bluuebunny/crossref_metadata_2025_split huggingface dataset:
Shear stress activation of platelet glycoprotein IIb/IIIa plus von Willebrand factor causes aggregation: filter blockage and the long bleeding time in von Willebrand's disease
Authors: O'Brien JR , Salmon GP 
Published: October 2019

Abstract
The article explores the finding that high shear alone applied to normal, native blood results in platelet aggregation. A filter with tortuous capillary-sized channels permits a study of the effect of shearing forces at different pressures. Native, heparinized, citrated and EDTA blood and platelet-rich plasma (PRP) were forced through the filter. Normal and von Willebrand's blood were studied, as were the effects of antibodies to platelet glycoproteins (GPr) and to von Willebrand's factor (vWf) and of “membrane-active” drugs. Normally, the filter blocked at 40 mmHg but not at 5 mmHg. Transmission electronmicroscopy of the filter at 40 mmHg showed blockage by platelet aggregates. Initially, the mean transit time through the filter was 8 milliseconds. Platelet retention in the filter occurred in two phases. From 0 to 3 seconds, only high-shear, vWf, and GPrIIb/IIIa were required. From 10 to 20 seconds, retention presumably involved these three attributes, but divalent cations were also essential. Only this phase was inhibited by some membrane-active drugs. ADP- and thrombin- induced aggregation requires GPrIIb/IIIaand fibrinogen. Shear-induced blocking of the filter by blood with a normal concentration of fibrinogen requires GPrIIb/IIIa and vWf. This indicates a different type of exposure of GPrIIb/IIIa. The long bleeding time in vW disease highlights the absolute requirement for vWf and emphasizes the difference in exposure of GPrIIb/IIIa induced by shear stress. Evidently, a process similar to that occurring in the filter is required in normal capillary hemostasis.
Phorbol esters sensitize platelets to activation by physiological agonists
Authors: Siess W , Lapetina EG 
Published: October 2019

Abstract
Phorbol esters such as phorbol 12, 13-dibutyrate (PdBu; 40 to 200 nmol/L) or 12-O-tetradecanoyl phorbol 13-acetate (20 to 80 nmol/L) added to aspirinized platelet-rich plasma (PRP) 5 to 15 seconds prior to various platelet stimuli (epinephrine, ADP, prostaglandin endoperoxide analog U44069, collagen, PAF, or vasopressin) potentiate the rate and extent of aggregation and ATP secretion induced by those agonists. Platelet aggregation, but not secretion, is potentiated at low concentrations of agonists; platelet secretion is potentiated at higher concentrations of the platelet stimuli. Potentiation of platelet responses was also observed when the preincubation time with PdBu was extended to 12 minutes and also occurred in washed platelets. The potentiating effect of phorbol esters is not mediated by formation of arachidonate metabolites or by released ADP. The sensitizing effect of PdBu on platelet aggregation induced by epinephrine is unique, since in contrast to the other platelet stimuli it is also found at maximal concentrations of epinephrine and does not diminish with prolonged preincubation of platelets with PdBu. Activation of protein kinase C ranges from 20% to 80% over control after 1 to 10 minutes of platelet pretreatment with PdBu but dramatically increases after subsequent addition of a stimulus such as vasopressin. In contrast, agonist- induced myosin light chain phosphorylation is reduced after platelet pretreatment with PdBu. The results indicate that protein kinase C activation enhances platelet aggregation and dense granule secretion triggered by physiologic stimuli, although it desensitizes agonist- induced myosin light chain phosphorylation.
Bone marrow transplantation for leukemia following a new busulfan and cyclophosphamide regimen
Authors: Tutschka PJ , Copelan EA , Klein JP 
Published: October 2019

Abstract
Busulfan 16 mg/kg and cyclophosphamide 120 mg/kg were used as conditioning prior to allogeneic marrow transplantation in 50 adult patients with acute nonlymphocytic leukemia (ANLL), acute lymphocytic leukemia (ALL), and chronic myelogenous leukemia (CML). A standard risk group of 20 patients included those with acute leukemia in remission and CML in chronic phase. A high-risk group of 30 patients included individuals with refractory acute leukemia, acute leukemia in relapse, acute leukemia following preleukemia, and CML in accelerated and blastic phase. Complete remission and sustained complete engraftment were achieved in all evaluable patients. The duration of aplasia was remarkably short (median of 8 days), resulting in a low infection rate during the period of neutropenia, a reduced need for blood product support, and a short length of hospital stay. Three-year actuarial relapse-free survival in both standard-risk (88.9% +/- 10.5%) and high- risk (50.5% +/- 9.6%) groups compares favorably with that reported with total body irradiation (TBI) containing regimens.
Intensive chemotherapy in aggressive lymphomas: updated results of LNH- 80 protocol and prognostic factors affecting response and survival
Authors: Coiffier B , Bryon PA , Ffrench M , Blanc M , Sebban C , Berger F , Viala JJ 
Published: October 2019

