bluuebunny/crossref_metadata_2025_split huggingface dataset:
Platelet retention in glass bead columns: adhesion to glass and subsequent platelet-platelet interactions
Authors: McPherson J , Zucker MB 
Published: October 2019

Abstract
In normal heparinized blood, the retention of platelets in glass bead columns was low in the first 1 or 2 ml, increasing to more than 80% by the 4th or 5th ml. Prior flushing of the columns with platelet-poor plasma or saline lowered retention in all 5 ml. Additional studies were carried out with a two-stage procedure in which a sample of blood (A) was pumped through a column, immediately flushed out with saline or plasma, and followed by a second blood sample (B). When as little as 1 ml of blood A preceded the flushing solution, retention was very high in all 5 ml of the subsequent blood B. This enhancement of retention in B occurred, providing blood A contained platelets (other than thrombasthenic), fibrinogen, and adequate divalent cations. Enhancement did not require von Willebrand factor (vWF) in A, nor was ADP necessary, since enhancement occurred even when heparinized blood as A contained prostaglendin E1 (PGE1) or creatine phosphokinase with creatine phosphate (CPK-CP). However, the presence of PGE1 or CPK-CP in the plasma used to flush the columns prevented the enhancement of retention in the first milliliter of B. Retention in the first milliliter of B (following normal blood as A and saline or normal plasma for flushing) was high when B was afibrinogenemic, moderately high when B contained PGE1 or CPK-CP, and low in thrombasthenic, EDTA, or vWF-deficient blood. Retention declined in subsequent milliliters of PGE1 or CPK-CP blood and remained low in thrombasthenic, vWF-deficient, or EDTA blood. Our findings suggest that (1) the platelets in A adhere to glass; this adhesion requires fibrinogen but not vWF or ADP; (2) the adherent platelets release ADP and become sticky; (3) adhesion of platelets in the first milliliter of B to the sticky platelets from A requires vWF and divalent cations but not ADP; (4) retention is maintained thereafter by repetitive platelet-platelet interactions involving ADP release, alteration of adherent platelets by released ADP, and adhesion of further platelets to these ADP-altered platelets which requires vWF.
B lymphocyte subpopulations in chronic lymphocytic leukemia
Authors: Rudders RA 
Published: October 2019

Abstract
We have defined two subpopulations of B lymphocytes in chronic lymphocytic leukemia (CLL). The major variant (termed typical) was characterized by the presence of a relatively homogeneous population of small-to-medium-sized lymphocytes with low-density SmIgM and no evidence of intracellular Ig synthesis. A minor group (termed atypical) was identified by the presence of a pleomorphic cell population with few small lymphocytes. The predominant SmIg was IgG, which was detected intracellularly as well as in the serum. The atypical group appeared to be an arrest at a later stage of differentiation where a switch from IgM to IgG synthesis and secretion had occurred. Clinical correlation suggested several clear-cut differences in clinicopathologic characteristics, but the median survivals for both groups at 2 yr was nearly identical.
Hyperlipidemia, hypercoagulability, and accelerated thrombosis: studies in congenitally hyperlipidemic rats and in rats and monkeys with induced hyperlipidemia
Authors: Kim WM , Merskey C , Deming QB , Adel HN , Wolinsky H , Clarkson TB , Lofland HB 
Published: October 2019

Abstract
Inbred Carworth Farms Nelson (CFN) congenitally hyperlipidemic rats had significantly shorter coagulation and prothrombin times and higher levels of coagulation factors, II, V, VII, VIII, and X than did controls. Conversely, congenitally hypolipidemic rats of the same strain had significantly longer coagulation and prothrombin times and lower levels of factors II, V, VII, X and XII and of blood platelets than did controls. A loop-shaped polyethylene cannula was inserted into the aorta to assess the potential for thrombosis. The hyperlipidemic group obstructed this significantly faster and the hypolipidemic group slower than did the controls. Normal CFN rats made hypertensive by unilateral renal artery clip developed hypertension together with significantly elevated serum cholesterol and factor VII and X levels. Rhesus monkeys with diet-induced hyperlipidemia showed shorter prothrombin times and higher factor X levels than did controls on normal diet. By selective breeding, two groups of squirrel monkeys were obtained. Both groups had similar serum cholesterol levels on a normal diet but one group (hyperresponders) showed higher serum cholesterol levels on a cholesterol-containing diet than did the other (hyporesponder) group. Both groups showed significantly elevated levels of factors II, V, VII, IX and X on a cholesterol-containing diet. There was good correlation between the levels of many coagulation factors and serum cholesterol in both rats and monkeys. If thrombosis is important in the genesis of atherosclerosis, these findings could indicate that elevation of plasma lipids may play a role, via the coagulation pathway, in the production of human vascular disease.
Infectious canine hepatitis: animal model for viral-induced disseminated intravascular coagulation
Authors: Wigton DH , Kociba GJ , Hoover EA 
Published: October 2019

