bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hemoglobin switching in sheep: characteristics of BFU-E-derived colonies from fetal liver
Authors: Barker JE 
Published: October 2019

Abstract
Two types of erythroid colonies were generated in vitro from sheep fetal liver cells. The first type consisted of single colonies of 8–256 cells that were well hemoglobinized by 4 days; these are thought to originate from CFU-E. The second type consisted of macroscopic colonies composed of several subcolonies that matured between days 3 and 8 in vitro. At maturity, each contained 256 to > 1000 cells that formed a discrete macroscopic cluster. The macroscopic colonies, not previously described in sheep, are thought to be derived from BFU-E. The characteristics of sheep BFU-E were defined and the production of fetal hemoglobin (HbF, alpha 1, gamma 2) and HbC (alpha 2 beta 2) was compared in colonies derived from CFU-E or BFU-E. Bursts developed at erythropoietin (epo) concentrations as low as 0.1 U/ml, although the number observed increased with epo concentration up to 10 U/ml. The number of bursts observed was approximately proportional to the number of cells plated. As shown by thymidine suicide, approximately 50% of both the BFU e and CFU-E were in S-phase when obtained from the fetus. BFU-E were smaller and partially separable from CFU-E after sedimentation at unit gravity. The beta c/gamma synthetic ratio in colonies derived from BFU-E was greater than in CFU-E-derived colonies. These data suggest that the capacity for generation of erythroblasts making HbC is greater in the earlier or more primitive erythroid stem cells in fetal liver.
Localized and indolent myeloma
Authors: Alexanian R 
Published: October 2019

Abstract
Criteria were defined for recognizing 29 patients with a localized plasmacytoma of bone and 20 patients with an indolent variety of multiple myeloma in order to justify long-term follow-up without chemotherapy. All patients with indolent myeloma were asymptomatic from their low tumor mass disease, had a hemoglobin greater than 10 g/dl, and showed no more than 3 lytic bone lesions. The presence of more than 200 mg/day of Bence Jones protein was usually followed by disease progression within 2 yr. Serial assessments of myeloma protein level provided a useful index of changing tumor load and the need for chemotherapy. In patients with localized disease, radiotherapy usually reduced myeloma proteins markedly with subsequent disease control for many years, even though small serum peaks persisted. Chemotherapy for multiple myeloma was not required for a median of 8 yr in patients presenting with localized disease and of 3 yr in those with indolent myeloma. The additional survival from the start of drug treatment was similar to that of comparable patients treated promptly for overt multiple myeloma. The delay of chemotherapy until evidence of tumor progression did not affect the long-term outcome of patients with localized or indolent myeloma.
Participation of ADP in the binding of fibrinogen to thrombin- stimulated platelets
Authors: Plow EF , Marguerie GA 
Published: October 2019

Abstract
Thrombin and adenosine diphosphate (ADP) supported the binding of 125I- fibrinogen to washed human platelets with similar kinetics and affinity. Platelet secretion, as measured by 14C-serotonin release, and fibrinogen binding exhibited an identical dependence on thrombin concentration. Enzymatic removal of ADP with apyrase or creatine phosphate/creatine phosphokinase (CP/CPK) from thrombin-stimulated platelets markedly inhibited 125I-fibrinogen binding, but pretreatment of platelets with CP/CPK prior to thrombin stimulation was without effect. Thus, ADP, released from the platelet, participates in the binding of fibrinogen to thrombin-stimulated platelets.
Bone marrow participates in the biosynthesis of human transcobalamin II
Authors: Frater-Schroder M , Nissen C , Gmur J , Kierat L , Hitzig WH 
Published: October 2019

Abstract
Studies concerning the site of synthesis of the vitamin B12 binding serum protein, transcobalamin II, have been done in various mammalian animals. The actual site of biosynthesis in man has not yet been defined. The finding that bone marrow derived cells release apo- transcobalamin II in the mouse led us to examine the genetic patterns of transcobalamin II in man, both before and after marrow transplantation. A gradual but incomplete transformation of the recipient's transcobalamin II type into donor's type, corresponding to 75% or less of the total activity, was registered in 4 cases. Surprisingly, persistent host-type TC II, in spite of different donor type, was observed in 4 further marrow recipients. We conclude that hematopoietic cells transferred with the transplanted marrow participate in the biosynthesis of human transcobalamin II.
Low molecular weight nonheme iron and a highly labeled heme pool in the reticulocyte
Authors: Pollack S , Campana T 
Published: October 2019

