bluuebunny/crossref_metadata_2025_split huggingface dataset:
Thrombin generation in acute promyelocytic leukemia
Authors: Bauer KA , Rosenberg RD 
Published: October 2019

Abstract
Six patients with disseminated intravascular coagulation (DIC) in association with acute promyelocytic leukemia (APL) were studied with sensitive radioimmunoassays that are able to quantitate the extent of thrombin generation within the human circulation. The levels of prothrombin activation fragment, F1 + 2, and thrombin-antithrombin complex (TAT) were obtained at clinical presentation and were then followed serially in several patients during induction chemotherapy. The antileukemic therapy often resulted in a rise in the plasma levels of these molecular species. Simultaneous measurements of fibrinopeptide A (FPA) were also obtained, and the concentrations of this polypeptide were correlated with the levels of F1 + 2 and TAT in patients who were not receiving heparin. Nine individuals with other morphological subtypes of acute nonlymphocytic leukemia (ANLL) were investigated and were usually found to have increased levels of F1 + 2, TAT, and FPA at clinical presentation. However, the magnitude of the elevations was considerably greater and the correlation between TAT and FPA levels was stronger in APL than in ANLL. These studies provide direct evidence that patients with APL, as well as ANLL, generate excessive amounts of thrombin within their vascular system. Furthermore, the data suggest that the concentrations of F1 + 2, compared with the levels of FPA, may be a more sensitive indicator of hemostatic system hyperactivity in individuals with DIC.
Fibrinogen competes with von Willebrand factor for binding to the glycoprotein IIb/IIIa complex when platelets are stimulated with thrombin
Authors: Gralnick HR , Williams SB , Coller BS 
Published: October 2019

Abstract
Two monoclonal antibodies--one that blocks ristocetin-induced platelet binding of von Willebrand factor to glycoprotein Ib and one that blocks adenosine diphosphate-induced binding of fibrinogen to the glycoprotein IIb/IIIa complex--were used to assess the binding site(s) for von Willebrand factor when platelets are stimulated with thrombin or adenosine diphosphate (ADP). Neither agonist induced binding of von Willebrand factor to glycoprotein Ib. ADP and thrombin induced von Willebrand factor binding exclusively to the glycoprotein IIb/IIIa complex. The results of the site of binding of von Willebrand factor with thrombasthenic platelets were consistent with the data obtained with the monoclonal antibodies and normal platelets. Human fibrinogen caused complete inhibition of thrombin-induced von Willebrand factor binding to normal platelets at concentrations considerably below that found in normal plasma. We conclude that thrombin induces very little binding of exogenous von Willebrand factor to platelets at normal plasma fibrinogen levels.
Differentiation stimuli induce receptors for plasma fibronectin on the human myelomonocytic cell line HL-60
Authors: Pommier CG , O'Shea J , Chused T , Takahashi T , Ochoa M , Nutman TB , Bianco C , Brown EJ 
Published: October 2019

Abstract
Plasma fibronectin (Fn) induces phagocytosis of C3b-opsonized sheep erythrocytes (EC3b) by human peripheral blood monocytes. However, Fn does not induce erythrophagocytosis of EC3b by human polymorphonuclear leukocytes (PMN), unless the PMN have been exposed to C5a or N-formyl- methionyl-leucyl-phenylalanine. Because of this difference, it is of great interest to examine Fn binding to cells that possess the capacity to differentiate into either granulocytes or monocytes. Hence, we have examined the consequences of Fn binding to the human myelomonocytic cell line, HL-60, both before and after in vitro differentiation of the HL-60, along a monocytoid or a granulocytoid pathway. Fn receptors were not found on undifferentiated HL-60, but several differentiating agents promoted the HL-60 binding of Fn-coated microspheres (Fn-ms). The peak of Fn-ms binding occurred four to five days after the induction of differentiation with dimethylsulfoxide (DMSO), and two days after induction by PMA. In addition, cells that differentiated along either the monocytoid or the granulocytoid pathway showed a marked increase in the phagocytosis of both IgG-coated erythrocytes (EA) and EC3b when they were exposed to Fn. Comparison of the effects of anti-Fn monoclonals on the binding of Fn-ms to the monocytes, PMN, and HL-60 showed that the same monoclonals block Fn-ms-binding and Fn-induced EC3b phagocytosis by all three cell types. Two monoclonal antibodies, M1/70 and A6F10, directed against membrane antigens on PMN and monocytes, inhibited Fn-ms binding. Both also blocked Fn-induced EC3b ingestion by these cells. However, neither antibody blocked Fn-ms binding or EC3b ingestion by differentiated HL-60. We conclude that differentiated HL-60 cells express functionally active Fn receptors, similar to monocytes and activated PMN, which, nonetheless, differ from normal cells in their association with the antigens recognized by M1/70 and A6F10.
Pattern of pyruvate kinase isozymes in erythroleukemia cell lines and in normal human erythroblasts
Authors: Max-Audit I , Testa U , Kechemir D , Titeux M , Vainchenker W , Rosa R 
Published: October 2019

