bluuebunny/crossref_metadata_2025_split huggingface dataset:
Acute monoblastic leukemia: a clinical and biologic study of 74 cases
Authors: Tobelem G , Jacquillat C , Chastang C , Auclerc MF , Lechevallier T , Weil M , Daniel MT , Flandrin G , Harrousseau JL , Schaison G , Boiron M , Bernard J 
Published: October 2019

Abstract
Seventy-four cases of pure acute monoblastic leukemia (AMol) have been retrospectively studied. All patients were treated at Hospital Saint- Louis between 1970 and 1978. Diagnosis was based on morphological and cytochemical features according to the FAB classification. This type of leukemia occurred at any age and in both sexes, with a high frequency of extramedullary involvements. Hyperleukocytosis was very frequent and was significantly correlated with increased blood and urine levels of lysozyme, with renal failure and hypokalemia, and with coagulation abnormalities. AMol still has a poor prognosis, despite a best remission rate (75%) obtained with rubidazone, since the duration of complete remission was short. Central nervous irradiation prolonged remission and prevented meningeal relapses, while 6 meningeal relapses occurred in the patients not irradiated. The high frequency of the extramedullary relapses, including gum and skin, emphasized the question of persistant blast cell sanctuaries after achievement of bone marrow remissions. A more intensive induction with several drugs active against monoblasts could be more efficient and prolong the duration of complete remissions.
Selective binding of the factor VIII/von Willebrand factor protein to human platelets
Authors: Morisato DK , Gralnick HR 
Published: October 2019

Abstract
The factor VIII/von Willebrand factor protein was radiolabeled after modification by galactose oxidase and reduction with tritiated potassium borohydride. This mild efficient method for labeling resulted in retention of over 90% of the biologic activities of the factor VIII/von Willebrand factor protein. Binding of this protein to platelets was found to be specific, and binding sites could be saturated in the presence of ristocetin. However, binding was highly dependent on ristocetin concentration, as the number of human factor VIII/von Willebrand factor molecules bound per platelet was a function of the ristocetin concentration. At a ristocetin concentration of 0.55 mg/ml, each platelet binds approximately 11,000 factor VIII/von Willebrand factor molecules per platelet. Scatchard analysis of the concentration-dependent binding sites yielded a hyperbolic plot that appeared to be related to the existence of two classes of binding sites. The higher affinity class had a Kd of 3.7 x 10(-10) M 3500 sites/platelet, while the lower affinity class had a Kd of 2.35 x 10(- 9) M and a capacity of 7500 sites/platelet. As with ristocetin-induced platelet agglutination, the carbohydrate content plays a significant role in the binding of the factor VIII/von Willebrand factor protein to the platelet.
Localizaton of fibrin converted by thrombin from released platelet fibrinogen
Authors: Chao FC , Campo SR Jr , Kenney DM 
Published: October 2019

Abstract
Treatment of platelets (10(9) cells/ml) with thrombin (1 U/ml) resulted in rapid disappearance of fibrinogen from the system as measured by the tanned red cell hemagglutination inhibition immunoassay (TRCHII). Plasmin digestion of individual pellet and supernatant fractions that had been previously separated from thrombin-treated platelet suspensions by centrifugation resulted in recovery of TRCHII-detectable material in platelet pellets. To elucidate the specific association of fibrin to platelet membranes, control and thrombin-treated platelets were homogenized by a modified glycerol-loading and nitrogen decompression technique. Ultracentrifugation of homogenates through 27% sucrose cushions yielded three subcellular fractions: supernatant, small membrane vesicles, and a particulate fraction for controls; and supernatant membrane vesicles, and aggregated membrane “ghosts” for thrombin preparations. Ultrastructurally identifiable fibrin was noted only in the thrombin fraction containing membrane ghosts. Fibrinogen recovered from 3 thrombin fractions was markedly decreased (3% of the control). Plasmin digestion produced 23% and 46-fold increase in TRCHII- detectable material from 3 subcellular fractions of control and thrombin preparations, respectively. More than 97% of TRCHII material recovered from thrombin preparations was in the fraction containing aggregated membrane fractions. Results suggest that platelet plasma membranes function as surfaces for fibrin deposition.
G6PD San Francisco: a new variant of glucose-6-phosphate dehydrogenase associated with congenital nonspherocytic hemolytic anemia
Authors: Mentzer WC Jr , Warner R , Addiego J , Smith B , Walter T 
Published: October 2019

