bluuebunny/crossref_metadata_2025_split huggingface dataset:
Proplatelets and stress platelets
Authors: Tong M , Seth P , Penington DG 
Published: October 2019

Abstract
The process of platelet formation by the fragmentation of megakaryocyte pseudopodia, termed proplatelets, demonstrable in the marrow sinusoids is poorly understood. “Stress” platelets produced under conditions of stimulated platelet production differ from normal circulating platelets with respect to volume and a number of functional characteristics. To clarify the relationship of stress platelets to proplatelets, rats were injected with heterologous platelet antiserum. Nondiscoid platelet forms, some characteristically beaded in appearance, strongly resembling bone marrow proplatelets, can be recovered in the circulation of normal rats. During the early period of recovery from acute thrombocytopenia, there was a substantial increase in the proportion of these elongated platelets in the citrated platelet rich plasma. Exposure to EDTA rendered them spherical. Circulating proplatelets may contribute significantly to the prompt increase in platelet volume during recovery from acute thrombocytopenia at a time prior to significant increase in megakaryocyte size and ploidy.
Sensitivity to 5-azacytidine of blast progenitors in acute myeloblastic leukemia
Authors: Wang C , McCulloch EA 
Published: October 2019

Abstract
In a previous study, we showed that the blast stem cells of acute myeloblastic leukemia (AML) were more sensitive to cytosine arabinoside (ara-C) when growing in suspension culture than during colony formation in methylcellulose. We suggested that the difference might be explained by considering the cellular mechanisms responsible for growth in suspension and colony formation. In the former, the clonogenic cells increase in number (self-renewal); in the latter, most of the divisions are terminal. The increased sensitivity to ara-C in suspension might then be attributed to its ability to inhibit self-renewal to a greater degree than cell division generally. A test of this hypothesis would be to compare the survival curves in suspension and in methylcellulose using a drug that spared or stimulated self-renewal. Such an agent is 5- azacytidine (5-aza) and has the additional advantage that its analogue, 6-azacytidine (6-aza) has no effect on self renewal. The data supported the hypothesis, since clonogenic AML blasts were much less sensitive to 5-aza in suspension than in methylcellulose. The effect of 6-aza, while qualitatively similar, was much less marked. Controls showed that the difference in survival curves could not be explained on a kinetic basis or by the secretion of growth factors by 5-aza-treated cells. We suggest that a comparison of the effects of drugs in suspension and in methylcellulose may be useful in preclinical screening of putative anti- AML compounds.
A murine antiglycoprotein Ib complex monoclonal antibody, SZ 2, inhibits platelet aggregation induced by both ristocetin and collagen
Authors: Ruan CG , Du XP , Xi XD , Castaldi PA , Berndt MC 
Published: October 2019

Abstract
A new monoclonal antibody (MoAb), SZ 2, reactive with the human platelet glycoprotein Ib complex has been produced by the hybridoma technique. SZ 2 immunoprecipitated the components of the glycoprotein Ib complex, glycoprotein Ib and glycoprotein IX, from Triton-X-100- solubilized, periodate-labeled platelets. Western blot analysis indicated that the epitope for SZ 2 was on the alpha-subunit of glycoprotein Ib. Scatchard analysis of SZ 2 binding to formaldehyde- fixed, washed platelets revealed a single class of binding sites with Kd = 6.6 +/- 3.3 X 10(-10) mol/L and 15,200 +/- 4,100 binding sites per platelet (mean +/- SD, n = 10). Intact antibody and its purified (Fab')2 fragments not only inhibited the ristocetin-dependent binding of von Willebrand factor to platelets and ristocetin-induced platelet agglutination but also inhibited platelet aggregation induced by Type I collagen and platelet-activating factor (PAF). SZ 2 inhibited platelet serotonin and beta-thromboglobulin release in response to these stimuli and also platelet thromboxane A2 formation in response to ristocetin and collagen. SZ 2 was without effect on platelet aggregation or release in response to other platelet stimuli such as ADP, thrombin, or arachidonic acid. The inhibition by SZ 2 of collagen- and PAF-induced platelet aggregation is surprising in that Bernard-Soulier syndrome platelets, which lack the glycoprotein Ib complex, respond normally to both these stimuli. SZ 2 was unreactive toward Bernard-Soulier syndrome platelets, as evaluated by fluorescence-associated cell sorting, and had no effect on the collagen- and PAF-induced aggregation of Bernard- Soulier syndrome platelets. The combined results suggest that the inhibition by SZ 2 of collagen- and PAF-induced aggregation of normal platelets is steric and are consistent with the glycoprotein Ib complex and the platelet collagen and PAF receptor(s) being adjacent in the human platelet plasma membrane.
Monoclonal antibody 1F5 (anti-CD20) serotherapy of human B cell lymphomas
Authors: Press OW , Appelbaum F , Ledbetter JA , Martin PJ , Zarling J , Kidd P , Thomas ED 
Published: October 2019

