bluuebunny/crossref_metadata_2025_split huggingface dataset:
In vivo modulation of murine myelopoiesis following intravenous administration of prostaglandin E2
Authors: Gentile P , Byer D , Pelus LM 
Published: October 2019

Abstract
The effects of in vivo administration of prostaglandin E2 (PGE2) on several hematologic parameters were investigated in intact mice under both steady-state conditions and in mice hematopoietically rebounding following a sublethal injection of cyclophosphamide. Intravenous injection of native PGE2, or 16,16 dimethyl-PGE2, an enzymatically stable analog of PGE2, resulted in the significant suppression of nucleated bone marrow and splenic cellularity, total resident nucleated peritoneal cells, and the absolute number of detectable granulocyte- macrophage progenitor cells (CFU-GM) per femur or spleen when administered for 3 or 7 consecutive days. The in vivo effects of 16,16 dimethyl-PGE2 were more pronounced on the cyclophosphamide-treated mice. Dose titration analysis of the effects of 16,16 dimethyl-PGE2 revealed significant suppression of hematologic parameters over a concentration range of 10 micrograms-10(-5) micrograms/mouse/day (10(- 5) M-10(-11) M). The reduction in total nucleated marrow, splenic, and peritoneal cellularity observed following PGE2 administration resulted from a selective effect on nonspecific esterase-positive cells. In situ morphological analysis of the progeny of CFU-GM proliferating in cultures established from mice treated with PGE2 in vivo indicated that the reduction in absolute CFU-GM observed resulted from a preferential effect on those colony-forming cells restricted to monocyte-macrophage differentiation. Prostaglandin F2 alpha was without stimulatory or inhibitory effects in vivo on the hematopoietic parameters investigated.
A monoclonal antibody (WT1) for detecting leukemias of T-cell precursors (T-ALL)
Authors: Vodinelich L , Tax W , Bai Y , Pegram S , Capel P , Greaves MF 
Published: October 2019

Abstract
The selectivity of a monoclonal anti-T antibody, designated WT1, has been assessed in a series of 906 leukemias and lymphomas. In acute lymphoblastic leukemias, WT1 reacts comprehensively and selectively with thymic acute lymphoblastic leukemia (ALL) cells in untreated or relapsed patients, thus overriding the extensive antigenic diversity of this cancer and the immaturity of the cell type involved. All 80 cases of thymic ALL examined were WT1-positive. In addition, 18 cases of presumptive prethymic ALL were also WT1-positive, but were unreactive with other maturation-linked T-cell markers. The phenotype WT1+ HLA-DR TdT+ appears to be unique to T-ALL and can therefore be used systematically for the differential diagnosis of this poor prognosis subtype of ALL. Virtually all ALL cases can now be placed into one of two major subgroups representing transformed precursors of either the T- or B-cell lineage. WT1 identifies a single polypeptide of approximately 40,000 mol wt and is similar to two previously described monoclonal antibodies.
Apparent molecular weight of purified human factor VIII procoagulant protein compared with purified and plasma factor VIII procoagulant protein antigen
Authors: Weinstein MJ , Fulcher CA , Chute LE , Zimmerman TS 
Published: October 2019

Abstract
We have compared apparent molecular weights of purified factor VIII procoagulant protein (VIII:C) and VIII:C antigen (VIII:CAg) by two different NaDodSO4 gel electrophoretic techniques. In a discontinuous NaDodSO4–7.5% polyacrylamide system, reduced and unreduced VIII:C, purified from commercial factor VIII concentrates by a monoclonal antibody immunoadsorption technique, showed a major doublet at mol wt 0.79 and 0.8 X 10(5) and less intense bands extending up to 1.9 X 10(5). In NaDodSO4–4% polyacrylamide/0.5% agarose gels (NaDodSO4–4% PAAGE), purified VIII:C had a major band of mol wt 1.0 X 10(5), with minor bands of mol wt 0.96, 1.1, 1.4, 1.6, 1.8, 2.2, and 2.4 X 10(5). In NaDodSO4–4% PAAGE of 125I-anti-VIII:C-Fab-VIII:CAg complexes, the major and minor forms of VIII:CAg in purified VIII:C had the same molecular weight as above when calculated by subtracting the molecular weight of 125I-Fab from 125I-Fab-VIII:CAg. In both plasma and factor VIII concentrate, a band of mol wt 2.4 X 10(5) predominated, and minor VIII:CAg forms of mol wt 2.6, 1.8, 1.2 and 1.0 X 10(5) were also visible. We conclude that the molecular weight of plasma VIII:CAg forms agree with those derived from protein stains of purified VIII:C in the NaDodSO4–4% PAAGE system, but that consistently lower molecular weight values are obtained for purified VIII:C in the discontinuous system. Both native and either disaggregated or proteolyzed VIII:C species are present in the purified VIII:C preparation.
Common ALL with pre-B-cell features showing (8;14) and (14;18) chromosome translocations
Authors: Mufti GJ , Hamblin TJ , Oscier DG , Johnson S 
Published: October 2019

