bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evidence for the Clonal Origin of Chronic Myeloid Leukemia From a Sex Chromosome Mosaic: Clinical, Cytogenetic, and Marrow Culture Studies
Authors: Moore M. A.S. , Ekert H. , Fitzgerald M. G. , Carmichael A. 
Published: October 2019

Abstract
Cytogenetic studies on a 7½-yr-old child presenting with clinical and hematological features of chronic myeloid leukemia (CML) revealed a constitutional 46 XY/47 XYY mosaicism in skin, blood, and marrow. A third 46 XY, Ph1 cell line predominated in the marrow on initial presentation and in subsequent acute transformation. Assessment of granulocytic colony-forming capacity in agar culture revealed that colony-forming cells (CFCs) were greatly increased in the circulation and possessed the abnormal light buoyant density and low susceptibility to tritiated thymidine killing which distinguishes leukemic CFCs from normal. During acute transformation colony-forming capacity was lost but small, poorly differentiated cell clusters persisted in culture. Only 46 XY, Ph1 metaphase were obtained following cytogenetic analysis of in vitro colonies and clusters displaying leukemic growth characteristics in agar culture. The coexistence of CML and sex chromosome mosaicism in this patient provides further support for the uniclonal origin of CML and indicates that cytogenetic instability implicated in mosaicism may carry an increased risk of further cytogenetic evolution with emergence of the Ph1 chromosome.
Inhibition of Hemoglobin Synthesis by Cyanate In Vitro
Authors: Alter Blanche P. , Kan Yuet Wai , Nathan David G. 
Published: October 2019

Abstract
Cyanate inhibits sickling and prolongs red cell survival in sickle cell anemia. However, cyanate markedly inhibits hemoglobin synthesis in vitro. Incorporation of radioactive amino acid into hemoglobin by human sickle reticulocytes or bone marrow and by rabbit reticulocytes (whole cell or cell-free lysate) was inhibited by as little as 2 mM cyanate and abolished by 50 mM. Both alpha- and beta-S chains were equally affected. The inhibition was only partially reversible by washing the cells after exposure to cyanate. Transport of radioactive amino acid into the cell was not impaired, and free intracellular amino acid was not carbamylated. Aminoacylation of transfer RNA was not inhibited; the acylated amino acid was not carbamylated. Examination of polysome patterns by sucrose density gradient centrifugation revealed degradation of polysomes to monosomes, suggesting inhibition of initiation of protein synthesis by cyanate. In a cell-free lysate, cyanate prevented hemin stimulation of initiation. We conclude that cyanate profoundly inhibits initiation of hemoglobin synthesis in vitro.
Hemoglobin LeporeBoston in Two Iranian Families
Authors: Rahbar S. , Golban-Moghadam N. , Saoodi H. 
Published: October 2019

Abstract
Hemoglobin LeporeBoston was found in two Iranian families presenting the clinical manifestations of β-thalassemia trait. Electrophoresic examination of the patients’ hemoglobin revealed the presence of an abnormal hemoglobin with Lepore characteristics. Fingerprints and amino acid analysis of selected peptides of this variant suggest that it is similar to LeporeBoston.
Regulatory Mechanism of Glutathione Reductase Activity in Human Red Cells
Authors: Yawata Yoshihito , Tanaka Kouichi R. 
Published: October 2019

Abstract
The mechanism by which glutathione reductase (GR) activity is regulated in relation to flavin metabolism was studied in red cells of normal adults, cord blood, and patients with severe metabolic disorders using spectrophotometric, fluorometric, and radiochemical methods. The increased activity of GR in red cells of adult patients with severe hepatic cirrhosis, chronic uremia, and glucose-6-phosphate dehydrogenase (G-6-PD) deficiency is related to the increased per cent saturation of GR with flavin adenine dinucleotide (FAD), and increased red cell flavin level. The per cent saturation of GR with FAD correlates with (1) the degree of clinical severity in hepatic cirrhosis or chronic uremia, and (2) total flavin level in red cells. Thus, the increased GR activity in these patients may be regulated actively or passively by the increased flavin level in red cells. This suggests that the increased requirement for enhanced activity of the pentose phosphate pathway may affect GR metabolism secondarily, leading to the association of GR with FAD through an increased uptake of riboflavin. In contrast to the results in adult red cells, cord erythrocytes show an unexpected metabolic pattern of GR and flavin metabolism. Although the total GR activity of cord red cells is considerably higher than in adult red cells, cord red cell GR is only partly saturated with FAD even in the presence of a significantly increased flavin level in cord red cells. Thus, cord red cells may have an additional control mechanism of GR activity.
Allogeneic Marrow Grafting for Treatment of Aplastic Anemia
Authors: Storb R. , Thomas E. D. , Buckner C. D. , Clift R. A. , Johnson F. L. , Fefer A. , Glucksberg H. , Giblett E. R. , Lerner K. G. , Neiman P. 
Published: October 2019

