bluuebunny/crossref_metadata_2025_split huggingface dataset:
Acute leukemia with megakaryocytic differentiation: a study of 12 cases identified immunocytochemically
Authors: Huang MJ , Li CY , Nichols WL , Young JH , Katzmann JA 
Published: October 2019

Abstract
Acute leukemia with megakaryocytic differentiation has been an uncommonly recognized disorder. We used specific monoclonal and polyclonal antibody reagents (HP1–1D antibody and anti-factor VIII antibody, respectively) and an immunocytochemical staining technique to identify the megakaryocytic nature of the leukemic cells of 12 patients who presented with acute leukemia. The leukemic cells of our patients demonstrated the presence of one or both of these platelet- and megakaryocyte-related antigens, but were negative for all of the commonly employed cytochemical and immunocytochemical staining reactions, except for diffuse acid phosphatase activity and granular PAS positivity. Morphologically, the leukemic cells varied in size from 10 to 40 microns in diameter, frequently had cytoplasmic budding, and contained occasional vacuoles and/or peroxidase-negative azurophilic granules. Five patients presented with syndromes of acute myelofibrosis, and seven patients had otherwise unclassifiable acute leukemias, including three patients who had secondary leukemias. Diffuse reticulin myelofibrosis was present in all cases in which it was sought. Chromosomal abnormalities of leukemic cells were found in five cases. Two patients had deficiencies of plasma coagulation factor V. Study of one patient revealed significant platelet dysfunction. When cytoreductive chemotherapy of leukemia was attempted, the observed response was generally poor, with the exceptions of one patient who has remained in complete remission following treatment with etoposide (VP- 16) and a second patient who attained remission following bone marrow transplantation. These cases of acute megakaryoblastic leukemia represented from 3.6% to 9.3% of all acute leukemia cases diagnosed concomitantly in our institution. Acute leukemia with megakaryocytic differentiation may occur more frequently than previously recognized, may present with differing syndromic features, and can be identified by the use of specific antibody reagents and relatively simple immunocytochemical techniques.
Comparison of the native prothrombin antigen and the prothrombin time for monitoring oral anticoagulant therapy
Authors: Furie B , Liebman HA , Blanchard RA , Coleman MS , Kruger SF , Furie BC 
Published: October 2019

Abstract
We have measured the fully carboxylated (native) prothrombin antigen and the undercarboxylated (abnormal) prothrombin antigen in patients treated with sodium warfarin using specific immunoassays to evaluate a new approach for monitoring oral anticoagulant therapy. Plasma and serum samples (391) were assayed for the prothrombin time, native prothrombin antigen, and abnormal prothrombin antigen. The results were correlated with the presence of bleeding or thromboembolic complications at the time of phlebotomy. The native prothrombin antigen correlated with the occurrence of complications in 95% of samples. Of 13 samples from patients with bleeding complications, 13/13 (100%) had a native prothrombin of 12 micrograms/mL or lower. Of seven samples from patients with thromboembolic complications, 6/7 (86%) had a native prothrombin of 24 micrograms/mL or greater. By comparison, a prothrombin time index of 1.5 to 2.5, 1.5 to 2.2, 1.5 to 2.0, or 1.3 to 1.8 identified 6/20 (30%), 9/20 (45%), 11/20 (55%), or 12/20 (60%) patients at risk, respectively. Although the prothrombin time index did correlate with the presence of bleeding complications, the native prothrombin antigen correlated closely with the presence of bleeding and thromboembolic complications. According to these results, the native prothrombin antigen, maintained in a range of 12 to 24 micrograms/mL by regular adjustment of the warfarin dosage, may be associated with a reduced risk of complications due to excessive or insufficient warfarin therapy. On the basis of these preliminary data, we recommend that the native prothrombin antigen be considered to monitor warfarin therapy.
Platelet-derived growth factor in vivo: levels, activity, and rate of clearance
Authors: Bowen-Pope DF , Malpass TW , Foster DM , Ross R 
Published: October 2019