Abstract
A 21-yr-old man presented with inguinal lymphadenopathy and splenomegaly. The peripheral blood showed a high blast cell count. The morphological and immunologic features of the blast cells were consistent with the diagnosis of common acute lymphoblastic leukemia (ALL) with 15% pre-B-cells. Banded karyotype analysis of the blood and the marrow cells, using the technique of methotrexate synchronization, revealed the presence of (8;14) and (14;18) chromosome translocations, a finding that has not been previously documented. The significance of these findings is discussed.
Pyruvate kinase isozyme (PK-Greenville) with defective allosteric activation by fructose-1,6-diphosphate: the role of F-1,6-P modulation in normal erythrocyte metabolism
Authors: Paglia DE , Valentine WN , Holbrook CT , Brockway R 
Published: October 2019

Abstract
A child with chronic hemolytic anemia since birth was found to have erythrocyte pyruvate kinase (PK) in a highly unusual form relative to other mutant isozymes when characterized by International Committee for Standardization in Hematology criteria. Most properties of the partially purified isozyme (designated PK-Greenville) were altered minimally, if at all, except for nearly total insensitivity to allosteric activation by fructose-1,6-diphosphate (F-1,6-P). One parent appeared to be heterozygous for a null gene and the other for an allele governing production of the mutant isozyme. Apparent restriction of the molecular defect to ineffective activation kinetics suggests that the F- 1,6-P binding site on erythrocyte PK is functionally as well as physically allosteric. The magnitude of the metabolic block at the PK step and the clinical severity indicate that allosteric modulation by F- 1,6-P is a crucial property of PK in normal erythrocyte metabolism.
Identification of hemopoietic cells responsive to colony-stimulating factor by autoradiography
Authors: Shadduck RK , Pigoli G , Caramatti C , Degliantoni G , Rizzoli V , Porcellini A , Waheed A , Shiffer L 
Published: October 2019

Abstract
Binding of radiolabeled L-cell colony-stimulating factor (CSF) was studied using murine bone marrow and fetal liver cells. With 10(7) cells, saturation of binding was seen with approximately 500,000 cpm of 125I-CSF. Minimal binding was detected after one hour incubation with tracer at 37 degrees C; however, marked cellular uptake of radioactivity was noted after 24-hr exposure to CSF. As judged by autoradiographs, small numbers of myeloblasts, promyelocytes, and large mononuclear cells were labeled with 1-hr exposure to tracer. By 6 hr of incubation, 50%-70% of myeloblasts and promyelocytes and small numbers of late granulocytic cells were labeled. Virtually all myeloblasts and promyelocytes and approximately 50% of myelocytes, metamyelocytes, polymorphonuclear granulocytes, and monocytes were labeled after 24-hr exposure to the radioiodinated CSF. Label was not detected on erythroblasts, eosinophils, or megakaryocytes. Suspensions of fetal liver cells had lower uptake of radioactivity than bone marrow cells. This appeared to result from a lesser concentration of granulocytic cells in fetal liver, as labeling of individual cells was similar with both tissues. In additional experiments, CSF binding to marrow cells was assessed after 30-min exposure to tracer at 0 degrees C. Uptake of 125I-CSF exceeded that observed after 24-hr incubation at 37 degrees C. With this technique, cellular label was also confined to granulocytic and monocytic cells. These findings suggest that purified CSF reacts with and may stimulate immature and mature cells of the granulocytic and monocytic lineages.
Retinoic acid treatment of acute promyelocytic leukemia: in vitro and in vivo observations
Authors: Flynn PJ , Miller WJ , Weisdorf DJ , Arthur DC , Brunning R , Branda RF 
Published: October 2019