Abstract
To further investigate the erythroid nature of the two human erythroleukemia cell lines, K562 and HEL-60, and to define the ontogeny of pyruvate kinase (PK) isozymes (R, M2) in developing human erythroid cells, we have studied the isozymic alterations, if any, during differentiation of these cell lines in vitro and normoblasts isolated from fetal liver in vivo. PK activity of erythroleukemic cell lines was intermediate between that observed in leukocytes and in fetal liver erythroblasts. These cell lines contained a high level of M2-PK, but R- PK was always present, albeit at low concentrations, in all the clones or subclones we studied. Erythroblasts from fetal liver were separated according to density on a Stractan gradient. R-PK levels were nearly constant in the different fractions, whereas M2-PK levels markedly decreased as the erythroblasts became mature and almost completely disappeared in late erythroid cells. Thus, these results clearly demonstrate the erythroid origin of these cell lines.
High-dose intravenous gammaglobulin in alloimmunized platelet transfusion recipients
Authors: Schiffer CA , Hogge DE , Aisner J , Dutcher JP , Lee EJ , Papenberg D 
Published: October 2019

Abstract
High-dose intravenous gammaglobulin (polyvalent immunoglobulin G) has been shown to be of benefit in some patients with immune thrombocytopenic purpura (ITP), possibly by producing reticuloendothelial system blockade. We studied this approach in patients refractory to random donor platelet transfusion using an IV IgG preparation manufactured by the Swiss Red Cross. Eleven adult patients with acute leukemia received either 0.4 g IgG/kg/d intravenously X five days (four patients) or 0.6 g/kg/d X five days (seven patients). All patients had high levels of lymphocytotoxic antibody and poor responses to random donor platelets. Except for mild headaches in two patients, there were no side effects related to the IgG infusions. All patients had significant elevations of serum IgG on the day after completion of treatment. Either random donor or partially HLA-matched platelet transfusions were administered the day after and, in some cases, during the IgG therapy. No patient had an improvement in one hour posttransfusion platelet count increments. Two additional patients received pooled platelet concentrates incubated for 30 minutes at 37 degrees C with IgG at a final concentration of 3 g% prior to transfusions. These results indicate that high-dose IgG, an extremely expensive treatment, cannot be recommended for alloimmunized adults with leukemia.
Growth, interleukin-2 production, and responsiveness to IL-2 in T4- positive T Lymphocyte populations from malignant cutaneous T cell lymphoma (Sezary's syndrome): the effect of cyclosporin A
Authors: Solbach W , Lange CE , Rollinghoff M , Wagner H 
Published: October 2019

Abstract
Functional analysis and surface phenotyping using monoclonal antibodies have revealed that malignant T lymphocyte populations in the peripheral blood of patients with Sezary's syndrome resemble the T helper cell populations from normal individuals. In this article we have studied the effects of the immunosuppressive drug cyclosporine A (CsA) on growth, interleukin-2 (IL-2) production, and the induction of IL-2 responsiveness of peripheral blood monocytes (PBMs) from five patients with Sezary's syndrome in vitro, using the lectin phytohemagglutinin (PHA) and the phorbol ester phorbol myristate acetate (PMA) as stimuli. The following results were obtained: PHA-induced cell proliferation was significantly more sensitive to inhibition by CsA than that induced by PMA or a combination of PMA and PHA (P less than .005). Sezary PBMs produced only small amounts of IL-2 in response to PHA. Stimulation with PMA, however, resulted in significant IL-2 production. PMA and PHA, when given in combination, acted synergistically. The low levels of IL-2 production induced by PHA or PMA were more sensitive to CsA- mediated suppression than those induced by a combination of PHA and PMA (75% and 55% suppression, respectively). CsA-mediated growth suppression could be overcome if the cultures were supplemented with appropriate amounts of exogenous IL-2. We conclude from our data, that CsA in Sezary PBMs inhibits T cell growth indirectly as a consequence of suppression of IL-2 growth indirectly as a consequence of suppression of IL-2 production. Moreover, like normal T lymphocytes, Sezary PBMs do not express the IL-2 receptor spontaneously, but can be induced to do so. CsA does not interfere with intracellular events leading to the expression and the biologic function of the IL-2 receptor.
Lipid analyses and fluidity studies by electron spin resonance of red cell membranes in hereditary high red cell membrane phosphatidylcholine hemolytic anemia
Authors: Yawata Y , Sugihara T , Mori M , Nakashima S , Nozawa Y 
Published: October 2019