Abstract
Twenty-four patients with severe aplastic anemia, 14 due to unknown cause, four associated with hepatitis, four drug or chemical related, one with paroxysmal nocturnal hemoglobinuria, and one possibly associated with a Fanconi syndrome did not show spontaneous recovery after 2-24 mo of conventional therapy. Eleven were infected and nine were refractory to random platelet transfusions at the time of admission. All received marrow grafts from HL-A identical siblings. Eighteen were conditioned for grafting by cyclophosphamide (CY), 50 mg/kg on each of 4 successive days, and 6 by 1000 rad total body irradiation (TBI). All received intermittent methotrexate (MTX) therapy within the first 100 days postgrafting to modify graftversus-host disease (GvHD). One patient died on the day of grafting of congestive heart failure possibly related to CY cardiac toxicity. One died on day 6 with septicemia. One died on day 24 without engraftment. Twenty-one patients showed prompt hemopoietic engraftment indicated by rising blood counts, return of marrow cellularity, and in most instances confirmed by blood genetic markers. Four rejected the graft and died on days 33, 41, 51, and 67. Four died between days 45 and 85 with GvHD. One died of cytomegalovirus infection on day 91. One with chronic active hepatitis died on day 427 of unknown causes. Eleven are alive with grafts and without GvHD more than 141, 144, 163, 186, 189, 255, 344, 472, 641, 746, and 823 days after grafting, and ten have returned to normal activity. These results show that normal stem cells will repopulate the marrow in patients with aplastic anemia and demonstrate that long-term stable chimerism is possible in man. They suggest that marrow grafting in patients with complete marrow failure and an HL-A matched sibling should be undertaken before major infections and refractoriness to blood transfusions complicate their course.
Chronic Granulocytic Leukemia (CGL) During the Course of Chronic Lymphocytic Leukemia (CLL): Correlation of Blood, Marrow, and Spleen Morphology and Cytogenetics
Authors: Whang-Peng Jacqueline , Gralnick Harvey R. , Johnson Ralph E. , Lee Elaine C. , Lear Arnold 
Published: October 2019

Abstract
Second malignancies occur with a greater frequency in patients with chronic lymphatic leukemia than in the general population. Previously, 20 patients having CLL have been reported as developing acute leukemia, but no cases of development of chronic granulocytic leukemia have been observed. In the present report, we will describe patients with Ph1 chromosome positive CGL associated with previously described CLL. One patient received total body radiation treatment for his CLL, while the second was not treated. It is apparent that previous therapy may not necessarily be a prerequisite for the development of a second malignancy in CLL. Cytogenetics offers a useful tool to confirm morphologic criteria in establishing the diagnosis of a second neoplasm.
Concentration of Fetal Red Blood Cells From a Mixture of Maternal and Fetal Blood by Anti-i Serum—An Aid to Prenatal Diagnosis of Hemoglobinopathies
Authors: Kan Yuet Wai , Nathan David G. , Cividalli Gabriel , Crookston Marie C. 
Published: October 2019

Abstract
Fetal red blood cells were concentrated from mixtures of maternal and fetal cells by differential agglutination with anti-i serum. This method will be useful for prenatal diagnosis of hemoglobinopathies when blood obtained from the fetus is heavily contaminated by maternal cells. The method is practical, except in very rare cases in which the maternal red cells are strongly agglutinated by anti-i.
Posthepatitic Severe Aplastic Anemia—An Indication for Early Bone Marrow Transplantation
Authors: Camitta Bruce M. , Nathan David G. , Forman Edwin N. , Parkman Robertson , Rappeport Joel M. , Orellana Tessa D. 
Published: October 2019