Abstract
We describe in vitro studies and a therapeutic trial of retinoic acid (RA) in a patient with acute promyelocytic leukemia (APL) refractory to chemotherapy. Bone marrow promyelocytes from the patient, prior to RA, matured morphologically in liquid culture with RA (97% maturing myeloid cells compared with 26% in control cultures at 7 days). RA-cultured cells displayed leukocyte alkaline phosphatase activity and cytoplasmic maturation (by electron microscopy). Retinoic-acid-treated cells, compared to controls, demonstrated increased functional maturation, with phagocytosis of opsonized zymosan (90% versus 10%) and production of superoxide (measured by nitroblue tetrazolium reduction) in response to phorbol ester, opsonized zymosan, or the chemotaxin F-met-leu-phe. There was no evidence of active proliferation in the cultures. RA- treated cells continued to show 15;17 chromosomal translocation after 7 days in culture. The patient was treated with oral 13-cis-retinoic acid (100 mg/sq m/day) for 13 days. During that time, the peripheral white blood count rose from 300 cu mm to 6,700 cu mm, and the maturing myeloid cell count rose from 54 cu mm to 3,800 cu mm. Bone marrow maturing cells increased from 1.8% to 8.0%. Despite the increasing number of maturing myeloid cells, the patient died on day 13 from disseminated candidiasis. These data confirm that RA induces maturation of leukemic promyelocytes in vitro and suggest that similar maturation is achievable in vivo. We suggest that oral retinoic acid may be a useful adjunct in the treatment of APL.
Characterization of a monoclonal antibody that reacts with an activation antigen on human B cells: reactions on mitogen-stimulated blood lymphocytes and cells of normal lymph nodes
Authors: Frisman D , Slovin S , Royston I , Baird S 
Published: October 2019

Abstract
We describe a monoclonal antibody that reacts with human B-lymphoid cells. We have characterized the reactions of this antibody on normal blood lymphocytes, with and without pokeweed mitogen stimulation, bone marrow lymphocytes, and on frozen sections of normal lymph nodes. The antibody, B532, appears to recognize an activation antigen on human B cells. This activation antigen can apparently be induced both by infection with Epstein-Barr virus and by stimulation with antigens and mitogens, but it is lost on plasma cells. In normal lymph nodes, the antigen is confined to germinal center cells and some of the cells of the “mantle” that surrounds germinal centers. The antigen is not present on T cells.
Characterization of human mast cells in long-term culture
Authors: Horton MA , O'Brien HA 
Published: October 2019

Abstract
Recent studies in rodents have demonstrated that mast cells derived from lymphoid tissues can be grown in longterm culture, provided that supportive growth factors or stromal fibroblasts are added; such findings have not been reported in man. Furthermore, although a hemopoietic origin for mast cells is supported by transplantation studies in mice, the exact origin of the human mast cell or its relationship to the circulating basophil and other hemopoietic cell lineages is unknown. We have investigated the requirements for in vitro growth of human mast cells derived from the infiltrated bone marrow of a patient with systemic mastocytosis, and have characterized both the mast cells proliferating in these cultures and those obtained from splenic infiltrates. Our data approached two questions: (1) Is there any evidence for the origin of mast cells from a bone-marrow-derived stem cell, and, if so, (2) what lineage relationship is there between mast cells and granulopoietic cells, including basophils? First, we have shown the expression of hemopoietic tissue-specific antigens by mast cells, strongly supporting a bone marrow origin for the mast cell in man (at least for those mast cells analyzed here). Second, the complete lack of granulocyte-monocyte markers contrasts with the phenotype of the basophil and suggests that mast cells diverge considerably from other granulopoietic cells during the acquisition of their differentiated specialized functions.
An immunologic study of spouses and siblings of asymptomatic hemophiliacs
Authors: Ragni MV , Bontempo FA , Lewis JH , Spero JA , Rabin BS 
Published: October 2019