Abstract
Membrane lipid analyses and electron spin resonance (ESR) studies of membrane fluidity were carried out on the red cells of a Japanese patient with hereditary high red cell membrane phosphatidylcholine hemolytic anemia (HPCHA). Increased amounts of phosphatidylcholine (PC) and cholesterol were found in the membrane lipids of the affected patient, despite normal plasma lipids. The order parameter of cholesterol-free pure phospholipid liposomes prepared from this patient's red cells was decreased, apparently because of the increased PC. In contrast, the order parameter of the total red cell lipid liposomes (containing free cholesterol) was essentially normal. The overall fluidity of the intact red cells was determined by ESR with a spin probe, 5-SAL. Again, the order parameters were normal in the intact red cells of the patient with HPCHA. This suggests that the concomitant increase of membrane cholesterol and phosphatidylcholine serves to maintain normal membrane fluidity in the HPCHA red cells.
Acquired von Willebrand's disease in the myeloproliferative syndrome
Authors: Budde U , Schaefer G , Mueller N , Egli H , Dent J , Ruggeri Z , Zimmerman T 
Published: October 2019

Abstract
An acquired hemorrhagic disorder developed in two patients in association with postsplenectomy thrombocytosis and leukocytosis during the course of the myeloproliferative syndrome. The presence of acquired von Willebrand's disease in these individuals was demonstrated by a decrease or absence of the larger von Willebrand factor (vWF) multimers, alteration of the repeating vWF multimeric “triplet,” decreased ristocetin cofactor activity (vWF:RCo), and prolonged bleeding time. The bleeding stopped in both patients after treatment with either 1-deamino-[8-D-arginine]-vasopressin (DDAVP) or Cohn fraction I. Treatment with thrombocytapheresis and azathioprine or busulfan resulted in reduction of the elevated platelet and white cell counts and was associated with partial correction of the vWF abnormalities and remission of the hemostatic abnormalities. In five additional patients with the myeloproliferative syndrome, but without bleeding symptoms, large multimers of plasma vWF were diminished also. These findings suggest that acquired von Willebrand's disease should be considered when a bleeding diathesis develops during the course of the myeloproliferative syndrome.
The generation of human long-term marrow cultures from marrow depleted of Ia (HLA-DR) positive cells
Authors: Keating A , Powell J , Takahashi M , Singer JW 
Published: October 2019

Abstract
Successful long-term cultures were generated from marrow buffy-coat cells incubated with either of two monoclonal anti-Ia antibodies, 7.2 and HBIOa, and complement. The mean CFU-GM toxicity for 7.2 and HBIOa was 81% and 94%, respectively, of the complement control. Cultures generated from marrows treated with 7.2 and complement produced between 30% and 163% of the CFU-GM (mean, 78.2 +/- 52.4%) and 33% of the BFU-E produced by the complement control cultures. Long-term cultures from marrows treated with the more cytotoxic HBIOa antibody yielded 261% of the CFU-GM present at culture initiation. Our data suggest that the progenitor cells necessary for generation of long-term cultures from human marrow are Ia-negative and may represent less mature stem cells than those measurable by semisolid colony assays. Furthermore, marrow treated with cytotoxic anti-Ia antibodies may be suitable for use in autologous transplantation.
Effects of variant gamma chains and sialic acid content of fibrinogen upon its interactions with ADP-stimulated human and rabbit platelets
Authors: Harfenist EJ , Packham MA , Mustard JF 
Published: October 2019