Abstract
Four patients with refractory malignant B cell lymphomas were treated with continuous intravenous (IV) infusions of murine monoclonal antibody (MoAb) 1F5 (anti-CD20) over five to ten days. Dose-dependent levels of free serum 1F5 were detected in all patients. Two patients had circulating tumor cells and in both cases 90% of malignant cells were eliminated from the blood stream within four hours of initiation of serotherapy. Antigenic modulation did not occur, and sustained reduction of circulating tumor cells was observed throughout the duration of the infusions. Serial bone marrow aspirations and lymph node biopsies were examined by immunoperoxidase and immunofluorescence techniques to ascertain MoAb penetration into extravascular sites. High doses (100 to 800 mg/m2/d and high serum 1F5 levels (13 to 190 micrograms/mL) were required to coat tumor cells in these compartments in contrast to the low doses that were adequate for depletion of circulating cells. Clinical response appeared to correlate with dose of MoAb administered with progressive disease (52 mg), stable disease (104 mg), minor response (1,032 mg), and partial response (2,380 mg) observed in consecutive patients. The patient treated with the highest 1F5 dose achieved a 90% reduction in evaluable lymph node disease, but the duration of this remission was brief (six weeks). This study demonstrates that high doses of 1F5 can be administered to patients with negligible toxicity by continuous infusion and that clinical responses can be obtained in patients given greater than 1 g of unmodified antibody over a ten-day period.
Comparative thrombolytic properties of single-chain forms of urokinase- type plasminogen activator
Authors: Stump DC , Stassen JM , Demarsin E , Collen D 
Published: October 2019

Abstract
The specific thrombolytic properties of urokinase and three molecular forms of single-chain urokinase-type plasminogen activator (scu-PA) were compared in a human plasma milieu in vitro and in an experimental thrombosis model in rabbits. These scu-PA molecules included Mr 54,000 scu-PA from human urine (urinary scu-PA), scu-PA from conditioned media of a human lung adenocarcinoma cell line (CALU-3,ATCC,HTB-55) (cellular scu-PA) and an Mr 32,000 proteolytic derivative of cellular scu-PA (scu- PA-32k). All four molecular forms induced significant lysis of a 125I- labeled human plasma clot immersed in citrated human plasma at concentrations between 50 and 200 IU/mL. None of the four showed absolute fibrin-specificity, but at equivalent lytic dose the three single-chain forms appeared to cause less fibrinogen degradation and alpha 2-antiplasmin consumption than two-chain urokinase. In addition, the fibrinolytic potential of the three single-chain forms was largely maintained during pre-incubation in plasma for up to 48 hours whereas that of urokinase was completely inhibited. Intravenous (IV) infusion of cellular scu-PA or scu-PA-32k into rabbits with a 125I-labeled thrombus in the jugular vein caused significant dose-dependent lysis at concentrations ranging from 8,700 to 35,000 and from 9,000 to 36,000 IU/kg respectively. Clot lysis was accompanied by minor alpha 2- antiplasmin consumption or fibrinogen breakdown. In contrast, urokinase induced lysis at doses between 20,000 and 200,000 IU/kg, but at higher doses was associated with significant systemic activation of the fibrinolytic system. It is concluded that scu-PA obtained from CALU-3 cell cultures has identical thrombolytic properties to that obtained from urine. In addition, the scu-PA-32k proteolytic derivative has the same fibrin-specific thrombolytic properties as the intact molecule. Cellular scu-PA and scu-PA-32k may therefore constitute more readily available alternatives for clot-selective thrombolytic therapy in man.
Structural polymorphism of glycophorins demonstrated by immunoblotting techniques
Authors: Lu YQ , Nichols ME , Bigbee WL , Nagel RL , Blumenfeld OO 
Published: October 2019