Abstract
One hundred patients with aggressive malignant lymphomas treated with the LNH-80 regimen were evaluated for long-term survival and pretreatment characteristics predictive of response and survival. LNH- 80 consists of three intensive courses of adriamycin cyclophosphamide vindesine bleomycin (ACVB) followed by sequential consolidation and final intensification. Eighty-four patients went into complete remission (CR), eight had a partial response (PR), three failed to respond, and five died during induction. Twenty-three patients (27%) relapsed, in two of whom a prolonged second remission was obtained. Sixty-three patients are currently alive, two of them with disease. Four patients died in CR. Median survival and median freedom from relapse survival were not reached with a median follow-up of 4 1/2 years. Characteristics negatively associated with response in multivariate analysis were: poor performance status, bone marrow involvement, and two or more extranodal sites of disease. Duration of CR was associated with splenic involvement. Three characteristics were negatively associated with survival in multivariate analysis: age, high grade subtypes, and bone marrow involvement.
High-dose intravenous gamma globulin improves responses to single-donor platelets in patients refractory to platelet transfusion
Authors: Zeigler ZR , Shadduck RK , Rosenfeld CS , Mangan KF , Winkelstein A , Oral A , Ramsey GE , Duquesnoy RJ 
Published: October 2019

Abstract
Ten patients, with bone marrow failure or malignant disorders, became refractory to platelet transfusions using random, as well as partial or fully HLA-matched, single-donor platelets. To determine its effect on platelet refractoriness, intravenous gamma globulin (IV IgG) was administered at 400 or 800 mg/kg/d for five days, and postinfusion platelet responses were monitored. Platelet transfusion responses following intravenous gamma globulin (IV IgG) were graded as follows: Excellent, 48-hour posttransfusion count greater than 50,000/microL; good, 48-hour count greater than 20,000 but less than 50,000/microL; Fair, increased increment, 48-hour count less than 20,000; and failed, no increased increment. Six of ten patients (60%) had improved responses to selected single-donor platelets (two were excellent, three were good, and one was fair). The time to achieve a platelet transfusion count greater than 25,000/microL ranged from one to nine days of IgG therapy. One individual had sustained benefit (greater than 1 year); the remaining responses persisted for 6 to 8 weeks. These results suggest that IV IgG may be useful in the management of platelet refractoriness, especially in patients receiving single-donor platelets.
Fibronectin is required for platelet adhesion and for thrombus formation on subendothelium and collagen surfaces
Authors: Bastida E , Escolar G , Ordinas A , Sixma JJ 
Published: October 2019

Abstract
Fibronectin (FN) plays a role in several adhesion mediated functions including the interaction of platelets with subendothelium. We investigated the role of plasma FN in platelet adhesion and platelet thrombus formation under flow conditions. We used two different perfusion models: the annular chamber with alpha-chymotrypsin-treated rabbit vessel segments, and the flat chamber with coverslips coated with fibrillar purified human collagen type III. Perfusates consisted of washed platelets and washed RBCs, suspended in normal or FN-depleted plasma. Perfusions were carried out for ten minutes at shear rates of 300 or 1,300 s-1. Platelet deposition and thrombus dimensions were evaluated morphometrically by a computerized system. We found that depletion of plasma fibronectin significantly reduced the percentage of total coverage surface and percentage of platelet thrombus, at both shear rates studied, and in both perfusion systems (P less than .01) (P less than .01). The dimensions of the platelet thrombi formed in perfusions at high shear rate were also significantly reduced in perfusions carried out with FN depleted plasma (P less than .01). Addition of purified FN to FN-depleted perfusates restored all values to those measured in the control perfusions. These results indicate that plasma FN is required for platelet aggregate and thrombus formation following adhesion under flow conditions.
Fibrin monomer induces binding of endogenous platelet von Willebrand factor to the glycocalicin portion of platelet glycoprotein IB
Authors: Parker RI , Gralnick HR 
Published: October 2019

