bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evidence for chemical differences in HLA-DR molecules on autologous acute lymphoblastic leukemia and B-lymphoblastoid cell lines [published erratum appears in Blood 1987 Apr;69(4):1272]
Authors: Graf L , Pesando JM 
Published: October 2019

Abstract
HLA-DR molecules on autologous acute lymphoblastic leukemia (ALL) and B- lymphoblastoid cell lines from two individuals were compared by immune precipitation and gel electrophoresis. Cells were surface labeled with 125I and proteins immunoprecipitated with specific monoclonal antibodies (MoAb). Two electrophoretically distinct bands were found in the HLA-DR beta chain region on both ALL cell lines in contrast to only one on each of the autologous B-lymphoblastoid cell lines. Differences in the electrophoretic mobility of the alpha chains were also observed with ALL and B-lymphoblastoid cell lines from one individual. Preclearing of radiolabeled cell lysates with MoAb specific for HLA-DQ and -DP molecules demonstrated that the complexity of the HLA-DR pattern is not the result of antibody cross-reactivity with alpha and beta chains from other class II products. Immunoprecipitation experiments indicated that two beta chain bands are observed with each of the parental HLA-DR molecules on the ALL but not the B- lymphoblastoid cell line from an HLA-DR3,7-positive individual. We conclude that the HLA-DR molecules expressed on ALL and B- lymphoblastoid cell lines from the same individual can differ chemically. Neuraminidase treatment reduced these electrophoretic differences, indicating that these molecules differ in their sialic acid content. Since small changes in class II molecules can profoundly alter cellular interactions, the functional significance of these differences requires further investigation.
Induction of NK activity in large granular lymphocyte leukemia: activation with anti-CD3 monoclonal antibody and interleukin 2
Authors: Loughran TP Jr , Draves KE , Starkebaum G , Kidd P , Clark EA 
Published: October 2019

Abstract
Large granular lymphocyte (LGL) leukemia is a rare disease characterized by clonal expansion of LGL associated with chronic neutropenia, multiple auto-antibodies, and occasionally polyarthritis. We studied cell surface antigen expression and functional activity of leukemic LGL from ten such patients. Using two-color flow cytometric analysis, we found that leukemic LGL from all ten patients expressed the CD3 and HNK-1 markers, while cells from only four patients expressed IgG Fc receptors (FcR). The LGL leukemic cells had little or no NK activity (defined as MHC-nonrestricted cytotoxicity against K562 target cells); however, NK activity could be induced in leukemic LGL by in vitro treatment with as little as 0.05 microgram/mL of anti-CD3 monoclonal antibody. Cell sorting experiments demonstrated that NK activity was induced in CD3+ leukemic LGL (either CD3+, HNK-1+ or CD3+, FcR+) with anti-CD3 monoclonal antibody but not in normal CD3+, FcR- T cells. Treatment with purified interleukin 2 (IL 2) also caused direct activation of some CD3+ leukemic LGL. Despite induction with anti-CD3 MAb or IL 2, activated leukemic LGL did not proliferate or express high density IL 2 receptors detectable by cell sorter analysis. Treatment with alpha interferon had minimal effect on NK activity of LGL leukemic cells. These results suggest that leukemic LGL may provide a useful model for examining the signals required for LGL maturation and activation.
Altered plasma membrane phospholipid organization in Plasmodium falciparum-infected human erythrocytes
Authors: Schwartz RS , Olson JA , Raventos-Suarez C , Yee M , Heath RH , Lubin B , Nagel RL 
Published: October 2019

