bluuebunny/crossref_metadata_2025_split huggingface dataset:
Serum Uracil Levels in Acute Childhood Leukaemia
Authors: Parry T. E. 
Published: March 2008

Serum ‘uracil + uridine’ expressed as uracil has been measured in 47 consecutive cases of acute leukaemia in children at the time of diagnosis, before treatment, and also both before and after therapy in a girl of 12 with Ph1 positive chronic myeloid leukaemia in blastic transformation, and in an adult male age 31 with acute undifferentiated leukaemia. The results were compared with 97 previously reported normal subjects. The skew distribution of results in acute leukaemia rendered the mean value and standard deviation meaningless but the range was considerably wider than in the normal controls (range 7.2–77.1 μmol/l. in acute leukaemia; mean 15.7 μmol/l., range 5.7–40.5 μmol/l., SD 5.26 in controls). In 10 (21%) of the patients with acute leukaemia the level was more than 3 SDs and in five more than 8 SDs above the normal mean. There was a high degree of correlation between uracil concentration and total white cell count (r= 0.7894, P<0.001) and blast cell count (r= 0.7160, P<0.001) but no correlation was observed between serum uracil and the blood urea or the serum uric acid, vitamin B12 or folate. The grossly elevated uracil levels, white cell and blast cell counts rapidly returned to normal or near normal after therapy.Retention of uracil by the kidney, increased DNA catabolism and the enzymatic deamination of cytosine are considered, and each in turn excluded, as a possible cause of the observed elevated uracil levels. It is submitted that the raised uracil level is a function of the circulating blast cell and that the results are consistent with the hypothesis that, at least in some cases of acute leukaemia, there may be an impairment in the amination of uracil to form cytosine akin to the impaired methylation of deoxyuridylate in the megaloblastic anaemias. The former would enhance the known mutagenic action of uracil, an action which is absent in the latter. The molecular mechanism, whereby this could give rise to a population of genetically abnormal cells incapable of normal differentiation, is discussed.
Erythrokinetic Studies in Myelofibrosis: Their Significance for Prognosis
Authors: Najean Yves , Cacchione Roberto , Castro‐Malaspina Hugo , Dresch Catherine 
Published: March 2008

Summary. Eighty‐three patients with myelofibrosis have been studied by erythrokinetics and have been followed up until death or for at least 12 months. Because of a large plasma volume the venous haematocrit gives only a poor idea of the red blood cell volume. The red cell survival was reduced in the majority of cases but significant haemolysis was rare. The amount of haemolysis of autologous and isologous red cells was similar, suggesting an extra‐corpuscular origin for the haemolysis. Plasma iron turnover was always increased, sometimes markedly, but red cell iron incorporation was reduced in 70% of cases, indicating ineffective erythropoiesis. Surface counting showed an absence on diminution of sacral iron fixation and a rapid and marked splenic uptake in more than 90% of the cases; uptake of iron by the liver occurred in half the cases, usually not very high; iron release from the spleen was absent or reduced in 67% of the cases.The degree of ineffective erythropoiesis as measured by radio‐iron incorporation and release by the spleen, the amount of haemolysis, and the red cell volume were strongly correlated with prognosis. These factors enabled a more precise prediction to be made of the clinical outcome in the 2 years following the study, than the clincal data alone. A prospective study might show whether erythrokinetic studies are also useful in determining the choice of treatment.
Constitutional Aplastic Anaemia: Defective Haematopoietic Stem Cell Growth in Vitro
Authors: Saunders E. F. , Freedman M. H. 
Published: March 2008

Summary. . Seven children with constitutional aplastic anaemia (one dyskeratosis congenita, one constitutional type without anomalies, five classical Fanconi's anaemia) were studied to define the pathogenesis of the marrow failure. Haematopoiesis was assessed by assay of granulocytic (CFU‐C) and erythrocytic (CFU‐E) colonies in vitro.Numbers of CFU‐C were profoundly reduced or absent in marrow cultures from all patients (range 0‐5 CFU‐C/105, control range 15‐106/105). Numbers of CFU‐E were also strikingly reduced or absent (range 0‐2 CFU‐E/105, control range 31‐317/105) with one exception. No CFU‐C could be grown from peripheral blood. Incubation of the patients' sera with control marrow failed to demonstrate inhibition of CFU‐C, colony stimulating activity (CSA), CFU‐E or erythropoietin (EPO). The peripheral blood lymphocytes from these patients in co‐culture experiments failed to inhibit CFU‐C or CFU‐E growth from control marrow. Aplastic marrow co‐cultured with control marrow also failed to demonstrate cellular inhibition. CSA production from patients’peripheral blood leucocytes averaged 93% of the activity of a standard control CSA, suggesting normal granulopoietic stimulation.The data indicate a problem early in haematopoiesis. Although a defect in the stromal microenvironment cannot be excluded, it is possible the defect is intrinsic to the haematopoietic stem cells, either an absence or marked reduction in stem cells, or a failure of stem cells to grow colonies in Vitro.
Formation of Transcobalamin II‐Vitamin B12 Complex by Guinea‐Pig Ileal Mucosa in Organ Culture After in Vivo Incubation with Intrinsic Factor‐ Vitamin B12
Authors: Rothenberg Sheldon P. , Weiss James P. , Cotter Richard 
Published: March 2008