Abstract
Congenital nonspherocytic hemolytic anemia in an adult male of Scandinavian ancestry was associated with virtual absence of G6PD activity in red cells. Characterization of G6PD purified from leukocytes using standard WHO techniques revealed diminished electrophoretic mobility, marked lability on heating at 46 degrees C, normal pH optimum and utilization of alternate substrates (2-deoxy G6P, D-amino NADP), elevated Km NADP, and striking susceptibility to NADPH inhibition. The variant G6PD, which appears to be unique, has been designated G6PD San Francisco. An unusual feature of the variant enzyme, susceptibility to inactivation by brief periods of dialysis, could be prevented by addition of 200 microM NADP to the dialysis solution. In red cells, where G6PD activity was essentially absent, regeneration of reduced glutathione was totally curtailed in vitro, while in leukocytes, where residual G6PD activity was approximately 60% of normal, hexose monophosphate shunt activity, oxygen consumption during phagocytosis, and bacterial killing were unimpaired. Thus, instability of the variant enzyme rather than its unfavorable kinetics appeared to be an important determinant of abnormal cell function.
Demonstration of transferrin receptors on human placental trophoblast
Authors: Galbraith GM , Galbraith RM , Temple A , Faulk WP 
Published: October 2019

Abstract
It has been postulated that the transplacental passage of maternal iron to the developing fetus requires binding of maternal transferrin to the trophoblast. We have therefore examined the ability of the human placenta to bind transferrin in vitro. Transferrin was demonstrated on trophoblast of human chorionic villi by immunohistologic methods. Moreover, after removal of transferrin bound in vivo by treatment of tissue with chaotropic solution or phosphate-buffered saline, freshly added transferrin was shown to bind in vitro in the same characteristic distribution. These findings suggest that placental iron transport is initiated by uptake of maternal transferrin iron to specific trophoblast binding sites.
Discrimination of human leukemia subtypes by flow cytometric analysis of cellular DNA and RNA
Authors: Andreeff M , Darzynkiewicz Z , Sharpless TK , Clarkson BD , Melamed MR 
Published: October 2019

Abstract
A newly developed flow cytometry technique for simultaneous measurements of three features of individual cells--DNA, RNA, and nuclear diameter--using acridine orange as a fluorescent metachromatic dye, has been applied to cell-cycle analysis. DNA stemline determination, and to classification of 102 cases of human leukemias in adults. Acute lymphoblastic leukemia (L1–2) was characterized by moderately increased RNA of G0/1 cells as compared to normal lymphocytes; acute nonlymphoblastic leukemia (M 1–5) by very high RNA of G0/G1 cells. Both had either diploid or aneuploid DNA stemlines. Chronic lymphocytic leukemia showed diploid DNA, very low proliferation, and low RNA, similar to that found by use to be typical for normal B cells. In chronic myelogenous leukemia, two cell populations were distinguished, one with high RNA, the other with very low RNA and elongated nuclear diameter due to stripped, unfolded nuclei of polymorphonuclear leukocytes. The number of leukemic blast cells, identified by aneuploid DNA values, correlates well with conventional microscopy counts and could be followed during the course of treatment. Thus, acridine orange flow cytometry can be used to discriminate subtypes of human leukemias, to determine cell cycle stages, and to detect and monitor aneuploid leukemia stemlines.
Urinary hydroxyproline excretion in myelofibrosis
Authors: Wang JC , Aung MK , Tobin MS 
Published: October 2019

Abstract
Urinary hydroxyproline measurements were performed in a group of health volunteers as well as patients with cancer and myelofibrosis. Patients in whom there was no metastatic involvement of bone marrow excreted an amount of hydroxyproline not different from that of the control group. Those who had marrow metastasis produced elevated levels of hydroxyproline; the highest excretions were observed when marrow fibrosis was associated with metastasis. These results contrasted with those observed in agnogenic myeloid metaplasia patients whose excretions were equivalent to the control group. The result suggests differences in the pathogenesis of myelofibrosis and a technique potentially useful for distinguishing between patients who may otherwise be diagnostic problems.
The influence of albumin and calcium on human platelet arachidonic acid metabolism
Authors: Stuart MJ , Gerrard JM , White JG 
Published: October 2019

