bluuebunny/crossref_metadata_2025_split huggingface dataset:
Release of human platelet factor V activity is induced by both collagen and ADP and is inhibited by aspirin
Authors: Vicic WJ , Lages B , Weiss HJ 
Published: October 2019

Abstract
Factor V activity in suspensions of human platelets washed by albumin density gradient separation increased in response to stimulation by both collagen and adenosine diphosphate (ADP). The appearance of factor V activity extracellularly had the characteristics of platelet secretion and was partially inhibited by aspirin and by the antimetabolites 2-deoxyglucose and antimycin A. Some increase in factor V activity was also observed in platelet suspensions during the initial response to ADP; this activity was not detected extracellularly, but remained associated with the platelets. Patients with storage pool deficiency (SPD) whose platelets are deficient only in dense granule substances released normal amounts of factor V activity, whereas decreased amounts were released in a patient whose platelets have both dense and alpha granule deficiencies. These findings suggest that a portion of platelet factor V is associated with, and released from, alpha granules.
Ultrastructural evidence for the common origin of human mast cells and basophils
Authors: Zucker-Franklin D 
Published: October 2019

Abstract
Although the functional similarity of basophils and mast cells is widely accepted, their distinctive morphological features have been taken to indicate the existence of two different, albeit functionally complementary, cell systems. The recent demonstration that mast cells as well as basophils originate from the bone marrow raises the possibility that these cells derive from the same precursor. This report provides evidence for this theory by describing a distinctive “intermediate” cell possessing the ultrastructural features typical of both basophils and mast cells. These cells were encountered in three patients with myeloproliferative diseases and may thus be more readily found in states of disturbed myelopoiesis. These observations have given impetus for the first comparative description of the ultrastructure of human basophils, human mast cells, and the newly recognized intermediate cell within a single report.
Factor V deficiency in Philadelphia-positive chronic myelogenous leukemia
Authors: Hasegawa DK , Bennett AJ , Coccia PF , Ramsay NK , Nesbit ME , Krivit W , Edson JR 
Published: October 2019

Abstract
Factor V deficiency has been identified in 8 of 8 patients 7--20 yr of age, with Philadelphia-positive (Ph1+) chronic myelogenous leukemia (CML). In these 8 patients, factor V deficiency was not due to hepatic dysfunction, factor V inhibitors, or disseminated intravascular coagulation. In 3 patients, factor V activity rose 10%--12% (0.10--0.12 U/ml) after the infusion of 28--31 ml/kg body weight of fresh frozen plasma (FFP). The rise persisted less than 14 hr. The mean measured postinfusion rise in factor V was 18% of the expected rise calculated from the volume of FFP infused in the patients' plasma volume. In 4 patients, a small transient rise in factor V activity occurred after splenectomy or plateletpheresis. Factor V deficiency was completely corrected after a marked reduction in bone marrow cellularity in 2 patients with Ph1+ CML treated with extensive chemotherapy, total body irradiation, and bone marrow transplantation. Factor V deficiency was retrospectively observed in 6 of 20 patients, ages 20--80 yr, with Ph1+ CML and 3 of 6 patients with other myeloproliferative disorders. The factor V deficiency appears to be associated with the large myeloid- megakaryocytic cell mass characteristic of CML and other myeloproliferative disorders.
Autoimmune and alloimmune phenomena in patients with aplastic anemia: cytotoxicity against autologous lymphocytes and lymphocytes from HLA identical siblings
Authors: Warren RP , Storb R , Thomas ED , Su PJ , Mickelson EM , Weiden PL 
Published: October 2019

Abstract
We have studied peripheral blood lymphocytes of 117 patients with severe aplastic anemia and 237 healthy individuals for reactivity against autologous lymphocytes and/or lymphocytes from HLA-identical siblings using a 51Cr release assay. Lymphocytes from 29% of the patients exhibited reactivity against their own lymphocytes, while only 3% of lymphocytes from normal individuals showed such reactivity. Lymphocytes from 49% of the patients showed reactivity against lymphocytes from their HLA-identical siblings compared to 4% of normal individuals. Correlation existed between allogeneic and autologous reactivities (p &lt; 0.001), suggesting a common pathway for cytotoxicity. Both reactivities showed an association with extremely low granulocyte counts (p &lt; 0.01) and an inability of the patient's mononulcear cells to stimulate in allogeneic mixed leukocyte culture (p &lt; 0.05) as well as an inverse correlation with time from diagnosis (p &lt; 0.001). At least two explanations exist for the transfusion-independent autologous and allogeneic cytotoxicities: (1) they could be epiphenomena secondary to the stem cell defect, such as the loss of a cell that suppresses (or regulates) naturally occurring cytotoxic cells, or (2) they may be involved in the cause of the disease.
Modification of hemoglobin by ninhydrin
Authors: Kokkini G , Stevens VJ , Peterson CM , Cerami A 
Published: October 2019