Abstract
This study demonstrates that when platelets are stimulated by thrombin in the presence of low concentrations of purified human fibrinogen (10 to 20 micrograms/mL, final concentration) binding of released platelet von Willebrand factor (plt-vWF) to the platelet membrane is enhanced. This effect appears to be mediated by fibrin monomer produced by the action of thrombin on the fibrinogen in the incubation suspension. When fibrin polymerization is inhibited, the binding of released plt-vWF to the platelets is markedly increased. This enhanced binding is dependent on platelet glycoprotein Ib (GPIb) as shown by a decreased response with Bernard-Soulier platelets and inhibition by both monoclonal and polyclonal antibodies against glycocalicin. The binding of fibrin to thrombin-activated platelets preincubated with monoclonal antibody against GPIIb/IIIa is increased when the predominant form of fibrin is fibrin monomer. The fibrin binding is also decreased in the presence of antibody against glycocalicin. Our data demonstrate that fibrin monomer facilitates plt-vWF binding to the glycocalicin portion of platelet GPIb on thrombin-stimulated platelets and that binding of fibrin monomer to glycocalicin is necessary for this response to occur.
Interleukin-2 production and response to interleukin-2 by peripheral blood mononuclear cells from patients after bone marrow transplantation: II. Patients receiving soybean lectin-separated and T cell-depleted bone marrow
Authors: Welte K , Keever CA , Levick J , Bonilla MA , Merluzzi VJ , Mertelsmann R , Evans R , O'Reilly RJ 
Published: October 2019

Abstract
The ability of peripheral blood mononuclear cells (PBMC) to produce and respond to interleukin-2 (IL-2) was evaluated in 50 recipients of HLA- identical bone marrow (BM) depleted of mature T cells by soybean agglutination and E rosetting (SBA-E-BM). In contrast to our previous findings in recipients of unfractionated marrow, during weeks 3 to 7 post-SBA-E-BM transplantation (BMT), PBMC from the majority of patients spontaneously released IL-2 into the culture medium. This IL-2 was not produced by Leu-11+ natural killer cells, which were found to be predominant in the circulation at this time, but by T11+, T3+, Ia antigen-bearing T cells. The IL-2 production could be enhanced by coculture with host PBMC frozen before transplant but not by stimulation with mitogenic amounts of OKT3 antibody, thus suggesting an in vivo activation of donor T cells or their precursors by host tissue. Spontaneous IL-2 production was inversely proportional to the number of circulating peripheral blood lymphocytes and ceased after 7 to 8 weeks post-SBA-E-BMT in most of the patients. In patients whose cells had ceased to produce IL-2 spontaneously or never produced this cytokine, neither coculture with host cells nor stimulation with OKT3 antibody thereafter induced IL-2 release through the first year posttransplant. Proliferative responses to exogenous IL-2 after stimulation with OKT3 antibody remained abnormal for up to 6 months post-SBA-E-BMT, unlike the responses of PBMC from recipients of conventional BM, which responded normally by 1 month post-BMT. However, the upregulation of IL- 2 receptor expression by exogenous IL-2 was found to be comparable to normal controls when tested as early as 3 weeks post-SBA-E-BMT. Therefore, the immunologic recovery of proliferative responses to IL-2 and the appearance of cells regulating in vivo activation of T cells appear to be more delayed in patients receiving T cell-depleted BMT. Similar to patients receiving conventional BMT, however, the ability to produce IL-2 after mitogenic stimulation remains depressed for up to 1 year after transplantation.
The metabolite 1 alpha,25-dihydroxyvitamin D3 enhances lymphokine- mediated activation of the oxidative metabolism of the U937 cell line and phosphorylation of a 48-kD respiratory burst-associated protein
Authors: Snipes RG , Ways K , D'Amico CN , Sivam G , Gray TK , Cohen MS 
Published: October 2019

Abstract
U937 cells respond to a variety of stimuli with increased differentiation as manifested by reduced growth, increased adherence, increased expression of several surface receptors, and increased capacity for phagocytosis and formation of reactive oxygen intermediates. In the present study the effects of lymphocyte conditioned media, recombinant interferon-gamma (IFN-gamma), and 1 alpha,25-dihydroxyvitamin D3 (1,25(OH)2D3) on the ability to form reactive oxygen intermediates by U937 cells were measured by using the luminol-dependent luminescence (LDL) assay. Neither 1,25(OH)2D3 alone nor IFN-gamma alone enhanced competence for phorbol myristate acetate- stimulated LDL. Cells were capable of moderate LDL after exposure to lymphocyte conditioned media, and this was enhanced by 1,25(OH)2D3 (10(- 8) mol/L) and other vitamin D metabolites at higher concentrations. This effect was not secondary to accelerated production of myeloperoxidase, which is important in the LDL assay. Enhanced phorbol myristate acetate-stimulated phosphorylation of a 48-kd substrate was observed in 32P-labeled intact cells treated with 1,25(OH)2D3 alone or in combination with IFN-gamma. Treatment of cells with IFN-gamma or lymphocyte conditioned media did not alter phosphorylation. These results support the concept that 1,25(OH)2D3 plays a role in phagocyte differentiation and activation beyond the effects of lymphokines. Protein kinase C-mediated phosphorylation reactions may be necessary for the ability of U937 cells to reduce O2 and required for maximal activity under some conditions of incubation.
Tumor necrosis factor: receptors on hematopoietic cells
Authors: Munker R , DiPersio J , Koeffler HP 
Published: October 2019