Abstract
The ligands that bind iron and heme in reticulocyte and may regulate their distribution are not known. Guinea pig reticulocyte hemolysates were labeled with 59Fe and filtered through molecular weight sieving columns. 59Fe-containing peaks of ferritin, transferrin, and hemoglobin were identified, as well as a low molecular weight peak containing predominantly nonheme iron, and a 17,000 mol wt heme containing peak with a specific activity (59Fe/heme) 20-fold greater than hemoglobin. We note that the low molecular weight peak, the existence of which has been postulated, has been identified for the first time without the addition of a chelating agent. We speculate that the 17,000 mol wt peak is an alpha-chain pool.
Glycosylated hemoglobin A2 components
Authors: Tegos C , Beutler E 
Published: October 2019

Abstract
Partially purified hemoglobin A2 has been examined for the existence of glycosylated components by isoelectric focusing and by acid agar gel electrophoresis. Bands analogous to the glycohemoglobin derivatives of hemoglobin A, hemoglobin-A1.a.b.c, were readily detected. Evidence that these minor bands are in fact glycohemoglobins was obtained by showing that 14C-glucose bound to hemoglobin A2 moved with these minor bands. The amounts of glycohemoglobin derivatives of hemoglobin A2 were increased in the blood of diabetic patients.
Nonrandom chromosomal aberrations in chronic lymphocytic leukemia revealed by polyclonal B-cell-mitogen stimulation
Authors: Gahrton G , Robert KH , Friberg K , Zech L , Bird AG 
Published: October 2019

Abstract
Peripheral blood lymphocytes from 11 patients with chronic lymphocytic leukemia were stimulated by Epstein-Barr virus (EBV), lipopolysaccharide from Escherichia (LPS), and phytohemagglutinin (PHA). Chromosome analysis with the Q-banding technique after 5 days incubation revealed an extra chromosome 12 in 5 of the patients and a translocation between chromosome 11 and chromosome 14 in 1. Two patients had a deletion of chromosome 6, and only 3 patients had a normal karyotype. In most patients, the abnormalities were found in the majority of metaphases after stimulation with EBV, LPS, or both mitogens, while PHA revealed a normal karyotype, with the exception of a total of 4 metaphases in 3 patients. An extra chromosome 12 appears to be specifically associated with chronic lymphocytic leukemia. The frequency of chromosomal abnormalities in this disease appears to be much higher than has previously been thought.
Stimulation of eosinophil production in vitro by eosinophilopoietin and spleen-cell-derived eosinophil growth-stimulating factor
Authors: Bartelmez SH , Dodge WH , Mahmoud AA , Bass DA 
Published: October 2019

Abstract
Eosinophilopoietin (EPP) was previously characterized by the ability to stimulate eosinophil production in vivo, but these studies could not ascertain whether EPP had a direct effect on the bone marrow or acted indirectly by causing release of eosinophilopoietic activity by other tissues. The present studies demonstrate that EPP stimulates eosinophil growth in liquid culture of mouse bone marrow in vitro. The timing of stimulation by EPP in vivo and in vitro were parallel, with maximal eosinophil growth after 48 hr. Moreover, EPP appears similar to, and possible identical with, the eosinophil growth-stimulating substance (EO-GSF) released by antigenic stimulation of immune nonadherent spleen cells. Both EPP and EO-GSF are of low molecular weight, both produce stimulation of eosinophil growth with identical kinetics, and both produced similar dose-response curves in the liquid culture system.
Morphometry of human leukocytes
Authors: Schmid-Schonbein GW , Shih YY , Chien S 
Published: October 2019

Abstract
In order to establish quantitative models of leukocyte functions, several morphometric parameters on individual white cells are needed. These include the diameter, volume, and membrane area of the cells and their nuclei in the undeformed state. A stereologic method was used to obtain these quantities from transmission electron microscopy of random sections through human white blood cells (neutrophils, lymphocytes, monocytes, and eosinophils). In order to estimate possible artifacts due to preparation of the cells for transmission electron microscopy, a detailed comparison with light microscopy was made. The results show that undeformed white cells in isotonic solution are spherical with many membrane foldings and have a significantly smaller diameter than that measured on blood smears. A method of chemical fixation was employed so that the shrinkage due to fixation of the cells is below the resolution of light microscopic measurements. Further, it was shown that all leukocytes, including lymphocytes, have much more membrane area than is needed to cover their volumes, and this membrane area remains constant when the cell is hypotonically swollen.
Use of spleen organ cultures to monitor hemopoietic progenitor cell regeneration following irradiation and marrow transplantation
Authors: von Melchner H , Metcalf D , Mandel TE 
Published: October 2019

