bluuebunny/crossref_metadata_2025_split huggingface dataset:
The mechanism of platelet release
Authors: Radley JM , Scurfield G 
Published: October 2019

Abstract
The mechanism of platelet release has been studied in mouse bone marrow, using scanning and transmission electron microscopy. Cytoplasmic processes extended into sinusoids by megakaryocytes were found to undergo attenuation, and at the distal end develop constrictions between segments of platelet size. Rupture at sites of constriction is thought to release platelets. Microtubules were present in the processes, orientated longitudinally, and became concentrated in the constrictions. The narrowest constrictions observed were about 0.2 micrometer in diameter and several microns in length. The structural similarity of the narrowest constrictions with those found in bridges separating midbody and cell in the terminal phase of cytokinesis suggests that platelets and cells share a common mechanism for release. The presence of a centriole in each cytoplasmic process was revealed by serial sectioning. It is suggested that the microtubules in each cytoplasmic process originate from an organizing center associated with the centriole, and that the number of cytoplasmic processes that emerge from a megakaryocyte is governed by its ploidy.
5-Azacytidine and renal tubular dysfunction
Authors: Peterson BA , Collins AJ , Vogelzang NJ , Bloomfield CD 
Published: October 2019

Abstract
During initial trials of 5-azacytidine in adults with advanced acute leukemia, we unexpectedly observed acid-base, fluid, and electrolyte abnormalities that contributed directly to the deaths of two early patients. To evaluate this toxicity further, we studied 22 patients who received a total of 33 courses of combination chemotherapy that included 5-azacytidine. During 29 courses (88%) of treatment, polyuria, glucosuria, and/or transient changes in the serum concentrations of bicarbonate or phosphorus were detected. Spontaneous polyuria with demonstrable salt wasting and orthostatic hypotension occurred during seven courses (21%) of treatment. Inappropriate glucosuria was observed in nine courses (27%). In 24 courses (73%) the serum bicarbonate fell below the normal range. The urine became alkaline during 12 of these instances; the anion gap was not increased during the acidosis. Hypophosphatemia with serum phosphorus concentrations as low as 0.3 mg/dl occurred in 21 of 32 evaluable courses (66%). In the three patients studied the tubular reabsorption of phosphorus was 10%-18%. The renal abnormalities that were observed suggest both proximal and distal tubular damage from 5-azacytidine. Patients receiving 5- azacytidine should be monitored closely for manifestations of renal toxicity.
Absence of platelet-specific alloantigens in Glanzmann's thrombasthenia
Authors: van Leeuwen EF , von dem Borne AE , von Riesz LE , Nijenhuis LE , Engelfriet CP 
Published: October 2019

Abstract
The platelets of 11 patients with Glanzmann's thrombasthenia and their nearest family members were studied for the expression of the platelet- specific alloantigens of the Zw-, Ko- and Bak systems. The strength of the expression of the Zwa antigen was diminished on the platelets of 3 patients, and the antigen was absent from the platelets of the other 8. The platelets of none of the patients reacted with anti-Zwb serum. Therefore, Glanzmann's thrombasthenia is probably a “Zw-null disease.” The expression of the Zwa antigen on the platelets of all the relatives was normal, as indicated on the cytoflurograph. Investigations on the expression of the Koa antigen were complicated by agglutinations of the platelets from genetically Koa-negative thrombasthenic patients with the anti-Koa serum. The Kob antigen was normally expressed. The Baka antigen was absent from the platelets of all thrombasthenic patients and a relatively high percentage of the relatives. A close association between the Glanzmann gene and the Bak(a-) gene is assumed on statistical grounds. Thrombasthenic platelets showed no reaction with EDTA-dependent antibodies, which are reactive with all normal platelets. Owing to immunization by multiple blood and platelet transfusions, serum samples of most patients studied contained HLA antibodies and platelet-specific alloantibodies. However, antibodies directed against the Zw-antigen-bearing glycoproteins were detected in the serum of only one patient and, therefore, seem to be rare.
Sucrose density gradient analysis of erythrocyte membranes in hemolytic anemias
Authors: Flynn TP , Johnson GJ , Allen DW 
Published: October 2019

