bluuebunny/crossref_metadata_2025_split huggingface dataset:
New approaches to the transfusion management of thalassemia
Authors: Propper RD , Button LN , Nathan DG 
Published: October 2019

Abstract
Recent advances in the treatment of patients with thalassemia major have centered around the removal of iron from individuals already overloaded due to repeated transfusions. In this report we present therapeutic maneuvers designed to decrease the rate of iron accumulation. We demonstrate that the persistent maintenance of hematocrits above 35% (“supertransfusion”) is not associated with an increased transfusion requirement because it produces a decrease in whole blood volume (21% +/- 2%). Supertransfusion is also associated with normalization or even prolongation of plasma iron turnover. In addition, we describe a method for obtaining units of blood from normal donors that contain primarily young red cells (“neocytes”). These cells have prolonged in vivo survival as measured by the interval between transfusions (30 +/- 2.5 days to 43 +/- 4.5 days) and 51Cr red cell survival (43.8 days versus 27.8 days). Supertransfusion with neocytes is effective in decreasing the rate of iron accumulation in thalassemia.
Cyclic oscillation of blood neutrophils in a patient with multiple myeloma
Authors: Chikkappa G , Chanana AD , Chandra P , Cronkite EP , Thompson KH 
Published: October 2019

Abstract
A patient with multiple myeloma developed periodic blood neutropenia (periodicity of 15–25 days) after 3 yr of intermittent treatment with cytotoxic agents. Peaks of serum colony-stimulating activity (CSA) level coincided with valleys of blood neutrophils. Fraction of marrow neutrophils in the multiplicative pool was high during blood neutrophil valleys and low during neutrophil peaks. In contrast, the maturation storage pool exhibited the reverse pattern. An increased fraction of marrow neutrophilic cells in the multiplicative pool was in active proliferation during a blood neutrophil valley and a decreased fraction during a blood neutrophil peak. These findings suggest that the marrow granulopoiesis was regulated through CSA. The defect causing the periodicity was probably related to the reduced number of neutrophils in the marrow maturation storage pool, which in turn may be related to a reduced and/or defective granulocytic stem cell pool size consequent to the long-term administration of cytotoxic drugs and/or infiltration of the marrow by myeloma cells.
Induction of unscheduled DNA synthesis in human myeloma cells
Authors: Lewensohn R , Ringborg U 
Published: October 2019

Abstract
Unscheduled DNA synthesis (UDS) induced by melphalan, nitrogen mustard and ultra-violet irradiation was studied in bone marrow cells from myeloma patients. In a previous study, normal bone marrow cells in various stages of maturation were found to display a gradual decrease in UDS parallel with the process of maturation. Myeloma cells showed a similar pattern. Poorly differentiated myeloma cells exhibited a similar level of UDS to myeloblasts and erythroblasts. Irrespective of which repair-inducing agent was used, the relationship between the levels of UDS in the various cell types was constant. This indicates that the differences in the level of UDS in the various cell types was not due to differences in the uptake of the repair-inducing agent.
Total lymphoid irradiation and cyclophosphamide as preparation for bone marrow transplantation in severe aplastic anemia
Authors: Ramsay NK , Kim T , Nesbit ME , Krivit W , Coccia PF , Levitt SH , Woods WG , Kersey JH 
Published: October 2019

Abstract
A new combination of total lymphoid irradiation and cyclophosphamide was used prior to bone marrow transplantation in an attempt to achieve decreased rejection rates and graft-versus-host disease. Nine previously transfused patients with severe aplastic anemia received marrow from an HLA-identical, MLC-compatible sibling following this preparative regimen. There were no episodes of graft rejection, and only one patient developed graft-versus-host disease. Of the 9 patients, 7 (78%) are surviving with a median follow-up of 400 days. The excellent results of this pretransplant combination of total lymphoid irradiation and cyclophosphamide warrants application of this regimen to a larger series of patients.
Pretreatment tumor mass, cell kinetics, and prognosis in multiple myeloma
Authors: Durie BG , Salmon SE , Moon TE 
Published: October 2019

