bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition of platelet function by organic nitrate vasodilators
Authors: Schafer AI , Alexander RW , Handin RI 
Published: October 2019

Abstract
There is evidence that platelet activation in the coronary circulation may be important in the pathogenesis of myocardial ischemia. Since organic nitrate vasodilators are commonly used in coronary artery disease, we have studied the in vitro effects of these drugs on platelet function. Nitroglycerin, isosorbide dinitrate, and their biotransformation product, inorganic nitrite, inhibited platelet aggregation with collagen, epinephrine, arachidonate, and ionophore, and blocked both primary and secondary aggregation in response to ADP. Nitroglycerin was studied in more detail. Its inhibitory effect was reversible and not dependent on external calcium concentration. It inhibited arachidonic acid oxygenation as measured by the arachidonate- induced oxygen burst and malonaldehyde production. These effects were not due to an increase in intracellular cyclic AMP. This unusual generalized inhibition of platelet function by nitroglycerin possibly contributes to its beneficial effect in myocardial ischemia in part by attenuating platelet reactivity in the coronary circulation.
Continuous human bone marrow culture: Ia antigen characterization of probable pluripotential stem cells
Authors: Moore MA , Broxmeyer HE , Sheridan AP , Meyers PA , Jacobsen N , Winchester RJ 
Published: October 2019

Abstract
The presence of Ia-like antigens on human CFU-C and BFU-e is confirmed and a cell type that lacked immediate capacity for granulocytic colony formation but generated CFU-c after brief incubation in simple suspension culture is identified. This pre-CFU-c, and its immediate progeny, was extremely sensitive to killing by anti-Ia serum with complement. In contrast, anti-Ia serum plus complement treatment of human bone marrow, while eliminating 93%-97% of all CFU-c and BFU-e, did not prevent the rapid regeneration of these progenitor cells and their production for some weeks under the conditions of continuous marrow culture. These studies suggest that the human equivalent of the pluripotential stem cell can replicate for some weeks in culture and generate committed progenitors, such as CFU-c and BFU-e. Furthermore, it would appear that Ia-like antigen is absent on the pluripotential stem cell, is rapidly gained as commitment to the various progenitor cell types occur, and is subsequently lost as these latter undergo differentiation within the marrow.
Localization of factor-VIII-related antigen in human vascular subendothelium
Authors: Rand JH , Sussman II , Gordon RE , Chu SV , Solomon V 
Published: October 2019

Abstract
Factor-VIII-related antigen has previously been shown to be synthesized by vascular endothelial cells. Using both an immunofluorescent staining technique and electron microscopy, we have demonstrated the presence of factor-VIII-related antigen in human vascular subendothelium. This finding may have implications in the mechanism of platelet adhesion to deendothelialized blood vessel surfaces.
The effect of hemodialysis and C5a des arg on neutrophil subpopulations
Authors: Klempner MS , Gallin JI , Balow JE , Van Kammen DP 
Published: October 2019

Abstract
Alterations in neutrophil subpopulations during human hemodialysis or following injection of C5a des arg into rabbits were studied. Whereas baseline peripheral blood neutrophils contained approximately 80% of cells that formed rosettes with IgG-sensitized erythrocytes, neutrophils harvested at the granulocyte nadir (20 min after initiating hemodialysis or the injection of C5a des arg) were markedly depleted of this population. This was seen in a change in ratio of rosette-forming neutrophils (RFN) to non-rosette-forming neutrophils (non-RFN) from 4:1 at 0 time to 1:2 at 20 min. Since non-RFN are less active in assays of adherence and chemotaxis, these alterations in circulating neutrophil populations were reflected in abnormal functional capacity of neutrophils harvested at 20 min. To study the mechanism of RFN depletion, we investigated the ability of C5a des arg to aggregate various human neutrophil suspensions. Unfractionated neutrophils and RFN demonstrated prompt in vitro aggregation in response to C5a des arg, whereas this activated complement fragment induced little aggregation in a population enriched for non-RFN. These results may explain the alterations in neutrophil adherence, chemotaxis, phagocytosis, and bactericidal activity, which have been reported to accompany clinical disorders characterized by in vivo complement activation (i.e., hemodialysis or gram-negative sepsis).
Influence of red cell water content on the morphology of sickling
Authors: Clark MR , Guatelli JC , Mohandas N , Shohet SB 
Published: October 2019

