bluuebunny/crossref_metadata_2025_split huggingface dataset:
Decreased life span and membrane damage of carbamylated erythrocytes in vitro
Authors: Lane TA , Burka ER 
Published: October 2019

Abstract
Red blood cells exposed to cyanate (CNO) in vitro have a concentration- dependent decreased cell survival time associated with an inhibition of the ability of the cell membrane to synthesize lipids. The t1/2 of rabbit erythrocytes exposed to 30 mM or 50 mM cyanate for 1 hr at 37 degrees C is reduced from the normal 24 days to 15 and 9 days, respectively. The cyanate-induced defect in membrane lipid metabolism is irreversible. Carbamylation of membrane proteins and damage to metabolism are minimized by limiting exposure in vitro to 15 mM cyanate at 4 degrees C for 30 min. Cells carbamylated under these conditions do not have a shortened life span. Levels of globin carbamylation of 0.5 moles CNO/mole hemoglobin, shown to be clinically effective in prolonging the life span of sickle erythrocytes, are obtained under these conditions and reach maximal levels after only 30 min of incubation. Carbamylation of blood in CPD anticoagulant is inferior to either ACD or heparin. The findings indicate that adequate carbamylation of sickle erythrocytes with minimal red cell membrane damage can be achieved without significant modification of the standard plasmapheresis procedure utilized by the working blood bank.
Complement-mediated granulocyte dysfunction in paroxysmal nocturnal hemoglobinuria
Authors: Craddock PR , Fehr J , Jacob HS 
Published: October 2019

Abstract
In paroxysmal nocturnal hemoglobinuria (PNH), infection, both viral and bacterial, disproportionate to the mild neutropenia seen in many such patients is responsible for significant morbidity. We report impaired granulocyte chemotaxis efficiency which may contribute to the problems induced by bacterial infections. PNH (but not normal) granulocytes, after exposure to very small concentrations of activated serum complement components, migrate poorly, as documented by their inhibited chemotaxis toward bacterial products or activated complement components in Boyden chambers. The granulocytes remain intact, excluding trypan blue, phagocytosing, and killing bacteria, despite this activated complement exposure. It is also suggested that this chemotactic defect may involve only a clone of cells, analogous to the clonal lysis of PNH erythrocytes; those few granulocytes capable of migration after exposure to activated complement contain normal quantities of leukocyte alkaline phosphatase (LAP), in contrast to the LAP deficiency of the overall PNH granulocyte population. Since bacterial infection may initiate or potentiate hemolysis, one of the major symptoms of the disease, these results could explain much of the morbidity of PNH.
Detection of soluble intermediates of the fibrinogen-fibrin conversion using erythrocytes coated with fibrin monomers
Authors: Largo R , Heller V , Straub PW 
Published: October 2019

Abstract
The presence of minimal amounts of fibrinogen-fibrin intermediates in human plasma was visualized by an agglutination reaction of glutaraldehyde-treated human erythrocytes coated with purified fibrin monomers. A degree of monomer coating was established which produced erythrocytes not agglutinated by normal plasma but by plasma containing minimal amounts of soluble complexes of fibrinogen with fibrin monomers. Under standardized conditions of coating, erythrocyte concentration, temperature, pH, and incubation time, the agglutination time varied with the ratio of soluble fibrin to fibrinogen in plasma. The test was sensitive down to a soluble fibrin concentration of 0.675% of the plasma fibrinogen concentration. Early fibrinogen and fibrin degradation products (FDP) in the plasma led to a prolongation of the agglutination time at a concentration of more than 16 mg/100 ml. Late FDP in a concentration of 100 mg/100 ml did not convert a positive test to negative. The test was not affected by heparin and protamine at concentrations of up to 12.5 and 50 NIH units/ml, respectively.
Identification of monocytes in suspensions of mononuclear cells
Authors: Rothbarth PH , Hendriks-Sturkenboom I , Ploem JS 
Published: October 2019

Abstract
A new histochemical technique for morphological studies of mononuclear cells and granulocytes, based on fluorescent staining with methyl green, pyronine Y, and stilbene-isothiocyanato disulfonic acid (MPS stain) is described. The method was applied to mononuclear cells isolated from the blood of normal human subjects by Ficoll-Isopaque density centrifugation. Three cell populations were distinguished, mainly on the basis of differences in morphology and cytochemistry, utilizing the MPS stain. One of the cell types had many of the morphological characteristics of the monocyte. This technique, augmented by lysosomal content and endocytosis capacity studies, revealed contimination of the cell suspension with a larger percentage of monocytes than has usually been reported in the literature.
Degranulation and abnormal bactericidal function of granulocytes procured by reversible adhesion to nylon wool
Authors: Klock JC , Bainton DF 
Published: October 2019