Abstract
The intraerythrocytic development of the malaria parasite is accompanied by distinct morphological and biochemical changes in the host cell membrane, yet little is known about development-related alterations in the transbilayer organization of membrane phospholipids in parasitized cells. This question was examined in human red cells infected with Plasmodium falciparum. Normal red cells were infected with strain FCR3 or with clonal derivatives that either produce (K+) or do not produce (K-) knobby protuberances on the infected red cells. Parasitized cells were harvested at various stages of parasite development, and the bilayer orientation of red cell membrane phospholipids was determined chemically using 2,4,6-trinitrobenzene sulphonic acid (TNBS) or enzymatically using bee venom phospholipase A2 (PLA2) and sphingomyelinase C (SMC). We found that parasite development was accompanied by distinct alterations in the red cell membrane transbilayer distribution of phosphatidylcholine (PC), phosphatidylethanolamine (PE), and phosphatidylserine (PS). Increases in the exoplasmic membrane leaflet exposure of PE and PS were larger in the late-stage parasitized cells than in the early-stage parasitized cells. Similar results were obtained for PE membrane distribution using either chemical (TNBS) or enzymatic (PLA2 plus SMC) methods, although changes in PS distribution were observed only with TNBS. Uninfected cohort cells derived from mixed populations of infected and uninfected cells exhibited normal patterns of membrane phospholipid organization. The observed alterations in P falciparum-infected red cell membrane phospholipid distribution, which is independent of the presence or absence of knobby protuberances, might be associated with the drastic changes in cell membrane permeability and susceptibility to early hemolysis observed in the late stages of parasite development.
Prevention of platelet alloimmunization in dogs with systemic cyclosporine and by UV-irradiation or cyclosporine-loading of donor platelets
Authors: Slichter SJ , Deeg HJ , Kennedy MS 
Published: October 2019

Abstract
To study the immunosuppressive effects of three different treatments, 30 dogs received at weekly intervals eight platelet transfusions from a single random donor dog. The three experimental protocols were daily oral cyclosporine (Cs) treatment of recipients; in vitro ultraviolet (UV)-irradiation of donor platelets; and Cs-loading of donor platelets. All nine recipients of Cs, 11/12 (92%) recipients of UV-irradiated platelets, and 5/9 (56%) recipients of Cs-loaded donor platelets remained nonimmunized to repeated transfusions of donor platelets. In contrast, only 3 of 21 untreated controls (14%) were not alloimmunized by donor platelets. Moreover, 44% to 67% of the nonimmunized recipients remained tolerant to continued platelet transfusions from their original donor even after experimental therapy was discontinued. Forty- three percent to 100% of transfusions from secondary donors were also accepted without causing alloimmunization, suggesting that tolerance induced by prior treatment was not specific for the primary donor. However, survival of both the original and secondary donor platelets was reduced to about half the starting level, suggesting that some immune response to platelets had occurred. Also, recipients immunized by their original donor's platelets frequently developed refractoriness to platelets from other donors.
Spectrum of natural antibodies against five HTLV-III antigens in infected individuals: correlation of antibody prevalence with clinical status
Authors: Franchini G , Robert-Guroff M , Aldovini A , Kan NC , Wong-Staal F 
Published: October 2019

Abstract
The genome of the HTLV-III/LAV retrovirus, the etiologic agent of the acquired immunodeficiency syndrome (AIDS), encodes the viral structural proteins (envelope and core proteins), the reverse transcriptase, a transactivation protein (tat-III), as well as two other proteins (3′orf, sor) of unknown function. We studied the prevalence of natural antibodies against envelope, gag, 3′orf, sor, and tat-III in the sera of HTLV-III infected individuals in an attempt to correlate clinical status with seropositivity to specific HTLV-III antigens. We selected 101 sera; 16 were obtained from normal donors with no known risk factors, and 85 were from patients with full-fledged AIDS (28 cases), AIDS-related complex (ARC, 22 cases), and healthy people at risk (homosexuals, intravenous [IV] drug users, relatives of AIDS patients; 35 cases). Seropositivity for antibodies against the envelope (gp41) and gag antigens (p15, p24) was determined by Western blot using disrupted HTLV-III virions. Of the 101 sera, all 16 from nonrisk donors and 3/35 from healthy at-risk donors were negative for antibodies against either the gp41 or p15 and p24. The remaining 82 sera were seropositive for either the gp41 and/or the p15 and p24. All sera were then tested against the three known HTLV-III antigens (3′orf, sor, and tat-III) that have been synthesized in bacteria. Our data indicate that all the HTLV-III antigens tested are immunogenic in vivo. No significant difference in antibody prevalence to gp41 (close to 100%) and to the 3′orf, sor, and tat-III proteins (approximately 50%) was observed with regard to stage of the disease. In contrast, the prevalence of antibodies against the core antigens decreased from approximately 100% in infected people with no clinical signs of disease to 50% in ARC and AIDS patients. The percentage of patients seropositive for all five antigens tested was increased in the AIDS group. These results indicate that the greatest antibody prevalence was obtained using viral envelope antigen and further suggest that screening with the newly identified 3′orf, sor, and tat-III proteins as antigens would confer no further diagnostic advantage. The pattern of natural antibodies observed during disease progression did not suggest any pathogenetic mechanism.
Dipyridamole stimulates urokinase production and suppresses procoagulant activity of rabbit alveolar macrophages: a possible mechanism of antithrombotic action
Authors: Hasday JD , Sitrin RG 
Published: October 2019