Abstract
We have explored the polymorphism of the glycophorin system in the human erythrocyte membrane using the immunoblotting techniques and examining 52 individuals selected without prior bias as to their serologic state and ten documented serologic variants of M, N, S, s blood group system. Polyclonal antisera to alpha glycophorin and to alpha glycophorin CNBr carboxyl terminal fragment C (residues 82–131) and M and N specific monoclonal antibodies (MoAbs) were used. The first two reagents detect specific regions of the alpha glycophorin molecule and all electrophoretically resolved species of glycophorins immunologically related to alpha and delta glycophorins (delta glycophorin, [alpha-delta] hybrids and other glycophorins with an alteration in the carboxyl terminal segment); the M and N MoAbs identified the glycophorin species containing or lacking the M or N determinant in the amino terminal octapeptide structures. We find that immunoblotting confirmed in all cases the serologically determined phenotype; we also find that polymorphic forms of the glycophorin system are relatively infrequent; immunoblotting, independent from serologic testing, was capable of detecting five mutants, two most likely S-s-U-phenotypes; a new glycophorin species was detected in normal red cells with both antiglycophorin and antipeptide C sera, which is not evident with MoAbs; immunoblots of known glycophorin variants (En(a-), U-, Mg, Mi I, II, III, V, and Sta) confirmed but also extended our knowledge of the abnormal glycophorins involved; and the He+ and Wrb(-) cells showed normal patterns.
Inosine monophosphate dehydrogenase and myeloid cell maturation
Authors: Knight RD , Mangum J , Lucas DL , Cooney DA , Khan EC , Wright DG 
Published: October 2019

Abstract
In previous studies of purine ribonucleotide metabolism in the human myeloid leukemia cell line HL-60, we observed that there is a down- regulation of guanine ribonucleotide biosynthesis from the central intermediate, inosine monophosphate (IMP) and a depletion of intracellular guanosine triphosphate (GTP) and guanosine diphosphate (GDP) pools that occur during the induced maturation of these cells. We also found that inhibitors of IMP dehydrogenase, the enzyme that catalyzes the first step of guanylate synthesis from IMP, are potent inducers of HL-60 maturation. Because of these observations we specifically investigated the activity of IMP dehydrogenase in HL-60 cells and in a new inducible human myeloid leukemia cell line, RDFD2– 25, both during maintenance culture and during induced maturation of the cells. Enzyme activity was examined directly in cell extracts with a radiometric assay that measures free 3H2O formed from [2–3H] IMP during the conversion of IMP to XMP. Uninduced HL-60 and RDFD2 cells in maintenance culture were found to have high levels of IMPD activity (5.2 to 5.7 pmol IMP metabolized/10(7) cells/min) compared with normal neutrophils and monocytes that had been purified from blood (less than 1.5 pmol IMP metabolized/10(7) cells/min). However, when HL-60 and RDFD2–25 cells were induced to mature with retinoic acid (10(-6) mol/L), dimethylformamide (6 X 10(-2) mol/L), or a known IMPD inhibitor, tiazofurin (10(-6) mol/L), IMPD activity in the cells fell by 51% to 80% within three to six hours. These changes in IMPD activity preceded detectable functional and antigenic maturation of the cells by at least 12 hours and were not temporally related to changes in cellular proliferation. These findings are consistent with the concept that the regulation of myeloid cell maturation may be influenced by intracellular concentrations of guanine ribonucleotides because IMP dehydrogenase activity is known to be rate limiting for the production of these nucleotides.
Cellular and subcellular localization of the bactericidal/permeability- increasing protein of neutrophils
Authors: Weiss J , Olsson I 
Published: October 2019

Abstract
Human and rabbit polymorphonuclear leukocytes contain a bactericidal/permeability-increasing protein (BPI), a potent cytotoxin active specifically against gram-negative bacteria. To identify the cell population(s) producing BPI, we have examined mature and immature human blood cells for BPI by immunofluorescence of intact cells and radioimmunoassay and bioassay of cell extracts. By immunofluorescence and radioimmunoassay of cells from peripheral blood, BPI was detected only in neutrophils; immunofluorescent staining was punctate, indicative of the granule localization of BPI. Nearly all (greater than 90%) BPI was recovered during the subcellular fractionation of neutrophils (N2 cavitation and discontinuous Percoll gradient) in fractions containing primary granules. Little BPI was released from intact cells during degranulation (cytochalasin B and f-Met-Leu-Phe) or could be extracted from isolated granules with salt or weak acid, which suggests that most granule-associated BPI is membrane bound. Double staining of bone marrow smears for BPI and lactoferrin revealed BPI only in neutrophil precursors including (pro)myelocytelike cells lacking lactoferrin, a marker of neutrophil secondary granules. Of several human cell lines tested, only the promyelocytelike HL-60 (and to a lesser extent, KG-1) cells contained BPI. BPI was present in a more mature subpopulation (less than 25%) of untreated HL-60 cells, recognized by surface marker analysis (rosetting with IgG-sensitized sheep RBC, the absence of proliferation-associated cell surface antigen). Induction of neutrophilic or monocytic differentiation caused, respectively, a small (approximately 50%) rise or fall in the BPI content. These findings indicate that BPI is a specific product of the neutrophil lineage and, hence, of the specialized cytotoxic apparatus of the neutrophil that plays an essential role in host defense v gram-negative bacteria.
Erythrocyte deformation in shear flow: influences of internal viscosity, membrane stiffness, and hematocrit
Authors: Kon K , Maeda N , Shiga T 
Published: October 2019