Abstract
One-hundred fifty patients with multiple (plasma cell) myeloma had pretreatment tumor mass staging, and 79 also had measurement of the pretreatment labeling index (LI%). There were clear differences in survival by pretreatment stage of disease. The pretreatment LI% of bone marrow plasma cells was an independent prognostic factor both in single factor and multivariate regression analyses, including myeloma stage (p less than 0.02). Other important prognostic factors (multivariate) included performance status, serum creatinine, presence of Bence Jones protein, age, and kappa/lambda subtype. A LI% of less than 1% was associated with long survival in each patient group. Patients with benign gammopathy had excellent survival and very low labeling indices. A pretreatment LI% of greater than 3% in high cell mass patients with a high total number of DNA synthesizing cells (S) conferred a very poor prognosis (p = 0.002). This subgroup of patients with high S values also had a high incidence of central nervous system relapse (27%), Bence Jones proteinuria, and elevated serum uric acid levels. We conclude that the pretreatment labeling index provides helpful prognostic information in addition to tumor mass staging.
Identification and separation of secreted platelet proteins by isoelectric focusing. Evidence that low-affinity platelet factor 4 is converted to beta-thromboglobulin by limited proteolysis
Authors: Niewiarowski S , Walz DA , James P , Rucinski B , Kueppers F 
Published: October 2019

Abstract
Low-affinity platelet factor 4 and beta-thromboglobulin are low molecular weight platelet secretory proteins that have common antigenic determinants. Four amino acids (Asn-Leu-Ala-Lys) at the amino terminus of beta-thromboglobulin are deleted, but the remaining sequences of the two peptides appear to be identical. Low-affinity platelet factor 4 and beta-thromboglobulin have respective isoelectric points at pH 8.0 and at pH 7.0. Identification, quantitation, and separation of both proteins was achieved by a method combining preparative isoelectric focusing and specific radioimmunoassay with anti-low-affinity platelet factor 4 antibody. It has been determined that the supernate processes immediately after platelet aggregation induced by ionophore A23187 or thrombin contains approximately 80% low-affinity platelet factor 4, 8% beta-thromboglobulin, and 12% highly cationic immunoreactive material (platelet basic protein). Experimental evidence suggests that low- affinity platelet factor 4 is originally secreted by platelets and then converted to beta-thromboglobulin by a platelet-derived, heat-labile protease that is inhibited by phenylmethylsulfonyl fluoride.
The effect of trimethoprim/sulfamethoxazole on Friend erythroleukemia cells
Authors: Steinberg SE , Campbell CL , Rabinovitch PS , Hillman RS 
Published: October 2019

Abstract
Cultures of Friend erythroleukemia cells were subjected to the antibiotics trimethoprim (T) and sulfamethoxazole (S) at levels equal to or below the usual therapeutic range. At T 8 microgram/ml and S 40 microgram/ml, cell growth was arrested, cells appeared megaloblastic, and the examination of cell-cycle distribution by flow microfluorimetry revealed arrest in S phase. With a tenfold reduction in drug levels (T, 08 microgram/ml; S, 4 microgram/ml) cell growth was less markedly inhibited, morphology remained megaloblastic, and S-phase block was still dramatic. A further tenfold reduction (T, 0.08 microgram/ml; S, 0.4 microgram/ml), well below effective antibacterial levels, allowed normal cell growth and morphology but DNA synthesis was still inhibited. Additions of folinic acid at 100 ng/ml averted all drug effects. Thus T/S can affect cell replication even at levels well below those usually employed and could prolong the rate of recovery of hematopoietic cells in the myelosuppressed patient.
Regulation of hematopoiesis: helper and suppressor influences of the thymus
Authors: Sharkis SJ , Spivak JL , Ahmed A , Misiti J , Stuart RK , Wiktor-Jedrzejczak W , Sell KW , Sensenbrenner LL 
Published: October 2019

Abstract
Thymocytes from normal mice strains as well as from genetically determined stem cell defective W/Wv anemic mice were cocultured with syngeneic (or congeneic) bone marrow cells. We assayed these cocultures for the proliferation of erythroid progenitor cell types (BFU-E and CFU- E) using the plasma clot technique. Results indicate that when concentrations of thymocytes were lower than bone marrow cells, significant suppression of erythroid growth was observed. However, when the concentration of thymocytes exceeded that of the bone marrow cells in culture (greater than 1:1), significant enhancement of erythroid growth was demonstrated. The W/Wv anemic bone marrow appears to respond to this interaction by enhancement at all concentrations of added normal thymocytes. The regulatory functions observed can be diminished by treatment of the thymocytes in vitro with anti-theta serum plus complement. Thus, we establish regulatory functions for anti-theta- sensitive regulatory cells (TSRC) with both positive (enhancement) and negative (suppression) components.
Thymus-dependent and thymus-independent subpopulations of intestinal intraepithelial lymphocytes: a granular subpopulation of probable bone marrow origin and relationship to mucosal mast cells
Authors: Mayrhofer G 
Published: October 2019