Abstract
To investigate the membrane abnormalities that may play a pathophysiologic role in several hemolytic anemias we determined the density distribution on sucrose density gradients of human red blood cell (RBC) membranes from patients with these disorders, from normal controls, and from incubated normal RBC. We analyzed the fractions for membrane-adsorbed hemoglobin (Hb), globin, and nonglobin cytoplasmic proteins. The relationship between the cytoplasmic proteins adsorbed on the membranes and the specific gravity (SG) of the membranes was linear. An increase in SG of the entire membrane population was seen in Hb C disease due to adsorbed Hb. Subpopulations of membranes with increased SG due to adsorption of nonglobin protein were evident in the membranes from two splenectomized patients with hemolytic glucose-6- phosphate dehydrogenase (G6PD) variants. Dense membrane subpopulations found in RBC membranes from three splenectomized patients with Hb Koln were associated with adsorbed globin, while similar subpopulations in RBC membranes from three splenectomized patients with hereditary spherocytosis demonstrated increased SG due to adsorbed Hb. Splenectomized normals had no such abnormality in membrane density. Sucrose density gradients demonstrate that membrane bound cytoplasmic protein is characteristic of the RBC membranes in several hemolytic disorders. Additionally, gradients are useful for the isolation and further analysis of those subpopulations of RBC membranes with abnormal SG and exaggerated membrane protein abnormalities.
Genetic variation in the quantitative levels of an NADP (H)-binding protein (FX) in human erythrocytes
Authors: Lenzerini L , Benatti U , Morelli A , Pontremoli S , De Flora A , Piazza A , Rinaldi A , Filippi G , Siniscalco M 
Published: October 2019

Abstract
FX is a red cell NADP(H)-binding protein that has been well defined biochemically and immunologically but whose function is still unknown. Preliminary data indicated that the levels of this protein are significantly increased in hemizygotes, heterozygotes, and homozygotes for the G6PD Mediterranean mutant, thus raising the question of whether or not the individual variation in FX levels is more or less directly influenced by X-linked genes. The present study, based on a large series of population and family data collected in Sardinia, confirms unequivocally the above mentioned interaction, but shows at the same time that the variances in FX levels “between sibships” are 2–3 times larger than those “within sibships,” when the analysis is done separately for the G6PD-normal or the G6PD-deficient sibs. From the comparison of the interclass and intraclass correlation coefficients, it appears that about 60% of the total variation of FX is of genetic origin. Moreover, the FX levels of children, analyzed in a pairwise manner, were found to be more positively correlated with those of their fathers (r = 0.39) than with those of their maternal grandfathers (0.20). This latter finding obviously favors the conclusion that “autosomal”; rather than “X-linked” genes are involved in the determination of the FX levels.
The relationship between plasma iron and plasma iron turnover in the rat
Authors: Bauer W , Stray S , Huebers H , Finch C 
Published: October 2019

Abstract
Plasma iron turnover has been evaluated in the growing rat. Consistent data were obtained with the intravenous injection of radioiron in the form of ferrous sulfate or ferric citrate. Plasma iron turnover changed as a function of plasma iron concentration. Only part of this effect in the rat was due to the different rates of clearance of mono-and differic transferrin, the latter having a higher iron delivery rate in vivo. An additional effect was shown to relate to the rate of red cell production. With decreased production, the effect of plasma iron on plasma iron turnover was reduced, whereas with increased erythropoiesis there was an additional increment in plasma iron turnover for any increase in plasma iron. Since this effect was observed when increased iron demands were due to an increase in erythroid precursors in the marrow but not in the circulating blood, it is attributed to limitations in iron flow to the marrow. This suggests that erythroid marrow activity and the adequacy of iron supply when studied by ferrokinetic techniques can best be defined by the response curve relating plasma iron concentration to plasma iron turnover.
Human myelogenous leukemia: enhanced clonal proliferation in the presence of phorbol diesters
Authors: Koeffler HP 
Published: October 2019

Abstract
Phorbol diesters, including 12–0-tetradecanoyl-phorbol-13-acetate (TPA) at low concentrations, enhanced the clonal proliferation of a human myelogenous leukemia cell line (KG-1). TPA (1.0 X 10(-9) -5.0 X 10(-11) M) increased KG-1 clonal growth by four to tenfold in the presence of suboptimal concentrations of colony stimulating factor (CSF) and by two to fourfold in the presence of maximally stimulating concentrations of CSF. The ability of TPA analogs to enhance KG-1 clonal growth paralleled their reported ability to promote tumors in mice. Only slight CSF activity was detected in the conditioned medium from KG-1 cells cultured in liquid medium with TPA. TPA was unable to increase myeloid clonal growth of CSF-stimulated normal human model to study TPA enhancement of CSF-stimulated growth.
Measurement of ploidy distribution in megakaryocyte colonies obtained from culture: with studies of the effects of thrombocytopenia
Authors: Levin J , Levin FC , Penington DG , Metcalf D 
Published: October 2019