Abstract
A transmissible agent may be responsible for the recent occurrence of the acquired immune deficiency syndrome (AIDS) in female heterosexual partners and infant contacts of AIDS victims or of persons at increased risk for AIDS. Therefore, we evaluated the clinical and immunologic status of 18 hemophiliac-spouse pairs and 19 hemophiliac-sibling pairs. Using surface marker assays of lymphocyte subpopulations, we found a mean T helper cell/T suppressor cell (H/S) ratio +/- SEM in 18 hemophiliac adults of 1.11 +/- 0.15 (11 less than 1.00), in their 18 spouses of 1.88 +/- 0.13 (none less than 1.00), in 19 hemophiliac children of 1.54 +/- 0.11 (3 less than 1.00), and in their 19 siblings of 1.87 +/- 0.11 (none less than 1.00). Both hemophiliac adult and hemophiliac children mean H/S ratios differed significantly (p less than 0.05) from the control mean ratio of 2.22 +/- 0.16 and from the mean of their respective nonhemophiliac spouse or sibling group (p less than 0.05). The mean ratio of hemophiliac adults differed significantly from that of hemophiliac children (p less than 0.05). These findings suggest that lymphocyte alterations in hemophiliacs are secondary to their therapy, are not influenced by genetic factors, and are not related to an infectious agent that is easily transmissible by close contact.
Lithium stimulation of murine hematopoiesis in liquid culture: an effect mediated by marrow stromal cells
Authors: Quesenberry PJ , Coppola MA , Gualtieri RJ , Wade PM , Song Z , Doukas MA , Shideler CE , Baker DG , McGrath EH 
Published: October 2019

Abstract
Lithium has previously been observed to stimulate in vitro Dexter culture hemopoiesis with increases in granulocytes, megakaryocytes, and pluripotent stem cells (CFU-S). In the present study, a two-phase murine Dexter culture system was established to study the mechanism of lithium-mediated stem cell stimulation. Different lots of horse sera or fetal calf sera were found to have markedly different effects on Dexter culture growth; given the appropriate sera supplementation, supernatant cells from Dexter cultures established from C57BL/6J mice 3 wk previously were free of stromal-forming capacity, but had stem cells and could grow on 900–950 R irradiated stroma. Conversely, in vitro irradiation (900–950 R) of 3-wk cultures resulted in a stem-cell-free adherent monolayer that could support growth for up to 9 wk in culture. The stroma from Dexter cultures preexposed to lithium chloride (1.0 mmole/liter) for 3 wk, irradiated (900 R), and then refed with 3-wk Dexter supernatant cells has an enhanced capacity to support cell production, CFU-S, and probably granulocyte-macrophage colony-forming cell (GM-CFU-C) production, as compared to stroma not preexposed to lithium. Lithium carryover was ruled out in these experiments. These data indicate that lithium stimulates CFU-S and in vitro granulopoiesis by an indirect effect on a radioresistant adherent stromal cell.
Transient versus permanent expression of cancer-related glycopeptides on normal versus leukemic myeloid cells coinciding with marrow egress
Authors: van Beek W , Tulp A , Bolscher J , Blanken G , Roozendaal K , Egbers M 
Published: October 2019

Abstract
Release of mature cells from the bone marrow (BM) into the peripheral blood (PB) compartment is supposed to be triggered by changes in cell surface constituents, most probably in glycoproteins. The supposed importance of glycoproteins in marrow exit prompted us to investigate glycopeptides, i.e., the carbohydrate part of the cell-surface-located glycoproteins of isolated human bone marrow cells of the myeloid series at different stages of maturation. Fractionation of cells was performed by a four-step procedure, comprised of density gradient centrifugation and velocity sedimentation at unit gravity in specially designed separation chambers. With this method, promyelocytes/myeloblasts, granulocytes from bone marrow, and granulocytes from peripheral blood were isolated in high quantity with purities up to 90%, 90%, and 100%, respectively. Surface glycopeptides of the various myeloid cells were investigated by gel filtration analysis after metabolic labeling with radioactive fucose or after external labeling with periodate- borotritide under mild conditions. Within the normal myeloid maturation sequence, mature granulocytes within the bone marrow were found to transiently express altered surface glycopeptides, which disappeared after release into the peripheral blood. These oligosaccharide structures appeared similar to those encountered on leukemic blast cells, known as “cancer-related glycopeptides.” In contrast to normal granulocytes from BM, leukemic blast cells retained these aberrant carbohydrate structures on their surface after marrow release. A possible role for cancer-related glycopeptides in the process of marrow cell exit might be hypothesized.
Perturbations in the erythroid marrow progenitor cell pools may play a role in the augmentation of HbF by 5-azacytidine
Authors: Torrealba-de Ron AT , Papayannopoulou T , Knapp MS , Fu MF , Knitter G , Stamatoyannopoulos G 
Published: October 2019

