bluuebunny/crossref_metadata_2025_split huggingface dataset:
Observations on the mechanical precipitation of oxy Hb S and other mutants
Authors: Roth EF Jr , Elbaum D , Nagel RL 
Published: October 2019

Abstract
Oxyhemoglobin S exhibits greater mechanical instability than oxyhemoglobin A. The rate of precipitation of Hb S when agitated by vortexing depends upon the geometry of the tube, the volume of the hemoglobin solution, and the concentration of hemoglobin. The rate of precipitation is inversely related to concentration. Precipitation is inhibited by temperatures near 4 degrees C and alkylureas whose protective capacity is approximately proportional to the carbon chain length of the alkyl group. Blocking the beta93 -SH group with parahydroxymercuribenzoate has only a small enhancing effect on the precipitation rate. Other mutants such as Hb Gun Hill, Leiden, (both heat unstable), and C-HARLEM are also unstable. In the case of C- HARLEM, the precipitation rate is greater than that for Hb S. The heat- unstable mutants are not as well protected by cold temperatures or alkyl ureas. D2O has only a minor stabilizing effect on hemoglobin S, but NaCl and related salts markedly enhance precipitation at concentrations of 0.5 M. It is concluded that mechanical instability of oxyhemoglobins is a multifactorial process involving surface denaturation, pH, ionic strength, hydrophobic interactions, protein conformation, and primary protein structure. This phenomenon will require more extensive investigation.
Short communication: possible association of newly absorbed serotonin with nonmetabolic, granule-located adenine nucleotides in human blood platelets
Authors: Holmsen H , Setkowsky CA , Day HJ 
Published: October 2019

Abstract
[3H]-adenine-labeled human platelets in plasma were incubated with or without nonradioactive serotonin. Release reaction was then induced by ADP, epinephrine, collagen, or thrombin. Platelets that had been incubated with serotonin released four times as much serotonin as platelets incubated without serotonin. The specific radioactivities of the ATP and ADP released to plasma during release reaction induced with all four inducers were the same in both systems. This shows that when serotonin is taken up by human platelets, it enters the compartment containing nonmetabolic, granula-stored ATP, and not the compartment with metabolic extragranular ATP. These results suggest that the mechanism of serotonin storage in human platelets is similar to that in other species investigated, i.e., rabbit, guinea pig, and pig.
The effect of EDTA, cations, and various buffers on the morphology of erythrocyte membranes: an electron-microscopic study
Authors: Pinteric L , Manery JF , Chaudry IH , Madapallimattam G 
Published: October 2019

Abstract
Membranes of human erythrocytes were prepared by stepwise osmotic hemolysis in Ca2+-free solutions. Examination with the electron microscope after negative staining showed some short, conelike protuberances on the surface of about 20 percent of the ghosts, while 80 percent were round, intact spheres. After Ca2+ treatment, all membranes were round and intact. After exposure to ethylenediaminetetraacetic acid (EDTA) (1.0 mM, pH 7.4), the entire ghost surface was covered with long, thin extrusions called stromalytic forms (about 460 per cell). Their sizes, shapes, and fine structure are described. Exposure to ionic calcium (1.4 times 10-minus 4M) abolished the EDTA-induced stromalytic forms. A second exposure to EDTA reversed this Ca2+ effect. ATP, like EDTA, produced stromalytic forms. EDTA- induced stromalytic forms were also abolished by Zn2+, La3+, and Nd3+ at concentrations of 1–5 times 10-minus 4 M. Mg2+ at 10-minus 2 M was ineffective. Ghosts were prepared by graded lysis in various buffers. Those prepared in phosphate were the most stable and provided consistent EDTA effects and Ca2+ reversal. Ghosts in Tris-HCl showed breakdown unless salt was added. Moderately satisfactory ghosts were also obtained in Hepes-NaOH buffer and salt.
Dominant inheritance of hemophilia A in three generations of women
Authors: Graham JB , Barrow ES , Roberts HR , Webster WP , Blatt PM , Buchanan P , Cederbaum AI , Allain JP , Barrett DA , Gralnick HR 
Published: October 2019

