bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ferritinophagy and Cell Cycle Control
Authors: Carlomagno Francesca 
Published: October 2019

Abstract
The autophagic degradation of the iron-storage macromolecule ferritin, called ferritinophagy, is critical to restore the appropriate cellular iron levels and influences systemic iron homeostasis. Under low iron conditions, nuclear receptor coactivator 4 (NCOA4) protein accumulates and promotes, as cargo receptor, ferritinophagy. We have recently demonstrated that mice carrying genetic ablation of NCOA4 were unable to mobilize iron from deposits, featuring tissue iron overload as well as mild anemia. Because of impaired ferritinophagy, NCOA4 null mice displayed a severe microcytic hypochromic anemia and ineffective erythropoiesis when fed with an iron low diet. Conversely, they poorly tolerated an iron rich diet, dying prematurely from iron toxicity. Since in previous studies we discovered that nuclear NCOA4 is a chromatin binding protein that acts as a negative regulator of DNA replication origin activation, inhibiting the MCM2-7 DNA helicase, we also investigated whether NCOA4 could regulate DNA replication as a function of iron bioavailability. Treatment with iron chelators promoted a G1 phase cell cycle arrest, blocking DNA replication origins activation. In cell fractionation experiments, we observed that iron depletion induced not only cytosolic but also nuclear NCOA4 stabilization, and by chromatin immunoprecipitation (CHIP) and co-immunoprecipitation assays, we demonstrated that NCOA4 enriches at canonical DNA replication origins increasing the binding to MCM2-7 complex. Silencing of NCOA4 induced an unscheduled activation of DNA replication under iron-depleted conditions that promotes replication stress and impairs cell viability. In conclusion, our data indicate NCOA4 as a novel key iron responsive protein able to couple DNA replication origin activation to cellular iron levels.

Disclosures
No relevant conflicts of interest to declare.
Modeling Diamond Blackfan Anemia and p53 Activation in the Zebrafish
Authors: Zon Leonard I. 
Published: October 2019

Marrow dysplasias are pre-leukemic conditions that include ribosomopathies, a group of rare genetic diseases, or myelodysplasia preceded by clonal expansion in older adults with somatic mutations. To discover novel therapies for ribosomopathies, we performed two chemical suppressor screens using a ribosomal protein mutant zebrafish and human induced pluripotent stem cells (iPSCs) derived from ribosomopathy patients. In the zebrafish screen, we found calmodulin inhibitors rescued the anemia in zebrafish and also rescued the erythroid defect of the mouse (in vivo) and human (in vitro) models of marrow failure. The screen in RPS19 mutant human iPSCs identified a compound, SMER28, which enhanced erythropoiesis in anemia models through an autophagy-dependent mechanism. The compounds identified in our chemicals screens have provided new insight into the etiology of marrow failure, and calmodulin inhibitors will soon be studied in a clinical trial with adult Diamond-Blackfan anemia patients. To study the abnormal clonal hematopoiesis associated with myelodysplasia, we have generated a new system using the zebrafish in which single stem cells and their progeny express unique combinations of fluorescent proteins, allowing them to be tracked over time by their specific color. Mosaic mutagenesis induced by clustered regularly interspaced short palindromic repeats /cas9 and/or gene overexpression in this system led to expansion of specifically colored blood, modeling the clonal hematopoiesis of human myelodysplasia. Our studies should provide new insight into the ribosomopathies and myelodysplasia.

Disclosures
Zon: Marauder Therapeutics: Equity Ownership, Other: Founder; Scholar Rock: Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Other: Founder; Fate, Inc.: Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Other: Founder.
Selective Occurrence of Glutathione Instability in Red Blood Corpuscles of the Various Jewish Tribes
Authors: SZEINBERG A. , SHEBA CH. , ADAM A. 
Published: October 2019