Abstract
Microdensitometric measurement of the DNA content of individual megakaryocytes was performed using megakaryocyte colonies obtained following culture, in soft agar, of hematopoietic cells from C57BL/6J mice. Two types of colonies were detected. After 7 days of culture, the big cell type contained 16 /+- 2.3 acetylcholinesterase (AChE) positive cells/colony, with a mean ploidy level of 16.8 /+- 0.8/cell and the ploidy distribution characteristic of recognizable megakaryocytes in bone marrow. The heterogeneous type contained 44 /+- 9.6 cells/colony (some of which were AChE negative), with a mean ploidy level of 6.8 /+- 0.7/cell. The ploidy distribution of heterogeneous colonies differed markedly from big cell colonies, with preponderance of 2N and 4N cells. Colony-forming cells, obtained 4–5 days after induction of acute thrombocytopenia, gave big cell colonies with a marked increase in DNA content. Mean ploidy level increased to 21.5 /%- 1.8/cell; the frequency of 32N cells increased from 17% to 30% and 64N cells from 0% to 6%. This is the pattern of change observed in bone marrow, in vivo, 24 to 48 hr after induction of acute thrombocytopenia. The number of cells/colony did not increase. In contrast, acute thrombocytopenia did not alter the ploidy of heterogeneous colonies. The different responses to the stimulus of acute thrombocytopenia suggest that there are at least two types of Meg-CFC. The delayed appearance of altered Meg-CFC that produced big cell colonies indicates that the pool of stem cells, from which committed megakaryocyte precursors are derived, may respond indirectly to the stimulus of platelet depletion.
Further evidence of the in vivo role of erythropoietin or companion molecules induced by hypoxia on proliferation and continuing differentiation of BFU-e in PCDC
Authors: Harigaya K , Cronkite EP , Miller ME , Moccia G 
Published: October 2019

Abstract
Normal and plethoric bone marrow cells were grown in plasma clot diffusion chambers (PCDC) implanted into the peritoneum of normal mice or mice submitted to 7 her of hypoxia (23,000 ft) daily, on a single day or on 2 consecutive days at different times after implantation of the PCDC's. Daily discontinuous hypoxia (DDH) produced more 6-day bursts than other treatments. Hypoxia on days 1 and 2 after implantation was nearly as effective as DDH on day-6 bursts. Later bouts of hypoxia or a singly hypoxic exposure on day 1 or 2 was less effective. Erythropoietin (Ep) levels were measured by bioassay on both diffusion chamber (DC) contents and serum. Serum Ep levels peaked at 160 mU/ml after a 7-hr hypoxic exposure while the DC content Ep levels were in the nondetectable range (less than 50 mU/ml). The data implies that either higher than normal Ep levels or a companion molecules (s) produced by hypoxia are required for 1–2 days early in the culture period of force an increasing number of BFU-d-e down the erythrocytic pathway and thus increase red cell production at times of need in vivo.
Interaction of platelet plasma membranes with thrombin-activated platelets
Authors: Prasanna HR , Edwards HH , Phillips DR 
Published: October 2019

Abstract
This study described the binding of platelet plasma membranes to either control or thrombin-activated platelets. Glycoproteins in plasma membranes isolated from human platelets were labeled by oxidation with periodate followed by reduction with [3H]NaBH4. Labeled membranes were incubated with either control or thrombin-activated platelets. The amount of membranes bound was measured by separating platelets with bound membranes from solution by rapid centrifugation through 27% sucrose and determining the amount of radioactivity associated with platelets. Five- to sevenfold more membranes bound to thrombin- activated platelets than to control platelets. This enhanced binding of labeled membranes was completely inhibited by an excess of unlabeled platelet membranes. Human erythrocyte membranes had little affinity for either washed or thrombin-activated platelets and therefore did not compete for platelet-membrane binding. Binding of platelet membranes to thrombin-treated platelets was inhibited by prior incubation of the platelets with PGI2 suggesting that the enhanced binding of membranes was to activated platelets. This study demonstrates that the purified platelet membranes have functional sites that can mediate membrane binding to platelets and that quantitation of membrane binding appears to reflect the increased aggregation capability of activated platelets.
Neutrophil surface markers in patients with acute leukemia
Authors: Hofmeister BG , Carrera CJ , Barrett SG 
Published: October 2019