Abstract
The Strecker degradation reaction was evaluated as a means of modifying hemoglobin in vitro, utilizing ninhydrin as a model compound. Ninhydrin led to modification of hemoglobin (when incubated with hemoglobin or red cells) at physiologic temperature and pH. Isoelectric focusing documented the formation of new hemoglobin bands, all with decreased (more negative) isoelectric points that hemoglobin A. Both alpha and beta chains were modified to an equal degree, although electrophoretic studies documented two modified species of alpha-chains and three modified species of beta-chains. Amino acid analysis of modified hemolysate following NaB3H4 reduction revealed peaks that coeluted with deaminated valine, epsilon-deaminated lysine, and a product with the guanidino group of arginine. The oxygen affinity of hemoglobin increased following its incubation with increasing concentrations of ninhydrin. These studies suggest that ninhydrin is representative of a class of carbonyl compounds that could be utilized to specifically modify that structure and function of hemoglobin variants.
Morphological classification, response to therapy, and survival in 263 adult patients with acute nonlymphoblastic leukemia
Authors: Mertelsmann R , Tzvi Thaler H , To L , Gee TS , McKenzie S , Schauer P , Friedman A , Arlin Z , Cirrincione C , Clarkson B 
Published: October 2019

Abstract
Bone marrow smears of 263 protocol patients with acute nonlymphoblastic leukemia (ANLL) and related disorders treated between 1970 and 1978 at MSKCC were reviewed blindly by two pairs of hematomorphologists and classified according to the FAB system. It was found necessary to add one category (MO) for acute undifferentiated leukemia and to define more precise quantitative criteria for the categories M1-M6 based on bone marrow differential counts. Using this modified FAB classification, agreement between the two observer groups based on morphology alone was 69%. Cytochemical stains were essential in establishing the diagnosis in 9%, led to a change of diagnosis by one observer team in 14%, and helped to confirm the diagnosis in 32% of cases. Complete remission rates, remission duration, and survival were not significantly different among diagnostic categories. Myelodysplastic syndromes (MDS: M6, RAEB, CMML; CR rate 48%) and ANLL without differentiation (M0, M1, M5a; CR rate 50%) appeared to do less well than ANLL with partial differentiation (M2, M3, M4, M5b; CR rate 59%) on all three protocols studied. Auer rods were present in 53% of all cases with 63% in the myeloid categories (M1-M4). Auer rods were found to be the single most important prognostic parameter in this study, with a complete remission (CR) rate of 68% in the Auer-rod- positive and of 40% in the Auer-rod-negative group (p < 0.0001). Survival was significantly longer for patients exhibiting Auer rods (p < 0.0002). Median survival for the total group was 13.5 mo and median remission duration for responders was 11.5 mo in the Auer-rod-positive group compared to 6.2 mo median survival and 9.2 mo median remission duration for the Auer-rod-negative group.
Membrane abnormality in red blood cells with weak type B expression
Authors: Yoshida A , Fujii H , Dave V , Cozant MJ , Morel PA 
Published: October 2019