Abstract
1. Experience with GSH stability test performed on blood samples to which glucose has been added is summarized and the procedure is recommended for routine use for the detection of sensitive subjects.
2. Glutathione stability of erythrocytes has been studied in various population groups of Israel. No case with instable GSH has been found among Jewish subjects originating from Eastern, Central or Western Europe. Instability of GSH was however found in about 20 per cent of subjects originating from Iraq and about 5 per cent of subjects originating from Yemen or North Africa. Isolated cases of this abnormality were also discovered among a small number of persons from other Oriental or Mediterranean countries as well as among the Arab inhabitants of Israel.
3. The genetic analysis points to a transmission of glutathione instability by a sex-linked, incompletely dominant gene with variable expressivity.
4. Variable expressivity of glucose-6-phosphate dehydrogenase activity has also been detected in the defective erythrocytes.
Platelet Adsorptive Properties and Platelet Extracts in Thromboplastin Generation
Authors: PERRY SEYMOUR , CRADDOCK CHARLES G. 
Published: October 2019

Abstract
(1) Simple incubation of normal platelets in saline for 10 minutes at 37 C. markedly diminishes their activity in the thromboplastin generation test. This loss of activity is due to the removel of a factor(s) from the platelet and is present in the saline extract.
(2) These "attenuated" platelets retain their effect on the recalcification time, prothrombin consumption, and clotting time of whole blood.
(3) Attenuated platelets, as well as platelets thought to be qualitatively defective, regain normal activity in the TGT after incubation in normal plasma or in plasmas from patients with qualitative platelet defects.
(4) Attenuated platelets, in contrast to qualitatively defective platelets, are restored to normal, as measured by the TGT, after treatment with saline extracts of normal platelets. Attenuated platelets, however, do not function normally after incubation with saline extracts of qualitatively defective platelets.
(5) The possible mechanisms involved are discussed, and it is concluded that the phenomenon involves the adsorption of plasma factor(s) by the platelet. The nature of the plasma factor(s) is not known.
The Effect of Acute Protein Deprivation upon Erythropoiesis in Rats
Authors: BETHARD W. F. , WISSLER R. W. , THOMPSON J. S. , SCHROEDER M. A. , ROBSON M. J. 
Published: October 2019

Abstract
1. Hemoglobin concentration, blood volume, and erythrocyte radioiron uptake were measured in rats subjected to acute protein deficiency.
2. Removal of protein from the diet was followed promptly by hemoconcentration, diminution in blood volume, and drastic reduction in erythropoiesis. These changes were reversible, after 35 days, upon addition of protein to the diet.
3. Protein intake is more essential for maintenance of normal erythropoiesis than is total caloric intake.
4. The data suggest that hemoglobin concentration within the vascular system is more important than red cell volume in regulating erythropoietic rate.
Erythrocyte Osmotic Fragility of Rats Receiving the Thermostable Plasma Erythropoietic Factor
Authors: LINMAN JAMES W. , LONG MARTHA J. 
Published: October 2019

Abstract
1. The thermostable erythropoietic factor in "anemic" rabbit plasma stimulates cellular division of marrow erythrocytic precursors in the normal rat producing erythrocytosis due to microcytes without evidence of augmented hemoglobin synthesis.
2. Study of erythrocyte osmotic behavior in these animals with a quantitative photocolorimetric method failed to demonstrate significant variation from the controls.
3. Osmotic fragility determinations by a direct cell enumeration technic revealed decreased resistance of the microcytes to lysis in hypotonic sodium chloride solutions.
4. It is concluded from these data that the erythrocytes in the normal rat injected with the heat stable plasma erythropoietic factor comprise two distinct cell types. They are microcytes with shortened survival times and normal erythrocytes.
5. The decreased viability of these microcytes is the apparent explanation for the rapid re-establishment of normal erythrocytic equilibrium after the "anemic" plasma extract injections are stopped.
Absorption of Cobalt60-Labeled Vitamin B12 After Subtotal Gastrectomy
Authors: LOEWENSTEIN FRITZ 
Published: October 2019

Abstract
Vitamin B12 absorption has been studied in patients with subtotal gastrectomy by means of the Co60 B12 urinary excretion test. Five patients tested before and after a conventional subtotal gastrectomy showed no significant change in absorption.
Of 22 patients who were tested at various intervals after a conventional (distal) subtotal gastrectomy, 19 had normal vitiamin B12 absorption and three had low absorption that was corrected to normal by giving gastric juice with the test dose. Three patients who had had a proximal gastrectomy showed normal vitamin B12 absorption, indicating that intrinsic factor was being produced by the remaining distal portion of the stomach.
The Efficiency of Oxidative Phosphorylation by Normal and Leukemic Human Leukocytes
Authors: DAVIS VIRGINIA E. , WILSON WILLIAM L. , SPURR CHARLES L. 
Published: October 2019