Abstract
In vivo observations on the kinetics of F cells and of fetal hemoglobin (HbF) synthesis and in vitro studies of erythroid progenitors, their number, and the gamma-gene expression in their progeny were carried out in baboons (Papio cynocephalus) treated with 5-azacytidine. Maximum effect on the increase of HbF production in vivo was observed only when an expanded erythroid marrow population was present. In these animals, as well as in normal animals, treatment resulted in a significant reduction of the late erythroid progenitor cell pools (erythroid clusters and erythroid colony-forming units, CFU-E) in the marrow. This reduction was more pronounced among those progenitors grown in the absence of added erythropoietin, and it was followed by a rebound a few days after treatment cessation, reflecting the accumulation of regenerating progenitors. An early increase in the in vitro synthesis of HbF in erythroid clusters and CFU-E colonies was observed. This increase was further documented at the cellular level, with immunofluorescent labeling of colonies with monoclonal anti-gamma- globin chain antibodies. In contrast to the findings in late progenitors, the number of erythroid burst-forming unit (BFU-E) colonies and the synthesis of HbF in these colonies was not influenced significantly by 5-azacytidine treatment. It is proposed that the toxic effects of 5-azacytidine on late progenitors, leading to faster mobilization of earlier progenitors to the next more mature compartment, play a role in the in vivo augmentation of HbF synthesis by this drug. This perturbation in the progenitor cell population kinetics and the presumed hypomethylation of the surviving differentiating cells may act synergistically to produce a maximum HbF response after 5-azacytidine treatment.
Primary therapy of acute promyelocytic leukemia: results of amsacrine- and daunorubicin-based therapy
Authors: Arlin Z , Kempin S , Mertelsmann R , Gee T , Higgins C , Jhanwar S , Chaganti RS , Clarkson B 
Published: October 2019

Abstract
Remission rates for patients with acute promyelocytic leukemia (APL) have improved with the use of anthracyclines and proper management of disseminated intravascular coagulopathy. In a prospective randomized trial of chemotherapy in patients with acute nonlymphoblastic leukemia, there were 16 patients with APL. All 7 of the patients receiving the amsacrine-containing regimen and 5 of 9 receiving the daunorubicin- containing regimen achieved a remission. All patients, except 2 of the 3 who underwent bone marrow transplantation, remain alive and in remission from 1+ to 25+ mo. Amsacrine is an effective replacement for daunorubicin in the treatment of APL, and its use does not compromise the favorable remission duration characteristic of APL.
Mechanical properties of oxygenated red blood cells in sickle cell (HbSS) disease
Authors: Nash GB , Johnson CS , Meiselman HJ 
Published: October 2019

Abstract
Little data exist for the mechanical properties of individual irreversible or reversible sickle cells (ISC and RSC, respectively), nor is the process of ISC formation well understood. For oxygenated ISC and density-fractionated RSC, we have used micropipette techniques to measure cell surface area (SA) and volume (V), membrane shear elastic modulus (mu), time constant for viscoelastic shape recovery (tc), and hence to calculate membrane surface viscosity (eta = mu X tc). Volume loss associated with increasing cell density was accompanied by a proportionately smaller surface area decrease; SA/V ratio thus increased for denser cells, with ISC having the highest values. Membrane area loss by fragmentation must thus be accompanied by an accelerated decrease in cell volume. ISC had relatively rigid membranes (mu 130% above normal controls) and tc close to normal values, so that their effective membrane viscosity was more than double control. RSC had viscoelastic properties close to control, but showed wider variation between sickle cell donors and within samples. Measurements on density-separated RSC showed that, on average, mu was nearly constant, but that tc was longer for the densest cells, with their eta approaching ISC levels. A small subpopulation of RSC were found that had mu close to ISC values. Hypotonically swollen ISC (with internal hemoglobin concentration decreased to normal levels) retained their increased membrane stiffness but had markedly decreased tc, so that their eta approached normal values. The results show that elevated hemoglobin concentration influences the viscoelastic behavior of ISC and RSC, but that an irreversible change in membrane elasticity also occurs for ISC. These data suggest that ISC formation occurs via a two- stage process: (1) accelerated volume loss leading to increased cytoplasmic and effective membrane viscosity; (2) a sharp rise in membrane rigidity, presumably linked to membrane structural alteration.