Abstract
The mechanisms of unusually weak blood group (A and B) expressions are not yet well understood. We examined properties of blood group galactosyltransferase (B-enzyme) and characteristics of red cell membrane components obtained from family members with A2Bm character. B- enzyme activity of the A1Bm plasma is in normal range, and kinetic properties (i.e., Km for UDP-Gal, Km for 2′-fucosyllactose, and pH optima) of B-enzyme from the A1Bm subjects are identical to that of normal B-enzyme. When A1Bm red cell were incubated with UDP-Gal and B- enzyme, the cells became strongly agglutinable with anti-B. When A1Bm membranes were incubated with B-enzyme or A-enzyme (i.e., blood group N- acetylgalactosaminyltransferase) and the appropriately labeled nucleotide sugar (UDP-Gal3H for B-enzyme and UDP-GalNAc3H for A- enzyme), significant incorporation of the sugar was observed. The amounts of the sugar incorporated into A1Bm membranes were about 40%- 50% of that incorporated into O membranes at saturation, indicating that about one-half of H-sites remained unglycosylated in A1Bm red cells. Examination of radioactive components by isoelectric focussing revealed that the labeled components of A1Bm membranes were distinctively different from that of O membranes. Therefore, one can conclude that the weak B expression is not due to direct mutation of ABO locus, but due to a secondary consequence of genetic abnormality of a membrane component (or components) associated with blood group substances.
Hormonal effects on cell proliferation in a human erythroleukemia cell line (K562)
Authors: Gauwerky C , Golde DW 
Published: October 2019

Abstract
We have investigated the hormonal responsiveness of K562 cells using a serum-substituted in vitro clonogenic assay. Dexamethasone inhibited colony formation by the K562 cells, and the inhibitory effect could be reversed by progesterone (10(-6) M). Fluoxymesterone caused a prominent enhancement of K562 colony growth, whereas estriol had no effect. Stimulation by triiodothyronine was maximal at 10(-7) M, and the thyroid effect could be abrogated by the beta 2-adrenergic antagonist butoxamine in equimolar concentrations. Using standard tissue culture conditions, the beta-adrenergic agent isoproterenol, but not the alpha catecholamine phenylephrine, enhanced the proliferation of K562 cells. When K562 cells were grown under hormone-depleted conditions, they developed responsiveness to phenylephrine and were no longer stimulated by isoproterenol. DbcAMP and prostaglandins of the E series also caused K562 colony enhancement. Prostaglandin F2 alpha had no effect on cell proliferation. Insulin was an effective stimulant of colony formation of K562 cells, as were human growth hormone and ovine prolacin. Bovine growth hormone had no effect. Our results are consistent with the identificaiton of K562 as an erythroid line, and they indicate that K562 cells respond to endocrine hormones in a manner analogous to normal erythroid progenitors.
Human T-cell antigens defined by monoclonal antibodies. Absence of T65 on committed myeloid and erythroid progenitors
Authors: Taetle R , Royston I 
Published: October 2019

Abstract
The complement-dependent cytotoxicity of monoclonal T-cell antibody (T101) for normal and abnormal hemopoietic progenitors was assessed. T101 demonstrated toxicity for normal T-colony-forming cells from peripheral blood and bone marrow. Cytotoxicity was absent for normal peripheral blood and bone marrow granulocytes/macrophage (CFU-C) and erythroid (BFU-E) progenitors. The antibody was also not toxic for peripheral blood blast progenitors from patients with acute myelogenous leukemia (AML). These studies indicate the absence of the antigen defined by T101 (T65) from normal progenitor cells and from blast progenitors in patients with AML. T101 may be used in the treatment of T-cell malignancies and in the prevention of graft-versus-host disease (GVHD) without damage to normal progenitor cells.
Clinical implications of glucocorticoid receptor studies in childhood acute lymphoblastic leukemia
Authors: Mastrangelo R , Malandrino R , Riccardi R , Longo P , Ranelletti FO , Iacobelli S 
Published: October 2019

Abstract
We have performed in parallel, in 19 children with acute lymphoblastic leukemia, a quantitative determination of glucocorticoid levels, in vitro steroid induced inhibition of nucleic acid precursors, and a short-term clinical trial of corticosteroids alone, before the treatment was given, which included corticosteroids and other drugs. From our results it appears that high glucocorticoid receptor levels in acute lymphoblastic leukemia of children do not guarantee a clinical response to corticosteroids. On the other hand, glucocorticoid receptors may turn out to be of value in predicting a poor response to corticosteroids only if their levels are considerably low.
Cord blood screening for hemoglobin abnormalities by thin layer isoelectric focusing
Authors: Galacteros F , Kleman K , Caburi-Martin J , Beuzard Y , Rosa J , Lubin B 
Published: October 2019