Abstract
Despite the use of androgens, corticosteroids, antibiotics, and blood product support, survival in posthepatitic severe aplastic anemia remains about 10%. Histocompatible bone marrow transplantation in this illness has been shown to be feasible. Therefore, marrow transplantation is indicated early in the course of severe aplasia following hepatitis. Delay of this procedure exposes patients to increasing risks of sepsis, hemorrhage, and sensitization to transplantation antigens by multiple transfusions. Weeks, not months, should elapse between diagnosis and transplantation if an appropriate donor, intensive supportive care, and a trained transplantation team are available.
Electrophoretic and Kinetic Studies of Mutant Erythrocyte Pyruvate Kinases
Authors: Nakashima Koji , Miwa Shiro , Oda Susumu , Tanaka Takehiko , Imamura Kiichi , Nishina Toshihiro 
Published: October 2019

Abstract
Thin-layer polyacrylamide electrophoresis and kinetic studies were used to differentiate three different mutant erythrocyte pyruvate kinase (PK) in congenital nonspherocytic hemolytic anemia. In the first family, proband and father had PK which migrated faster than the normal and high Michaelis—Menten constants (Km), whereas mother had normal migration and kinetics, but low PK activity. In the second family, proband and mother had PK which migrated slower than the normal. Proband had markedly high Km and mother intermediately high Km. In the third family, proband and mother had faster migrating PK than the normal. Proband had high Km and mother had intermediately high Km. The parents in the second and third families were consanguineous. Inherited molecular abnormalities of erythrocyte PK were proven to exist by abnormal electrophoretic mobilities, as well as abnormal results of kinetic studies.
The Ingestion of IgG-sensitized Erythrocytes by Abnormal Neutrophils
Authors: Zipursky A. , Brown E. J. 
Published: October 2019

Abstract
The ingestion of IgG-sensitized erythrocytes was compared in monocytes and neutrophils. Normally neutrophils do not ingest IgG-sensitized erythrocytes, and it has been suggested that phagocytosis of IgG-sensitized erythrocytes is restricted to cells of the monocyte series. Neutrophils from 15 patients with acute leukemia and six patients with leukocytosis were studied in experiments with anti-D (IgG) sensitized erythrocytes. Normally these cells are not ingested by neutrophils, although monocyte erythrophagocytosis occurs. In contrast, neutrophils of patients with acute leukemia and leukocytosis ingested anti-D-sensitized erythrocytes following binding of these cells through a specific IgG receptor site. These results show that neutrophil function differs greatly, dependent on the pattern of myelopoiesis. Neutrophils formed during abnormal myelopoiesis may have erythrocyte binding and ingestion characteristics similar to that of the monocyte.
The Effect of Autologous Serum on Lymphocyte Response to Human Leukemia Cells
Authors: Bryan J. Hugh , Johnson Gloria E. , Leventhal Brigid G. 
Published: October 2019

Abstract
The normal lymphocytes of 11 of 18 patients with acute leukemia in remission showed a positive blastogenic response in vitro to autologous leukemia cells. The effect of autologous serum on this response was studied to determine if there were factors which might abrogate or "block" this response. Serum obtained at diagnosis (i.e., during a tumor-bearing period) was compared with remission serum with the expectation of demonstrating a "blocking" effect of the former and no effect or perhaps even facilitation with the latter. However, this was not the case, and no consistent differences in blastogenesis in the presence of the two sera were seen. In addition, during the period of observation, there was little correlation between the presence or absence of in vitro response to autologous tumor and prognosis.
Platelet Satellitism
Authors: Kjeldsberg Carl R. , Swanson John 
Published: October 2019

Abstract
Platelet adherence to polymorphonuclear leukocytes, or so-called platelet satellitism, has, to our knowledge, been reported in only four patients. We had the opportunity to study this phenomenon in two patients. Platelet satellitism was only seen in EDTA anticoagulated blood, and the platelets were seen to surround polymorphonuclear leukocytes only. Electron microscopic studies demonstrated focally opposed regions of platelet and neutrophil plasma membranes. Phagocytosis of platelets was also observed. In vivo and in vitro platelet functions were normal. Platelet satellitism is an in vitro phenomenon, the cause of which is unknown. We are unable to relate it to functional abnormalitles of the blood, the clinical condition of the patient, or to drugs. This phenomenon has some clinical importance in that it causes spurious thrombocytopenia.
Parameters of Marrow Proliferative Capacity In Vitro: Detection of a Sex Difference in Normal Human Granulopoiesis
Authors: Rosenblum Alan L. , Bull Joan M. , Carbone Paul P. , Stashick Eleanor , McKoy Wilma M. K. 
Published: October 2019