Abstract
Intraepithelial lymphocytes have been examined histochemically in the small intestines of normal rats and mice and in thymus-deficient animals (B rats and nude mice). It is concluded that these cells are heterogeneous, consisting of at least two subpopulations. One population contains granules, is thymus-independent, and is probably bone-marrow-derived. The other population does not contain granules and appears to be thymus-dependent. It is suggested that the granular cell, which may be a precursor of mucosal mast cells, is more properly a previously unrecognized nonlymphoid leukocyte of bone marrow origin.
In vivo radiolabeling of platelet proteins: a new method with identification of platelet factor XIII
Authors: Rider DM , McDonagh RP , McDonagh J 
Published: October 2019

Abstract
A method for radiolabeling platelets in vivo was developed in which 3H- arginine was injected into the bone marrow of normal dogs. On the third day after injection, a maximum of 6%--7% of the radioactivity had been incorporated into the total platelet mass. This method of isotope administration resulted in a 50--60-fold increase in maximum uptake of radiolabel by platelets, as compared to values obtained by others using intravenous injections of various radioactive compounds. Tritium- labeled platelets were harvested from the animals and then were washed to remove unbound 3H-arginine. On polyacrylamide gel electrophoresis 7 labeled protein bands, with molecular weights ranging from 29,000to 132,000, were obtained from the platelet-soluble fraction. One 3H- containing protein with a molecular weight of 81,000 was identified immunologically and enzymatically as platelet factor XIII.
Circulating immunoglobulin-secreting cells in patients with plasma cell dyscrasia
Authors: Shimizu K , Murate T , Kunii A 
Published: October 2019

Abstract
Immunoglobulin-secreting cells (ISC) in peripheral blood mononuclear cells (PBM) isolated from patients with plasma cell dyscrasia of various stages were studied using reverse hemolytic plaque assay. Normal healthy individuals contained 35 +/- 16 ISC/10(5) PBM. Aleukemic or subleukemic patients with overt myeloma contained 825 +/- 713 ISC, whereas leukemic patients contained 12,675 +/- 2520 ISC. Patients of premyelomatous stage, however, contained ISC/10(5) PBM of normal range. The relationship between ISC and clinical stage or laboratory data is discussed.
Two new sickle cell syndromes: HbS, Hb Camden, and alpha-thalassemia; and HbS in combination with Hb Tacoma
Authors: Honig GR , Mason RG , Shamsuddin M , Vida LN , Rao KR , Patel AR 
Published: October 2019

Abstract
Hemoglobin variants having electrophoretic mobility more rapid than that of HbA were identified in combination with sickle hemoglobin in two patients at the Cook County Hospital. Neither individual had symptomatic hematologic disease. In one patient, the rapidly migrating hemoglobin had the amino acid substitution characteristic of Hb Tacoma (beta-40 arg leads to ser), a mildly unstable variant. In the other patient, Hb Camden (beta-131 gln leads to glu) was identified, and the hematologic findings also indicated that he has alpha-thalassemia trait. In the patient with HbS-Camden--alpha-thalassemia, globin synthesis was unbalanced (alpha/beta 0.66), and HbS represented only 19.5% of the total hemoglobin. The latter finding suggests that under conditions of limited alpha-chain availability beta Camden may combine with alpha subunits at least as efficiently as does betaA. HbS represented 56% of the hemoglobin of the patient with HbS Tacoma, although the rate of synthesis of beta Tacoma by her reticulocytes was consistently greater than that of betaS. A time-course synthesis study demonstrated a progressive increase in the specific activity of beta Tacoma in relation to that of betaS, suggesting that the unstable beta- chains of Hb Tacoma underwent selective intracellular degradation. This process appears to explain the disparity between the rates of synthesis of the two beta chains and the relative representation of HbS and Hb Tacoma in the patient's erythrocytes.
The mechanism of thrombin-induced platelet factor 4 secretion
Authors: Ginsberg MH , Taylor L , Painter RG 
Published: October 2019