Abstract
When platelets are stimulated with adenosine diphosphate (ADP), fibrinogen binds to receptors on the platelet membrane, and the platelets aggregate. The primary platelet recognition sites of human fibrinogen are reported to be at the COOH-terminal ends of the gamma chains, with secondary sites in the A alpha chains. Normal human fibrinogen, which consists of three pairs of disulfide-bonded peptide chains, (A alpha, B beta, gamma)2, is heterogeneous with respect to sialic acid content and also contains a small proportion of molecules with a variant gamma chain (designated gamma'), elongated by a peptide extension at the COOH-terminus of the normal gamma chain. We separated fibrinogen into three fractions by chromatography on DEAE cellulose and tested the interactions of these fractions with ADP-stimulated human and rabbit platelets. Two fractions had the normal chain composition, (A alpha B beta, gamma)2, but different sialic acid contents (6.6 and 7.2 mol/mol), and the third fraction had the chain composition (A alpha, B beta)2 gamma gamma' and a sialic acid content of 7.2 mol/mol, which is similar to that of one of the normal fractions. In binding and aggregation experiments, we detected no significant differences between the reactions of the first two fractions, but ADP-stimulated platelets bound only 50% as much of 125I-fibrinogen from the fraction with the gamma' chains and also aggregated less extensively in the presence of this fraction. We conclude that the sialic acid content of fibrinogen does not significantly affect its interactions with platelets, but the elongated gamma' chains bind less effectively to ADP-stimulated platelets, and thus reduce the ability of fibrinogen to support aggregation. This may result from a conformational change caused by the gamma' extension or from the deletion of a portion of the normal gamma chain recognition site.
High incidence of monoclonal proteins in the serum and urine of chronic lymphocytic leukemia patients
Authors: Deegan MJ , Abraham JP , Sawdyk M , Van Slyck EJ 
Published: October 2019

Abstract
Chronic lymphocytic leukemia (CLL) is generally considered a nonsecretory B cell immunoproliferative disorder. Conventional electrophoretic and immunoelectrophoretic methods have revealed serum monoclonal proteins in less than 10% of these patients. However, there is increasing experimental evidence from in vitro studies demonstrating that CLL cells may secrete immunoglobulins, particularly free light chains. We examined the serum and urine of 36 consecutive CLL patients for monoclonal proteins using sensitive immunochemical methods (high resolution agarose gel electrophoresis combined with immunofixation). The results obtained were correlated with the Rai stage, quantitative immunoglobulin levels, and lymphocyte membrane immunoglobulin phenotype of the leukemic cells. Twenty-three monoclonal proteins were identified in the serum or urine of 22 patients, an incidence of 61%. Six patients had serum monoclonal proteins, seven had only urinary monoclonal proteins, and nine had monoclonal proteins in serum and urine. In every instance the monoclonal protein was the same light chain type as expressed on the leukemic cells. Our findings suggest that the monoclonal proteins observed in the serum or urine of CLL patients are secretory products of the tumor cells and that their discovery is a function of the sensitivity of the method used for their detection.
Coagulation Factor IX concentrate: method of preparation and assessment of potential in vivo thrombogenicity in animal models
Authors: Menache D , Behre HE , Orthner CL , Nunez H , Anderson HD , Triantaphyllopoulos DC , Kosow DP 
Published: October 2019

Abstract
Thrombosis and/or disseminated intravascular coagulation (DIC) are complications specifically associated with the use of factor IX complex in some patients. Assuming that these complications might result from zymogen overload, we have produced, using diethylaminoethyl (DEAE)- Sephadex (Pharmacia, Piscataway, NJ) and sulfated dextran chromatography, a factor IX concentrate (coagulation factor IX) that is essentially free of prothrombin, factor VII, and factor X. Factor IX specific activity is at least 5 U/mg protein, a 250-fold purification compared to plasma. Amounts of factors II, VII, and X are less than 5 units each per 100 units of factor IX. The concentrate is essentially free of activated clotting factors and contains no added heparin. In the rabbit stasis model, a dose of 200 factor IX U/kg was less thrombogenic than 100 factor IX U/kg of the DEAE-Sephadex eluate from which the concentrate was derived. Infusion of 200 factor IX U/kg did not induce DIC in the nonstasis rabbit model, whereas 100 factor IX U/kg of the DEAE-Sephadex eluate resulted in DIC in this model. Several factor IX lots were found to have shortened nonactivated partial thromboplastin times (PTTs), but were nonthrombogenic in both animal models. These data indicate that coagulation factor IX concentrate is less thrombogenic than factor IX complex.
Characterization of erythrocyte quality during the refrigerated storage of whole blood containing di-(2-ethylhexyl) phthalate
Authors: Estep TN , Pedersen RA , Miller TJ , Stupar KR 
Published: October 2019