Abstract
A bleeding diathesis is described which is phenotypically indistinguishable from hemophilia A and which has been transmitted as a dominant trait in three generations of women in a North Carolina kindred. The abnormal phenotype is characterized by clinical mildness and slightly abnormal clotting time, prothrombin consumption, and partial thromboplastin time. Bleeding time, platelet count, clot retraction, tourniquet test, and prothrombin time are normal. Concentration of factors I, II, V, VII, IX, X, and XII are normal, while factor VIII activity is reduced to 2%-5% of control values. De novo synthesis of factor VIII does not occur after transfusion; factor VIII-related antigen is normal; patients'plasmas aggregate platelets normally in the presence of ristocetin, and a typical protein pattern is seen when a chymotryptic digest of cryoprecipitate of the proband is examined by SDS-polyacrylamide gel electrophoresis. Six possible genetic explanations are entertained. Balanced X-autosomal translocation of hemophilia A heterozygotes has been excluded by cytogenetic analysis of metaphase chromosomes. Classes von Willebrand's disease (vWd) is probably excluded on the basis of the laboratory data, and extreme lyonization of hemophilia A heterozygotes on probabilistic grounds. The genetic possibilities which cannot be excluded include a previously unrecognized variant mutation at the vWd locus, a dominant mutation at the hemophilia A locus on the X chromosome, and dominant mutation at a hypothetical fourth locus involved in factor VIII synthesis and control.
Studies on a circulating anticoagulant in systemic lupus erythematosus: evidence for inhibition of the function of activated plasma thromboplastin antecedent (factor XIa)
Authors: Krieger H , Leddy JP , Breckenridge RT 
Published: October 2019

Abstract
Plasma proteins which interfere with blood coagulation have often been described in patients with systemic lupus erythematosus (SLE). The most frequent type interferes with the conversion of prothrombin to thrombin and thus prolongs the prothrombin time. Infrequently, SLE patients exhibit anticoagulants which appear to block the earlier stages of coagulation such as those involving factor VIII or the formation of activated factor XI (factor XIa). The anticoagulant reported here was studied by means of a sequential clotting system utilizing crude coagulation factors and was noted to interfere with the action of activated plasma thromboplastin antecedent (PTA) during the activation of factor IX. This anticoagulant was found in gamma-globulin-rich ethanol fractions of plasma. After gel filtration, it was found principally in fractions containing IgM globulins but also, to a lesser extent, in IgG-rich fractions. In this respect, it is similar to anticoagulants reported in certain other cases of SLE. Attempts to confirm the immunoglobulin nature of the anticoagulant by immunoabsorption were, however, inconclusive.
Effect of papain on the interaction between human monocytes, erythrocytes, and IgG
Authors: Kenna MA , Cooper RA , Schrieber AD 
Published: October 2019

Abstract
The mechanism by which papain detaches IgG-sensitized erythrocytes from the monocyte surface has been explored in an in vitro assay for the monocyte IgG receptor using red cells quantitatively sensitized with IgG anti-Rh D immunoglobulin. Papain treatment of IgG-sensitized erythrocytes diminished the ability of these cells to bind to the monocyte surface; however, treatment of erythrocytes with papain prior to sensitization with IgG did not inhibit binding, and at papain concentrations is greater than or equal to 38 mug/ml binding was enhanced. IgG receptor activity was not diminished by prior treatment of monolayer cells with papain and was enhanced with high concentrations of papain. These studies suggest that papain detaches erythrocytes from the monocyte surface by virtue of its proteolytic effect on IgG and not by an effect of papain on the D antigen of red cells or the IgG receptor on monocytes.
Characteristics of the membrane defect in the hereditary stomatocytosis syndrome
Authors: Wiley JS , Ellory JC , Shuman MA , Shaller CC , Cooper RA 
Published: October 2019

