bluuebunny/crossref_metadata_2025_split huggingface dataset:
A heparin‐like anticoagulant in an 8‐month‐old boy with acute monoblastic leukemia
Authors: Bussel James B. , Steinherz Peter G. , Miller Denis R. , Hilgartner Margaret W. 
Published: February 2007

AbstractAn 8‐month‐old male with acute monoblastic leukemia died during induction chemotherapy of severe bleeding refractory to repeated infusions of platelets and clotting factors. A heparin effect was suggested by prothrombin time (PT) of 26 seconds, partial thromboplastin time (PTT) of 94 seconds, thrombin time 240 seconds, and reptilase time 18.4 seconds, with a fibrinogen of 88 mg/dl. Both plasma mixed with the patient's urine and the patient's plasma had their thrombin times corrected toward normal by both PF4 and protamine. Synergism of of the anticoagulant with antithrombin III was demonstrated not only by enhanced inhibition of thrombin but also by an increased rate of formation of thrombin‐antithrombin III complexes in the presence of the anticoagulant, which was eliminated by preincubation with heparinase. Since the anticoagulant activity was not found in the blasts themselves, it is presumed that the anticoagulant is heparin/heparan liberated from the endothelial lining by products of the cell destruction secondary to chemotherapy.
The multiple coagulopathies of biliary atresia
Authors: Yanofsky R. A. , Jackson V. G. , Lilly J. R. , Stellin G. , Klingensmith W. C. , Hathaway W. E. 
Published: February 2007

AbstractDetailed coagulation studies were done prospectively on 43 patients with biliary atresia who had undergone Kasai operation (hepatic portoenterostomy). Patients were divided into three groups based on levels of factor V, factor II, and Echis II and/or response to vitamin K: no coagulopathy (46.5% of patients); coagulopathy of liver disease (30.2% of patients); and coagulopathy of vitamin K deficiency (23.3% of patients). Patients with the coagulopathy of liver disease had significantly lower levels of factors XII, V, and antithrombin III as well as longer thrombin times than patients with no coagulopathy or vitamin K deficiency. Factor V levels were decreased only in patients with more advanced liver disease; normal levels of factor V were not usually helpful in differentiating liver disease and vitamin K deficiency. The prothrombin time, factor VII‐X levels, and factor II levels were significantly different for all three groups; the most abnormal values occurred in the vitamin K‐deficient group. Comparison of the Echis II level to factor II coagulant activity was helpful in deciding whether a coagulopathy was due to liver disease, vitamin K deficiency, or both. Factor VIII levels were elevated in all groups. Factor VIII coagulant activity was significantly higher by the two‐stage (TGT) method than by the one‐stage (PTT) method. Hypersplenism causing neutropenia and thrombocytopenia was commonly seen after the age of 5 years. Vitamin E deficiency was more common than vitamin K deficiency; however, all vitamin K‐deficient patients were vitamin E deficient. Coagulation status correlated well with hepatobiliary scan data, but not serum bilirubin levels. Recommendations for treatment of patients with vitamin K deficiency and/or liver disease are discussed.
An analysis of prognostic factors in preleukemia: Interest of bone marrow scintigraphy
Authors: Chomienne C. , Najean Y. , Vigneron N. , Dresch C. , Rain J. D. 
Published: February 2007

AbstractSimultaneous bone marrow scintigraphy with 99m Technetium colloids and 111 Indium transferrin was performed on 34 cases of preleukemic anemias and was shown to be of good prognostic value. Groups of different outcome were defined: for a normal and parallel uptake of the two markers, 90% of the patients died of acute leukemia; for a low Indium and high Technetium uptake, only 1 patient out of 15 died of leukemia (P < 0.001). Standard clinical and hematological data were of no predictive value. Iron kinetic data and CFU/GM colony growth were correlated to the scintigraphic results. Taken together, these three kinetic parameters have a good sensitivity and specificity for the prognosis of preleukemic states.
Factor VIII: Structure and function in blood clotting
Authors: Chavin Stephen I. 
Published: February 2007