Abstract
Tumor necrosis factor (TNF) is a monokine that is cytotoxic/cytostatic for a variety of tumor cells and has multiple effects on normal cells. We demonstrate that normal and malignant human myeloid cells express a single class of high-affinity receptors (400 to 1,900 per cell, KD 20 to 90 pmol/L) for TNF. Mitogen-stimulated lymphocytes have a similar number of TNF receptors, whereas resting lymphoid cells have fewer receptors. RBCs and platelets have no detectable TNF receptors. No correlation is observed between the receptor number, receptor affinity, and the cytotoxic effect of TNF on myeloid cell lines. Significant cytotoxic effects of TNF on the most sensitive myeloid cell line (HL-60 promyelocytes) could be seen at concentrations tenfold lower than those concentrations at which one half of the TNF receptors were occupied. Our data show that significant biologic effects of TNF can occur at low levels of receptor occupancy and resistance to TNF is not related to the absence of TNF receptors on certain myeloid leukemic cell lines.
Expression of myelomonocytic antigens on chronic lymphocytic leukemia B cells correlates with their ability to produce interleukin 1
Authors: Morabito F , Prasthofer EF , Dunlap NE , Grossi CE , Tilden AB 
Published: October 2019

Abstract
We analyzed the expression of myelomonocytic-associated antigens on lymphocytes from B cell chronic lymphocytic leukemia (B-CLL) patients. Blood mononuclear cells were depleted of monocytes by one-step Percoll density gradient centrifugation and tested for antigen expression by fluorescent microscopy and flow cytometry. The reactivity of patient lymphocytes was as follows: 26 of 31 were positive for CD14 (Myr), 22 of 31 for a monocyte Fc receptor (MFC-1), 22 of 31 for CD11b (C3bi receptor), eight of 31 for CD15 (Leu-M1), five of 18 for CD13 (My 7), seven of 18 for My 9, and five of 30 for Mo 2. The B lymphocytes of B- CLL patients were also tested for the ability to produce interleukin 1 (IL-1) after depletion of monocytes and T lymphocytes. In 13 of 17 cases, B lymphocytes of patients produced IL-1 as detected in a mouse thymocyte proliferation assay and, in selected cases, a radioimmunoassay specific for IL-1 beta. The 13 cases that produced IL- 1 were also positive for the expression of one or more myelomonocytic- associated antigens, whereas the four cases that did not produce IL-1 lacked expression of these antigens. In conclusion, the malignant B cells of B-CLL patients frequently express a variety of antigens generally considered specific for myelomonocytic cells, and expression of these antigens is associated with the ability to produce IL-1.
Analysis of the erythroid phenotype of HEL cells: clonal variation and the effect of inducers
Authors: Papayannopoulou T , Nakamoto B , Kurachi S , Nelson R 
Published: October 2019

Abstract
The erythroid phenotype of HEL cells, before and after the addition of a variety of inducers, was assessed at the cellular and biochemical level. Among 14 inducers used, delta-aminolevulinic acid (delta-ALA) was identified as the most optimal inducer of heme and globin synthesis in HEL cells. The relative synthesis of globin chains produced by HEL cells, mainly gamma and alpha chains with traces of epsilon and zeta chains, was not influenced by the majority of the inducers used. However, delta-ALA and bromodeoxyuridine did increase the relative synthesis of alpha and epsilon chains respectively. Subcloning experiments revealed heterogeneity in the constitutive expression of alpha globin; however, the latter was inducible in all clones by either hemin or delta-ALA. One rare clone of HEL cells was found to produce, in contrast to parental cells, significant amounts of epsilon globin. This clone differed from K562 cells by the absence of any zeta globin expression, thus demonstrating the independent regulation of the two embryonic chains, epsilon and zeta. Changes in the expression of several surface markers specific for erythroid cells were found to accompany the globin accumulation in these cells, and some of these changes appeared to be inducer specific. Thus, the unique globin and nonglobin phenotypic properties of HEL cells and their subclones make them valuable cellular models complementary to the existing K562 cells for studying regulatory aspects of erythroid-specific proteins.
Association of hemoglobin H disease with Hb J-Iran (beta 77 His---- Asp): impact on subunit assembly
Authors: Rahbar S , Bunn HF 
Published: October 2019