Abstract
Dipyridamole, an inhibitor of platelet aggregation, has been shown to have beneficial effects in disorders characterized by extravascular fibrin deposition. Mononuclear phagocytes are present in extravascular sites and are capable of expressing both plasminogen activator and procoagulant activities, which suggests these cells play a central role in extravascular fibrin turnover. We therefore sought to determine whether dipyridamole affects the expression of plasminogen activator and procoagulant activities by rabbit alveolar macrophages cultured in vitro. We found that dipyridamole (10 to 100 mumol/L) caused increases in both cell-associated and released plasminogen activator activity, which reached levels of 240% (P less than .05) and 543% (P less than .01) of controls, respectively. In contrast, dipyridamole decreased the cell-associated procoagulant activity of alveolar macrophages to as little as 21.3% of controls (P less than .01). Similar effects were seen in cells cotreated with lymphokines. The procoagulant activity expressed by these cells functioned as a tissue thromboplastin. The plasminogen activator of control and treated cells was a urokinase as determined by molecular weight characteristics (50 kilodaltons) and by antibody neutralization profiles using polyclonal antibodies against human urokinase and tissue plasminogen activator. These effects of dipyridamole could not be duplicated by structurally dissimilar agents sharing some of the pharmacological actions of dipyridamole; however, two pyrimidopyrimidine compounds structurally similar to dipyridamole effectively mimicked the effects on both procoagulant and plasminogen activator activities. We conclude that dipyridamole may have antithrombotic effects by directly modulating the role of mononuclear phagocytes in fibrin turnover. Thus, dipyridamole may be useful in situations where extravascular fibrin deposition is important to the pathogenesis of tissue injury and repair.
Synergistic action of two murine monoclonal antibodies that inhibit ADP- induced platelet aggregation without blocking fibrinogen binding
Authors: Newman PJ , McEver RP , Doers MP , Kunicki TJ 
Published: October 2019

Abstract
We have used two murine monoclonal antibodies, each directed against one component of the human platelet membrane glycoprotein (GP) IIb-IIIa complex, to examine further the molecular requirements for fibrinogen binding to the platelet surface and subsequent platelet-platelet cohesion (aggregation). Although neither AP3, which is directed against GPIIIa, nor Tab, which is specific for GPIIb, were individually able to inhibit adenosine diphosphate (ADP)-induced fibrinogen binding, platelet aggregation, or secretion, the combination of AP3 and Tab completely abolished platelet aggregation and the release reaction. Unexpectedly, this synergistic inhibition of platelet-platelet cohesion occurred in the presence of apparently normal fibrinogen binding. Both the number of fibrinogen molecules bound and the dissociation constant for fibrinogen binding remained essentially unchanged in the presence of these two antibodies. Inhibition of aggregation was dependent upon the divalency of both AP3 and Tab because substitution of Fab fragments of either antibody for the intact IgG resulted in a complete restoration of both aggregation and secretion. In contrast to ADP induction, thrombin-activated platelets neither aggregated nor bound fibrinogen in the presence of AP3 plus Tab but were fully capable of secretion, which illustrated the multiple mechanisms by which the platelet surface can respond to different agonists. These data demonstrate that fibrinogen binding to the platelet surface alone is not sufficient to support platelet-platelet cohesion and that an additional post-fibrinogen-binding event(s) that is inhibitable by these two monoclonal antibodies may be required.
Oral contraceptives and gender affect protein S status
Authors: Boerger LM , Morris PC , Thurnau GR , Esmon CT , Comp PC 
Published: October 2019