Abstract
Platelet-derived growth factor (PDGF) is a potent mitogen for many cultured connective tissue cells. It is present in concentrated form within the platelet alpha-granules and is believed to be released during platelet degranulation at sites of vascular injury. We have used a sensitive radioreceptor assay to measure PDGF levels in whole blood serum from normal humans [17.5 +/- 3.1 (SD) ng/mL] and baboons (2.7 +/- 1.2 ng/mL). PDGF was not detected in plasma from either species. In addition, plasma was found to substantially reduce the ability of added purified PDGF to bind to the cell surface PDGF receptor on cultured cells, suggesting that plasma may contain a PDGF-binding protein that would serve to inactivate PDGF released into plasma. Calculations of PDGF concentrations in serum have been corrected for the effects of the binding protein. 125I-PDGF injected intravenously into normal baboons was cleared rapidly from the plasma (t1/2 = two minutes). The rapid clearance of 125I-PDGF did not result from iodination damage, as purified unlabeled PDGF was cleared with comparable kinetics. The rapid clearance of purified and iodinated PDGF did not result from changes in PDGF structure during purification or from removal of PDGF-associated proteins during purification, as PDGF present in freeze-thaw lysates of fresh platelets was cleared equally rapidly. We conclude that release of PDGF at sites of vascular injury would greatly increase the local concentration of PDGF and that PDGF not localized to the site of injury would be rapidly cleared from the circulation.
Endogenous peroxidase in the nuclear envelope and endoplasmic reticulum of human monocytes in vitro: association with arachidonic acid metabolism
Authors: Deimann W , Seitz M , Gemsa D , Fahimi HD 
Published: October 2019

Abstract
he development of peroxidase (PO) reaction in the nuclear envelope (NE) and endoplasmic reticulum (ER) of monocytes differentiating in vitro and its relationship with arachidonic acid metabolism were studied. The PO, as visualized by the diaminobenzidine (DAB) technique, appeared in the NE and ER of the majority of monocytes within 24 hours of culture, with a substantial decrease thereafter. The influence of three major groups of agents--inhibitors of PO, of prostanoids, and of protein biosynthesis--upon the development of the PO reaction was examined. When aminotriazole, a PO inhibitor, was added to the culture medium, the appearance of PO was suppressed in the monocytes. The cyclooxygenase blocker, indomethacin, however, did not influence the development of PO. Also the blockers of protein synthesis, puromycin, cycloheximide, and actinomycin D, did not affect the appearance of PO. The prostanoids released from the monocytes, ie, prostaglandin E and thromboxane B2, were determined by radioimmunoassay and showed a time sequence of secretion that corresponded to the appearance of PO in the cells: a marked increase within the first 24 hours with a substantial decrease thereafter. The presence of the PO inhibitors aminotriazole and sodium azide in the culture medium produced a suppression of prostanoid release from the monocytes comparable with that of indomethacin. The data suggest that the PO in the NE and ER of differentiating monocytes in vitro (1) is associated with arachidonic acid metabolism, and (2) is not formed by de novo protein synthesis but rather by an activation process.
Impaired erythrocyte calcium homeostasis in beta-thalassemia
Authors: Shalev O , Mogilner S , Shinar E , Rachmilewitz EA , Schrier SL 
Published: October 2019

Abstract
ntracellular calcium (Ca) concentration in erythrocytes (RBCs) is controlled by a low passive influx through a relatively impermeable membrane and by active efflux catalyzed by Ca2+,Mg2+-ATPase. Since precipitation of alpha-globin chains in thalassemic RBCs may interfere with normal membrane function, we studied the RBC intracellular Ca content and the RBC membrane Ca2+,Mg2+-ATPase activity in two groups of patients with nonsplenectomized (n = 9) and splenectomized (n = 9) beta- thalassemia intermedia and in two groups of matched controls. The mean +/- SD Ca concentration in the nonsplenectomized (n = 12) and splenectomized (n = 6) controls were 6.1 +/- 6.0 and 5.8 +/- 3.4 mumol Ca per liter of RBCs, respectively, compared with 26.0 +/- 7.6 (P less than .001) and 85 +/- 24.4 (P less than .001) in the nonsplenectomized and splenectomized thalassemia patients, respectively. The mean +/- SD Ca2+,Mg2+-ATPase activity in the eight nonsplenectomized patients was 0.77 +/- 0.58 mumol inorganic phosphate (Pi) per milligram of protein per hour compared with 0.66 +/- 0.41 in the controls (P = NS). Similar values were obtained for the splenectomized patients and their controls. No correlation was found between either the intracellular Ca content or the Ca2+,Mg2+-ATPase activity with the peripheral nucleated RBC count. These findings suggest that there is a major defect in the membrane of the thalassemic RBC leading to an increased Ca content that is more pronounced in splenectomized patients.
Human erythrocyte antigens: II. The In(Lu) gene regulates expression of an antigen on an 80-kilodalton protein of human erythrocytes
Authors: Telen MJ , Palker TJ , Haynes BF 
Published: October 2019