Abstract
Granylocyte bactericidal capacity, chemotaxis, hexose monophosphate shung activity (before and after phagocytic stimulus), and quantitative nitroblue tetrazolium reduction and enzyme content were examined in cells obtained by filtration leukaphresis (FL) and continuous-flow centrifugation (CFC). A decrease in the bactericidal efficiency of FL- produced cells compared to that of both normal and CFC-procured granulocytes was found; the decrease was 17% with a cell-to-bacteria ratio of 5:1, and 55% with a 1:1 ratio. Moreover, FL-acquired cells were often vacuolated and consistently contained less acid phosphatase and beta-glucuronidase than did normal granulocytes. When normal cells were incubated for 1–2 hr with nylon wool, 30% of the total acid phosphatase and beta-glucuronidase was released, with no evidence of cell death, thus suggesting degranulation. Similar results were obtained with glass, cotton, or polysulfone plastic fibers. Electron microscopic and peroxidase cytochemical studies of the adherence of normal granulocytes to nylon fibers were also carried out. After 30 min of incubation, cell-to-fiber attachment and cellular aggregation had occurred, although the cells per se appeared normal. After 60 and 120 min, other changes became apparent: (1) a decrease in the amount of cytoplasmic granules; (2) large, intracytoplasmic vaculoles; and (3) extracellular peroxidase on fiber surfaces. We conclude that granulocytes obtained by adherence to nylon fibers show both morphological and biochemical evidence of degranulation and diminished bactericidal capacity, and that these abnormalities may be causally related to decreased granulocyte survival in transfusion recipients.
Severe aplastic anemia: a prospective study of the effect of early marrow transplantation on acute mortality
Authors: Camitta BM , Thomas ED , Nathan DG , Santos G , Gordon-Smith EC , Gale RP , Rappeport JM , Storb R 
Published: October 2019

Abstract
A prospective randomized trial of therapy for severe aplastic anemia was designed to compare early bone marrow transplantation with conventional treatments. All patients with a sibling matched at the major histocompatibility region were transplanted. Transplantation was performed with 17–100 (median 33) days of original diagnosis. Conventional treatments included transfusion support with or without androgens. Twenty-four of 36 patients intered on the transplant arm are alive after 4–20 (median 9) mo with full marrow reconstitution. Only two are limited by chronic graft-versus-host disease. In contrast only 12 of 31 conventionally treated patients are alive. Six of these survivors have improved, five incompletely. The 19 nontransplant deaths have occurred within 1–11 (median 3) mo of diagnosis. Compared to nontransplant regimens, early transplantation more effectively restores normal marrow function and decreases the acute mortality of severe marrow aplasia (p = 0.006). Pending longer follow-up, early marrow transplantation appears to be the most effective available treatment for severe aplastic anemia.
Role of copper in mitochondrial iron metabolism
Authors: Williams DM , Loukopoulos D , Lee GR , Cartwright GE 
Published: October 2019

Abstract
Heme synthesis by copper-deficient cells was investigated to elucidate the nature of the defect in intracellular iron metabolism. Iron uptake from transferrin by copper-deficient reticulocytes was 52% of normal, and the rate of heme synthesis was 33% of normal. Hepatic mitochondria isolated from copper-deficient animals were deficient in cytochrome oxidase activity and failed to synthesize heme from ferric iron (Fe III) and protoporphyrin at the normal rate. The rate of heme synthesis correlated with the cytochrome oxidase activity. Heme synthesis from Fe(III) and protoporphyrin by normal mitochondria was enhanced by succinate and inhibited by malonate, antimycin A, azide, and cyanide. It is proposed that an intact electron transport system is required for the reduction of Fe(III), thereby providing a pool of ferrous iron (Fe II) for protoheme and heme a synthesis.
Potassium uptake and release by human blood platelets
Authors: Wiley JS , Kuchibhotla J , Shaller CC , Colman RW 
Published: October 2019