Abstract
Sixteen bone marrow aspirates from normal males, cultured in vitro at various concentrations, were compared with ten aspirates from normal females. Marrow from males produced a significantly higher colony count than females when plated at a standard concentration of 2.0 x 105 cells per dish. This difference in colony-forming ability was found to be cell-dose related when dose-response studies for each marrow were obtained at concentrations of 1.0, 1.5, and 2.0 x 105 cells per plate. To more fully characterize marrow proliferative capacity in vitro, two additional parameters of growth were defined: (1) the slope of the dose-response curve and (2) the extrapolated cell concentration at "zero" colony growth. These parameters were found to differ significantly between male and female marrows and suggest that the mechanism of steady-state regulation of resting marrow may differ in males and females.
Recurrent Attacks of Abdominal Pain and Fever With Familial Segmentation Arrest of Granulocytes
Authors: Murros J. , Konttinen A. 
Published: October 2019

Abstract
In a family four sisters have suffered, the oldest two for nearly 20 yr, from recurring attacks of abdominal pain and fever of unknown etiology. Clinical similarity to familial Mediterranean fever is striking. However, they all have a segmentation arrest of granulocytes, which resembles the Pelger-Huet anomaly. It seems that the association is more than a mere coincidence.
Sideroblastic Anemia Treated With Immunosuppressive Therapy
Authors: Zervas J. , Geary C. G. , Oleesky S. 
Published: October 2019

Abstract
A case of apparently primary sideroblastic anemia, in an elderly woman, refractory to hematinic therapy and requiring many blood transfusions, was treated with azathioprine. Over a period of 6 mo, the hemoglobin level gradually rose to normal, no further transfusions have been required in the 30 mo since then, and the marrow picture shows a considerable decrease in the degree of mitochondrial iron overload. There was a simultaneous fall in the titer of HL-A cytotoxic antibodies. The possible role of immunologic factors in this sequence of events is discussed.
Serum Colony-stimulating Activity of Dogs With Cyclic Neutropenia
Authors: Yang T. J. , Jones J. B. , Jones E. S. , Lange R. D. 
Published: October 2019

Abstract
Bone marrow cells, from both normal and cyclically neutropenic (CN) dogs, treated with CN or normal dog serum produced large numbers of leukocytic colonies in soft agar cultures. The largest number of colonies was formed in cultures treated with serum taken from CN dogs at the nadir of the neutropenia. The serum colony-stimulating activity was shown to be inversely related to the CN dog’s peripheral neutrophil counts, suggesting a negative feedback control of granulopoiesis.
Inhibition of Human Platelet Aggregation by Plasmin Digests of Human and Bovine Fibrinogen Preparations: Role of Contaminating Factor VIII-related Material
Authors: Culasso D. E. , Donati M. B. , de Gaetano G. , Vermylen J. , Verstraete M. 
Published: October 2019

Abstract
Preparations of human fibrinogen, digested by plasmin, inhibited ADP-induced platelet aggregation; the inhibitory activity was confined to the small dialyzable fragments accumulating during the degradation. Purified large molecular weight fragments D and E had no effect on ADP-induced aggregation, but fragment E inhibited thrombin-induced aggregation. Extensively degraded bovine fibrinogen preparations also inhibited platelet aggregation by ADP. Both human and bovine fibrinogen preparations were contaminated with factor VIII-related material (factor VIII-related antigen and factor VIII procoagulant activity, respectively); separation of factor VIII-related material from human or bovine fibrinogen by gel chromatography and subsequent plasmin digestion of the fractions revealed that the inhibitory activity was mainly linked to digested factor VIII-related material. This inhibitory activity was dialyzable. The effect of fibrinogen digests on platelet aggregation should therefore be reconsidered.
Studies of Leukemic Cell Populations in Culture
Authors: Aye M. T. , Niho Y. , Till J. E. , McCulloch E. A. 
Published: October 2019