Abstract
1. A new modification of existing methods has been described for the separation of leukocytes from whole blood which provides a procedure for the rapid isolation of uninjured cells suitable for the study of oxidative phosphorylations.
2. This method has been employed in a study of the relative efficiency and yield of oxidative-linked phosphorylations mediated by normal and leukemic or immature leukocytes. The maximum aerobic phosphorylating capacity was exhibited by chronic lymphocytic leukemic leukocytes, followed in decreasing order of activity by acute monocytic leukemic leukocytes and chronic myelocytic leukemic leukocytes. Oxidative phosphorylation was not demonstrated with normal leukocytes.
3. Results of this study suggest that expression of leukocyte metabolic data on a unit nitrogen basis more accurately reflect the morphologically obvious size differences among the various leukocytes than presentation of data on a unit cell basis.
4. The aerobic phosphorylations mediated by leukemic leukocytes were found to be dependent upon substrate addition and were depressed by low levels of dinitrophenol. Under the experimental conditions employed in this study, glucose-6-phosphate was formed in stoicheiometric amounts. These results indicate that leukemic leukocytes are capable of the aerobic esterification of inorganic phosphate accompanying the oxidation of selected Kreb's cycle intermediates.
On the Occurrence of a Plasminogen-like Substance in Human Tissues
Authors: KOWALSKI E. , KOPEC M. , LATALLO Z. , ROSZKOWSKI S. , SENDYS N. 
Published: October 2019

Abstract
Evidence is presented for the occurrence of a plasminogen-like proenzyme in human tissues.
When homogenates of human connective tissue are incubated with SK they dissolve fibrin clots far more easily than control homogenates without SK. This dissolution of fibrin clots by tissue extracts is a proteolytic reaction similar to the dissolution of fibrin clots by plasma enzyme.
The chemical features of tissue "plasminogen" are the same as of blood plasminogen. It can be extracted at very high and very low PH, precipitated at pH 5.3 (isoelectric point), and inhibited by ions of heavy metals in exactly the same manner as blood plasminogen.
A similar behavior was found in the case of tissue plasminogen in accordance with recent views on the complex nature of the blood fibrinolytic system. The occurrence of tissue inhibitors of plasmin was proven, and it was shown, on comparing the activity of human and bovine tissues, that there is the possibility that in tissues there also exist a "proactivator" and "plasminogen" in accordance with Müllertz and Astrup.
Tissue "plasminogen" occurs chiefly in organs rich in connective tissue, like the aorta wall, fascia, etc. In other organs the "plasminogen" activity is negligible.
It is suggested that tissue "plasminogen" may be of significance in the pathogenesis of certain diseases of connective tissue, e.g. rheumatoid arthritis, in which proteolysis is postulated to be an important pathogenic factor.
Blood Coagulation in Acute Iron Intoxication
Authors: WILSON SLOAN J. , HEATH HELEN E. , NELSON PAUL L. , ENS G. GEORGE 
Published: October 2019

Abstract
Acute intestinal iron intoxication was produced in rabbits and the levels of serum were correlated with changes in blood coagulation.
Acute intestinal iron intoxication resulted in a prolongation of the coagulation time or a complete absence of coagulation, thrombocytopenia, hypoprothrombinemia, and qualitative changes in the fibrinogen. Clot retraction was decreased to absent.
The most marked defect occurred in fibrinogen. In the postiron period the fibrin clot was rust-colored, friable, and fragmented easily. The iron content of the fibrin was tremendous. The physiologic activity of the fibrinogen was decreased and coagulation prolonged.
Fibrinolytic studies revealed no increase in the lysis of the fibrin.
The decrease in the physiologic activity of the fibrinogen frequently produced a hemorrhagic level of prothrombin as measured by the one-stage method. The prothrombin as measured by the two-stage method, although decreased, was not in the hemorrhagic zone. Modification of the one-stage method, correlated with the prothrombin values as determined by the two-stage technic, revealed a defect in both prothrombin and fibrinogen.
Hemoglobin H-Thalassemia Disease
Authors: WOLFF JAMES A. , MICHAELS RICHARD H. , VON HOFE FREDERICK H. 
Published: October 2019