Abstract
The response of sickle cells with varying water content to alterations in oxygen tension has been studied. Cells that were severely dehydrated while sickled retained the characteristic sickled morphology even after prolonged reoxygenation. When the cell water content was increased by reduction of the suspending medium osmolality, the cells unsickled. Cells that were dehydrated before deoxygenation were unable to assume the spiculated morphology typical of sicked cells. This was true both for high mean cell hemoglobin concentration (MCHC) discoid sickle cells and for irreversibly sickled cells. When such cells were resuspended in hypotonic medium before deoxygenation, they sickled with the characteristic morphology of sickle cells with normal MCHC. The morphological behavior of Ca-loaded sickled cells as well as irreversibly sickled cells showed a major influence of increased hemoglobin concentration and extremely high internal viscosity. Constraint on cell morphology by putative membrane rigidity was not observed.
Factor VIII-related protein circulates in normal human plasma as high molecular weight multimers
Authors: Hoyer LW , Shainoff JR 
Published: October 2019

Abstract
The size of human factor VIII-related protein in plasma has been determined by sodium dodecyl sulfate (SDS) glyoxyl agarose electrophoresis. The protein was immobilized after the electrophoresis by coupling it to the modified agarose, and it was identified by autoradiography using purified rabbit anti-factor VIII-related antigen (VIIR:Ag). A series of multimeric forms was identified with Mr of 0.85- 12 x 10(6). The distribution of VIIR:Ag multimers was the same in heparin and citrate anticoagulated plasmas and in serum, and the pattern was the same after freezing as in plasma kept at 37 degrees C from the time of venipuncture until the electrophoresis was complete. These observations indicate that VIIR:Ag circulates in normal plasma as a population of very large multimers and that the size distribution is not an artifact induced by purification methods, freezing, or calcium chelation.
The detection and use of hemoglobin mutants in the direct analysis of human globin genes
Authors: Little PF , Whitelaw E , Annison G , Williamson R , Kooter JM , Flavell RA , Goossens M , Sergeant GR , Montgomery D 
Published: October 2019

Abstract
Many human globin-chain mutants contain amino acid replacements that result from single base changes in the corresponding globin gene. Using recombinants, the coding sequences of each of the alpha-, beta-, Ggamma- , and Agamma-globin genes have now been determined. Those sequences of DNA that are cleaved by a number of specific restriction endonucleases have been identified and accurately positioned. Mutations at these sequences abolish the restriction site, and therefore, the pattern of DNA fragments containing hybridizing globin-gene sequences is altered compared to DNA from normal persons. This allows the identification of one of a pair of cross-hybridizing human globin-gene sequences, as is shown here for the two alpha-globin, the two gamma-globin, and the delta- and beta-globin genes.
Ia antigen is a differentiation marker on human eosinophils
Authors: Koeffler HP , Billing R , Levine AM , Golde DW 
Published: October 2019

Abstract
Evidence suggests that the “la-like” or antigen is a differentiation marker that is expressed on early human hematopoietic precursor cells, but is absent on their mature progeny. The eosinophil precursor cell (CFU-EO) is distinct from the granulocyte-monocyte colon-forming cell (CFU-C). We provide data that indicate that the ia antigen is expressed on the human eosinophil colony-forming cells and is absent on mature eosinophils. All CFU-EO were inhibited in the presence of rabbit la antiserum at a titer of 1:30. Cytotoxicity was complement-dependent. The metamyelocytic eosinophil and more mature eosinophil forms did not express the la antigen.
Regulation of iron absorption and storage iron turnover
Authors: Rosenmund A , Gerber S , Huebers H , Finch C 
Published: October 2019