Abstract
A suspension culture technique for the study of peripheral blood cells from patients with leukemia is described. Cells from patients in relapse were preserved by freezing with dimethylsulfoxide at -70°C to ensure the availability of the same population of cells for repeated experiments of varying designs. Cells from one AML patient proliferated only in the presence of phytohemagglutinin (PHA) or leukocyte-conditioned medium (LCM). Cells taken at a later date, after commencement of chemotherapy, failed to proliferate in response to PHA, although the responsiveness to LCM was retained. Proliferation of the cells obtained after chemotherapy could also be stimulated by culture supernatants from the original PHA-responsive cells. Eight other patients studied showed varying responses to LCM and PHA. It is proposed that cells from leukemic patients are made up of two interacting populations, one which produces stimulatory factors and another which responds to these factors by proliferation. Delineation of these two populations and the factors produced may provide a better understanding of leukemic cell proliferation.
Stimulation of Lipid Synthesis in Reticulocytes as a Response to Membrane Damage
Authors: Ballas Samir K. , Burka Edward R. 
Published: October 2019

Abstract
Exposure of rabbit reticulocytes to agents which damage the cell membrane by a variety of different mechanisms stimulates the incorporation of radioactive acetate and glycerol into membrane lipids. An increase in the rate of lipid synthesis occurs within minutes at 37°C at concentrations of the agents which do not cause spontaneous cell lysis. Different agents do not increase synthesis of different classes of reticulocyte lipids to the same extent. 1.5 x 10-4M vincristine stimulates the incorporation of precursors only into neutral lipids while, in contrast, 10-3M puromycin stimulates only synthesis of the three carbon backbone of phospholipids. The effects of these two agents are additive, confirming their selective action on distinct pathways. The effect of puromycin is independent of its ability to inhibit protein synthesis. 3.6 x 10-3M butanol stimulates pathways for synthesis of both neutral lipids and phospholipids to approximately equal extents. The major effect of 4% hydrogen peroxide is to increase exchange of labeled fatty acids, but it also increases phopholipid synthesis. The evidence indicates that a metabolic response of the reticulocyte to membrane damage is to increase synthesis of neutral lipid and phospholipid, and the particular pathway or pathways which respond are related to the agent used to induce damage.
Correlations Between Quantitative Assay of Red Cell-bound C3, Serologic Reactions, and Hemolytic Anemia
Authors: Fischer Jörg Th. , Petz Lawrence D. , Garratty George , Cooper Neil R. 
Published: October 2019

Abstract
A new immunochemical method was used to quantitate the number of C3 molecules bound to human red cells in vitro or in vivo and to assess the clinical significance of cell-bound C3 in immune hemolysis. In addition, results utilizing the immunochemical method were compared with those obtained using commonly performed semiquantitative serologic techniques such as the antiglobulin test and antiglobulin titration score. The antiglobulin test using anti-C3 antiglobulin serum became weakly positive with 60-115 molecules C3 per red cell, and was strongly positive with 1000 molecules C3 per red cell. Antiglobulin titration scores correlate well with immunochemical assessment of the number of C3 molecules per red cell. Therefore, a simple extension of the routine antiglobulin test affords clinically useful data concerning the relative degree of sensitization of red cells by C3. Two of fourteen patients with fewer than 1100 molecules C3 per red cell had hemolytic anemia, whereas 8 of 11 patients with greater than 1100 molecules C3 per red cell had overt hemolysis. The presence or absence of hemolysis was not explained by variations in the amount of IgG on these patients’ RBC. It thus appears that the amount of C3 per red cell is an important determinant of hemolysis in human immune hemolytic anemias.
Löffler’s Endomyocardial Fibrosis With Eosinophilia in Association With Acute Lymphoblastic Leukemia
Authors: Blatt P. M. , Rothstein G. , Miller H. L. , Cathey W. J. 
Published: October 2019

Abstract
The association of eosinophilia and Löffler’s endomyocardial fibrosis with acute lymphoblastic leukemia in a 9-yr-old boy is reported. During the illness, there were three leukemic relapses, each preceded by eosinophilia which subsided upon induction of remission. It is suggested that the eosinophilia in this case was not "eosinophilic leukemia," but more likely a nonneoplastic response to an antigenic stimulus from the leukemic process.
Unusual Inclusions Occurring in the Blasts of Four Patients With Acute Leukemia and Down’s Syndrome
Authors: Brunning Richard D. , Parkin Janet , Dick Fred , Nesbit Mark 
Published: October 2019

Abstract
The blast cells from four patients with acute leukemia and Down’s syndrome were found to contain unusual inclusions which manifested similar morphologic and cytochemical characteristics. Ultrastructure studies of the blasts from one of these patients revealed the inclusions to be single membrane-bound structures containing electron-dense amorphous debris, membranous substance, and virus-like particles.