Abstract
We have previously shown that a murine monoclonal antibody (A3D8) identifies a human erythrocyte protein antigen whose expression is regulated by the Lutheran inhibitor [In(Lu)] gene. In the present study, we demonstrated by immunoprecipitation and Western blot techniques that the antigen defined by A3D8 was on an 80-kD erythrocyte membrane protein. A second 170-kD protein was coprecipitated with the 80-kD protein but failed to show antigen activity by Western blot analysis. The 170-kD protein, when analyzed by sodium dodecyl sulfate- polyacrylamide gel electrophoresis in two dimensions, was composed of 50- and 30-kD disulfide-linked subunits. In(Lu) Lu[a-b-) erythrocytes differed from Lu(a+b+) or Lu(a-b+) erythrocytes in that In(Lu) deoxycholate erythrocyte membrane extracts contained trace amounts of immunoprecipitable 80-kD protein compared with detergent-solubilized erythrocyte membrane extracts prepared from Lu(a+b+) or Lu(a-b+) subjects.
Genetic polymorphism of platelet glycoprotein Ib
Authors: Moroi M , Jung SM , Yoshida N 
Published: October 2019

Abstract
Platelet glycoprotein (GP) Ib from 131 healthy Japanese was analyzed using SDS-polyacrylamide gel electrophoresis and specific staining with peroxidase-coupled wheat germ agglutinin after it was transferred to nitrocellulose membranes. Four slightly different species of GPIb were observed and designated as A, B, C, and D for glycoproteins with molecular weights of 168,000, 162,000, 159,000, and 153,000 daltons, respectively. The respective gene frequencies were calculated to be .073, .011, .561, and .355 for A-, B-, C-, D-type GPIb. Portions from each type of GPIb molecule (alpha-chain and glycocalicin) showed heterogeneity with the same molecular weight difference, indicating that the variance would be derived from the polypeptide portion that is exposed to the outer medium. The different types of GPIb were the same with respect to their accessibility to lactoperoxidase, reactivity to lectins, and affinity to TLCK-thrombin. Although Bolin et al reported patients with a bleeding tendency whose platelets have double GPIb bands, here we found that platelets with different GPIb phenotypes showed no significant differences in aggregating activity and platelet retention. Analysis of GPIb phenotype should be important for structural and physiologic studies on GPIb and glycocalicin.
Light scattering by polymorphonuclear leukocytes stimulated to aggregate under various pharmacologic conditions
Authors: Yuli I , Snyderman R 
Published: October 2019

Abstract
Enhancement of light transmission has been widely accepted as an empirical measure of cell aggregation in suspension. Several years ago, this measurement was introduced to the study of polymorphonuclear leukocyte (PMN) aggregation by adapting a hypothesis originally developed for platelets. Accordingly, an increase in light transmission is attributed to cell aggregation and a decrease in transmission below baseline level is indicative of increased cell symmetry. We tested this hypothesis for human PMNs by comparing the whole cell shape or the cells' aggregation state with the light transmission under particular experimental conditions. The PMN light response to the chemoattractant, f-Met-Leu-Phe, in the presence of low doses of aliphatic alcohols was associated with transient enhanced transmission, followed by a rapid decrease below baseline. In contrast to the platelet hypothesis, the below-baseline effect coincided with a decrease in PMN symmetry from spheres to wedge-shaped (polarized) cells. PMNs fixed mildly with various doses of formaldehyde (0.1% to 0.3%) were completely aggregated by the addition of 50 micrograms/mL phytohemagglutinin (PHA). Despite the complete aggregation of the PMNs, there was a dose-dependent inhibition of the above-baseline level transmission response by the fixative, demonstrating a clear dichotomy between aggregation and increased light transmission. However, PMN aggregation could be monitored by observing the pattern of enhanced light transmission coupled with decreased perpendicular light scattering immediately after the stirring of the cell suspensions was stopped. PMNs aggregated by PHA cleared from suspension very rapidly (t1/2 less than or equal to one minute), whether or not they were formalin-fixed. In contrast, unaggregated cells revealed constant transmission and perpendicular scattering intensities for as long as five minutes after the stirring was stopped. The clearance patterns of f-Met-Leu-Phe-stimulated PMNs initiated even at the time of maximally increased light transmission were indistinguishable from those of the unstimulated cells, indicating the absence of aggregation. The lack of correlation between light output and changes in cell shape or degree of aggregation of PMNs causes us to reject the hypothesis that attributes enhanced light transmission to PMN aggregation. We suggest that modulation of light transmission by PMNs stimulated with chemoattractants is due to changes in light output from subcellular objects.
Effect of a thymic factor on T lymphocytes in B cell chronic lymphocytic leukemia: in vitro and in vivo studies
Authors: Lauria F , Raspadori D , Tura S 
Published: October 2019