Abstract
The regulation of iron supply to plasma was studied in male rate. Repeated exchange transfusions were first carried out with plasma from iron-deficient or iron-loaded animals. There was no recognizable effect on the amount of iron entering the plasma as evidenced by plasma iron concentration or iron absorption by recipient animals. In other studies, iron compounds having different tissue distribution were injected. Subsequent iron release was greater from reticuloendothelial cells than from other iron-loaded tissues. When requirements for transferrin iron were increased by exchange transfusion with high reticulocyte blood, within minutes there was a doubling of the rate of tissue iron donation. It was concluded from these studies that (1) iron turnover in the plasma is primarily determined by the number of tissue receptors for iron, particularly those of the erythron, (2) that the amount of iron supplied by each donor tissue is dependent on the output of other donor tissues, and (3) that a humoral mechanism regulating iron exchange is unlikely in view of the speed of response and magnitude of changes in plasma iron turnover. It is proposed that there is some direct mechanism that determines the movement of iron from donor tissues to unsaturated transferrin binding sites.
Hemopathologic consequences of protracted gamma irradiation: alterations in granulocyte reserves and granutocyte mobilization
Authors: Seed TM , Cullen SM , Kaspar LV , Tolle DV , Fritz TE 
Published: October 2019

Abstract
Aplastic anemia and myelogenous leukemia are prominent pathologic effects in beagles exposed to continuous, daily, low-dose gamma irradiation. In the present work, granulocyte reserves and related mobilization functions have been sequentially assessed by the endotoxin stress assay during the preclinical and clinical phases of these hemopoietic disorders. Characteristic patterns of granulocyte reserve mobilization are described that reflect given stages of pathologic progression. For radiation-induced leukemia, a five stage pattern has been proposed. In contrast, a simple pattern of progressive, time- dependent contraction of granulocyte reserves and mobilization capacity was noted in the development of terminal aplastic anemia. Early preclinical phases of radiation-induced leukemia appear to involve an extensive depletion of the granulocyte reserves ((phase I) during the first approximately 200 days of exposure followed by a partial renewal of the reserves and associated mobilization functions approximately 200 and 400 days (phase II). Sustained, subnormal granulocyte mobilizations (phase III) following endotoxin stress typify the responses of dogs during the intermediate phase, whereas late preclinical, preleukemic stages (phase IV) are characterized by a further expansion of the reserves and in the mobilization capacities, particularly of the less mature granulocytes. Such late alterations in the pattern of granulocyte mobilization, together with other noted cellular aberrancies in the peripheral blood and marrow, appear to indicate leukemia (phase V) onset.
A staphylococcal slide test for detection of antineutrophil antibodies
Authors: Harmon DC , Weitzman SA , Stossel TP 
Published: October 2019

Abstract
We describe a simple test for direct or indrect detection of antineutrophil antibodies. Sensitized leukocytes adherent to glass slides and fixed with paraformaldehyde can be stored in buffer for at least 3 wk. Killed Cowan I staphylococci, containing protein A, bind to sensitized but not control cells, and binding is ascertainable by light microscopy. Indirect tests were positive for 39/41 patients suspected of having immune neutropenia and found to have antineutrophil antibodies by an indirect radiochemical opsonic method. Fifty-four control sera from healthy persons, patients with bone marrow failure, or with immune complex diseases without neutropenia, gave negative indirect tests. Direct tests for cell-bound antibody could be done even during severe neutropenia by reacting fixed autologous cells with staphylococci in the absence of added serum. In some patients only the direct test was positive.
The familial occurrence of polycythemia vera: report of a father and son, with consideration of the possible etiologic role of exposure to organic solvents, including tetrachloroethylene
Authors: Ratnoff WD , Gress RE 
Published: October 2019

Abstract
The occurrence of polycythemia vera in a father and son, both of whom had intermittent exposure to organic solvents, including tetrachloroethylene and Stoddard solvent, is reported. Only three other well substantiated familial occurrences of polycythemia vera, none encompassing successive generations, were found among many reported instances.
Mitogen stimulation of chronic lymphocytic leukemic lymphocytes: defective phytohemagglutinin stimulation independent of immunologic cell surface markers
Authors: Davis S , Rambotti P 
Published: October 2019