Abstract
The effects of in vitro changes in calcium and albumin on human platelet arachidonic acid metabolism were evaluated. Hypoalbuminemia enhanced the conversion of released 14C-arachidonic acid from prelabeled platelet phospholipids to the metabolites of the platelet cyclooxygenase and lipoxygenase pathways. This effect was, however, associated with a decreased release of arachidonic acid in the presence of hypoalbuminemia, such that the overall conversion of released 14C- arachidonic acid to platelet thromboxane B2 was similar in the presence of physiologic albumin concentration (3.5 g/dl) or at decreased albumin concentrations of 0.7 and 0.0 g/dl. External calcium was shown to be important for optimal platelet arachidonic acid release, with maximal release occurring at 1 mM calcium.
Prediction of chemotherapy response in human leukemia using an in vitro chemotherapy sensitivity test on the leukemic colony-forming cells
Authors: Park CH , Amare M , Savin MA , Goodwin JW , Newcomb MM , Hoogstraten B 
Published: October 2019

Abstract
An in vitro test system to quantitatively assess the chemotherapy sensitivity of human acute leukemic colony-forming cells (L-CFU) in relation to normal granulocytic precursor cells (CFU-C) has been developed. After simultaneous exposure of leukemic and normal bone marrow cells to individual drugs in vitro, cells were grown using an improved agar culture method with daily feeding. A sensitivity index (SI) was determined as the ratio of survival fraction of CFU-C to that of L-CFU, L-CFU being more (or less) sensitive than CFU-C if the SI were higher (or lower) than unity. Thirty SI were determined for 6 single drugs actually given in various combinations to a total of 9 patients (8 with acute nonlymphocytic leukemia and 1 with chronic myelomonocytic leukemia). A highly significant correlation was observed between high (or low) SI and achievement of (or failure to achieve) complete remission, with only 6 false correlations (p = 0.0013). Also, the mean of these SI (MSI) for the multiple single drugs given to each patient as components of a combination chemotherapy was used to indicate an overall sensitivity for each trial of the chemotherapy. Among the 10 chemotherapy trials (1 trial each for 8 patients and 2 trials for 1 patient), 4 trials resulting in complete remission had MSI higher than 1.0, and 6 trials not resulting in complete remission had MSI lower than 1.0 (p = 0.0048). This assay system appears useful in predicting the response of patients to chemotherapy and in the selection of the most effective drugs for use in individual patients.
Positive Coombs test in Hodgkin's disease: significance and implications
Authors: Levine AM , Thornton P , Forman SJ , Van Hale P , Holdorf D , Rouault CL , Powars D , Feinstein DI , Lukes RJ 
Published: October 2019

Abstract
To clarify the clinicopathologic characteristics of Coombs' positivity in Hodgkin's disease, the records of 71 cases were reviewed. The direct Coombs test was positive in seven. Mean age of the seven was 22 yr (range 11–33). All were males. All had extensive disease (pathologic stage III or IV) and six had systemic (B) symptoms. Four had mixed cellularity; three had nodular sclerosis. The positive Coombs test was detected at original diagnosis in three and at time of relapse in four. Although all were anemic, only three had evidence of overt hemolysis. The antibody responsible for Coombs positivity was characterized in three and fulfilled the criteria for IgG anti-It. The presence of a positive direct Coombs test in the patient with Hodgkin's disease suggests active and advanced disease. The presence of IgG anti-It may represent a unique antibody in the Coombs-positive hemolytic anemia associated with Hodgkin's disease.
Effect of short-term protein deprivation on hemopoietic functions of healthy volunteers
Authors: Catchatourian R , Eckerling G , Fried W 
Published: October 2019