Abstract
Hemoglobin variants can be successfully identified in cord blood samples. The methods most commonly used include cellulose acetate (CAC) and citrate agar (CAG) electrophoresis. Recently thin layer isoelectric focusing (TLIF) has been shown to be an excellent method for identifying hemoglobin variants. To determine the applicability of TLIF for cord blood screening, we compared the results of 835 samples obtained by TLIF with that obtained by CAC, CAG, and the combination of both CAC and CAG. In 100 of these samples we detected an abnormal hemoglobin pattern using TLIF. In contrast, we detected only 80 abnormal samples by CAC, 70 by CAG, and 80 by using the combination of CAC and CAG. Due to the increased resolution provided by TLIF, we correctly diagnosed two sickle cell trait samples by TLIF that were incorrectly suspected to be homozygous for sickle cell disease by CAC and CAG. We identified 41 samples containing Bart's hemoglobin by TLIF in contrast to only 21 using CAC and 14 using CAG. The time and cost of TLIF was comparable to that using the combination of both methods. We, therefore, conclude that TLIF is the method of choice for cord blood screening.
Significance of Ph1-negative marrow cells in Ph1-positive chronic granulocytic leukemia
Authors: Sokal JE 
Published: October 2019

Abstract
Fifty-six of 195 Ph1-positive patients with chronic granulocytic leukemia were found to have Ph1-negative metaphases in marrow aspirates on one or more occasions. In 22 cases, Ph1-negative cells were found prior to initiation of antileukemic therapy. Five patients were in the blastic stage of the disease when Ph1-negative mitoses were seen. The finding of Ph1-negative cells appeared to be related principally to short duration of CGL and to administration of antileukemic therapy (conventional agents and doses, in most cases). Ph1-negative cells were usually not found more than 2 yr after the diagnosis of leukemia, but in a few cases, they were seen as long as 5–10 yr after diagnosis. Only a minority of metaphases analyzed were Ph1-negative, except in the case of 6 patients who transiently had 50% or more Ph1-negative cells after antileukemic therapy. The presence of Ph1-negative cells in marrow was not associated with any survival advantage in this series.
The in vitro sensitivity of leukemic and normal leukocytes to hydrocortisone induced cytolysis
Authors: Galili U , Prokocimer M , Izak G 
Published: October 2019

Abstract
A marked sensitivity of CLL lymphocytes to hydrocortisone in vitro was demonstrated in each of the 25 patients tested. The sensitivity was manifested by the eventual lysis of the affected cells. Malignant lymphocytes from 8 out of 14 ALL patients were found also to be in vitro sensitive, whereas CML cells, AML cells, normal BM cells, thymocytes, peripheral blood lymphocytes, and polymorphonuclear cells were resistant. Within a tested CLL lymphoid suspension it is proven that the hydrocortisone causes the specific lysis of the malignant cells leaving the normal lymphocytes undamaged. The cytolysis is not an immediate action, but is expressed within 7–8 hr of incubation. However, 30 min incubation with the hormone is sufficient for the cytolytic effect to occur 20 hr later. The possible mechanisms involved in the specific glucocorticoid induced cytolysis are discussed.
Prenatal diagnosis of hemoglobinopathies: comparison of the results obtained by isoelectric focusing of hemoglobins and by chromatography of radioactive globin chains
Authors: Dubart A , Goossens M , Beuzard Y , Monplaisir N , Testa U , Basset P , Rosa J 
Published: October 2019

Abstract
Isoelectric focusing (IEF) of hemoglobin was compared to the classical chromatography of labeled globin chains for 22 antenatal diagnoses of hemoglobinopathies: 11 for beta thalassemia, and 11 for sickle cell disease. In all cases, the two methods gave identical results. The diagnosis was confirmed after birth or abortion. Three fetuses homozygous for beta thalassemia and one homozygous for sickle cell disease exhibited no Hb A by IEF, in contrast to normal fetuses or those heterozygous for one of the two hemoglobinopathies. In addition, blood samples obtained in other centers after abortion of 22 fetuses homozygous for beta + or beta 0 thalassemia exhibited no Hb A when analyzed by IEF. When Hb A was present, the respective proportions of Hb A and acetylated Hb F were determined by densitometry of the IEF gel. The Hb A/acetylated Hb F ratio obtained by IEF correlated well with the beta A/gamma ratio of globin chain synthesis, IEF requires 0.1 mg of unlabeled hemoglobin. It is performed in 90 min and several samples can be analyzed simultaneously. If present, maternal contamination of fetal blood must be eliminated by selective lysis of maternal (RBC) using the Orskov reaction. Improvements in this method to obtain suitable samples for IEF analysis are described.
Improved exercise performance after exchange transfusion in subjects with sickle cell anemia
Authors: Miller DM , Winslow RM , Klein HG , Wilson KC , Brown FL , Statham NJ 
Published: October 2019