Abstract
The objective of this study was to characterize the hemostatic defect in dogs with infectious canine hepatitis (ICH), a naturally occurring viral disease of dogs. Five littermate dogs were inoculated with 10(3) TCID50 of ICH virus intravenously. Two littermates were controls. The clinicopathologic manifestations of ICH were fever, depression, anorexia, hematemesis, melena, widespread mucocutaneous petechiae, prolonged bleeding from venipunctures, faceial edema, leukopenia, and proteinuria. The hemostatic defect of ICH was characterized by thrombocytopenia, abnormal platelet function, prolonged one-stage prothrombin time and activated partial thromboplastin time, normal thrombin times, depressed factor VIII activity, and increased fibrin- fibrinogen degradation products. These findings suggested that the central pathologic mechanism of the abnormal hemostasis in ICH was disseminated intravascular coagulation (DIC). ICH is an example of DIC induced by viral infection. This disease is a suitable model for investigation of the detection, pathogenesis, and therapy of DIC.
A study of the large heparin requirements in the generalized Shwartzman reaction
Authors: Gurewich V , Lipinski B , Wetmore R 
Published: October 2019

Abstract
The heparin requirements necessary to inhibit intravascular fibrin deposition and soluble fibrin monomer (FM) formation in the generalized Shwartzman reaction (GSR) were evaluated. Fibrin deposition was measured by a quantitative technique utilizing 125I-labeled rabbit fibrinogen. FM was measured semiquantitatively by gel exclusion chromatography and by the serial dilution protamine sulfate (SDPS) test. There was a fourfold increase in heparin requirement 5 min after compared with 5 min before the second dose of endotoxin. This increase in heparin requirement was not related to thrombin elaboration, since FM was not found until more than 1 hr after the second dose of endotoxin. Neither was there any evidence of diminished sensitivity to the anticoagulant effect of heparin. The heparin requirements in the GSR rabbits were found to be in excess of those needed to neutralize a defibrinating dose of thrombin. It was concluded that a potent, heparin- resistant clotting activity developed within 5 min of the second endotoxin injection. The mechanism by which the activity caused the gradual elaboration of a thrombin-like enzyme is diffucult to explain on the basis of traditional coagulation reactions. The apparent role of white cells is discussed.
Direct implantation of Ph1 chromosome-positive myeloblasts into newborn hamsters
Authors: Miyoshi I , Kubonishi I , Uchida H , Hiraki S , Toki H 
Published: October 2019

Abstract
Peripheral leukocytes from a male patient with chronic myelogenous leukemia in blast crisis were implanted directly into the intraperitoneal cavity of seven newborn hamsters treated with antilymphocyte serum. At sacrifice 17–19 days after implantation, three hamsters were found to have disseminated tumors. The other four hamsters were cannibalized. Chromosome analysis of cells from the enlarged lymph nodes revealed the presence of a human male karyotype. Most metaphase cells were pseudodiploid with the Ph1 chromosome and isochromosome 17, while a few metaphase cells were classically diploid. Identical chromosome constitutions were observed in the original peripheral leukocytes of the patient. The results strongly suggested simultaneous heterotransplantation of Ph1-positive leukemic and normal leukocytes.
Improved techniques for liquid culture of human and mouse bone marrow
Authors: Cline MJ , Golde DW 
Published: October 2019