Abstract
A child of Italian parentage is presented as an example of Hgb H-thalassemia disease. A family study is included. Previous documented reports have included individuals of Chinese, Thai, Greek and Filipino parentage. Genetic aspects of the association of Hgb H with thalassemia are discussed. It is suggested that the study of other patients who present a clinical picture resembling mild Cooley’s anemia may reveal the presence of hemoglobin variants.
Therapy of Polycythemia Vera with Myleran
Authors: WALD NIEL , HOSHINO TAKASHI , SEARS MARY E. 
Published: October 2019

Abstract
Myleran was used in the therapy of nine relapses of polycythemia vera in five patients. Clinical examinations, blood studies, and, in three instances, radioisotope tracer tests before and after treatment demonstrated the effectiveness, safety and simplicity of the treatment. Further trial of Myleran therapy in polycythemia vera seems warranted.
The Efficiency of Oxidative Phosphorylation by Normal and Leukemic Human Leukocytes
Authors: Davis Virginia E. , Wilson William L. , Spurr Charles L. 
Published: October 2019

Abstract
Davis, Virginia E., Wilson, William L. and Spurr, Charles L.: The efficiency of oxidative phosphorylation by normal and leukemic human leukocytes. Blood 13:367-375 (April), 1958.
P. 369, line 11: for "reagent bank," read "reagent blank."
P. 370, line 5: for "3 µM DNP," read "3 µM DPN."
P. 370, table 1, column 1: for "DNP," read "DPN."
Chromatin Clumping in Mature Leukocytes: A Hitherto Unrecognized Abnormality
Authors: GUSTKE SUSAN S. , BECKER GARY A. , GARANCIS JOHN C. , GEIMER NICHOLAS F. , PISCIOTTA ANTHONY V. 
Published: October 2019

Abstract
A 62-year-old man and a 73-year-old woman were found to have a nuclear abnormality characterized by exaggerated clumping of the chromatin in the mature granulocytic and erythroid cells. The mature granulocytes showed loss of normal segmentation. The abnormality was not noted in other family members and appeared to be related to an atypical leukemic process. The nuclear abnormality was shown to be associated with a defect in cellular production within the marrow. Granulocyte precursors and normoblasts incorporated 3H-TdR but did not divide. Electron microscopy suggested the distribution of more than normal quantities of heterochromatin to mature leukocytes. Ferrokinetic studies disclosed ineffective erythropoiesis. The sharing of this abnormality by the myeloid and erythroid cells suggests a common stem cell origin.
A functional defect of phagocytosis and cellular aggregation was demonstrated in the neutrophils, but bacterial killing was not affected. The nuclear anomaly described herein may be a pre-leukemic abnormality.
Since this paper was submitted for publication, we have treated two more patients with an identical nuclear defect; an 82-year-old woman and a 79-year-old man. The woman succumbed of acute leukemic transformation, while the man is still alive.
Subcellular Distribution of 51Cr and Characterization of its Binding Sites in Human Platelets
Authors: STEINER MANFRED , BALDINI MARIO G. 
Published: October 2019

Abstract
Subcellular fractionation of human platelets labeled with radioactive sodium chromate was utilized to study distribution and characterization of the 51Cr binding sites in these cells. The cytoplasmic fraction of the platelets contained the major portion of the radioactivity while microsomal and mitochondrial fractions played a minor role in the binding of chromate. The stromal sediment had approximately one third of the total radioactivity. Only about 20 per cent of the 51Cr taken up by the platelets was in a free ionic form and was in the cytoplasmic fraction. The major portion of the 51Cr in the platelets was bound to nucleotides in the platelet cytoplasm. Nucleotides of the α-granules had no radioactive chromate. Hypertonic media and platelet antiserum produced marked release of 51Cr from the platelets, whereas aggregating agents produced none.
In physiologic conditions, elution of 51Cr from labeled platelets is very limited because there is only little 51Cr in free ionic form in the cells. Release of considerable amount of 51Cr from the platelets can occur only in case of cell damage with release of nucleotides from the cytoplasmic pool. This was seen with hypertonic solutions and with platelet antibody. Platelet degranulation, as it occurs with aggregating agents, is not associated with release of 51Cr since the granular pool of nucleotides is not labeled by this compound.
A monoclonal antibody-defined membrane antigen complex is required for neutrophil-neutrophil aggregation
Authors: Schwartz BR , Ochs HD , Beatty PG , Harlan JM 
Published: October 2019