Abstract
After lethal irradiation of C57BL mice followed by the injection of 10(7) marrow cells, total cellularity and progenitor cell levels exceeded pretreatment levels within 12 days in the spleen, but regeneration remained incomplete in the marrow. The exceptional regenerative capacity of progenitor populations in the spleen was observed in organ cultures of spleen slices prepared 24 hr after irradiation and transplantation, excluding continuous repopulation from the marrow as a significant factor in splenic regeneration.
Crotalocytin: characterization of the timber rattlesnake platelet activating protein
Authors: Schmaier AH , Colman RW 
Published: October 2019

Abstract
Crotalocytin, a platelet activating protein from timber rattlesnake venom, was studied to characterize its nature and to investigate its action on platelets. It exhibited proteolytic activity on the substrate azocoll and amidolytic activity on several peptide p-nitroanilides. The platelet activating and amidolytic activity of Crotalocytin was inhibited by diisopropylfluorophosphate. In addition, phenylmethylsulfonyl fluoride inhibited Crotalocytin's ability to stimulate platelets. Active site titration with p-nitrophenyl guanidobenzoate indicated that 52% of Crotalocytin's molecules were active and that the enzyme could also hydrolyze the titrant. These studies showed that Crotalocytin is a serine protease. Like thrombin and collagen, Crotalocytin induced simultaneous platelet aggregation and adenosine triphosphate (ATP) secretion. EDTA and prostaglandin E (PGE1) blocked Crotalocytin's ability to activate platelets; hirudin and antithrombin III did not. Crotalocytin stimulated the secretion of serotonin from dense granules and low affinity platelet factor 4 and fibrinogen from alpha-granules. Crotalocytin did not cause platelet lactic dehydrogenase loss or agglutinate formalin-fixed platelets, but it did aggregate chymotrypsin-treated platelets. Studies with antimycin A and 2 deoxy- D-glucose showed that Crotalocytin-induced platelet secretion was dependent on metabolic energy. Furthermore, Crotalocytin's induction of platelet secretion was prevented by eliminating exogenous ADP and blocking activation of the arachidonate pathway. Timber rattlesnake venom contains a serine protease that is unique, potent platelet activator.
Quantitation of hemoglobins within individual red cells: asynchronous biosynthesis of fetal and adult hemoglobin during erythroid maturation in normal subjects
Authors: Dover GJ , Boyer SH 
Published: October 2019

Abstract
We outline a method for estimating either HbF or HbA content in single erythrocytes and their precursors. Our method depends on microphotometric assay of darkfield reflectance arising from individual pericellular immunoprecipitates developed with anti-HbF or anti-HbA. When uniform-diameter latex microspheres were used to normalize comparisons between preparations, mean coefficient of variation for HbF reflectance among separate preparations of the same sample was < 3%. Reflectance is a faithful (r = 0.99) linear function of the logarithm of picograms per cell in samples with known HbF or HbA content. The following features emerged from such analyses. First, despite the use of antigenically-specific antihemoglobins from different sources, the least detectable quantity of HbF (3.2 pg) and HbA (14.8 pg) remained invariant. Second, these detection thresholds depends on antihemoglobin affinity constants but are little influenced by antibody concentration. Third, our procedure is equally valid for persons with normal HbF constant (mean +/- SD = 4.4 +/- 0.3 pg per cell, 15 subjects) and for those with much higher levels. Fourth, like the percentage of HbF- bearing cells, HbF content is usually unchanging in serial samples. Fifth, the utility of the method is evidenced in bone marrow analyses of five hematologically normal persons in whom HbF content, unlike HbA content, remained constant throughout maturation from erythroblasts to erythrocytes. In vivo HbF biosynthesis is thus normally completed long before HbA production.
Organization of alpha-globin genes in Hb Hasharon (alpha 47 asp replaced by his) carriers
Authors: Giglioni B , Comi P , Taramelli R , Ottolenghi S , Ciocca-Vasino MA , Ane C , Cappellini MD , Gianni AM 
Published: October 2019