AbstractFactor VIII (antihemophilic factor) is the protein that is deficient or defective in patients with classical hemophilia and Von Willebrand syndrome. Factor VIII in plasma is thought to be associated in a complex with the highest molecular weight multimers of another glycoprotein, Von Willebrand protein. Highly purified human factor VIII appears to have an Mr of between 200, 000 and 300,000 and to consist of several polypeptide chains. The concentration of factor VIII in plasma is around 100‐200 ng/ml, equivalent to around 1 nM. The purified proteins retain one or more of the known properties of factor VIII, including the acceleration of factor IXa‐mediated activation of factor X, ability to be activated by thrombin and factor Xa, inactivation by activated protein C, and by human antibodies to factor VIII.Among the known clotting factors, factors VIII and V are exceptional in not possessing enzymatic activity. Factors IX3 and VIII and X appear to form a functional complex, all of which need to be present and active simultaneously for optimal activation of factor X. The mechanism by which factor VIII promotes activation of factor X by factor IXa is not known, but the major effect is to increase the rate of the reaction.Following treatment of factor VIII with thrombin, a new and smaller polypeptide Mr around 70,000 ± 5,000 is produced. Factors IXa and Xa also have been reported to activate factor VIII. It is not known whether limited proteolytic cleavage is required absolutely for the expression of factor VIII activity or if it only increases an activity already expressed by the uncleaved protein. Factor VIII is inactivatd by thrombin and by activated protein C. Thus, factor VIII can be modulated by at least four of the serine proteases in the clotting system. A major goal for future research is to increase our understanding of the role in blood clotting played by factor VIII, and to apply this information to clinical problems which result from inherited abnormalities of factor VIII.
Effect of epinephrine on fibrinogen receptor exposure by aspirin‐treated platelets and platelets from concentrates in response to ADP and thrombin
Authors: Peerschke Ellinor I. B. 
Published: February 2007

AbstractSynergistic effects between agonists on platelet aggregation have long been appreciated. Recently epinephrine was reported to induce maximal aggregation of aspirin‐treated platelets when combined with ADP or thrombin, and to increase fibrinogen binding of nonaspirin‐treated platelets stimulated with low doses of ADP. The present study extends these observations to correlate fibrinogen binding in response to various combinations of ADP, epinephrine, and thrombin with platelet aggregation and 14C‐serotonin release using aspirin‐treated platelets as well as platelets from stored concentrates. When fresh platelets were stimulated with epinephrine (5 μM) together with either ADP (10 μM) or thrombin (150 mU/ml), fibrinogen binding increased by 180% compared to binding observed in response to ADP or thrombin alone. This was accompanied by enhanced platelet aggregation, but no increase in 14C‐serotonin release. While both ADP and epinephrine potentiated the aggregation and fibrinogen binding of stored platelets in response to high doses of thrombin (150 mU/ml), maximal aggregation was achieved only with thrombin (150 mU/ml) and epinephrine (5μM) in combination. The data thus suggest that 1) epinephrine induces maximal aggregation of aspirin‐treated platelets stimulated with thrombin or ADP by significantly enhancing fibrinogen receptor exposure independently of the cyclooxygenase‐mediated release reaction; 2) epinephrine stimulates platelets by a mechanism different from that of thrombin or ADP; and 3) as demonstrated by others, the ability of platelets from stored concentrates to aggregate and to bind fibrinogen in response to ADP can be enhanced by epinephrine, and, in addition, these platelets can aggregate and bind fibrinogen maximally when stimulated with combinations of epinephrine and thrombin.
Monocyte transferrin‐iron uptake in hereditary hemochromatosis
Authors: Sizemore Delton J. , Bassett Mark L. 
Published: February 2007

AbstractTransferrin‐iron uptake by peripheral blood monocytes was studied in vitro to test the hypothesis that the relative paucity of mononuclear phagocyte iron loading in hereditary hemochromatosis results from a defect in uptake of iron from transferrin. Monocytes from nine control subjects and 17 patients with hemochromatosis were cultured in the presence of 59Fe‐labelled human transferrin. There was no difference in 59Fe uptake between monocytes from control subjects and monocytes from patients with hemochromatosis who had been treated by phlebotomy and who had normal body iron stores. However, 59Fe uptake by monocytes from iron‐loaded patients with hemochromatosis was significantly reduced compared with either control subjects or treated hemochromatosis patients. It is likely that this was a secondary effect of iron loading since iron uptake by monocytes from treated hemochromatosis patients was normal. Assuming that monocytes in culture reflect mononuclear phagocyte iron metabolism in vivo, this study suggests that the relative paucity of mononuclear phagocyte iron loading in hemochromatosis is not related to an abnormality in transferrin‐iron uptake by these cells.
A further characterization of the selective K movements observed in human red blood cells following acetylphenylhydrazine exposure
Authors: Orringer Eugene P. 
Published: February 2007