Abstract
Thrombin is known to reduce the K+ content of human platelets, but the subcellular origin of the lost K+ is not known. The effect of aggregating agents on K+ release was studied in platelets labeled in plasma by preincubation with 42KCI. Platelets were separated from plasma by gel filtration through Sepharose 2B equilibrated with K+ - free Tyrode's buffer. Platelet K+ was 116nEq/10(8) platelets, of which 23% was found to be extracellular immediately after gel filtration. K+ influx was 65 nEq/10(8) platelets/hr at pH 7.5 and was more rapid at pH 7.9. About 70% of cell K+ exchanged with plasma in 4 hr with first- order kinetics, while a minor fraction of about 30% exchanged with a slower time course. This slowly exchanging fraction of platelet K+ was thought to arise from heterogeneity in the platelet population. Epinephrine and ADP aggregated gel-filtered platelets and released serotonin, but with loss of only 5%-10% of cell K+ and no beta- glucuronidase. In contrast, thrombin released up to 30% of platelet K+, whether aggregation occurred or was prevented by not stirring the cells. The specific activity of K+ released by all aggregating agents was identical to the specific activity of total platelet K+. Thrombin (0.01–0.2 NIH U/ml) released serotonin and also beta-glucuronidase (an enzyme of the alpha-granule), and there was a linear relation between release of K+ and this enzyme (r = 0.88). No lysis of platelets occurred, since lactic dehydrogenase was not detected. Pretreatment of platelets with aspirin in vitro inhibited thrombin-induced release of serotonin but had no effect on the loss of K+ or beta-glucuronidase. In contrast, the ingestion of aspirin by mouth inhibited the release of serotonin, beta-glucuronidase, and K+ by thrombin. The data suggested that the K+ loss induced by thrombin was primarily derived from release of alpha-granules and that these organelles contained about 20% of the total platelet K+ in a freely exchangeable and nonsequestered state.
Phospholipid transfer between plasma and platelets in vitro
Authors: Joist JH , Dolezel G , Lloyd JV , Mustard F 
Published: October 2019

Abstract
Washed rabbit platelets were resuspended in plasma in which all of the major phospholipids had been isotopically labeled by injection of 32PO4 into rabbits. At certain time intervals during a 6-hr incubation at 37 degrees C, aliquots were removed from the incubation mixture and the platelets were isolated and subjected to lipid extraction and phospholipid analysis. A continuous rise in platelet non-lipid-bound and lipid-bound radioactivity was observed through-out the incubation period. Two platelet phospholipids, lecithin and lysolecithin, were significantly labeled, whereas little or no labeling of the other phospholipids was found. There was no detectable change in total or individual platelet phospholipid content. At 6 hr, 4% of total platelet phospholipid, 43% of platelet lysolecithin, and 7% of platelet lecithin were labeled. Platelets incubated in plasma from rabbits with diet- induced hyperlipidemia took up and incorporated significantly more label into their phospholipids than did platelets in normal plasma. Labeling of both platelet lysolecithin and lecithin could be due to uptake and metabolism of plasma lysolecithin by platelets. However, labeling of platelet lecithin could at least in part be the result of direct exchange of this phospholipid with the plasma. Uptake and incorporation of endogenous plasma lysolecithin by platelets and, possibly, direct exchanged of platelet lecithin may be important mechanisms in the modification by plasma lipids of platelet membrane phospholipid fatty acid composition and platelet function.
Spinal cord disease in hereditary spherocytosis: report of two cases with a hypothesized common mechanism for neurologic and red cell abnormalities
Authors: McCann SR , Jacob HS 
Published: October 2019

Abstract
Two unrelated patients with hereditary spherocytosis developed idiopathic spinal cord dysfunction. This coincidence, combined with similar individual case reports in the older European literature, suggests that abnormalities may exist in constituents common to red cell membranes and nerve tissue. A similar conclusion has been proposed to explain red cell membrane abnormalities in some of the muscular dystrophies.
Antibody-induced von Willebrand's disease: a newly defined inhibitor syndrome
Authors: Handin RI , Martin V , Moloney WC 
Published: October 2019

Abstract
A patient is described with clinical and laboratory evidence of von Willebrand's disease (VWD) in association with lymphosarcoma. He consistently had a bleeding time of over 20 min; factor VIIAHF, VIIAGN, and VIIVWF under 20%; and severe, diffuse hemorrhage, Following transfusion with cryoprecipitate, the patient had the expected rise in VIIAGN and VIIAHF. The patient's plasma contained an inhibitor which prevented aggregation of normal platelets by ristocetin, but which did not interfere with the measurement of VIIAGN or inactivate VIIAHF activity. The inhibitor was present in serum heated at 56 degrees C for 30 min, was present in a purified IgG fraction of serum, and was precipitated by anti-human IgG. The antibody did not interact directly with washed platelets, but appeared to interact with that portion of the factor VII protein that supports ristocetin aggregation (VIIIVWF). The data provide the first explanation for the pathophysiology of the acquired von Willebrand's syndrome.
Acquired storage pool disease in platelets during disseminated intravascular coagulation
Authors: Pareti FI , Capitanio A , Mannucci PM 
Published: October 2019