Abstract
The effect of shear force (depending on shear rate and viscosity of extracellular medium) and hematocrit of RBC suspension on RBC deformation was studied quantitatively using a cone-plate rheoscope with various kinds of cells, ie, partially hemolyzed (PH) cells, density-fractionated intact cells, and diamide-treated cells. The deformation index (DI) of ellipsoidally deformed cells was shown to be a function of beta gamma eta ex(eta ex/eta in)alpha, where gamma eta ex is applied shear stress, eta ex and eta in are external and internal viscosities, respectively, and alpha and beta are adjustable parameters related to the membrane viscoelastic properties. The increase of suspension viscosity at higher hematocrits (Hts) generally enhanced the ellipsoidal deformation of cells, in the same manner as increasing the suspending medium viscosity of a diluted cell suspension. The suppressing effect on cell deformation appeared above a certain Ht. When intact cells were mixed with glutaraldehyde-treated, hardened cells, the ellipsoidal deformation of intact cells was disturbed. The suppression of deformation probably occurred through disturbance of laminar flow-lines around intact cells.
High-dose cytosine arabinoside and mitoxantrone: a highly effective regimen in refractory acute myeloid leukemia
Authors: Hiddemann W , Kreutzmann H , Straif K , Ludwig WD , Mertelsmann R , Donhuijsen- Ant R , Lengfelder E , Arlin Z , Buchner T 
Published: October 2019

Abstract
In a clinical phase I/II study, high-dose cytosine arabinoside and mitoxantrone (HAM) were given in combination to 40 patients with refractory acute myeloid leukemia. All patients had received a 9-day combination of thioguanine, Ara-C, and daunorubicin (TAD-9) as standardized first-line treatment. Refractoriness was defined as (a) nonresponse against two TAD-9 induction cycles, (b) early relapse within the first 6 months on monthly maintenance or after TAD-9 consolidation, (c) relapse after 6 months with nonresponse against one additional TAD-9 cycle, and (d) second and subsequent relapses after successful TAD-9 therapy at the preceding relapse. Therapy consisted of HD-Ara-C 3 g/m2 every 12 hours on days 1 through 4; mitoxantrone was started at 12 mg/m2/day on days 3, 4, and 5 and was escalated to 4 and 5 doses of 10 mg/m2/day on days 2 through 5 and 2 through 6. Of the 40 patients, 21 achieved a complete remission (53%), 1 patient had a partial remission, and 5 patients were nonresponders. Thirteen patients died in aplasia due to infections (n = 11), pericardiac effusion, or acute cardiomyopathy. Nonhematologic side effects consisted predominantly of nausea and vomiting, mucositis, and diarrhea. Central nervous system (CNS) symptoms were observed during six treatment courses. Recovery of blood counts occurred at a median of 27 days from the onset of treatment; the median time to complete remission was 36 days. Two of the 21 responders underwent successful bone marrow transplantations. The median remission duration for the remaining 19 patients is 4.5 months, and the median survival time is 9 months. These data emphasize that HAM has high antileukemic activity in refractory AML and strongly suggest starting the combination at earlier stages in AML therapy.
In vitro and in vivo effects of deferoxamine in neonatal acute leukemia
Authors: Estrov Z , Tawa A , Wang XH , Dube ID , Sulh H , Cohen A , Gelfand EW , Freedman MH 
Published: October 2019