AbstractFollowing brief exposure to acetylphenylhydrazine, the potassium permeability of the human erythrocyte membrane is selectively augmented. While a similar increase in potassium permeability results from the intracellular accumulation of calcium (the Gardos phenomenon), we have found a number of features that allow these two pathways to be distinguished from one another. The acetylphenylhydrazine pathway does not require calcium for its activation, and can be seen even in the presence of a molar excess of the calcium chelator EGTA. The transmembrane potassium movement via this channel has a specific requirement for the anion chloride, and it can be inhibited by furosemide. The potassium that moves through the Gardos pathway, on the other hand, can be accompanied by any permeant anion, and is inhibitable by quinidine or cetiedil. Thus, acetylphenylhydrazine exposure seems to promote K + Cl cotransport, whereas the Gardos pathway represents a potassium conductive channel.While full demonstration of both these pathways requires harsh in vitro manipulation, the large electrochemical potassium gradient favoring the movement of this cation out from the erythrocyte suggests that even a partial activation of either pathway could cause intracellular dehydration and thus contribute importantly to the pathophysiology of in vivo red cell destruction.
Absence of platelet activating factor (PAF) mediated platelet aggregation: A new platelet defect
Authors: Pelczar‐Wissner Catherine J. , McDonald Elizabeth G. , Sussman Ira I. 
Published: February 2007

AbstractThe failure of normal human platelets to aggregate in response to platelet activating factor (PAF) has not been previously observed. We report here the first case of a patient whose platelets did not aggregate to PAF on multiple occasions.
Serum from outdated human platelet concentrates: An alternative supplement for tissue (fibroblast) culture media
Authors: Schwartz Kenneth A. , Lu Gina , Trosko James E. , Chang Chia‐Cheng 
Published: February 2007

AbstractFetal calf serum (FCS) is used as a component of the media for cells grown in culture. However, the high cost of FCS has stimulated a search for a possible alternative. Approximately 10% of human platelet concentrates prepared for clinical transfusions are outdated. Sera prepared from platelet concentrates were compared with FCS and calf serum (CS) as a media supplement. A similar number of fibroblast (NSF‐791) colonies grew in media supplemented with the three different sera. However, colonies grown in the presence of human platelet serum (HPS) were larger than those grown in media containing CS and FCS. Hence, serum prepared from outdated human platelet concentrates may be substituted for fetal calf serum as a cell culture nutrient, for fibroblasts.
Effects of thymocytes on marrow cells from normal and Busulfan‐treated mice
Authors: Adler Solomon S. 
Published: February 2007

AbstractTo study the effects of thymocytes on hemopoiesis, we 1) cocultured marrow cells with and without thymocytes in an erythroid burst (BFU‐E) culture system, 2) injected marrow cells with and without thymocytes into supralethally irradiated mice to assay CFU‐S, and 3) assessed the survival of supralethally irradiated mice transplanted with marrow cells with or without thymocytes. The marrow cells used were either from mice given six injections of busulfan and then permitted to rest for 2, 5, or 10 weeks or from mice treated similarly with the busulfan vehicle alone. Thymocytes did not alter spleen surface colony counts or survivorship in any of the test groups. Thymocytes did effect an increase in BFU‐E cultured from marrow obtained from the vehicle‐treated mice but not from marrow of busulfan‐treated mice. Thus, in addition to decreasing the population of hemopoietic precursors in the marrow, busulfan alters the nature of the remaining early erythroid precursor cell population rendering it unresponsive to thymocytes in vitro.
Enzymes of purine metabolism in B‐chronic lymphocytic leukemia
Authors: Vertongen F. , Cauchie C. , Courtois P. , Fondu P. , Mandelbaum I. M. 
Published: February 2007