Abstract
The presence of complement and Fc receptors on neutrophils from patients with acute leukemia was investigated at different stages of the leukemic process. Both Fc receptors (Fc-H and Fc-R) and one complement receptor (C3d) were normal when patients were studied at diagnosis, in relapse, and in remission. In contrast, the C3b receptor was significantly reduced on te neutrophils at the time of diagnosis, but returned to normal levels when patients entered remission. Variable amounts of C3b activity were observed in patients relapse, with approximately one-half of the patients showing decreased C3b activity. To determine whether the reduction inC3b receptors was specific for patients at diagnosis, three patients were studied at different times during their diseases. Normal receptor levels were detected in these patients during remission, but the C3b receptor was markedly reduced at diagnosis and at relapse.
Human T-lymphocyte growth factor: regulation of growth and function of T lymphocytes
Authors: Ruscetti FW , Gallo RC 
Published: October 2019

Abstract
The discovery of T-cell growth factor (TCGF) has made it possible to now routinely grow in tissue culture normal and neoplastic human T cells for long periods and in large amounts. TCGF has been recently purified. It is a small protein released by a subset of mature T cells following lectin-antigen activation, which in turn acts upon other T- cell subsets that have developed specific receptors for TCGF after lectin-antigen stimulation. Thus, release of TCGF and development of receptors for it appear to be obligatory for the clonal expansion of all activated T cells. Unlike normal T cells, neoplastic T cells respond directly to TCGF, requiring no prior in vitro lectin-antigen activation. This has led to the development of several new cell lines from patients with T-cell leukemias and lymphomas. In some cases, these cells become independent of exogenous TCGF by producing their own growth factor, implying a role for TCGF in the continuous proliferation of these cells. These developments necessitate a reevaluation of some concepts of immunoregulation of T-cell activities in terms of production and response to TCGF. In addition, this information has clinical implications. Recent results have shown that a major defect of the athymic nude mouse is the inability to produce TCGF and that some immunosuppressive agents, such as glucocorticosteroids and cyclosporin- A, exert their effects on T cells by disrupting the TCGF-T-cell interaction. Some human immune deficiencies might be due to a failure to respond to or to produce TCGF, which in some cases might be corrected by exogenous TCGF.
Alloimmunization following platelet transfusion: the absence of a dose- response relationship
Authors: Dutcher JP , Schiffer CA , Aisner J , Wiernik PH 
Published: October 2019

Abstract
A major concern about the use of prophylactic platelet transfusions is the development of alloimmunization. To determine whether the rate of alloimmunization is related to the number of platelet transfusions, we measured the development of lymphocytotoxic antibody in the first 2 mo of induction therapy in patients with acute nonlymphocytic leukemia. All patients received prophylactic random donor platelets and packed red blood cells during induction. No patient had lymphocytotoxic antibody present at admission. One hundred and six patients received an average of 9.3 platelet transfusions (range 2–34) containing an average of 61 U (range 9–236). The rate of alloimmunization was 38% overall and correlated with refractoriness to platelet transfusions. Ten of 19 patients receiving less than or equal to 4 transfusions became immunized, compared with 30/87 patients receiving less than 4 transfusions. There was no relationship between the number of platelet transfusions given and the rate of severity of alloimmunization, suggesting prophylactic platelets need not be withheld expressly to prevent alloimmunization.
Correlation of the biologic effects and binding of cytochalasins to human polymorphonuclear leukocytes
Authors: Howard TH , Casella J , Lin S 
Published: October 2019