Abstract
Restriction enzymes analysis of the DNA from two unrelated Italian families with Hb Hasharon, a variant Hb (alpha 47asp replaced by his) frequently occurring in the Polesine area in Italy, indicates that this variant is associated to an alpha globin gene deletion. The alpha Hash genotype most likely results from a mutation on an alpha thal2 genotype.
"Aspirinated" platelets are hemostatic in thrombocytopenic rats with "nonaspirinated" vessel walls--evidence from an exchange transfusion model
Authors: Dejana E , Barbieri B , de Gaetano G 
Published: October 2019

Abstract
The contrasting effects of aspirin on bleeding time (BT) might be related to the drug's inhibitory activity on platelets and vascular prostaglandin I2 (PGI2). To test this, we developed an exchange transfusion model in the rat and studied the BT in animals whose platelets but not vessels had been exposed to aspirin. Rats with severe experimental thrombocytopenia were exchange-transfused with blood from normocythemic rats pretreated with aspirin 6 hr before. The platelet count was raised from 2% to about 70% of basal level and the BT returned to control values even though the platelets neither responded to arachidonic acid nor produced detectable amounts of malondialdehyde and vascular PGI2 was not inhibited. These results indicate that “aspirinated” platelets may be hemostatically active and that the BT is not necessarily affected by unbalanced prostaglandin production in platelets and the vessell wall.
Quantitative immunoferritin microscopy of Fya, Fyb, Jka, U, and Dib antigen site numbers on human red cells
Authors: Masouredis SP , Sudora E , Mahan L , Victoria EJ 
Published: October 2019

Abstract
The Fya, Fyb, Jka, U, and Dib antigen site numbers and ultrastructural distribution patterns on the human erythrocyte membrane were determined using quantitative immunoferritin microscopy. For homozygous antigen- positive red cells, the average number of determinants per red cell was about 14,000 for Jka, 17,000 for Fya and Fyb, 19,000 for Dib, and 23,000 for the U antigen, assuming that the equilibrium binding observed represented 80% saturation of the accessible antigen sites. The site numbers for this group of antigens were less than that for the Rh antigens, but considerably more than the Kell and Cellano antigens. The technique used was capable of demonstrating a twofold difference in antigen density between heterozygous and homozygous Fy (a+) red cells. More than 85% of the Fya and Fyb antigen sites were lost following pretreatment of the red cells with papain, consistent with the serologic lability of the Fy antigens following proteolysis. The ferritin distribution observed following conjugate staining of antibody- sensitized ghost membranes was similar for all five antigens studied and showed a random, clustered ferritin pattern. Although the quantitative estimates are valid, the remarkable similarity in antigen distribution pattern for this diverse group of antigens, as well as other considerations, suggest that the findings with ghose membranes probably do not reflect faithfully the antigen arrangement on the intact red cell membrane.
Anti-inhibitor Coagulant Complex (Autoplex) for treatment of factor VIII inhibitors in hemophilia
Authors: Abildgaard CF , Penner JA , Watson-Williams EJ 
Published: October 2019

Abstract
Fourteen individuals with severe hemophilia complicated by factor VIII inhibitors (1 to 132 Bethesda Units) were treated for 33 bleeding episodes with a new activated prothrombin complex concentrate, Anti- Inhibitor Coagulant Complex (Autoplex, Hyland, Glendale, Calif.). Excellent or good results were observed in 21 of 25 minor bleeding episodes treated, which included joint, soft tissue, and mucous membrane hemorrhages. Eight major bleeding problems (an epidural bleed, a puncture wound, 2 serious soft tissue hemorrhages, 2 lacerations, and 2 major surgical procedures) were treated with excellent (6) or good (2) results. No serious complications were encountered, but two children developed transient hypofibrinogenemia following Autoplex infusion. Although some shortening of the prothrombin time and activated partial thromboplastin time was noted after infusion of Autoplex, there is no useful laboratory test for monitoring therapy. Despite the unknown mechanism of action for bypassing factor VIII, Autoplex appears to be a useful and needed interim product and is safe and effective. In view of the possible potentiation of thrombosis concurrent use of fibrinolytic inhibitors should be avoided.
Evidence for both oxygen and non-oxygen dependent mechanisms of antibody sensitized target cell lysis by human monocytes
Authors: Klassen DK , Sagone AL Jr 
Published: October 2019