Abstract
Ten patients with sickle cell anemia underwent partial exchange transfusion with hemoglobin-A-containing cells using a technique that allowed hemoglobin concentration and blood volume to remain constant. The mean fraction of hemoglobin-A in these patients increased from 9% to 55%, but the mean hemoglobin concentration increased by only 1.44 g/dl. The exchange resulted in a large improvement in submaximal exercise capacity: the mean of the anaerobic threshold (the work at which lactic acid begins to accumulate in the blood) increased from 68 to 114 W. The mean work performed at a heart rate of 170/min, an estimation of maximal work capacity, increased from 128 to 187 W. Improved exercise performance after partial exchange transfusion may result from the superior flow properties of hemoglobin-A-containing red cells. Furthermore, we believe that exercise testing in sickle cell anemia has great potential utility as a means to monitor therapy and to evaluate the benefits of exchange transfusion.
The nature and action of granulocyte-macrophage colony stimulating factors
Authors: Burgess AW , Metcalf D 
Published: October 2019

Abstract
Granulocyte-macrophage colony stimulating factor (GM-CSF) stimulates the in vitro proliferation and differentiation of granulocytic and macrophage cells. This regulator is now known to act at other levels of hemopoietic regulation. The heterogeneity of GM-CSFs is not only related to the tissue of origin and the in vitro production method, but also to functional subclasses of the molecule that have distinct biologic specificities. Most adult mouse organs produce GM-CSF (mol wt 23,000), but a macrophage (M)-CSF has been detected in fetal conditioned medium (CM) and isolated from L-cell CM. Murine endotoxin serum appears to contain a M-CSF, GM-CSF, and G-CSF, the last of which cofractionates with a differentiation factor active on leukemic cells. Human GM-CSFs, G-CSF, and EO-CSFs active on human cells have been detected in a variety of CM, but as yet none have been purified. Again, there are subclasses of progenitor cells that respond to particular forms of human active CSFs. GM-CSF isolated from mouse lung CM stimulates multipotential progenitor cells, the initial proliferatin of progenitors in the erythroid, eosinophil, and megakaryocyte series, as well as mature cells in the GM series. While GM-CSF is also able to stimulate the differentiation of myeloid leukemic cells, other factors appear to be more potent in this respect. Information on the regulation of GM-CSF production, on the modulators of its action on specific target cells, and on its role in vivo will be required before the physiologic function of this molecule can be properly assessed.
Human red cell membrane adenylate cyclase in normal subjects and patients with hereditary spherocytosis, sickle cell disease and unidentified hemolytic anemias
Authors: Piau JP , Delaunay J , Fischer S , Tortolero M , Schapira G 
Published: October 2019

Abstract
We have investigated adenylate cyclase in ghosts from normal and pathologic human red blood cells. Basic parameters such as specific activity, apparent Michaelis constant (KMapp), and response to effectors: sodium fluoride (NaF), 5′-guanylyl imidodiphosphate (Gpp (NH)p), isoproterenol, and PGE1 were investigated. Basal and NaF- stimulated activities were measured in ghosts from patients with hereditary spherocytosis, sickle cell disease, and various unidentified hemolytic anemias. Both activities were increased in any of these pathologic conditions as compared with those of normal red blood cells. Normal values were found in patients with hereditary spherocytosis after splenectomy and in patients with heterozygous sickle cell disease. There was a good correlation between the reticulocyte count and adenylate cyclase activity in hereditary spherocytosis and in sickle cell disease with reticulocyte count lower than 10%. The enzyme activity of the first group was about three times that of the second group. There was no correlation at all in sickle cell disease with higher reticulocytosis and in the group of unidentified hemolytic anemias. These results suggest that increased adenylate cyclase activities are not specific of any of these diseases. In the patients with hereditary spherocytosis, the adenylate cyclase activity seems to be essentially related to younger mean age of red blood cell population while in the patients with sickle cell disease and in others with unidentified hemolytic anemias some additional factors might interfere directly with the enzyme and alter its activity.