AbstractIn order to study if enzymes of purine metabolism could be used as cell markers in B‐chronic lymphocytic leukemia (B‐CLL), the activities of adenosine deaminase (ADA), purine nucleoside phosphorylase (PNP), and 5′‐nucleotidase (5′N) were repeatedly measured in blood mononuclear cells from B‐CLL patients and were compared to those obtained in normal controls. Enzyme activities in patients were also compared to other biological parameters indicative of B‐CLL to activities of ADA and PNP in erythrocytes.Results show that B‐leukemic cells display abnormal enzyme patterns: subnormal ADA activity is characteristic; 5′N activity is depressed in 60% of the cases but increased in 15%. An inverse relationship between PNP activity and corresponding lymphocytosis is observed in leukemic but not in normal cells. The enzymatic anomalies seem to be linked to the presence of an unusual peripheral lymphocytic population, induced by the leukemic process. Indeed, ADA and PNP are not abnormal in erythrocytes. In untreated nonevolutive patients, the enzyme profile tends to remain stable throughout the course of the illness; normalization of enzyme patterns in treated patients occurs only when therapy induces improvement in T and B cell distribution.
Comparison of continuous and intermittent factor VIII concentrate therapy in hemophilia A
Authors: Hathaway W. E. , Christian M. J. , Clarke S. L. , Hasiba U. 
Published: February 2007

AbstractComparison of continuous versus intermittent (every 12 h bolus) infusion of a highpurity Factor VIII concentrate in 12 severe hemophilia A patients undergoing surgical procedures indicated that a higher (50 u/dl versus 35 u/dl) minimal plasma level was seen with the same amount of product when given continuously. A continuous VIII concentrate infusion of 2 u/kg/h produces a mean VIIIc level of about 50 u/dl or, alternatively, about 0.04 u/kg/h raises the VIIIc level by 1 u/dl (1%). None of the patients showed any abnormal bleeding. Higher plasma levels of VIIIc were noted by the two‐stage VIIc assay than by the one‐stage VIIIc assay. Fibrinogen levels were normal or only slightly elevated, and the monomer test was consistently negative.
Confirming evidence for the clonal development and stem cell origin of philadelphia chromosome‐negative chronic myelogenous leukemia
Authors: Kaye Frederic J. , Najfeld Vesna , Singer Jack , Cuttner Janet , Fialkow Philip J. 
Published: February 2007

AbstractA 74‐year old woman with Ph1‐negative chronic myelogenous leukemia (CML) and heterozygous for glucose‐6‐phosphate dehydrogenase (G6PD) was studied. Both A and B types of G6PD were found in skin. In contrast, white blood cells and platelets showed only a single G6PD type A. These results provide further evidence that Ph1‐negative CML has a stem cell origin and develops clonally.
Antioxidant metabolism during blood storage and its relationship to posttransfusion red cell survival
Authors: Lachant Neil A. , Noble Nancy A. , Myrhe Byron A. , Tanaka Kouichi R. 
Published: February 2007

AbstractThe status of the erythrocyte antioxidant defense system and its relationship to posttransfusion red cell survival were determined in erythrocytes stored for 35 or 42 days in CPD‐A1 anticoagulant with a saline‐adenine‐glucose additive. As storage progressed, there was a significant increase in incubated Heinz body formation (P < .001) and a significant decrease in reduced glutathione (GSH) stability (P < .001). Stimulated pentose phosphate shunt activity also declined during storage (P < .06), while unstimulated shunt activity remained unchanged. The increase in Heinz body formation was associated with decreased GSH stability (r = –.77, P < .001), which in turn was associated with the decline in stimulated pentose shunt activity (r = .67, P < .001). The changes in Heinz body formation (r = ‐.85), GSH stability (r = .83). and stimulated pentose shunt activity (r = .54) were all significantly (P < .001) related to the decline in adenosine triphosphate (ATP) content of the erythrocyte. Red cell survival 24 hours after transfusion was significantly related to the GSH stability (r = .80, P < .001) and to the ATP concentration (r = .76, P < .005) on the day of transfusion. Thus, dysfunction of the erythrocyte antioxidant defense system occurs during blood storage and appears to be related, in part, to ATP depletion. The ability to maintain a normal reduced glutathione concentration during oxidant stress appears to be an important determinant of red cell survival in the peritransfusion period.
In vitro elevation of red blood cell 2,3‐diphosphoglycerate with fructose, phosphate, and methylene blue
Authors: Farber Mark O. , Rubin Leslie R. , Manfredi Felice 
Published: February 2007