Abstract
Cation permeability and lipid composition have been studied in the red cells of five patients with various features of the hereditary stomatocytosis syndrome. Hemolysis was compensated in four patients, and only one patient was anemic. Cell NA+ was increased an average of 3 mueq per ml cells and cell K+ decreased 14 mueq per ml cells. Both active and passive fluxes of Na+ and K+ were increased by two to six times normal. Tritiated ouabain binding was increased an average of 2.5- fold, suggesting a proportionally greater number of cation pumps per cell. The coupling ratio of active Na+:K+ fluxes was normal (3:2). Calcium permeability was increased compatible with the degree of reticulocytosis, and cell Ca2+ content was normal. The lowered sum of Na+ plus K+ was associated with a high MCHC and low cell water. When examined in wet preparations, red cells assumed either a bowl-shaped or an irregular contour, and they appeared as target cells on dry smears. Only when cell water was increased in hypotonic media were stomatocytes seen on smear. The total lipid content of red cells was increased in four patients, although it was normal in one. The mole ratio of cholesterol to phospholipid was always normal; however, phospholipid analysis showed an increased proportion of phosphatidyl choline. The abnormal cells were osmotically resistant due to both an increased membrane surface area and a low total cation content. These patients show two hallmarks of hereditary stomatocytosis: bowlshaped red cells observed on wet preparations and a marked increase in Na+ and K+ permeability. The heterogeneity of this syndrome in our patients and in others reported with hereditary stomatocytosis appears to result from (1) variability in the increase in surface area which results from an excess of membrane lipid content, particularly phosphatidylcholine, and (2) a variability in cell water content which may be either decreased or increased as a result of changes in the sum of Na+ plus K+ ions.
Elevated platelet count and megathrombocyte number in sickle cell anemia
Authors: Freedman ML , Karpatkin S 
Published: October 2019

Abstract
Eight adult patients with sickle cell anemia were followed over a 6-mo period. During this time all patients had elevated plateletcounts, 1.7- fold (mean, 438,398 +/- 86,223), and megathrombocyte numbers, 2.3-fold (mean, 79,535 +/- 38,907), during asymptomatic periods. These data are interpreted as suggesting that the elevated platelets and megathrombocytes in asymptomatic sickle cell patients result from lack of splenic sequestration. During three crises in two patients, both megathrombocyte number and platelet count fell significantly. It is speculated that platelets may be associated with the pathology in this disease. Platelet function studies performed during crises, therefore, must take into account the number of megathrombocytes.
Clinical and laboratory observations on serum folate-binding protein
Authors: Eichner ER , Paine CJ , Dickson VL , Hargrove MD Jr 
Published: October 2019

Abstract
We studied the effect of serum folate-binding protein (FBP) on folate radioassays and the relationship of the serum level of unsaturated FBP to the serum folate level in various clinical states. Our modification of a heat-extracted radioassay was compared to a whole serum radioassay. Our results confirmed the existence of elevated serum levels of unsaturated FBP in some normal subjects, in some women taking oral contraceptives, and in most patients with uremia. Elevated levels of unsaturated FBP will produce falsely low results in folate radioassay unless the FBP has been destroyed by heat, as was done in the modified radioassay here presented. In normal and uremic subjects, serum folate and unsaturated FBP levels tended to correlate, whereas in patients taking large doses of folic acid the level of unsaturated FBP fell as the level of serum folate rose.
The influence of temperature on red cell deformability
Authors: Williamson JR , Shanahan MO , Hochmuth RM 
Published: October 2019

Abstract
This study was undertaken to examine the influence of temperature on physical properties of red cell membranes. Red cells adhering to cover slips were subjected to fluid shear stress in a rotating disc apparatus for 1 min or for 10 min at temperatures ranging from 2 degrees to 50 degress C. They were fixed while subject to shear stress by addition of glutaraldehyde and then processed for examination and photography by reflected-light microscopy. Cell dimensions were obtained with a computerized planimeter. At shear stresses under 2 dynes/sq cm, cells changed shape from biconcave discs to tear drops, the dimensions of which were influenced very little by temperature or duration of shear stress. Above 2 dynes/sq cm, filamentous processes or “tethers” developed at attachment points of cells to cover slips. Tether length and the percentage of cells possessing tethers increased markedly with increasing temperature and duration of shear stress. At approximately 48 degrees C, a dramatic change occurred over a narrow temperature range such that cells were markedly elongated and irregularly deformed by a shear stress of 1 dyne/sq cm or less. These observations demonstrate that elongation of human red cells subjected to fluid shear stress in a rotating disc system is markedly influenced by temperature as well as by magnitude and duration of shear stress. They also indicate that significant increases in red cell membrane fluidity occur between 2 degrees and 24 degrees-37 degrees C and again between 48 degrees and 50 degrees C.
Abnormal erythroid maturation in mice induced by isoniazid
Authors: Morse BS , Guiliani D , Minak V , Nussbaum M 
Published: October 2019