Abstract
To ascertain the effects of protein deprivation on hemopoietic parameters in otherwise healthy subjects, three volunteers were placed on diets containing 0.15 g protein/kg body weight for 8 days followed in 2 mo by another 8-day study period during which they ingested their usual diets containing more than 0.9 g protein/kg body weight. Complete blood counts, serum protein determinations, and tests of in vitro and in vivo leukocyte chemotaxis were performed prior to and at the conclusion of each study period. Subjects were phlebotomized of 500 ml on day 7 of each study period. Twenty-four-hour urinary erythropoietin excretion rates were assayed just prior to and again postphlebotomy. Reticulocyte counts were performed at intervals up to 1 wk postphlebotomy. Some of these determinations were replicated during a subsequent study. The hemoglobin and hematocrits decrased slightly but significantly after 8 days on low protein diets. Erythropoietin excretion rates and reticulocyte responses to phlebotomy were also less marked while subjects were on protein depleted diets. Leukocyte chemotaxis, measured both in vitro and in vivo, was also markedly reduced while subjects were on protein-depleted diets. We conclude that 8 days of moderately severe protein deprivation significantly impairs erythropoiesis and leukocyte function in otherwise healthy individuals.
The molecular mechanism of the inherited phosphofructokinase deficiency associated with hemolysis and myopathy
Authors: Vora S , Corash L , Engel WK , Durham S , Seaman C , Piomelli S 
Published: October 2019

Abstract
Normal human erythrocyte phosphofructokinase (ATP:c D-fructose-6, P-1- phosphotransferase, EC 2.7.1.11; PFK) has recently been shown to consist of a heterogeneous mixture of five tetrameric isozymes: M4, M3L, M2L2, ML3, and L4 (M, muscle type; L, liver type). In the light of these findings, we have investigated the molecular basis of the inherited erythrocyte PFK deficiency associated with myopathy and hemolysis (Tarui disease). The propositus, a 31-yr-old male, suffered from muscle weakness and myoglobinuria on exertion. He showed mild erythrocytosis despite laboratory evidence of hemolysis. In his erythrocytes a metabolic crossover point was found at the level of PFK; 2,3-diphosphoglycerate (2,3-DPG) was also significantly reduced. The PFK from the patient's erythrocytes consisted exclusively of the L4 isozyme, and there was a complete absence of the other four. The leukocyte and platelet PFKs from the patient showed normal activities, chromatographic profiles, and precipitation with anti-M4 antibody. These studies provide direct evidence that in Tarui disease the M-type subunits are absent; but the liver- and platelet-type subunits of PFK are unaffected. The paradox of mild erythrocytosis despite hemolysis reflects the decreased production of 2,3-DPG.
Defective delivery of iron to the developing red cell of the Belgrade laboratory rat
Authors: Edwards JA , Sullivan AL , Hoke JE 
Published: October 2019

Abstract
Erythroid cell iron and transferrin uptake and release was studied in the anemia of the Belgrade laboratory rat (gene symbol, b), an autosomal recessive trait characterized by hypochromia and hyperferrinemia. When reticulocyte-rich red cells were incubated in vitro with doubly (59Fe, 125I) labeled transferrin, b/b cells demonstrated a significantly higher uptake of transferrin (164% of control at 60 min), and a significantly lower uptake of iron (21% of control at 60 min) than control cells. These findings with b/b cells were simulated by sodium-fluoride-treated control cells, but not by trypsin-treated control cells. When reticulocytes exposed to doubly labeled transferrin were incubated in normal rat plasma, there was a substantial loss of 125I from both the b/b cells (mean 71%) and control cells (mean 49%), but only a loss of 59Fe from the b/b cells (mean 21%). These findings suggest a defect in the delivery of iron to the b/b reticulocyte, which is distal to the binding of transferrin to its cell surface receptor.
Transient leukemoid reaction and trisomy 21 mosaicism in a phenotypically normal newborn
Authors: Brodeur GM , Dahl GV , Williams DL , Tipton RE , Kalwinsky DK 
Published: October 2019

Abstract
Transient leukemoid reactions that resemble acute leukemia have been well described for infants with trisomy 21 (Down syndrome). We report a phenotypically normal 3-day-old boy with hepatosplenomegaly, leukocytosis, and circulating myeloblasts. On chromosome analysis, trisomy 21 was found in all blood and bone marrow cells. However, only 4% of cultured skin fibroblasts were trisomic and the other 96% were normal, thus indicating mosaicism. Without treatment, the leukocyte count gradually returned to normal and the organomegaly diminished. Subsequently, chromosome analysis of blood and bone marrow disclosed a predominance of cells with a normal karyotype. These findings suggest that mosaicism could be responsible for the transient leukemoid reactions in some newborns--i.e., the trisomic cells may temporarily gain a proliferative advantage over the normal cells, perhaps by inhibiting their growth. Serial cytogenetic studies, as well as chromosome analysis of more than one tissue, may help to distinguish transient leukemoid reactions from acute leukemia in infants.
Alpha globin gene number: population and restriction endonuclease studies
Authors: Brittenham G , Lozoff B , Harris JW , Kan YW , Dozy AM , Nayudu NV 
Published: October 2019