Abstract
A six week old infant with acute leukemia failed to attain remission with chemotherapy. Because we previously demonstrated that the iron chelator deferoxamine (DFO) has antiproliferative properties and modulatory effects on cell differentiation, a protocol was designed for in vitro study and for clinical use in the patient. At diagnosis, blast cells were morphologically undifferentiated, had nondiagnostic cytochemistry, showed an abnormal karyotype (t[4;11]), expressed markers of B cell lineage, and demonstrated C mu gene rearrangement. Tissue culture of marrow or blood cells yielded colonies of leukemic blasts. Increasing concentrations of DFO produced a dose-dependent suppression of patient's blast colony growth in vitro, and blasts within colonies showed a marked change in surface antigen expression from lymphoid to myelomonocytic markers, became monocytic in appearance, and developed intense staining for nonspecific esterase. When DFO was given intravenously to the patient as a single agent for 48 hours, blasts no longer expressed lymphoid antigens and became strongly positive for myelomonocytic markers, identical to the in vitro findings. Intravenous DFO halted rising peripheral blood blast cell numbers and allowed a several-fold increase in normal hematopoietic progenitor colony growth. When combined with low-dose cytosine arabinoside in the treatment protocol, DFO caused striking leukemic cytoreduction. Our findings indicate that DFO has antileukemic properties by virtue of its effects on proliferation and differentiation, and they prompt further experimental and clinical studies with this agent.
Multilineage synergistic activity produced by a murine adherent marrow cell line
Authors: Quesenberry P , Song ZX , McGrath E , McNiece I , Shadduck R , Waheed A , Baber G , Kleeman E , Kaiser D 
Published: October 2019

Abstract
We reported previously that a cell line (TC-1) derived from adherent marrow cells produced colony-stimulating factor 1 (CSF-1) and a separate activity that acts synergistically with CSF-1 to stimulate giant macrophage colonies. We now report that an activity in TC-1 conditioned media (CM) separate from CSF-1 also synergizes multilineage colony formation by pure interleukin 3 (IL 3) and a crude source of granulocyte-macrophage colony-stimulating activity (GM-CSA) (murine lung-conditioned media). IL 3-induced megakaryocyte colony formation is also synergized. The CSF-1-dependent synergistic activity is not blocked by antibodies to IL 3 and is characterized as a nondialyzable (mol wt cutoff 3,000), heat-stable (56 degrees C, 30′) activity that binds to DE-52 cellulose under conditions in which IL 3 does not. This material has an apparent mol wt of approximately 200,000 by Sephadex G100 chromatography, and the bulk of it binds to Concanavalin A (Con A) and elutes off with alpha-methyl mannoside, indicating that it is a glycoprotein. As reported separately, these purified active fractions also have a pre-B cell-inducing activity. In addition, a non-IL 3 activity stimulates proliferation of the factor-dependent cell lines FDC-P1 and DA-1. These data indicate that an adherent marrow cell line produces a growth factor(s) that synergizes with IL 3, GM-CSA, and CSF- 1 and induces pre-B cell formation. This may be an important regulator of early multilineage lymphohemopoiesis.
Value of monoclonal anti-CD22 (p135) antibodies for the detection of normal and neoplastic B lymphoid cells
Authors: Mason DY , Stein H , Gerdes J , Pulford KA , Ralfkiaer E , Falini B , Erber WN , Micklem K , Gatter KC 
Published: October 2019

Abstract
Two monoclonal antibodies (To15 and 4KB128) specific for the B cell- associated CD22 antigen (135,000 mol wt) are described. On immunoenzymatic analysis of cryostat tissue sections, these antibodies strongly label both mantle zone and germinal center B lymphoid cells in secondary lymphoid follicles (and also scattered extrafollicular lymphoid cells) but are unreactive with other cell types (with the exception of weak reactivity with some epithelioid histiocytes). These reactions differ from those of monoclonal antibodies B1 and B2 (anti- CD20 and CD21) but are similar to those of the pan-B antibody B4 (anti- CD19). One of the anti-CD22 antibodies (To15) has been tested extensively by immunoenzymatic labeling on greater than 350 neoplastic lymphoid and hematological samples. The CD22 antigen was found in tissue sections in most B cell-derived neoplasms, the major exceptions being myeloma (all cases negative) and a small proportion of high-grade lymphoma (6% of cases negative). In cell smears, the antigen could be found on neoplastic cells in most B cell lymphoproliferative disorders, including common acute lymphoblastic leukemia (ALL) (90% positive) and B cell chronic lymphocytic leukemia (CLL) (89% positive). We conclude that anti-CD22 antibodies are of value for identification of human B cell lymphoproliferative disorders (especially when used in conjunction with anti-CD19 antibodies). Previous reports that the CD22 antigen is absent from many B cell neoplasms are probably due to its being expressed within the cytoplasm of immature B cells rather than on their surface.