Abstract
Abnormalities of T lymphocytes in B cell chronic lymphocytic leukemia (B-CLL) have been extensively documented by several immunologic investigations. Following recent studies pointing to the favorable effect of TP-1, a partially purified extract of calf thymus, on the T cell-mediated immunity of several diseases, including Hodgkin's disease, we have used monoclonal antibodies and the enriched T lymphocytes of 16 untreated B-CLL patients to evaluate the proportion of T cell subsets before and after the administration of TP-1. In addition, the proliferative response to phytohemagglutinin (PHA) and the helper function in a pokeweed mitogen (PWM) system were assessed. In ten cases, the effect of TP-1 was also studied in vitro by evaluating the same parameters before and after incubation of B-CLL T cells with the drug. The study demonstrated that in vivo administration of TP-1 increases significantly (P less than .001) the proportion of the defective helper/inducer T cell population (OKT4-positive cells) in B-CLL, leading to a near normal OKT4/OKT8 ratio. Furthermore, the improved phenotypic profile was accompanied by an increased proliferative response to PHA and, in particular, by a significant increase (P less than .01) of T helper capacity; this increase was, however, insufficient to enable the normalization of the serum immunoglobulin levels. The in vitro incubation of B-CLL T lymphocytes did not succeed in producing significant modifications in distribution and function.
The idiotypic characteristics of human antibodies to factor VIII
Authors: de la Fuente B , Hoyer LW 
Published: October 2019

Abstract
We have prepared an antiidiotype antibody that specifically reacts with and inactivates a human autoantibody to factor VIII (VIII:C). The antiidiotype specificity of this rabbit antibody was evident in solution, as specific inhibition of anti-VIII:C activity, and in solid- phase studies. The antiidiotype antibody inhibited both plasma anti- VIII:C and Fab' fragments prepared from that plasma's IgG. Although the antibody had a greater inhibitory effect on the anti-VIII:C used for immunization than it did for other anti-VIII:C, partial inhibition was identified with ten of 25 other human anti-VIII:C. The demonstration that antiidiotype antibodies can be prepared to human anti-VIII:C indicates the feasibility of this approach to the immunochemical characterization of human anti-VIII:C inhibitors. Moreover, antiidiotype reagents have a potential role in the treatment of inhibitor patients.
Ethanol raises prostacyclin in vivo and in vitro
Authors: Landolfi R , Steiner M 
Published: October 2019

Abstract
Moderate doses of ethanol were shown to induce a significant rise in prostacyclin (PGI2) concentration in cultures of endothelial cells derived from umbilical veins. Administration of 32 g of ethanol to six volunteers elevated plasma levels of PGI2 in parallel with those of blood alcohol. Although not specific for ethanol, this alcohol induced the largest change in PGI2. Withdrawal of the stimulant alcohol caused prompt reduction of the elevated prostacyclin to baseline values. The activity of ethanol appears to be due to a direct stimulation of cyclooxygenase. The release of [14C]arachidonic acid from prelabeled endothelial cells was decreased by ethanol. PGE2 production was also enhanced by exposure of endothelial cells to ethanol. The physiologic significance of these alcohol-induced changes in PGI2 levels remains to be established.
Surface phenotype of clonogenic cells in acute myeloid leukemia defined by monoclonal antibodies
Authors: Lange B , Ferrero D , Pessano S , Palumbo A , Faust J , Meo P , Rovera G 
Published: October 2019