Summary. The in vivo incubation of intrinsic factor‐[57Co]vitamin B12 in an ileal loop of a guinea‐pig followed of in vitro culturing of segments of the ileum for 180 min has been used to study the transepithelial transport vitamin B12. Analysis of the solubilized supernate of mucosa following the in vivo phase demonstrated that 44% of the [57Co]vitamin B12 was bound to intrinsic factor (IF), 26% was free, and 16% was bound to transcobalamin II (TCII). Following culture, similar analysis demonstrated that 18% of the vitamin was now bound to IF, 49% was free, and 35% was bound to TCII. In the culture medium, 54% of the [57Co]vitamin B12 was free and 37% was bound ot TCII. The formation of TCII‐[57]vitamin B12 did not occur if homogenized mucosa was incubated with free [57Co]vitamin B12 but it did form in cultures of ileal segments from animals given an excess of unlabelled vitamin to saturate all circulating TCII, and in the medium containing puromycin. Indirect immunoflourescence using chicken anti‐TCII demonstrated that TCII was associated with the mucosal cells of both the ileum and jejunum.These studies demonstrate that following transepithelial flux of vitamin B12 through the ileal mucosa, the vitamin becomes coupled to TCII. This coupling requires a structurally intact mucosa and the source of the TCII appears to be the ileal mucosal cell rather than unsaturated TCII circulating in the blood.
Critical Re‐examination of the Specificity of Auto‐anti‐Rh Antibodies in Patients with a Positive Direct Antiglobulin Test
Authors: Issitt Peter D. , Pavone Beverly G. 
Published: March 2008

SummaryForty‐eight autoantibodies with apparent 'simple’anti‐Rh specificity (anti‐e, ‐E, ‐c, ‐D, ‐C, ‐Ce, ‐G), have been studied by means of multiple absorption tests. The finding that 34 (70.8%) of these antibodies could bind to red blood cells lacking the antigens that the antibodies appeared to define, indicated that the antibodies had different specificities than seemed to be the case in initial antibody identification tests. Those autoantibodies that at first appeared to be directed against the Rh antigens e, E or c, most often had anti‐Hr or anti‐Hro specificity.These data explain why some apparent anti‐Rh autoantibodies can be eluted from the red blood cells of patients negative for the antigens that the antibodies appear to define. However, they also illustrate that the phenomenon of autoantibodies mimicking specificities that they do not possess is common in patients positive for the antigens against which their autoantibodies appear to be directed. An explanation for the mode of action of these autoantibodies in complexing with the Rh agglutinogen is proposed, and the significance of the antibodies in transfusion therapy is considered.
The Inhibitory Effect of Aspirin on Platelet and Vascular Prostaglandins in Rats cannot be Completely Dissociated
Authors: Villa Silvia , Livio Manuela , de Gaetano Giovanni 
Published: March 2008

Summary. Blood platelets and vascular endothelium generate prostaglandin derivatives with opposing effects: cyclic endoperoxides and thromboxane A2 (TXA2) aggregate platelets, whereas prostaglandin I2 (PGI2, prostacyclin) inhibits aggregation. Since aspirin inhibits the synthesis and effects of all these metabolites of arachidonic acid, the rationale for clinical use of this drug in thrombosis prevention trials is questionable. Treatment schedules would have to be calibrated to inhibit proaggregating platelet prostaglandins and TXA2 without affecting protective vascular prostaglandins (PGI2). This important clinical information cannot easily be obtained from studies in man.The present study indicates that normal rat platelets are more sensitive to aspirin (ID50=3.6 mg/kg) than arterial tissues (ID50=25.0 mg/kg) and are almost as sensitive as venous tissues (ID50=2.3 mg/kg). Platelet prostaglandin production was monitored through the measurement of malondialdehyde (MDA) output under standard stimulation with thrombin. PGI2‐like activity released from the abdominal aorta and inferior vena cava was determined as platelet aggregation inhibitory potency and characterized by standard criteria.The inhibitory effect of aspirin (at doses of 10 and 50 mg/kg) on platelet MDA production lasted much longer in platelets (96–120 h) than in venous (24–72 h) or arterial tissue (less than 24 h). The findings suggest that in rats the (potentially antithrombotic) effect of aspirin on platelet prostaglandin and TXA2 generation may be distinguished, though not completely, from the (potentially prothrombotic) effect on vascular PGI2 on the basis of duration of inhibition more than on the sensitivity of the target cells to the drug. The different capacities of anucleated platelets and of nucleated vascular endothelial cells to overcome aspirin inhibition could be exploited for more rational clinical use of this drug.
Detection of Haemophilia A Carriers by Replicate Factor VIII Activity and Factor VIII Antigenicity Determinations
Authors: Seligsohn Uri , Zivelin Ariela , Perez Chava , Modan Michaela 
Published: March 2008