Abstract
Protein S is a plasma protein that serves as a cofactor for the anticoagulant effects of activated protein C. Congenital protein S deficiency is often associated with thromboembolic disease. During pregnancy a decrease in the functional and antigenic levels of protein S occurs; this change in protein S status may contribute to the thromboembolic complications that sometimes occur during pregnancy. In certain patients, oral contraceptive use has also been associated with thrombotic complications. In this study, protein S status was determined in 21 women taking oral contraceptives and compared with that of 21 women not taking oral contraceptives and that of 21 men. The results show that women taking oral contraceptives have significantly lower total protein S (24.3 +/- 3.6 micrograms/mL; mean +/- SD) than women not taking oral contraceptives (28.6 +/- 3.9 micrograms/mL) (P less than .005). Men had significantly higher protein S levels (30.9 +/- 3.9 micrograms/mL, P less than .01) than age-matched women not taking oral contraceptives. In plasma, an equilibrium exists between free (functionally active) protein S and protein S complexed to C4b-binding protein, which is functionally inactive. The mean levels of C4b-binding protein were essentially the same among the three groups, but the levels of free protein S were significantly different and reflected different total protein S antigen levels. Additionally, we found that inflammation significantly elevated C4b-binding protein levels and could result in a further significant decrease in free protein S levels. These data indicate that plasma protein S levels are significantly affected by hormonal status and inflammation.
Modulation of endothelial cell functions by different molecular species of interleukin 1
Authors: Dejana E , Breviario F , Erroi A , Bussolino F , Mussoni L , Gramse M , Pintucci G , Casali B , Dinarello CA , Van Damme J 
Published: October 2019

Abstract
Different molecular species of interleukin 1 (IL 1) were examined for the spectrum of responses elicited in human endothelial cells (HEC), including synthesis of prostacyclin (PGI2), tissue-type procoagulant activity (PCA), platelet activating factor (PAF), and plasminogen activator inhibitor (PA-I). The IL 1 preparations utilized for the present study included a natural, partially purified IL 1, a preparation purified to homogeneity with extensive homology with the derived aminoacid IL 1 beta (pI7) sequence denominated “22K factor,” murine recombinant IL 1 alpha, human recombinant IL 1 alpha (pI5) and beta (pI7). Natural, partially purified IL 1, a mixture of alpha and beta species, induced the entire spectrum of responses in HEC. Production of PA-I was elicited by all forms of IL 1 tested. PGI2 and PCA were elicited by “22K factor” and by human recombinant IL 1 beta and alpha but not by murine recombinant IL 1 alpha. PAF synthesis was stimulated by murine and human recombinant IL 1 alpha but not by human recombinant IL 1 beta and 22K factor. Thus the available different molecular forms of IL 1 elicit largely but not completely overlapping patterns of responses in HEC. The IL 1 pathway of regulation of HEC functions might provide a basis for novel strategies in therapeutically oriented research on vessel wall disorders.
Increased resistance to membrane deformation of shape-transformed human red blood cells [published erratum appears in Blood 1987 Sep;70(3):893]
Authors: Chabanel A , Reinhart W , Chien S 
Published: October 2019

Abstract
The study of shape-transformed human erythrocytes is of hematological interest since several clinical conditions are associated with erythrocyte shape changes. Using the micropipette technique, we examined the rheological behaviors of echinocytes induced by sodium salicylate or ATP depletion and of stomatocytes induced by chlorpromazine. Both the discocyte-echinocyte and discocyte-stomatocyte transformations resulted in an increased resistance to extension. Sodium salicylate-treated erythrocytes could be returned to normal morphology and normal membrane rheology by addition of chlorpromazine. We conclude that these morphological changes are associated with detrimental effects on the intrinsic membrane deformability of the human erythrocyte.
Abnormal prothrombin in the plasma of rats carrying hepatic tumors
Authors: Shah DV , Engelke JA , Suttie JW 
Published: October 2019

Abstract
Vitamin K is required for the posttranslational formation of gamma- carboxyglutamyl residues in a number of plasma clotting factors. Interference with vitamin K action results in the appearance of abnormal (des-gamma-carboxy) forms of prothrombin in human plasma. Vitamin K-sufficient patients with primary hepatocellular carcinoma also secrete significant quantities of abnormal prothrombin; this response has now been studied in a rat model. Normal Buffalo strain rats had 9 micrograms/mL of circulating plasma abnormal prothrombin, whereas Buffalo strain rats carrying the transplantable Morris hepatoma tumor no. 7777 had 33 micrograms/mL at 3 weeks after transplant. Vitamin K-dependent carboxylase activity was normal in the liver of these rats, but very low in the tumor tissue. Rats carrying Morris hepatoma tumors no. 9618A and 5123D did not secrete significant amounts of abnormal prothrombin. Carboxylase activity in these tumors was 15 times that of the 7777 tumor. The data suggest that the secretion of abnormal prothrombin by hepatocellular tumors is the result of normal expression of the prothrombin gene by those tumors and a failure of the tumor to express the carboxylase gene.
Sodium fluoride mimics effects of both agonists and antagonists on intact human platelets by simultaneous modulation of phospholipase C and adenylate cyclase activity
Authors: Kienast J , Arnout J , Pfliegler G , Deckmyn H , Hoet B , Vermylen J 
Published: October 2019

