plated (corrected colony count, CC) was significantly higher when 2.5 X 10(5) or less PB MNC were cultured than when 5 or 10 X 10(5) cells were cultured. This decrease in CC when large numbers of cells were cultured was not present when the nonadherent cells only were cultured. The inhibition was reproduced when adherent cells were added back to the nonadherent cells. The inhibition appeared to be proportional to the number of monocytes present. A model depicting the role of monocytes in the PB CFU-C assay system is presented. The increased understanding of cellular interaction represents an important step towards the standardization of the PB CFU-C assay.
Myeloid-associated differentiation antigens on stem cells and their progeny identified by monoclonal antibodies
Authors: Andrews RG , Torok-Storb B , Bernstein ID 
Published: October 2019

Abstract
Within the hematopoietic system, monoclonal antibodies reactive with antigenic determinants, expressed in a lineage- and stage-restricted fashion, can be used to map myeloid differentiation. We have generated a series of monoclonal antibodies that reacts with myeloid-associated determinants on committed myeloid stem cells and their progeny. Their reactivity with peripheral blood cells was identified by immunofluorescence assays, with bone marrow cells by fluorescence- activated cell sorting, and with committed hematopoietic progenitor cells by both cytotoxic assays and fluorescence-activated cell sorting. Antibody 1G10, which has previously been reported to react with cells of the granulocytic lineage and with a minor subset of mature monocytes, was shown to react with granulocyte-macrophage colony- forming units (CFU-GM). Three antibodies not previously characterized (T5A7, L4F3, L1B2) were shown to react with both granulocytic and monocytic cells and in fluorescence-activated cell sorting studies to detectably stain granulocytic cells at different stages of maturation. These three antibodies also react with CFU-GM, two (L4F3 and L1B2) reacting with all CFU-GM, while T5A7 reacts with only a portion of the day 7 CFU-GM. Antibody L4F3 also reacts with a portion of erythroid burst-forming units (BFU-E). In contrast, the previously reported antibody 5F1, which reacts with monocytic cells, nucleated erythroid cells, and platelets, was shown to react with erythroid colony-forming units (CFU-E). Potential applications of these antibodies to studies of normal and malignant hematopoiesis are discussed.
Functional studies of Willebrand factor using monoclonal antibodies
Authors: Bowie EJ , Fass DN , Katzmann JA 
Published: October 2019

Abstract
Previously described monoclonal antibodies to porcine Willebrand factor were used to study various functional assays of Willebrand factor. These antibodies comprise at least five separate specificities as determined by differential reactivity in three distinct binding assays. The antibodies were tested for their effect on the in vivo bleeding time, in vitro bleeding time, and ristocetin cofactor activity. The titers of the antibodies in a binding assay did not correlate with any inhibitory activities, and the ability to inhibit a given functional test was independent of inhibitory activity in the other assays. These data suggest that the antibodies are able to detect specific structures on Willebrand factor involved in specific functional assays and that the structure(s) involved in ristocetin cofactor activity is not identical to those mediating the in vivo or in vitro bleeding time.
Reexpression of normal stem cells in erythroleukemia during remission
Authors: Ferraris AM , Canepa L , Mareni C , Baule G , Meloni T , Salvidio E , Forteleoni G , Gaetani GF 
Published: October 2019

Abstract
A patient with erythroleukemia and heterozygous for the Mediterranean variant of the X-linked enzyme glucose-6-phosphate dehydrogenase (G6PD) was studied to determine the number and type of progenitor cells in which the disease arose. G6PD mosaicism was assessed by the different rate of utilization of 2-deoxy-glucose-6-phosphate (2dG6P) by normal and Mediterranean variants of G6PD. Erythroleukemia is established as a clonal disease involving a precursor cell common to the erythroid and myeloid lines. After intensive chemotherapy, restoration of nonmonoclonal hemopoiesis is achieved, as indicated by the reappearance of the mosaic phenotype in hemopoietic cell populations.
Enhanced iron removal from liver parenchymal cells in experimental iron overload: liposome encapsulation of HBED and phenobarbital administration
Authors: Rahman YE , Cerny EA , Lau EH , Carnes BA 
Published: October 2019