Abstract
Peripheral blood lymphocytes (PBL) from 107 untreated patients with chronic lymphocytic leukemia (CLL) were analyzed for the presence of surface immunoglobulin (Ig) and the ability to form rosettes with sheep erythrocytes (SRBC). Four groups were identified based on the cell surface markers: (1) 81 patients' PBL expressed primarily IgM kappa or IgM lambda, 4 further patients' PBL expressed IgM with equal percentages of kappa and lambda surface markers; (2) 13 patients had equal percentages of PBL expressing lg and SRBC receptors; (3) 6 patients' PBL primarily formed rosettes with SRBCs, and (4) in 3 patients and the majority of cells had no detectable markers (null cells). Lymphocytes from all patients within each group were tested for their ability to respond to phytohemagglutinin (PHA) and pokeweed mitogen (PWM). The maximum response in PHA-stimulated normal cell cultures appeared at 2--3 days; for PWM-stimulated cultures, maximal response was at 3--5 days. CLL cultures from all patients in each of the four groups required 5--7 days to develop a maximal PHA response. The response of CLL lymphocytes in all groups to PWM stimulation was similar to normal lymphocytes. Thus, the abnormal PHA response of CLL lymphocytes was independent of the presence or pattern of cell surface markers.
The effects of acute thrombocytopenia on megakaryocyte-CFC and granulocyte-macrophage-CFC in mice: studies of bone marrow and spleen
Authors: Levin J , Levin FC , Metcalf D 
Published: October 2019

Abstract
The effects of acute thrombocytopenia, produced by platelet antiserum (PAS), on both megakaryocyte colony-forming cells (Meg-CFC) and granulocyte-macrophage colony-forming cells (GM-CFC) were studied. During the 1-hr to 14-day period following acute thrombocytopenia (platelet counts &lt; 5% of normal), bone marrow and splenic cells of C57BL/6J mice were obtained and cultured for 7 days in 0.3% agar. Numbers of GM and Meg colonies were determined. At no times were alterations in frequency of GM-CFC and Meg-CFC detected in femoral bone marrow. In contrast, GM-CFC in spleen were increased from 3 to 7 days after PAS and from 4 to 7 days after normal serum (NS). Increase in Meg- CFC in the spleen occurred from 3 to 5 days after PAS with a lesser, not significant increase after NS. Alterations in white blood cells and hematocrit values were not detected. Similar responses were observed in germ-free mice and after rechallenge of animals that had received PAS or NS 14 days previously. The delayed increase in Meg-CFC indicates that they are unlikely to be responsible for the altered megakaryopoiesis previously reported in bone marrow after acute thrombocytopenia and was not due to inhibition by PAS. The increase in GM-CFC may reflect stimulation of the reticuloendothelial system by heterologous proteins.
Thrombotic thrombocytopenic purpura: a ten-year experience
Authors: Cuttner J 
Published: October 2019

Abstract
Splenectomy, corticosteroids, and antiplatelet agents have improved survival in thrombotic thrombocytopenic purpura (TTP). In 1974 we reported the successful treatment in 5 of 6 patients using splenectomy, corticosteroids, and average molecular weight dextran. This report describes a 10-yr experience with TTP at Mount Sinai Hospital (MSH). Twenty patients with TTP were seen. Possible inciting factors included pregnancy, oral contraceptives, and surgery. Splenectomy was performed in 18 patients and typical findings of TTP were found in 14 (78%). Fifteen patients were treated with splenectomy, corticosteroids, and average molecular weight dextran. Two of the 15 patients received, in addition, ASA and dipyridamole and a third received only dipyridamole. Thirteen of the 15 (87%) have survived and remain disease-free.
Prediction of response to chemotherapy in acute myelocytic leukemia
Authors: Preisler HD 
Published: October 2019

Abstract
Marrow specimens obtained from 23 patients with acute myelocytic leukemia were exposed to cytosine arabinoside and/or daunorubicin in vitro, and the effects of these agents on colony formation in vitro was determined. Thymidine suicide indices were determined as well, which permitted a distinction to be made between kinetic and metabolic resistance to cytosine arabinoside. The sensitivity of the colony- forming cells to the two chemotherapeutic agents did not correlate with each other, indicating that sensitivity to each was independently determined. The relationship between in vitro sensitivity to daunorubicin and cytosine arabinoside and response to 25 courses of in vivo therapy with these two agents administered to 21 patients was determined. These studies indicated a clear-cut relationship between in vitro drug sensitivity and in vivo response with patients whose leukemic cells were sensitive to both agents entering complete remission, whereas patients whose leukemic cells were insensitive to one or both drugs in vitro failed to enter remission.
Phorbol myristate acetate stimulates macrophage differentiation and replication and alters granulopoiesis and leukemogenesis in long-term bone marrow cultures
Authors: Greenberger JS , Newburger PE , Sakakeeny M 
Published: October 2019