Abstract
Previous studies using the in vitro diffusion chamber (Marbrook) have shown that bone marrow grown in this system will undergo limited stem cell replication and differentiation to mature granulocytes and mononuclear phagocytes. A series of studies with modified culture systems was initiated to improve cell production and committed stem cell (CFU-C) proliferation in vitro. Introduction of a continuous-flow system and a migration technique providing means of egress for mature neutrophils resulted in substantially improved performance. CFU-C were found to be capable of migration through a 3-mu pore membrane. These studies indicated that membrane surface area, culture medium circulation, and mature cell egress were among the conditions that could be optimized for maximum hematopoietic cell proliferation in suspension culture. The present observations also suggested that large- scale in vitro growth of mammalian bone marrow may be feasible.
In vitro regulation of granulopoiesis in human leukemia: application of an assay for colony-inhibiting cells
Authors: Broxmeyer HE , Baker FL , Galbraith PR 
Published: October 2019

Abstract
We describe two assays to detect the action of colony-inhibiting cells. In the first assay, we used a simple density separation technique to remove dense neutrophils (PMN) from suspensions of blood and of bone marrow cells prior to culture in semisolid agar. Conditions were arranged to ensure that control suspensions of unseparated cells and test suspensions of buoyant mononuclear cells differed only in their content of neutrophils. The control and test suspensions contained equal numbers of mononuclear cells (and granulocyte precursors). Colony (and cluster) formation was invariably enhanced in neutrophil-depleted cultures of normal cells. In the second assay, dense PMN, treated by an adherence separation procedure, were recovered, and the non-adherent dense PMN were added back to PMN-depleted cultures. A reproducible dose- related decrease in colony (and cluster) formation to basal levels resulted. The inhibitory effect was identical when the PMN were added directly to the culture (overlayer) or to the underlayer. In PMN- depleted cultures obtained from patients with leukemia and other hemopoietic disorders, neither colony nor cluster formation was enhanced, and sometimes it was reduced. When we compared the effect of adding patient and normal non-adherent PMN to target cultures of normal and patient PMN-depleted cells, some leukemic PMN were noninhibitory. Our results suggest that abnormalities of cellular interactions in vitro detected in the first assay may have more than one explanation, as shown when they are subjected to the closer scrutiny possible with the second assay.
Oxidation of epinephrine by a cell-free system from human granulocytes
Authors: Babior BM , Kipnes RS 
Published: October 2019

Abstract
Homogenates of normal human granulocytes were found to catalyze the oxidation of epinephrine to adrenochrome. This reaction was abolished by superoxide dismutase and catalase, but not by albumin or boiled dismutase, indicating that epinephrine oxidation was dependent on O2- AND H2O2. Elimination experiments to identify the electron donor for O2- production showed that the reaction was not inhibited by gel filtration of the homogenate or by removal of glucose, sucrose, or phosphate from the reaction mixture, raising the possibility that epinephrine itself was the reducing agent for the production of O2-. However, we could obtain no evidence for the direct involvement of epinephrine in this step. To explain our observations, we have proposed a mechanism of adrenochrome production involving a radical chain process with one or more enzyme-catalyzed steps. Reactants participating in this chain were postulated to be O2-,-OH (produced by the reaction of O2- with H2O2), and various intermediate products of oxidation of epinephrine. An unidentified endogenous constituent was postulated as the agent responsible for the initial conversion of oxygen to O2-.
Prophylactic granulocyte support in experimental septicemia
Authors: Tobias JS , Brown BL , Brivkalns A , Yankee RA 
Published: October 2019

Abstract
The purpose of this study was to determine the value of prophylactic granulocyte transfusions in preventing death from sepsis. An intravenous dose of 10(9) Escherichia coli was lethal when given to granulocytopenic rats 6 days following irradiation with 750 rads. Only one of 22 irradiated animals survived the septicemia. Although normal (nonirradiated) animals experienced a transient leukopenia from this dose of organisms, it was less than LD10 for the normal host. There were no deaths in a group of animals receiving irradiation only. A group of 14 irradiated animals was given a single granulocyte transfusion 2 hr before the septic inoculum, and 57% of these animals survived (p less than 0.01). No antibiotic therapy was administered to any of these animals. Irradiated animals who received granulocytes and recovered from sepsis had earlier granulocyte reconstitution than animals irradiated but not given the septic challenge. Platelet reconstitution was the same in both groups. In the rat model, prophylactic granulocyte support of septc animals led to improved survival. It was concluded that granulocyte prophylaxis may be of value in selected patients with transient bone marrow failure who are therefore at high risk from sepsis.
Granulocyte function in experimental human endotoxemia
Authors: Territo MC , Golde DW 
Published: October 2019