Abstract
We have measured thrombin-induced secretion of platelet factor 4 antigen (PF4) and simultaneously followed its intracellular translocation by immunofluorescence. In permeable resting platelets, speckled intracellular immunofluorescent staining for PF4 was observed. Addition of thrombin to washed platelets at 22 degrees C resulted in secretion of PF4 and formation of large (approximately 0.5 micrometer) immunofluorescent masses. These masses moved to the cell periphery during secretion and were virtually absent at the conclusion of secretion. Ultrastructural examination of thrombin-treated platelets revealed vacuoles corresponding in size, shape, and time of occurrence to the large immunofluorescent masses of PF4. These vacuoles contained PF4 by immunoferritin staining of frozen thin sections; they therefore appear to represent the ultrastructural counterpart of the large PF4 masses. When intact cells were stained for PF4 after thrombin addition, only 5.6% of the large masses stained. Thus, during secretion, PF4 antigen is consolidated into large closed pools that appear as vacuoles in the electron microscope.
A new human monoclonal cold agglutinin Sa recognizing terminal N- acetylneuraminyl groups on the cell surface
Authors: Roelcke D , Pruzanski W , Ebert W , Romer W , Fischer E , Lenhard V , Rauterberg E 
Published: October 2019

Abstract
A human homogeneous IgM/K cold agglutinin (CA) Sa is described, whose corresponding antigen on erythrocytes (RBC) was abolished by neuraminidase. This indicated that the antigen was related to N- acetylneuraminic acid, similar to Pr and Gd antigens. In contrast, this antigen was only partially destroyed by proteases, whereas Pr antigens are completely destroyed and Gd antigens are not influenced by proteases. Sa antibody activity was inhibited by sialyllactose NeuAc (alpha 2 leads to 3) (alpha 2 leads to 6) Gal (beta, 1 leads to 4) Glc like anti-Gd but in contrast to anti-Pr. The corresponding antigen was associated with an RBC membrane glycoprotein fraction like Pr, Sa is one of a spectrum of human monoclonal CA against cell surface neuraminyl groups.
Influence of the amount of platelet-bound IgG on platelet survival and site of sequestration in autoimmune thrombocytopenia
Authors: Kernoff LM , Blake KC , Shackleton D 
Published: October 2019

Abstract
Seventeen patients with idiopathic autoimmune thrombocytopenic purpura were studied in order to establish whether the amount of platelet-bound antibody influenced the rate and site at which these platelets were destroyed. Platelet-bound antibody was measured by a quantitative antiglobulin consumption technique, and platelet survival and sites of sequestration were determined by the use of 51Cr-labeled platelets and surface radioactivity measurements. A correlation significant at the 5% level was observed between the amount of platelet-bound antibody and the rate of platelet destruction. A highly significant correlation (p less than 0.001) existed between antiplatelet antibody and spleen: liver surface radioactivity ratios, demonstrating that greater amounts of antibody bound to platelets result increasingly in their destruction within the liver.
Erythropoietic stress, macrocytosis, and hemoglobin switching in HbAA sheep
Authors: Mohandas N , Clark MR , Wyatt JL , Garcia JF , Eisenberg PD , Shohet SB 
Published: October 2019

Abstract
Hemoglobin switching and macrocytosis were studied in homozygous hemoglobinAA sheep. An abrupt initiation of erythropoietic stress, accompanied by a pulsed elevation of circulating erythropoietin levels, was induced by phlebotomy. Sequential blood samples were separated according to density on Stractan gradients to isolate cells newly entering the circulation from the marrow each day. Analysis of hemoglobin phenotype and cell volume distribution in these young reticulocytes revealed a distinct temporal separation in the appearance of hemoglobin C and increased cell volume. The appearance of macrocytes within 24 hr of erythropoietin elevation suggests that macrocytosis could be the result of the action of erythropoietin during the late stages of erythroid maturation. The 72-hr delay in the appearance of hemoglobin C indicates that commitment to a particular hemoglobin phenotype occurs at an early stage of differentiation and involves immature erythroid stem cells. The results of this study show that these consequences of erythropoietic stress are initiated at two different developmental stages, resulting in the production of macrocytosis and hemoglobin switching.
Inhibitors of complement derived from the erythrocyte membrane in paroxysmal nocturnal hemoglobinuria
Authors: Chua C , Hoffmann EM , Adams JP , Rosse WF 
Published: October 2019