Abstract
Di-(2-ethylhexyl) phthalate (DEHP) accumulates in blood brought into contact with materials utilizing this compound as a plasticizer. To determine whether this phthalate diester affects red blood cell integrity, we have compared cell morphology, plasma hemoglobin accumulation, micro-vesicle production, and the concentration of intracellular metabolites and electrolytes of erythrocytes from blood stored at 4 degrees C with and without DEHP. When sufficient emulsified DEHP was mixed with blood to give a final concentration of 300 micrograms/mL, plasma hemoglobin accumulation was reduced by an average of 70%, the percentage of cells exhibiting normal morphology was enhanced by at least 20-fold, and the volume of microvesicles released from red blood cells was reduced by 50% after 35 days of refrigerated storage compared to the values obtained from corresponding samples stored without added phthalate. Similar effects were observed regardless of whether blood was stored in nonplasticized polypropylene or tri-(2-ethylhexyl) trimellitate plasticized polyvinylchloride containers and with DEHP solubilized by a variety of emulsifiers. When 300 micrograms/mL DEHP was added to stored blood containing erythrocytes predominantly in the echinocyte conformation, many of the cells reverted to the normal discoid morphology. The addition of this quantity of DEHP to blood had no significant effect on the course of storage-induced changes in erythrocyte adenosine triphosphate (ATP), 2,3-diphosphoglycerate (2,3-DPG), sodium or potassium concentrations. The data are consistent with the hypothesis that DEHP inhibits the deterioration of the red blood cell membrane that results from the refrigerated storage of whole blood.
Terminal transferase positive acute promyelocytic leukemia: in vitro differentiation of a T-lymphocytic/promyelocytic hybrid phenotype
Authors: Paietta E , Dutcher JP , Wiernik PH 
Published: October 2019

Abstract
In a case of acute promyelocytic leukemia (APL), the expression of terminal deoxynucleotidyl transferase (TdT), an early lymphoid marker, was detected. Double-fluorescent staining for the myeloid-specific antigens VIM-2 and VIM-D5 in combination with specific antiserum for TdT suggested a mixed leukemic cell population consisting of a morphologically, cytochemically, and immunologically promyelocytic component (80%) and a lymphoid, TdT+ component (20%) that was myelomonocytic in morphology but otherwise without any evidence of nonlymphoid nature. Fluorescent-activated cell analysis revealed that a greater number of cells reacted with monoclonal anti-T antibodies (OKT3, OKT6, and OKT11) than could be identified as lymphoid by TdT expression. As confirmed by double-staining fluorescence microscopy, a large fraction of the promyelocytic leukemia cells were biphenotypic, expressing both myeloid and lymphoid markers (50% positive for VIM-D5 and OKT6, 30% positive for VIM-D5 and OKT3). Subsequently, in vitro differentiation experiments were performed. While treatment of the cells with GCT-conditioned medium favored proliferation, with only a weak and delayed promotion of the cells towards maturation as reflected by enhanced expression of the mature T-marker T3 but persistent expression of the thymocyte antigen, exposure to all-trans and 13-cis retinoic acid resulted in marked differentiation of both the myeloid and the lymphoid cell characteristics. Retinoid treatment resulted in the loss of TdT, a partial disappearance of the T6-antigen, and the expression of the late T cell antigen T3 by almost 70% of the cells. In addition, myeloid maturation was obvious from the morphologic appearance of the cells, as well as from the expression of the OKM1- associated antigen by a majority of the cells. This report concerns a unique case of APL in which, for the first time, a coexistence of promyelocytic and lymphoid elements was detected, with exposure of the cultured leukemic cells to retinoic acid inducing maturation along both the myeloid and the lymphoid lineage.