Abstract
The effects of the tumor-promoter phorbol myristate acetate (PMA) on normal hemopoiesis and Friend leukemia virus (FLV) granulocytic leukemogenesis in long-term bone marrow cultures were examined. FLV- anemia-inducing strain (FLV-A) infected, Rauscher R-MuLV clone M52R infected, or uninfected control NIH Swiss mouse marrow cultures were treated weekly with PMA or 4-O-methyl-PMA at 2.0 ng/ml or 200.0 ng/ml. Addition of PMA to control uninfected or R-MuLV-infected cultures decreased production of nonadherent granulocytic cells and granulocyte- macrophage progenitor cells (GM-CFU-c), and increased the numbers of adherent macrophages. Addition of PMA to FLV-A-infected cultures did not inhibit generation of granulocytic leukemia cell lines even though the numbers of adherent adipocytes were decreased and adherent macrophages were increased. PMA treatment of freshly explanted whole bone marrow but not purified nonadherent GM-progenitor cells from long- term bone marrow cultures stimulated GM-CFU-c and cluster formation in the absence of added colony-stimulating factor (CSF). The sensitivity of purified GM-progenitor cells to L929 or WEHI-3 CSF was not altered by PMA; however, PMA treatment of bone marrow macrophages or peritoneal exudate macrophages stimulated detectable GM-CFU-c and cluster formation by purified GM-progenitor cells under conditions where equal numbers of untreated macrophages failed to be stimulatory. Thus, several PMA effects on hempoietic stem cells in vitro are mediated through indirect action on adherent stromal cells including macrophages.
Enhancement of human erythroid progenitor cell growth by media conditioned by a human t-lymphocyte line
Authors: Hamburger AW 
Published: October 2019

Abstract
Recent studies have shown that soluble factors elaborated by human T lymphocytes enhance erythroid burst formation by human peripheral blood null cells. This study demonstrates that media conditioned by a long- term T lymphocyte line augmented the growth of erythroid colonies in vitro in the presence of erythropoietin (Ep). ATCC.CCl 119 (CCRF-CEM) was derived from a patient with ALL of T-lymphoblast origin. Cells from the stocks used in these experiments maintained T-cell characteristics as determined by histochemical and rosetting techniques. Increased numbers of 16 day BFU-E were seen when Ficoll-Hypaque separated peripheral blood leukocytes were cultured in the presence of a 10% (v/v) concentration of CCL 119 conditioned medium (CM). CM increased the number of BFU-E even when Ep or fetal calf serum were not growth limiting. CM also increased the number of late BFU-E observed in cultures of nonadherent bone marrow cells. When peripheral blood mononuclear cells were depleted of E-rosetting cells, only small numbers of BFU-E grew. Addition of 119 CM increased the numbers of BFU- E in E-rosette-depleted cultures. CM from B-cell, macrophage, or other T-cell lines tested did not stimulate BFU-E growth as consistently. These studies indicate that CM obtained from ATCC.CCL 119 cells contained burst-promoting activity, one of the factors required for proliferation of early erythroid progenitors.
Switching of the nonallelic forms of fetal hemoglobin during late gestation
Authors: Vedvick TS , Wheeler SA , Koenig HM 
Published: October 2019

Abstract
The gamma chains of human fetal hemoglobin occur in two nonallelic forms, designated G gamma and A gamma, which differ from one another in having either glycine or alanine as their 136th residue respectively. In newborns, G gamma comprises about 75% of the total gamma chains, while in adults, G gamma comprises about 40% of the total gamma chains. The timing of the switching events that lead to the alteration of the rates of production of G gamma and A gamma are still unknown. Umbilical cord red blood cells from term infants were separated by density gradient fractionation into four age-dependent fractions. Red blood cell size and reticulocyte content decreased and the percent fetal hemoglobin increased with increasing gradient densities, confirming age- dependent density separation. The percent G gamma was determined by two methods on fractionated cord red blood cells to determine if the switch in the production ratio of the nonallelic forms of gamma chains began during late gestation. The G gamma content of fetal hemoglobin was found to decrease with decreasing red blood cell age, demonstrating that the switch from predominately glycine-containing gamma chains to predominately alanine-containing gamma chains begins during late gestation.