Abstract
Defective arythropoiesis characterizes the sideroblastic anemias. The present studies were undertaken to assess the effects of isoniazid, an inhibitor of heme synthesis, on erythropoietin-induced erythroid maturation in hypertransfused mice. Isoniazid was administered at intervals during a wave of induced erythropoiesis, and the effects were assessed in both the bone marrow and peripheral blood. The data showed that isoniazid interfered with heme synthesis and erythroid maturation. The most inhibitory effect of isoniazid was noted at the intermediate normoblast stage. A transient increase in the reticulocyte nonheme iron pool was also found.
The heterogeneity and properties of folate binding proteins from chronic myelogenous leukemia cells
Authors: Fischer CD , da Costa M , Rothenberg SP 
Published: October 2019

Abstract
Previous studies have demonstrated that some chronic myelogenous leukemia cells contain a macromolecular binding factor for folic acid. This binder, which previously was believed to be a single factor, has now been resolved into two distinct binding proteins. Separation of each binder was obtained by DEAE chromatography of the partially purified lysate of chronic myelogenous leukemia cells. One binder has a molecular weight of 30;000–35,000, and the second binder has a molecular weight of 40,000-45,000. Both proteins bind the mono-, di-, and triglutamates of folic acid, N10-methyl-folate, dihydro-folate, and N5-methyltetrahydrofolate. Neither binder has determinants for N5- formyltetrahydrofolate or methotrexate. The preferred substrates for both binders appear to be the fully oxidized and partially reduced folates rather than the fully reduced folates. The lower-molecular- weight folate binding protein shows reversible binding with partially and fully reduced folates but irreversible binding with oxidized folates. This property suggests that this binder may have some function in the transport and storage of folate. The higher-molecular-weight folate binding protein, however, has only slight reversibility of binding with the partially and fully reduced folates, and it is therefore more difficult to postulate a physiologic function for this binding factor.
Abnormal erythrocyte metabolism in hepatic disease
Authors: Smith JR , Kay NE , Gottlieb AJ , Oski FA 
Published: October 2019

Abstract
Erythrocyte (RBC) metabolic studies were done on 114 patients with severe hepatic disease. Heinz body formation after incubation of RBCs with acetyl phenylhydrazine was found to be significantly higher in patients than in controls. RBC-reduced glutathione levels were lower than those of controls both before and after incubation with acetyl phenylhydrazine, and patients with the highest Heinz body counts had the lowest reduced glutathione levels. RBC methylene blue-stimulated hexose monophosphate (HMP) shunt metabolism and glucose recycling through the shunt were significantly lower in patients with active hepatic disease than in controls. There was no difference in resting HMP shunt activity or in resting recycling of glucose. Despite impairment of shunt metabolism, total glucose consumption was greater in patients than in controls. The patients with the lowest stimulated HMP shunt metabolism and glucose recycling had the highest Heinz body counts, lowest reduced glutathione, and highest total glucose consumption. A continuum of abnormal shunt metabolism was seen, from a mild reduction of stimulated HMP shunt activity to a severe combined decrease in both the HMP shunt and glucose recycling. When measured, glutathione reductase, glutathione peroxidase, glucose-6-phosphate dehydrogenase, and transketolase were normal or increased. Sequential studies were done on 11 patients who had abnormal metabolic studies. Coincident with improvement of HMP shunt metabolism, the Heinz body counts became lower, reduced glutathione higher, hematocrit higher, and liver function improved. Impaired HMP shunt metabolism appears to be a common, acquired RBC abnormality in patients with severe, active liver disease.
Matching of histocompatibility (HL-A) antigens for platelet transfusion
Authors: Mittal KK , Ruder EA , Green D 
Published: October 2019

Abstract
The average in vivo platelet survival was measured by both per cent recoveries (%R) and half-lives (t 1/2) of 51Cr-labeled platelets in 69 transfusions given to 43 thrombacytopenic patients. The results demonstrated that (1) increase in the number of HL-A incompatibilities in the platelet donor was significantly associated with decreased %R and t 1/2 of the infused platelets; (2) survival of transfused platelets from HL-A-matched single donors was consistently superior to those pooled from several grossly mismatched donors; and (3) survival of platelets infused when patients had circulating lymphocytotoxic antibodies was consistently lower than when patients did not have such antibodies, regardless of whether it was the first, second, or third such infusion.
Immunologic studies on human factor VIII (anti-hemophilic factor A, AHF) components produced by low-ionic-strength dialysis
Authors: Bouma BN , van Mourik JA , de Graaf S , Hordijk-Hos JM , Sixma JJ 
Published: October 2019