Abstract
Using intact human platelets, we studied the effect of sodium fluoride (NaF) on platelet aggregation and release reaction and correlated the functional changes to intracellular events specific for either agonist- induced or antagonist-induced platelet responses. At lower concentrations, with a peak activity between 30 and 40 mmol/L, NaF induced aggregation and release of adenosine 5′-triphosphate (ATP) that was associated with increased formation of inositol phosphates, a rise in cytosolic free Ca2+, and phosphorylation of 20-kd and 40-kd proteins. At NaF concentrations greater than 40 mmol/L, aggregation and ATP release decreased dose-dependently in parallel with a decrease in Ca2+ mobilization, whereas neither inositol phosphate formation nor 40- kd protein phosphorylation was reduced. At these concentrations, NaF caused a dose-dependent transient rise in platelet cyclic adenosine 3′,5′-monophosphate (cAMP) levels that was sufficient to account for the observed reduction in Ca2+ mobilization, aggregation, and ATP release. Stimulated cAMP levels started declining rapidly within 30 seconds of addition of NaF, however. Similarly, prostacyclin (PGI2)- induced cAMP accumulation was temporarily enhanced but subsequently suppressed by NaF, suggesting either stimulation of a cAMP phosphodiesterase or delayed inhibition of adenylate cyclase. Evidence for the latter was provided by the finding that NaF pretreatment of platelets resulted in partial inhibition of PGI2-stimulated cAMP formation in the presence of the cAMP phosphodiesterase inhibitor 3- isobutyl-1-methyl-xanthine (MIX). We conclude that NaF exerts a dual (stimulatory and inhibitory) effect on adenylate cyclase in intact platelets that is accompanied by simultaneous activation of a phosphoinositide-specific phospholipase C; in addition, a cAMP phosphodiesterase may be activated.
Cell surface phenotyping of megakaryoblasts
Authors: Koike T , Aoki S , Maruyama S , Narita M , Ishizuka T , Imanaka H , Adachi T , Maeda H , Shibata A 
Published: October 2019

Abstract
Surface phenotypic characterization of megakaryoblasts, identified by platelet peroxidase activity, was investigated in four patients who showed increased proliferation of megakaryoblasts: one patient with typical features of acute leukemia, one presenting with acute myelofibrosis, and two with Down's syndrome in whom blasts disappeared spontaneously (transient abnormal myelopoiesis, TAM). MY10 and/or MY9 antigens were expressed on the surface of some megakaryoblasts, but MY7, and MY4, antigens specific to granulocytic or monocytic cells, were not. Some megakaryoblasts were positive for only anti-HLA-DR antibodies. It was speculated that, during the differentiation of the megakaryocytic lineage, MY9 antigen appears transiently on the surface of megakaryoblasts that have lost HLA-DR antigens and have gained the glycoprotein IIb/IIIa antigen. This study also demonstrated that the proliferating blasts in some patients with TAM were mainly megakaryoblasts and suggested that the target cells in TAM are CFU-GEMM.
bcr-abl RNA in patients with chronic myelogenous leukemia
Authors: Shtivelman E , Gale RP , Dreazen O , Berrebi A , Zaizov R , Kubonishi I , Miyoshi I , Canaani E 
Published: October 2019

Abstract
The major consequence of the formation of the Philadelphia (Ph1) chromosome characteristic of leukemia cells of patients with chronic myelogenous leukemia (CML) is fusion of c-abl and bcr genes. Using a sensitive RNase protection technique, we analyzed mRNA from a large number of CML patients. In most, we identified one or both species of bcr-abl chimeric transcripts. These two mRNAs vary in the specific bcr exon joined to abl exon II and are translated into slightly different proteins. The amounts of the fused mRNA within leukemia cells vary considerably between individuals and do not correlate with the phase of the disease.