Abstract
The effects of endotoxin administration on in vitro granulocyte function were studied in normal man. Four healthy volunteers received an intravenous injection of Pseudomonas endotoxin, 0.1 mug/kg. Endotoxemia resulted in transient neutropenia followed by a rebound neutrophilia. The nadir of the granulocyte count occurred at about 1 hr and maximal neutrophilia 2–4 hr after endotoxin administration. Throughout this time period, neutrophil phagocytosis and killing of Candida albicans were normal, as were resting and postphagocytic glucose metabolism and leukocyte random migration. However, postendotoxin neutrophils demonstrated a markedly decreased chemotactic response in Boyden chambers. The defect was maximal 1 hr after endotoxin administration and persisted 3–4 hr. These observations suggest that, in addition to neutropenia, endotoxin can transiently cause a chemotactic defect or select for a population of circulating neutrophils with an impairment of chemotactic activity.
Effect of phorbol myristate acetate on the oxidative metabolism of human polymorphonuclear leukocytes
Authors: DeChatelet LR , Shirley PS , Johnston RB Jr 
Published: October 2019

Abstract
The addition of 0.1 mug/ml of phorbol myristate acetate (PMA) to a suspension of resting human neutrophils causes a marked stimulation of all aspects of cellular oxidative metabolism normally associated with phagocytosis. PMA induces a greatly increased rate of glucose oxidation via the hexose monophosphate shunt, increased production of superoxide anion and of hydrogen peroxide, increased cellular chemiluminescence, and increased iodination of protein material. The time course of hexose monophosphate shunt activation and of chemiluminescence are similar to those observed following phagocytosis of opsonized zymosan; the levels of activation achieved in all cases approximate those seen following phagocytosis. These phenomena are not simply reflections of altered cellular permeability, since PMA actually inhibits the uptake of radioactive 2-deoxyglucose and of uniformly labeled amino acids. The addition of PMA similarly inhibits the uptake of 14C-labeled bacteria, suggesting a competition between the effect of the chemical and the process of phagocytosis. These results suggest that PMA activates the cell in the same manner as does phagocytosis. This compound should provide a useful tool for elucidating the metabolic events underlying the phenomena of phagocytosis and bacterial killing by polymorphonuclear leukocytes.
Chediak-Higashi syndrome: reversal of increased susceptibility to infection by bone marrow transplantation
Authors: Kazmierowski JA , Elin RJ , Reynolds HY , Durbin WA , Wolff SM 
Published: October 2019

Abstract
Transplantation of normal bone marrow to mice with the Chediak-Higashi syndrome (CHS) resulted in normal granulopoiesis and a reversal of their increased susceptibility to challenge with intravenous Candida albicans. These findings suggest that (1) the leukocyte defect in CHS can be reversed by marrow transplantation and (2) the mechanism for increased susceptibility to infection in these animals is due to a bone- marrow-derived cellular defect. Because of similarities between murine and human CHS, bone marrow transplantation might be considered as a mode of therapy in selected cases of the human disease.
The anemia of chronic renal failure and chronic diseases: in vitro studies of erythropoiesis
Authors: Wallner SF , Kurnick JE , Ward HP , Vautrin R , Alfrey AC 
Published: October 2019

Abstract
The presence of a serum factor in chronic renal failure (CRF) which inhibits erythropoietin-stimulated erythropoiesis was studied, using a technique in which dog marrow cells were stimulated to produce heme in the presence of human serum. In the total series comparing 27 normal sera with 52 CRF sera, less heme was synthesized when the system contained CRF sera (total series, p = 0.0001). There was no evidence of inhibition of heme synthesis by serum from 12 patients with the anemia of chronic diseases (CD). Mixing experiments with normal and CRF sera suggested that this defect in CRF serum was not due to lack of a factor necessary for heme synthesis. Addition of urea, creatinine, and guanidinosuccinic acid to normal serum did not impair its ability to support erythropoiesis in this system. These data demonstrated that serum from patients with CRF contains a material inhibiting erythropoiesis in vitro, We propose that the material is responsible, in part, for the clinically severe anemia seen in these patients.
Premature chromosome condensation in human leukemia
Authors: Williams DM , Scott CD , Beck TM 
Published: October 2019