Abstract
Since dialysis of human factor VIII against buffers of low ionic strength yielded two distinct components, and since the factor VIII fraction isolated from normal plasma showed von Willebrand factor activity as defined by the corrective effect on abnormal platelet retention and ristocetin aggregation in von Willebrand's disease, the present studies were performed to determine if the correcting activities could be attributed to one or both of the components. Dialysis of factor VIII against buffers of low ionic strength led, however, to a decrease in factor VIII procoagulant activity and the reduction of the correcting activities, which suggested that the intact aggregate was required for procoagulant activity and for von Willebrand factor activity. In this respect dialysis of factor VIII at low ionic strength differed from dissociation at high salt concentrations. The two low ionic strength components were identified by the use of a rabbit antiserum against factor VIII, and could be distinguished on the basis of specific antigenic structures. Dialysis of factor VIII at low ionic strength led to a decrease in antigenic determinants closely related to factor VIII function. Specific antibodies to the low ionic strength components inhibited factor VIII activity in normal plasma, but the residual factor VIII was higher than that after inhibition with antibodies against intact factor VIII. Both antibodies interfered with von Willebrand factor activity.
Effect of a congenital defect in hemopoiesis on myeloid growth and the stem cell (CFU) in an in vivo culture system
Authors: Tyler WS , Stohlman F Jr , Chovaniec M , Howard D 
Published: October 2019

Abstract
W/Wv mice with congenitally defective CFU proliferation and their normal, congenic littermates were used as hosts for diffusion chamber (DC) implants. CFU growth in implanted allogenic CF1, or congenic +/+ marrow was significantly greater in W/Wv than in control hosts. When W/Wv mice were “cured” of their hemopoietic defect, CFU proliferation in the DCs decreased, but not to the control level. These observations have provided evidence for humoral control of CFU growth related to a genetic stem cell defect. Diffusion chamber myelopoiesis was also enhanced in W/Wv hosts. In comparison with their congenic controls, W/Wv mice were neutropenic and had decreased numbers of marrow myeloid elements. Thus, a humorally mediated feedback related to a defective myelopoiesis in the hosts might have accounted for increased DC myelopoiesis. However, a “spillover”effect from increased stem cell growth has not been excluded.
Granulopoiesis in severe congenital neutropenia
Authors: Amato D , Freedman MH , Saunders EF 
Published: October 2019

Abstract
The pathogenesis of the granulopoietic failure in three children with severe congenital neutropenia was studied. Mature neutrophils were absent from both peripheral blood and bone marrow. Assay of bone marrow granulocyte colony-forming cells (CFU-C) in a methylcellulose tissue culture system using colony-stimulating activity (CSA) from peripheral blood leukocytes demonstrated normal or increased concentrations of CFU- C compared to those from marrows of 60 age-matched controls. Colonies were of normal size and by light microscopy appeared to contain granulocytes in all stages of maturation including the mature polymorphonuclear neutrophil. CFU-C from peripheral blood of two patients were normal. Production and activity of CSA from the patients' peripheral blood leukocytes and urinary CSA excretion were normal. No serum inhibitors against CFU-C or CSA could be demonstrated using both control and autologous marrow. The defect did not appear to be due to a lack of granulocytic stem cells, a reduction of humoral stimulators of granulopoiesis, nor the presence of an inhibitor as measured by these techniques.
Protein-mediated uptake of vitamin B12 by isolated mitochondria
Authors: Gams RA , Ryel EM , Ostroy F 
Published: October 2019

Abstract
Protein-mediated B12 uptake by isolated rat liver mitochondria has been shown to be enhanced by plasma transcobalamin (TC-II) but not by salivary R binder in vitro. The process is enhanced by calcium and depends on active mitochondrial respiration. Following uptake, cyanocobalamin is converted to adenosyl and methylcobalamins and released from the mitochondria. TC-II appears to be required for both cellular and mitochondrial uptake of vitamin B12.