Abstract
A patient with clinical and laboratory evidence of disseminated intravascular coagulation associated with deep-vein thrombosis and pulmonary embolism developed a qualitative platelet abnormality characterized by a defective release reaction. Second-phase aggregation induced by ADP and adrenaline was impaired, and reduced collagen- induced aggregation was accompanied by defective release of ADP and ATP. The decrease in total platelet ATP and ADP, the high ATP:ADP ratio in the presence of normal amounts of metabolic adenine nucleotides, and the low content of serotonin associated with abnormal uptake and metabolism of the exogenous amine suggested that the defective platelet function was due to lack of the platelet organelles in which serotonin and nonmetabolic adenine nucleotides are normally stored. Acquired storage pool disease is likely to be related to exposure of circulating platelets to aggregating agents, with their degranulation occurring during disseminated intravascular coagulation.
A platelet abnormality in the Chediak-Higashi syndrome of man
Authors: Costa JL , Fauci AS , Wolff SM 
Published: October 2019

Abstract
Platelets from two probands homozygous for the Chediak-Higashi syndrome have approximately 10% of the normal number of serotonin-containing dense bodies as visualized electron microscopically in air-dried whole mounts. Since transport of serotonin across the platelet plasma membrane proceeds at a normal rate, and the few dense bodies present appear to store normal amounts of serotonin, the absence of dense bodies may account for the low platelet serotonin values found in these patients.
Fibrinolysis in normal plasma and blood: evidence for significant mechanisms independent of the plasminogen-plasmin system
Authors: Moroz LA , Gilmore NJ 
Published: October 2019

Abstract
Fibrinolytic activity of normal plasma and blood has been measured by 125l-fibrin solid phase assay. Activity of plasma is not affected by removal of plasminogenplasmin by affinity chromatography. Activities of euglobulin and pseudoglobulin fractions are approximately equal. epsilon-aminocaproic acid (EACA) (10 mM), tranexamic acid (10 mM), diisopropylfluorophosphate (DFP, 50 mM), and soybean and lima bean trypsin inhibitors (100 mug/ml) do not inhibit plasma activity at concentrations that inhibit pure plasmin and urokinase-activated plasma. Activity is not affected by glass contact and is not inhibited by inhibitors of contact or enzymatic activation of Hageman factor (hexadimethrine bromide, 100 mug/ml; cytochrome C, 250 mug/ml; spermidine, 2 mM; phenylmethylsulfonylfluoride, 1 mM). It is inhibited partially (30%-40%) by heating (56 degrees C, 30 min) and by zymosan (2.5 mg/ml; 40%-90% inhibition), and is increased by hydrazine (20 mM), salicylaldoxime (20 mM), DFP (50 mM), and tosyl-L-arginine methyl ester (TAMe, 10 mM)-the latter two at concentrations known to inhibit Cls of the classic, and factor D of the alternate complement pathways. Increase fibrinolytic activity with TAMe is associated with reciprocal decrease in classic and alternate complement pathway activity. It is concluded that normal plasma fibrinolytic activity is relatively independent of plasmin as the ultimate fibrinolytic enzyme, that Hageman factor-dependent pathways are of minor importance, and that significant heat-stable and heat-labile nonplasmin fibrinolytic activities are operative. These may include proteinases involved in complement activation, and in common control of classic and alternate complement pathways, as well as other nonplasmin proteinases.
Synthesis of cobalamin coenzymes by human lymphocytes in vitro and the effect of folates and metabolic inhibitors
Authors: Quadros EV , Matthews DM , Hoffbrand AV , Linnell JC 
Published: October 2019