Abstract
Restriction endonuclease analysis was used to test a proposed genetic model using alpha-globin gene number to account for the observed distributions of the proportions of hemoglobin (Hb) S in sickle cell trait. In a subsample of specimens collected during a population survey in India, these studies confirmed that the postulated genotype was present in 22 of the 23 individuals examined. In the study population, the number of alpha-globin genes explains about 90% of the variance in the proportion of HbS in sickle cell trait (r2 = 0.895, p less than 10(- 10)).
Binding of immunoglobulin classes to subpopulations of human red blood cells separated by density-gradient centrifugation
Authors: Alderman EM , Fudenberg HH , Lovins RE 
Published: October 2019

Abstract
Human erythrocytes (RBC) from whole blood were separated according to their specific densities by centrifugation on a polyvinyl-pyrrolidine- coated colloidal silica matrix (Percoll) into four major subpopulations. By indirect immunofluorescence assay, the most dense RBC subpopulation, with specific density greater than 1.110 g/ml (3%-5% of total RBC), was positive for membrane-bound immunoglobulin; the remaining, less dense subpopulations were negative. IgG was present on 85%-95%, IgM on 28%-32%, and IgA on 15%-20% of the RBC in the most dense population. When these immunoglobulins were eluted, radiolabeled, and used in binding studies with autologous RBC fractions subjected to thermal and/or enzymatic treatment, they reacted specifically with the less dense RBC subpopulations. These results suggest that previously cryptic antigens were revealed by the activity of neuraminidase on the plasma membranes of the treated RBC.
A new improved clinical staging system for multiple myeloma based on analysis of 123 treated patients
Authors: Merlini G , Waldenstrom JG , Jayakar SD 
Published: October 2019

Abstract
The effect of the presenting clinical features on survival time was evaluated in 173 patients of a population of 201 individuals with multiple myeloma observed at Malmo General Hospital during the 11-yr period 1960 to January 1, 1971. Complete follow-up was continued until December 1978. One-hundred and five of the patients came from the city of Malmo and constitute a complete nonselected myeloma population. Bivariate correlation and multivariate regression analyses showed that the survival (i.e., the prognosis) could be accurately predicted in IgG and pure Bence Jones myeloma patients from (A) serum creatinine level, (B) serum calcium level, and (C) bone marrow plasma cell percentage; and in IgA myeloma patients from (A) hemoglobin level, (B) serum calcium level, and (C) serum M-component level. The results were synthesized to produce a simple and reliable clinical staging system with three stages (i.e., risks of death). To facilitate the clinical application, multivariate regression equations were developed to optimally predict the prognosis, and graphs were constructed in order to make the staging of the myeloma patients easier and quicker. The comparison of the duration of survival between the three groups of staged patients confirmed the high reliability of the present staging system.
An oxygen-dependent mechanism of neutrophil-mediated cytotoxicity
Authors: Weiss SJ , LoBuglio AF 
Published: October 2019

Abstract
Human neutophils stimulated with phorbol myristate acetate were able to rapidly destroy autologous red blood cell targets. Neutrophil-mediated cytotoxicity was related to phorbol myristate acetate concentration and neutrophil number. The ability of stimulated neutrophils to lyse red blood cell targets was markedly impaired by catalase or superoxide dismutase but not by heat-inactivated enzymes or albumin. Despite a simultaneous requirement for O2.- and H2O2 in the cytotoxic event, a variety of OH. and 1O2 did not effect cytolysis. The myeloperoxidase inhibitor cyanide did not reduce red blood destruction, while azide consistently impaired cytolysis. The inability of cyanide to reduce cytotoxicity coupled with the protective effect of superoxide dismutase suggests that cytotoxicity is independent of the classic myeloperoxidase-H2O2-halide system. We propose that neutrophils, stimulated with phorbol myristate acetate, generate O2.- and H2O2, which play an integral role in a novel cytotoxic mechanism.