Abstract
The effectiveness of N,N′-bis[2-hydroxybenzyl]-ethylene-diamine-N,N′- diacetic acid (HBED) in removing radioiron introduced into the parenchymal cells of mouse liver as 59Fe-ferritin has been investigated. The effectiveness of HBED, an iron chelator of low water solubility, has also been compared with that of desferrioxamine (DF), an iron chelator of high water solubility and currently in clinical use for treatment of transfusional iron overload. Using the 59Fe excretion as the measure of effectiveness of chelation therapy and a standardized single chelator dose of 25 mg/kg, we have found that: (1) a saline suspension of HBED, prepared by sonication and given intraperitoneally to mice, promotes a small but significant increase in excretion of radioiron compared to the untreated controls, whereas DF, in its free form, is ineffective; (2) HBED encapsulated in lipid bilayers of liposomes and given intravenously is superior to nonencapsulated HBED; (3) DF encapsulated in small unilamellar liposomes is ineffective in removing iron given in the form of ferritin; (4) administration of phenobarbital in drinking water, at a concentration of 1 g/liter, induces a 30%-55% increase of iron excretion from untreated control mice and also from mice given HBED either in liposome-encapsulated or nonencapsulated form. We have demonstrated that HBED is superior to DF for removal of storage iron from liver parenchymal cells and that liposomes are useful carriers for iron chelators of low water solubility.
Red blood cell size is important for adherence of blood platelets to artery subendothelium
Authors: Aarts PA , Bolhuis PA , Sakariassen KS , Heethaar RM , Sixma JJ 
Published: October 2019

Abstract
The hematocrit is one of the main factors influencing platelet adherence to the vessel wall. Raising the hematocrit causes an increase of platelet accumulation of about an order of magnitude. Our studies concern the role of red cell size. We have studied this effect using an annular perfusion chamber, according to Baumgartner, with human umbilical arteries and a steady-flow system. Normal human red blood cells (MCV 95 cu mu) increased platelet adherence sevenfold, as the hematocrit increases from 0 to 0.6. Small erythrocytes from goats (MCV 25 cu mu) caused no increment in adherence in the same hematocrit range. Rabbit erythrocytes (MCV 70 cu mu) caused an intermediate increase in adherence. Red blood cells from newborns (MCV 110–130 cu mu) caused a larger increase in platelet adherence than normal red cells at hematocrit 0.4. These results were further confirmed with large red blood cells from two patients. Experiments with small red cells (MCV 70 cu mu) of patients with iron deficiency showed that platelet adherence was similar to normal red cells, provided the red cell diameter was normal. Small red blood cells of a patient with sideroblastic anemia caused decreased adherence. These data indicate that red cell size is of major importance for platelet adherence. Red cell diameter is more important than average volume. However, for size differences in the human range, the hematocrit remains the dominant parameter.
Genetic evidence for fetal origin of transcobalamin II in human cord blood
Authors: Porck HJ , Frater-Schroder M , Frants RR , Kierat L , Eriksson AW 
Published: October 2019

Abstract
Phenotypes of transcobalamin II (TC2) were determined in 95 maternal- cord serum pairs in order to identify the origin of TC2 in human cord blood. Unsaturated (apo) TC2 in serum was labeled with radioactive (57Co) cobalamin (CbI) and separated into isoproteins by polyacrylamide gel electrophoresis and autoradiography. Discordancy between the maternal and the cord serum type was observed in 45% of the pairs. The results demonstrated that, at the end of pregnancy, the fetus is capable of TC2 synthesis and that there is no detectable transplacental passage of maternal apo-TC2. Presence of maternal saturated (holo) TC2 in cord serum could be excluded in 9 informative discordant pairs by exchanging endogenously bound CbI with 57Co-CbI. Our finding that TC2 in human cord serum is of fetal rather than maternal origin suggests an essential role for fetal TC2 in CbI utilization and appears to contradict the hypothesis that transplacental passage of maternal TC2 may explain the normal fetal development in cases of congenital TC2 deficiency. The total immunoreactive TC2 content in 23 maternal serum samples collected at the end of pregnancy (812 +/- 175 pM CbI equivalent) was significantly higher than in the corresponding cord sera (605 +/- 148 pM; p less than 0.001) and did not significantly differ from the value in a control group of healthy male and female adults (841 +/- 192 pM). At the end of pregnancy, the apo-TC2 content in 12 maternal serum samples (760 +/- 347 pM) was significantly higher than in the corresponding cord sera (501 +/- 254 pM; p less than 0.05) and did not significantly differ from the value in the control group (747 +/- 137 pM).