Abstract
The uptake of 57Co-cyanocobalamin (CN-Cbl) and its conversion to 5- deoxyadenosylcobalamin (Ado-Cbl), methylcobalamin (Me-Cbl), and hydroxocobalamin (OH-Cbl) has been studied in phytohemagglutinin (PHA)- transformed lymphocytes from normal subjects and patients with patients with pernicious anemia. Uptake and conversion were much greater by PHA- stimulated lymphocytes than by mature non-transformed lymphocytes. In normal cells, uptake of 57Co-CN-Cbl and synthesis of the cobalamin coenzymes were approximately linear between 3 and 48 hr incubation. Ado- Cbl was the major cobalamin formed, and after 72 hr the cells contained about twice as much Ado-Cbl as Me-Cbl. Uptake by lymphocytes from patients with untreated pernicious anemia (PA) was greater than that by normal lymphocytes, but the proportions of Ado-Cbl and Me-Cbl synthesized by each were similar. Folic acid and methyltetrahydrofolate enhanced synthesis of Me-Cbl both in normal and in PA cells, while methotrexate and 5-fluorouracil depressed it. This depression was overcome by 5-formyltetrahydrofolate, suggesting that an uninterrupted folate cycle may play an important role in Me-Cbl synthesis.
Surface markers of human eosinophils
Authors: Gupta S , Ross GD , Good RA , Siegal FP 
Published: October 2019

Abstract
Peripheral blood eosinophils from patients with eosinophilia and from healthy subjects were studied for surface immunoglobulins, receptors for the Fc region of IgG, complement receptors, and spontaneous rosette formation with sheep and mouse erythrocytes. Eosinophils were found to have receptors for complement and for aggregated IgG, and to have the same two types of complement receptors as do lymphocytes and monocytes. Immune adherence type receptors were specific for C4 or C3b, while C3d receptors were specific for C3d but unreactive with C4. Eosinophils differed from fully mature neutrophils in that the former had C3d receptors and relatively weak immune adherence (C4 or C3b) receptors, while the later did not have the C3d receptors and had strong immune adherence receptors. Eosinophil phagocytosis of complement-receptor bound erythrocytes was dependent on the presence of IgG in the antibody coating the red blood cells; this requirement for IgG resembled that found in neutrophil phagocytosis. No surface Ig or spontaneous erythrocyte rosette formation was observed with eosinophils.
Mechanisms involved in enhancement of plasma fibrinolytic activity by chloroform
Authors: Moroz LA , Gilmore NJ 
Published: October 2019

Abstract
The effects of a single 1-min extraction with chloroform (CHCl3) on plasma fibrinolytic activity has been examined by 125I-fibrin solid phase assay, using normal plasma and plasma depleted of plasminogen (PLG) by lysine-Sepharose affinity chromatography. Fibrinolytic activity of normal plasma is increased (40%-175%), and more than 95% of antiplasmin activity is removed. The increase is demonstrable in PLG- depleted plasma, and is not inhibited by tranexamic acid (0.01 M). Purified PLG is not activated to plasmin by ChCl3 treatment. Bio-Gel A 0.5 m fractionation of CHCl3-extracted, PLG-depleted plasma reveals fractions with the following activities: (1) streptokinase-activatable, PLG-independent fibrinolytic activities; (2) PLG activator activities; and (3) plasmin-stimulated but PLG-independent fibrinolytic activities, which include activities inhibited by hexadimethrine bromide and which cofractionate in part with plasmin-stimulated procoagulant activities. In addition, similar fractionation of nonextracted plasma reveals two non-plasmin fibrinolytic activities (approximately 30,000 and 13,000 daltons) activated by streptokinase and plasmin, respectively. The findings indicate that the enhanced fibrinolytic activity resulting from CHCl3 treatment is independent of plasmin as the ultimate fibrinolytic enzyme, although activities stimulated by plasmin may contribute, and that such treatment is a useful maneuver for study of PLG-dependent and PLG-independent fibrinolytic mechanisms, and their interactions.
The effect of chelating agents on iron mobilization in Chang cell cultures
Authors: White GP , Jacobs A , Grady RW , Cerami A 
Published: October 2019

Abstract
The investigation of chelating agents with potential therapeutic value in patients with transfusional iron overload has been facilitated by the use of Chang cell cultures. These cells have been incubated with [59Fe]transferrin for 22 hr, following which most of the intracellular radioiron is found in the cytosol, distributed between a ferritin and a nonferritin form. Iron release from the cells depends on transferrin saturation in the medium, but when transferrin is 100% saturated, which normally does not allow iron release, desferrioxamine, 2,3- dihydroxybenzoic acid, rhodotorulic acid, cholythydroxamic acid, and tropolone all promote the mobilization of ferritin iron and its release from cells. They are effective to an approximately equal degree. The incubation of [59Fe]transferrin with tropolone in vitro at a molar ratio of 1:500 results in the transfer of most of the labeled iron to the chelator, reflecting the exceptionally high binding constant of this compound. How far these phenomena relate to therapeutic potentially remains to be seen.