Abstract
Recent studies suggest that the generation of reactive oxygen species (ROS) such as hydrogen peroxide (H2O2) or superoxide (O2-) may play a role in monocyte antibody-dependent cytotoxicity (ADCC). We studied ADCC by normal human monocytes, and monocytes from chronic granulomatous disease (CGD) patients, cells unable to generate ROS, toward anti-D sensitized human red cells (RBC) and an antibody sensitized lymphoblastoid cell line (CEM) by 51Cr release. The effects of hypoxia, scavengers of ROS, and the activity of the hexose monophosphate shunt pathway (HMPS) were examined. We found that monocyte HMPS activity increased two to threefold during ADCC toward RBC but was unchanged during ADCC toward CEM cells. Hypoxia decreased lysis of RBC targets by 80% but did not affect lysis of CEM cells even though hypoxia markedly decreased monocyte HMPS activity. Monocytes from CGD patients had impaired lysis of RBC but lysed CEM cells normally. We could not, however, demonstrate protection by scavengers of ROS. We conclude that monocyte ADCC involves two independent mechanisms: a nonoxidative mechanism active in the lysis of CEM cells, and an oxidative mechanism that may involve an unidentified ROS activated during ADCC toward RBC. The activation and possible interaction of these two mechanisms is determined by the nature of the target cell and sensitizing antibody.
Blood tests for the diagnosis of venous and arterial thrombosis
Authors: Hirsh J 
Published: October 2019

Abstract
There are many reports in the literature of blood test abnormalities occurring in patients with venous or arterial thrombosis. Most of these have not used acceptable criteria for establishing an association between thrombosis and blood tests and, therefore, their interpretation is questionable. Recently, sensitive and specific assays have been developed for the detection of products of intravascular thrombin formation, of plasmin digests of fibrin or fibrinogen and of platelet specific proteins that are released into the plasma when platelets react with stimuli. Blood abnormalities have been sought that can either predict or detect venous thrombosis. Many of the predictive tests evaluated are nonspecific acute phase reactant responses to inflammation; of these, only reduced fibrinolytic activity has been consistently reported to be associated with postoperative venous thrombosis. Hereditary antithrombin III deficiency has been consistently shown to predispose patients to venous thrombosis. Abnormalities of the plasminogen and fibrinogen molecule have also been described in patients with familial or recurrent venous thrombosis but these are rare and the association could be coincidental. Two blood tests, the fibrinopeptide A assay and the assay for fibrin/fibrinogen fragment E are highly sensitive to acute venous thromboembolism in symptomatic patients but both are nonspecific. Elevated levels of beta thromboglobulin and platelet factor 4 have been reported in patients with arterial thromboembolism but the sensitivity and specificity of these findings is presently unknow.
Isolation and characterization of cloned DNA: the delta and beta globin genes in homozygous beta + thalassemia
Authors: Burns AL , Spence S , Kosche K , Ramirez F , Mears JG , Schreiner H , Miller C , Baird M , Leibowitz D , Giardina P , Markenson A , Bank A 
Published: October 2019

Abstract
We have isolated and characterized a clone of human DNA from a patient with beta+ thalassemia containing the entire delta and beta structural genes and their flanking sequences. Partial Eco RI digestion of spleen DNA was used to obtain 15 to 20 kilobase (kb) pieces of human DNA that were then ligated to charon 4A lambda phage DNA. The 8 x 10(5) recombinants obtained were grown and screened for their content of beta gene sequences. Four positive clones were found, and one (beta T1–1) has been extensively analyzed. Subclones containing the entire beta gene and the large beta intervening sequence (IVS 2) have been isolated in the plasmid pBR 322. The fragments generated by restriction enzyme digestion in these subclones have been compared to those in similar subclones from normal beta genes. No differences have been found indication no significant rearrangements of deletions of the delta and beta genes. With the enzymes used, 11.2% of IVS 2 have been compared, and thus far no differences between the thalassemic and normal genes have been detected. The 24 enzymes used include Hph I, which recognizes the 5′ end of IVS 2, and AIu I that cleaves at the 3′ end. Thus, there appears to be conservation of nucleotide sequences at the ends of IVS 2 in this beta + thalassemia patient, although RNA metabolism studies suggest a possible defect in RNA processing.