Abstract2,3‐Diphosphoglycerate (2,3‐DPG) is an important regulator of hemoglobin oxygen affinity and thus can theoretically affect tissue oxygenation. Marked stimulation of DPG with substances that would likely be well tolerated by humans has not been reported previously. In order to achieve such stimulation, we investigated (n = 102) the effect of various combinations of fructose (2.8–11.1 mM) and sodium phosphate (1.0–130.0 mM) on 2,3‐DPG production by perfusing fresh human blood in dialysis tubing, 37°C, pH 7.15–7.70, with the appropriate solutions and with compressed air or 100% O2 for up to 6 hours. The DPG increased significantly with fructose/phosphate incubations for 6 hours. At pH > 7.35 the average increase was 25%; at pH < 7.35, 12%; PO4 > 6 mM + pH > 7.35 yielded the highest changes, 28%. Methylene blue 2.5–7.5 μM + PO4 > 2.5 mM + pH > 7.35 yielded similar results. Glucose + PO4 showed no effect on DPG. Results were comparable at all fructose levels either with compressed air or 100% O2. Significant elevations in 2,3‐DPG were also noted at 4 hours but were of lesser magnitude.In conclusion, significant elevations in 2,3‐DPG can be achieved by incubating whole blood with fructose/phosphate solutions or with methylene blue and phosphate for 4–6 hours. It should be possible to adapt these solutions for human use to raise 2, 3‐DPG. The potential physiologic value of rightward shifts in hemoglobin oxygen affinity can then be tested under appropriate conditions.
Hemoglobin miyada: DNA analysis of the anti‐lepore βδ fusion gene
Authors: Driscoll M. Catherine , Ohta Yoshiro , Nakamura Frank , Bloom Arthur , Bank Arthur 
Published: February 2007

AbstractHemoglobin Miyada, an anti‐Lepore hemoglobin, represents the protein product of a nonhomologous crossover between β and δ genes. The mutant globin is β‐like from the N terminus to amino acid 12, and δ‐like from amino acid 22 through the C terminus, thus predicting a crossover site in the first coding region of the gene. DNA analysis, using multiple restriction endonucleases and hybridization to δ and β globin gene‐specific probes, confirms that the βδ hybrid gene 1) is located on a single chromosomal fragment between normal δ and β genes, and 2) has 5′ β promoter sequences, δ IVS 1 and 2, and 3′ coding and flanking sequences.
Chronic anemia progressing to auer rod‐positive and TdT‐positive acute leukemia with 5q– chromosomal anomaly
Authors: Xavier Anita M. , Kasimis Basil S. 
Published: February 2007

AbstractThe 5q– syndrome is a recently described entity characterized by partial deletion of the long arm of chromosome No. 5 and by hematologic findings of chronic anemia with reticulocytopenia, nonlobulated megakaryocytes, and megathrombocytes. We report on a patient with the hematologic features of the 5q– syndrome who progressed to acute leukemia and whose uniqueness consisted of 1) lack of additional cytogenetic abnormalities, 2) presence of blasts with Auer rods, and 3) bone marrow cells positive for terminal deoxynucleotidyl transferase. His leukemia was refractory to conventional chemotherapy.
5‐azacytidine and fetal hemoglobin
Authors: Heller Paul , Desimone Joseph 
Published: February 2007

AbstractThe evidence that 5‐azacytidine stimulates the production of Hb F and F cells in baboon and man is reviewed. The mechanism of this effect is not entirely clear, but 5‐azacytidine produces hypomethylation of the γ gene at certain sites, and gene expression and DNA hypomethylation are related phenomena in many other systems. Other mechanisms have been postulated by other investigators. The therapeutic significance of increased Hb F levels in homozygous β thalassemia and sickle cell anemia is exemplified. The potential risk of carcinogenicity has delayed more extensive clinical trials.
Monitoring of intensive phlebotomy therapy in iron overload by serum ferritin assay
Authors: Van Oost Bernard A. , Beld Bep Van Den , Van Asbeck B. Sweder , Marx Joannes J. M. 
Published: February 2007

AbstractFour patients with idiopathic hemochromatosis were treated with intensive phlebotomy therapy. In 1 to 2 years, 8.8–16.7 g iron was removed. In three out of four patients hemoglobin levels fell at the end of therapy. Serum ferritin was continuously measured during therapy. The greatly elevated serum ferritin levels normalized or decreased to subnormal levels in all patients after therapy. Despite some fluctuations in the first phase of therapy, the fall in serum ferritin was regular with halving of the ferritin levels after about 50% of the excess iron was removed. The normalization of serum ferritin occurred in advance of the hemoglobin decrease at the end of therapy, indicating that in the later stages of therapy the normal iron stores are also depleted. It is emphasized that serum ferritin measurements are useful for monitoring of intensive phlebotomy therapy, and in particular to indicate the end of therapy before anemia develops.