Abstract
Treatment of human PMNs with cytochalasins (CE, CD, CB, and H2CB) results in alteration of cell morphology and inhibition of cell motility. Morphological changes are similar to those reported for nonamoeboid fibroblasts--rounding, zeiosis, and arborization. Mean cell velocity of PMNs, as measured by quantitative analysis of time-lapse videotape recordings, was reduced to 0.1 micron/min (control, 7.3 +/- 4.2 micron/min). Phagocytosis by PMNs, as measured by phagocytosis of latex beads, was inhibited by 75%. The relative potency of the cytochalasins for inducing morphological change or for inhibiting locomotion and phagocytosis is similar to their relative potencies for affecting non-amoeboid cells: CE greater than CD greater than CB greater than or equal to H2CB. Quantitative binding of 3H-CB to purified PMNs under equilibrium conditions reveal two types of specific CB binding sites: high-affinity sites (KD approximately 3 x 10(-7) M, 3 x 10(6) sites/cell) and low affinity sites (KD approximately 2 x 10(-6) M). The relative affinities of the cytochalasins for the high-affinity and low-affinity CB binding sites parallel their relative potencies for inducing biologic effects (i.e. CE greater than CD greater than CB greater than or equal to H2CB).
Generation of CFU-C/suppressor T cells in vitro: an experimental model for immune-mediated marrow failure
Authors: Bacigalupo A , Podesta M , Mingari MC , Moretta L , Piaggio G , Van Lint MT , Durando A , Marmont AM 
Published: October 2019

Abstract
T cells were derived from the bone marrow of 8 healthy donors and fractionated, according to their receptors for the Fc fragment of IgG, into TG+ and TG- lymphocytes. These were then cocultured with autologous or allogeneic bone marrow cells in agar in the CFU-C assay. No significant suppresion of colony formation could be detected. Total T, TG+, and TG- cells were then incubated for 18 hr with PWM, washed, and cocultured with bone marrow cells. PWM-treated TG- cells showed no significant CFU-C suppressor activity, whereas PWM-treated total T and TG+ cells inhibited colony formation of both autologous and allogeneic marrow cells. The supernatant of PWM-treated total T and TG+ cells also inhibited colony formation. PWM alone enhanced colony formation. The results of this study indicate that normal T cells can be activated in vitro to become CFU-C/suppressor cells after PWM stimulation, and that this effect is mediated by T cells with the Fc receptor for IgG.
Intraplatelet serotonin and plasma 5-hydroxyindoles in health and disease
Authors: Shuttleworth RD , O'Brien JR 
Published: October 2019

Abstract
Using a fluorometric test sensitive to serotonin (5-HT) and to other 5- hydroxyindoles (5-HIs) it was shown that platelets take up 5-HT and that the added 5-HT and the inherent test-positive material in platelet lysate can be directly measured. However, platelets do not take up 5- hydroxyindole acetic acid or the 5-HIs from the plasma. Thus, 5-HT and the other 5-HIs can be distinguished. Various methods of liberating intraplatelets 5-HT were investigated. Several anticoagulants, temperatures, and speeds of centrifugation were employed, with no effect on the results. It was found that in healthy donors, with increasing age, there was a decrease in intraplatelet 5-HT and an increase in plasma 5-HIs. The quantities of these substances were inversely related. In acute myocardial infarction, the 5-HT was normal taking age into account, but the plasma 5-HIs were increased. In postoperative patients, the platelet 5-HT was low and the plasma 5-HIs were normal. In patients with chest pain but no myocardial infarction, both platelet 5-HT and plasma 5-HIs were normal. The relevance of these findings to 5-HT metabolism and the evidence for in vivo activation of platelets is discussed.
Comparative density of the human T-cell antigen T65 on normal peripheral blood T cells and chronic lymphocytic leukemia cells
Authors: Wormsley SB , Collins ML , Royston I 
Published: October 2019

Abstract
A 65,000 dalton T-cell specific antigen previously demonstrated to be present on the surface of normal and malignant T cells, but not normal B cells, has been detected on the surface of leukemic cells from patients wih nonsecretory, surface immunoglobulin-positive chronic lymphocytic leukemia (CLL). By means of immunofluorescence and flow cytometry, the relative surface density of the T65 antigen on CLL cells was compared to that on normal peripheral blood T cells and human thymocytes, as well as cell lines of T-cell lineage. In all cases, the CLL cells had a more homogeneous and a lower median fluorescence intensity than that of normal circulating T cells. Thymocytes were composed of three populations, two with low surface density of T65 resembling the CLL cells and the other with higher density similar to normal T cells. The staining of cell lines varied from bright, heterogeneous staining (8402) to uniform, low-density staining (Molt- 4). The implications of these findings with regard to lymphocyte differentiation are discussed.