Abstract
Extracts of the membranes of normal red cells and red cells from all subpopulations of paroxysmal nocturnal (PNH) red cells inhibited antibody-mediated complement activation. These extracts were shown to accelerate decay of the complement complex. C42, and the relative amount of inhibitory activity was similar in normal and PNH membranes. Inhibitors derived from normal red cells markedly decreased lysis of both PNH and normal cells when antibody was present in excess and complement was limiting. These same inhibitors decreased PNH cell lysis to a much lesser degree when complement was activated with cobra venom or acidified serum. The susceptibility of the PNH cell to complement lysis because of an increased fixation of C3 to its membrane is not due to a difference in membrane-associated accelerator of the decay of the C42 complex.
Differentiation of human leukemias in response to 12-0- tetradecanoylphorbol-13-acetate in vitro
Authors: Pegoraro L , Abrahm J , Cooper RA , Levis A , Lange B , Meo P , Rovera G 
Published: October 2019

Abstract
Leukemic cells from patients with acute myeloid leukemia underwent morphological, functional, and histochemical changes within 24–48 hr after treatment with 1.6 x 10–18 M 12–0-tetradecanoylphorbol-13-acetate (TPA). The changes included adhesion to the plastic substrate, a 4–6- fold increase in the number of phagocytic cells, and an increase in the number of alpha-naphthyl-acetate esterase (alpha-NAE) positive cells. In contrast, TPA treatment of cells from patients with acute lymphoblastic leukemia caused some aggregation of cells in suspension, but no changes in adhesion, phagocytosis, or alpha-NAE. Of the four cases of undifferentiated or unclassified leukemias studied, two failed to respond to TPA, one responded with a myeloid (adhesion) pattern, and one with a lymphoid (aggregation) pattern. These data suggest that leukemic myeloblasts retain the ability to express a variety of differentiated functions, and in some cases, it may be possible to use TPA as a tool to test the differentiative potential of undifferentiated human leukemias.
Chronic myelocytic leukemia: eosinophils involved in the malignant clone
Authors: Koeffler HP , Levine AM , Sparkes M , Sparkes RS 
Published: October 2019

Abstract
Chronic myelocytic leukemia (CML) is a clonal disorder involving neutrophil, monocyte, erythrocyte, and platelet precursors. In order to determine if the eosinophils are also involved in the leukemic clone, we purified the eosinophils from a woman heterozygous for the common electrophoretic variants of the G6PD gene. Only type B enzyme was demonstrable in the eosinophils, neutrophils, and red cells, but both A and B enzymes were found in the fibroblasts. The data provide evidence that the eosinophil is involved in the malignant clone.
Isolation of hybrid cell clones that contain deletion and non-deletion defects of alpha-thalassemia in man
Authors: Deisseroth A , Bode U , Lebo R , Dozy A , Kan YW 
Published: October 2019

Abstract
We have succeeded in isolating hybrid mouse erythroleukemia cell clones from a patient with hemoglobin H disease, which exhibit either deletion or nondeletion mutations of the human alpha-globin genes. Analysis of one of these hybrid clones that had retained a human chromosome 16 from the patient's cells showed that both human alpha-globin had been deleted. Several clones of another hybrid cell had retained a human chromsome 16 from the patient's cells, which contained both human alpha- globin genes on an EcoRI fragment of 23 kilobases (kb). These latter hybrid clones showed the presence of human alpha-globin chains at detectable but low levels. These studies show that there are two different types of human chromosome 16 in this patient and that the nondeletion mutation of human alpha-globin genes leading to hemoglobin H diseases in this patient acts in cis to the two alpha-globin genes remaining in his cells. The close correlation between the pattern of human alpha-globin gene expression in the patient and in the hybrid cells suggests that this method of transfer of human globin genes to rodent cells will be a useful one for study of mutations affecting the expression of differentiated genes that lead to disease in man.