Abstract
Premature chromosome condensation (PCC) has previously been observed in tissue culture and is believed to arise from asynchronous mitotic activity in multinucleated cells in which the affected nucleus is in interphase and at least one nucleus is in metaphase. Such cells have been noted following fusion induced by virus infection, spontaneously, and after treatment with cytochalasin B. The phenomenon has also been observed in malignant pleural effusions, but has not previously been described as a feature of hematologic disease. In this study, we report the observations of PCC in seven patients. Six of these patients had either acute myeloblastic leukemia or acute myelomonoblastic leukemia in association with the features of erythroleukemia, i.e., leukoerythroblastic reaction in the blood, and erythroid multinuclearity, “megaloblastoid” changes, and PAS-positive staining of erythroid precursor cells in the bone marrow. In all patients, erythroid multinuclearity has been noted. However, not all patients with erythroleukemia exhibit PCC. In this series, three additional patients have had similar bone marrow morphologic changes without PCC. The finding of PCC in erythroleukemia may have important implications as to etiology of this disorder.
Polyamine concentrations in bone marrow aspirates of children with leukemia and other malignancies
Authors: Rennert O , Miale T , Shukla J , Lawson D , Frias J 
Published: October 2019

Abstract
High-pressure liquid chromatography analysis of polyamines in bone narrow from leukemic and nonleukemic subjects demonstrated increased concentrations of putrescine, spermidine, and spermine associated with increased cellularity. The most striking abnormality was the marked elevation of putrescine. Bone marrow polyamine analysis may be an adjunct for evaluation of leukemia patients.
Separation of the erythropoietin-responsive progenitors BFU-E and CFU-E in mouse bone marrow by unit gravity sedimentation
Authors: Heath DS , Axelrad AA , McLeod DL , Shreeve MM 
Published: October 2019

Abstract
The sedimentation velocity profiles of the entities in mouse bone marrow responsible for erythropoietic burst formation (BFU-E) and for erythrocytic colony formation (CFU-E) have been studied under conditions designed to determine whether the values observed are real or result from cell interactions occurring during culture of the fractions. Bone marrow cells of adult C3Hf/Bi mice were subjected to unit gravity sedimentation in a bovine serum albumin gradient, and fractions were assayed in plasma culture. Because it was found that cell concentration affected the efficiency of erythropoietic burst formation in culture, aliquots were plated at two different cell concentrations, as well as at a fixed proportion of each fraction. The modal sedimentation velocity of the BFU-E population averaged 3.9 mm/hr and that of the CFU-E population, 6.4 mm/hr; both were found to be independent of cell concentration or method of dividing the fractions. Cells from fractions of different sedimentation velocity were mixed with one another or with unfractionated cells. No significant inhibition or stimulation of erythropoietic burst formation was seen. We concluded that the observed values represented the true modal sedimentation velocities of BFU-E and cfu-e in normal mice. To determine whether a change in the physiologic state of the animals affected the sedimentation velocities of BFU-E or CFU-E, marrow cells from mice hypertransfused with red cells were compared with those from controls. The modal sedimentation velocity of BFU-E was unaffected by hypertransfusion, nor was there any change in the number of BFU-E under these conditions. The number of CFU-E was substantially reduced without a significant change in modal sedimentation velocity.
Aplastic anemia: failure of patient leukocytes to stimulate allogeneic cells in mixed leukocyte culture
Authors: Mickelson EM , Fefer A , Thomas ED 
Published: October 2019

Abstract
One-way mixed leukocyte cultures were used to study the ability of cells from 53 patients with aplastic anemia and 65 of their HLA- identical siblings to stimulate and to respond to cells from unrelated individuals. The capacity of leukocytes from 28 of 53 patients to stimulate was diminished or absent, wheras their ability to respond remained comparable to that of cells from their HLA-identical siblings. Leukocytes from the group of patients with the lowest peripheral lymphocyte count were least stimulatory. The results indicate that in acquired aplastic anemia there exists a dissociation between stimulation and response in mixed culture.