Abstract
A young Iranian female was found to be heterozygous for hemoglobin (Hb) J-Iran (beta 77 His----Asp) in combination with Hb H disease. The proportion of Hb J in the patient's hemolysate was surprisingly high: 65% Hb J, 30% Hb A. Thus, the interaction of a negatively charged beta subunit variant of Hb with alpha-thalassemia leads to a marked increase in the relative amount of the variant Hb within red cells. This observation provides further support for an electrostatic model of Hb subunit assembly.
Refinement of lymphoma cytogenetics by the chromosome 18q21 major breakpoint region
Authors: Lipford E , Wright JJ , Urba W , Whang-Peng J , Kirsch IR , Raffeld M , Cossman J , Longo DL , Bakhshi A , Korsmeyer SJ 
Published: October 2019

Abstract
A small (2.8-kilobase, kb) major breakpoint region localized to segment 18q21 rearranges in greater than 70% of t(14;18)(q32;q21) lymphomas. This rearrangement interrupts the Bcl-2 gene and introduces it into the Ig locus at 14q32. The rearrangement between the joining region (JH) of Ig on chromosome 14 and the 18q21 region creates a translocation- specific DNA rearrangement. We generated probes that distinguish the 14;18 juncture on the derivative (der) 14 and der (18) chromosomes, providing a molecular approach to t(14;18) identification. Approximately 60% of unselected follicular lymphomas, 20% of diffuse large cell lymphomas, and 50% of adult undifferentiated non-Burkitt lymphomas demonstrated 14;18 rearrangements within the major breakpoint region. Examination of DNA for 14;18 rearrangements resolved the identity of 14q+ chromosomes in two patient's cells that lacked an obvious reciprocal partner. Identification of the exact restriction fragments that mediate translocations complements routine cytogenetics. The detection of DNA rearrangements does not require dividing cells or the presence of an identifiable reciprocal partner and can detect clonal translocation rearrangements when the neoplastic cells are only a minority of all cells present.
Human blood basophils display a unique phenotype including activation linked membrane structures
Authors: Stain C , Stockinger H , Scharf M , Jager U , Gossinger H , Lechner K , Bettelheim P 
Published: October 2019

Abstract
To evaluate the membrane marker profile of human basophils a panel of well-established monoclonal antibodies (MoAbs, n = 60) was used for a combined toluidine/immunofluorescence staining procedure. Myeloid- associated MoAbs (particularly MoAbs against the LFA-1 family (CD11, CDw18), MoAbs directed against lactosylceramide (CDw17), anti- glycoprotein (gp) 150 MoAbs MCS 2 and MY 7 (CDw13), anti-gp 67 MoAb MY 9, anti Fc gamma-receptor (mol wt 40 kd) MoAb CIKM5, anti-CR 1 MoAb E 11, and the antiglycolipid MoAb VIM-2) were reactive with basophils, indicating a close relationship to other mature myeloid cells. Under normal conditions, basophils surprisingly express at least three activation-linked structures not detectable on mature neutrophils, ie, the p45 structure defined by MoAbs OKT-10 and VIP-2b, the p24 structure identified by the CD9 MoAb BA-2, and the receptor for interleukin 2 (IL 2) recognized by three different MoAbs (anti-TAC, IL2RI, anti-IL 2). Moreover, under short-term culture conditions basophils both in mononuclear cell (MNC) suspension and as purified fractions display the HLA-DR and T4 antigens. The neutrophilic/eosinophilic structure 3- fucosyl-N-acetyllactosamine is expressed on basophils only after neuraminidase treatment. Basophils were not stained at all by CD 16 MoAbs directed against the Fc gamma-receptor (mol wt 50 to 70 kd) of neutrophils, by the MoAb 63D3 (CDw12) recognizing the monocyte/granulocyte-associated p 200 antigen, and by the CDw 14 antibodies (VIM-13, Mo 2) defining the monocyte-specific structure p 55. Enriched basophils freshly obtained from chronic granulocytic leukemia (CGL) patients yielded identical results in FACS analyses. In summary, these data indicate that basophils generate a unique combination of surface determinants and possibly represent an activated cell population.