Abstract
We examined the aggregation responses of normal neutrophils treated with the murine monoclonal antibody (MoAb) 60.3. Addition of MoAb 60.3 to normal neutrophils produced dose-dependent inhibition of neutrophil aggregation in response to phorbol myristate acetate, zymosan-activated plasma, and N-formyl-methionylleucylphenylalanine. We conclude that the membrane glycoprotein complex recognized by MoAb 60.3--designated CDw18- -is required for neutrophil-neutrophil aggregation in vitro.
Phosphorylated Forms of Activated Caspases Are Present in Cytosol From HL-60 Cells During Etoposide-Induced Apoptosis
Authors: Martins Luis M. , Kottke Timothy J. , Kaufmann Scott H. , Earnshaw William C. 
Published: October 2019

Treatment of HL-60 human leukemia cells with etoposide induces apoptotic cell death and activation of at least 18 electrophoretically distinct cysteine-dependent aspartate-directed protease (caspase) isoforms, several of which differ only in their isoelectric points. The purpose of the present study was to determine whether activated caspases are phosphorylated. Phosphatase treatment of cytosolic extracts containing active caspases followed by affinity labeling with N-(N-benzyloxycarbonylglutamyl-N-biotinyllysyl)aspartic acid [(2,6-dimethylbenzoyl)oxy] methyl ketone (Z-EK(bio)D-aomk) showed a mobility shift in several of the labeled species, suggesting that phosphorylated forms of these enzymes are present in the extracts. Metabolic labeling with 32P followed by etoposide treatment and subsequent affinity purification of affinity-labeled caspases confirmed that at least three caspase species were phosphorylated. To detect effects of the phosphorylation on enzymatic activity, caspase-mediated cleavage of aspartylglutamylvalinylaspartyl-7-amino-4-trifluoromethylcoumarin (DEVD-AFC) and poly(ADP-ribose) polymerase (PARP) by phosphorylated and dephosphorylated extracts was measured. No significant changes in Km or vmax were detected using DEVD-AFC. In contrast, a slight, but significant enhancement of PARP cleavage was observed in dephosphorylated extracts, suggesting that phosphorylation of active caspases could have an inhibitory effect on enzyme activity. These observations, which provide the first evidence that caspases are phosphoproteins, suggest that caspases may be targets for some of the growing list of protein kinases that are involved in apoptotic events.© 1998 by The American Society of Hematology.
Endothelin-1 Induces Production of the Neutrophil Chemotactic Factor Interleukin-8 by Human Brain-Derived Endothelial Cells
Authors: Hofman F.M. , Chen P. , Jeyaseelan R. , Incardona F. , Fisher M. , Zidovetzki R. 
Published: October 2019

Increased levels of endothelin-1 (Et-1), a potent vasoconstrictor, have been correlated with hypertension and neuronal damage in ischemic/reperfusion injury. The presence of polymorphonuclear cells (PMNs) in the brain has been shown to be directly responsible for this observed pathology. To address the question of whether Et-1 plays a role in this process, human brain-derived endothelial cells (CNS-ECs) were cultured with Et-1. The results demonstrate that Et-1 induces production of the neutrophil chemoattractant interleukin-8 (IL-8) twofold to threefold after 72 hours; mRNA was maximal after 1 hour of stimulation. Conditioned culture medium derived from Et-1–stimulated CNS-ECs induced a chemotactic response in the PMN migration assay. The inflammatory cytokines tumor necrosis factor- (TNF) and IL-1β functioned additively with Et-1 in increasing IL-8 production. In contrast, transforming growth factor-β (TGF-β), but not IL-10, completely abolished the effect of Et-1 on IL-8 production. However, Et-1 did not modulate intercellular adhesion molecule-1 (ICAM-1) expression. These data demonstrate that Et-1 may be a risk factor in ischemic/reperfusion injury by inducing increased levels of the neutrophil chemoattractant IL-8.© 1998 by The American Society of Hematology.