Abstract
Colony-forming cells in ten cases of acute myeloid leukemia (AML) were studied with six cytotoxic monoclonal antibodies that react with antigens expressed at discrete stages of differentiation of normal and leukemic hematopoietic cells. The reactivity of the whole leukemic population was measured by indirect immunofluorescence, and the reactivity of the colony-forming cells was established by complement- mediated cytotoxicity and by fluorescence activated cell sorting. Comparison of the immunofluorescent reactivity with cytotoxicity and cell sorting showed that colony-forming cells were found within a fraction of the leukemic subpopulations that expresses these antigens. This finding implies that immunofluorescence reactivity of the total leukemic population does not necessarily predict the phenotype of the clonogenic cells. When the surface phenotype of the clonogenic leukemic cells was compared to that previously established for normal marrow hemopoietic clonogenic cells, several patterns were seen: (1) in four of ten cases, the clonogenic cells expressed a phenotype like that of relatively mature normal granulocyte-macrophage colony-forming cells (late CFU-GM) or, (2) in two cases, a phenotype similar to the less mature colony-forming cells (early CFU-GM or CFU-GEMM), and (3) in four cases, a composite phenotype of early and late CFU-GM. Thus, the level of impairment of differentiation in AML may vary from case to case. In those cases phenotypically similar to the late CFU-GM, it may be possible to separate leukemic clonogenic cells from less mature normal clonogenic cells using monoclonal antibodies selectively cytotoxic for the late CFU-GM.
The effect of high ascorbic acid supplementation on body iron stores
Authors: Cook JD , Watson SS , Simpson KM , Lipschitz DA , Skikne BS 
Published: October 2019

Abstract
The level of assimilation of dietary iron is believed to have an important influence on iron status. To examine the effect of enhancing the availability of dietary iron on iron balance, 17 adult volunteer subjects were given 2 g of ascorbic acid daily with meals for 16 weeks. Serum ferritin levels before and after the study averaged 46 and 43 micrograms/L, respectively, indicating a negligible effect on iron stores. When vitamin C supplementation was continued for an additional 20 months in five iron-replete and four iron-deficient subjects, serum ferritin determinations again failed to indicate any significant effect of the vitamin C on iron reserves. These findings were not explained by intestinal adaptation to the enhancing effect of the vitamin, because radioisotopic measurements of nonheme iron absorption showed no reduction in the enhancing effect of 1 g of ascorbic acid after four months of megadoses of vitamin C. It is concluded that altering the availability of nonheme dietary iron has little effect on iron status when the diet contains substantial amounts of meat.
Heparan sulfate and dermatan sulfate inhibit the generation of thrombin activity in plasma by complementary pathways
Authors: Ofosu FA , Modi GJ , Smith LM , Cerskus AL , Hirsh J , Blajchman MA 
Published: October 2019

Abstract
Heparan with a low affinity for antithrombin III has previously been demonstrated to inhibit thrombin generation in both normal plasma and plasma depleted of antithrombin III. In addition, standard heparin and heparin with a low affinity for antithrombin III have been demonstrated to have equivalent inhibitory actions on thrombin generation in plasma depleted of antithrombin III. These observations prompted the investigation of the effects of four normal vessel wall glycosaminoglycans (heparan sulfate, dermatan sulfate, chondroitin-4- sulfate, and chondroitin-6-sulfate) on the intrinsic pathway generation of thrombin and factor Xa and on the inactivation of thrombin and factor Xa in plasma. Heparan sulfate inhibited thrombin generation and accelerated the inactivation of added thrombin and factor Xa in normal plasma but not in antithrombin III-depleted plasma. In contrast, dermatan sulfate inhibited thrombin generation in both normal and antithrombin III-depleted plasma. In addition, heparan sulfate was an effective inhibitor of factor Xa generation, while dermatan sulfate was not. Neither chondroitin-4-sulfate nor chondroitin-6-sulfate inhibited the generation of thrombin or factor Xa nor did they accelerate the inactivation of factor Xa or thrombin by plasma. These results suggest that heparan sulfate acts primarily by potentiating antithrombin III, while dermatan sulfate acts by potentiating heparin cofactor II. The inhibition of thrombin generation by heparan sulfate and dermatan sulfate thus appears to occur by complementary pathways, both of which may contribute to the anticoagulation of blood in vivo.
Deferoxamine: a reversible S-phase inhibitor of human lymphocyte proliferation
Authors: Lederman HM , Cohen A , Lee JW , Freedman MH , Gelfand EW 
Published: October 2019

Abstract
Deferoxamine is widely used therapeutically as a chelator of ferric ion in disorders of iron overload. This study demonstrates that this drug is a potent inhibitor of DNA synthesis by human B and T lymphocytes in vitro, but has relatively little effect on the synthesis of RNA and protein. The inhibitory effects of deferoxamine are completely reversible by washing or by adding stoichiometric amounts of Fe3+. Micromolar concentrations of deferoxamine decrease intracellular levels of deoxyribonucleoside triphosphates, which is similar to the effects of hydroxyurea. The binding of iron by deferoxamine likely causes an inhibition of ribonucleotide reductase activity, thereby preventing cells from completing the S phase of the cell proliferation cycle. As a reversible and nontoxic S-phase inhibitor, it may have important experimental and therapeutic applications.