Summary. Factor VIII (fVIII) activity and antigenicity were determined on replicate fresh blood samples drawn on three separate occasions in 48 normal females and 37 obligatory haemophilia A carriers, in an attempt to improve the detection rate. fVIII activity was assayed by a one‐stage method and fVIII antigenicity by the Laurell's technique employing an anti‐fVIII antiserum prepared in rabbits. The mean results for the individual subjects were analysed after establishing a discriminant function. The probability of being a carrier was determined on the basis of laboratory data and family history. The probability data were translated into more simple terms applicable for genetic counselling by defining three categories: Definite carriers, doubtful carriers and definite normals. Of the obligatory carriers, 83·8% were classified definite carriers, 13·5% doubtful carriers and 2·7% as definite normals. Of the normal females, 4·2% were classified as definite carriers, 18·7% doubtful carriers and 77·1% as definite normals. Adjustment of the results according to age was found unnecessary.The precision of the determinations of fVIII antigenicity and fVIII activity in individual subjects was calculated for different numbers of replicate tests performed in the same individual. It was found that if only one test is performed, a substantial error might occur. Three replicate tests considerably diminish this error, although it is still in the range of ±16–29%. For suspected carriers who fall in the doubtful category it is suggested that six or even more tests are performed.
Congenital Non‐spherocytic Haemolytic Anaemia Variants with Primary and Secondary Pyruvate Kinase Deficiency
Authors: Ważewska‐Czyżewska Maria , Gumińska Maria 
Published: March 2008

Summary. The patterns of survival of isotope‐labelled erythrocytes were examined in patients suffering from two variants of congenital non‐spherocytic haemolytic anaemia with decreased erythrocyte pyruvate kinase (PK) activity.In one variant, with primary PK defect (PPKD) randon destruction of erythrocytes was predominant in the process of haemolysis. In the second variant, with primary magnesium activated adenosine triphosphatase (ATP‐ase) (Mg++) deficiency and a secondary decrease in PK activity, erythrocytes were destroyed by senescence. Two subpopulations of labelled erythrocytes with different destruction rates were observed in all patients examined, except one with the second variant, with very mild haemolysis.Splenectomy, performed on two patients, was successful only in the variant with PPKD.
Cycles of Agglutination‐Disagglutination Induced by Ristocetin in Thrombasthenic Platelets
Authors: Chediak J. , Telfer M. C. , Laan B. Vander , Maxey B. , Cohen I. 
Published: March 2008

Summary. An oscillatory pattern of platelet agglutination‐disagglutination in response to Ristocetin (R) at narrow concentration ranges was observed in citrated platelet rich plasma (PRP) of 10 patients with Glanzmann's thrombasthenia. The cyclic pattern decreased in intensity over time, was reproducible, and was not pH dependent. Formalin‐fixed thrombasthenic platelets agglutinated with R but did not show a cyclic pattern.Incubation with 2.5 μm ADP inhibited R oscillation response, but small increases in R dose overcame this inhibition. The addition of ATP or creatine phosphate/creatine phosphokinase to thrombasthenic platelets inhibited by ADP restored the R oscillation response. In the platelets of a single patient, intracellular levels of ADP and ATP were shown to diminish during an oscillation response to R. There was an increase in AMP levels during the same period of time. The changes in these three intracellular nucleotides were gradual over time and did not vary with phases of the oscillation. Acetyl salicylic acid (ASA), at concentrations shown to block cyclooxy‐genase activity in control platelets, enabled thrombasthenic platelets to respond to R with full agglutination without oscillations. Lower concentrations of ASA in the PRP gave a return of the oscillation response.Our data suggest that the disagglutination phase of the R response of thrombasthenic platelets is not a function of the known glycoprotein membrane defect, but depends on materials originating in the platelet whose release is blocked by ASA.
The Value of the Standardized Partial Thromboplastin Time in Detecting Heparin during Low‐Dose Prophylaxis
Authors: Taberner D. A. , Norman C. , Poller L. , Burslem R. W. , Jones J. B. 
Published: March 2008

Summary. The sensitivity of the standardized partial thromboplastin time technique in detecting circulating heparin during low‐dose calcium heparin prophylaxis in gynaecological surgery has been evaluated and compared with an anti Xa assay and a chomogenic substrate method. The PTT test and anti Xa test were performed daily on plasmas from eight control and seven heparin treated patients. Both the PTT and anti Xa test showed significant prolongation in heparin‐treated patients receiving the 5000 units regime 12‐hourly. In control patients the PTT test showed a significant shortening, maximal on the fifth day after operation. This interferes with the detection of heparin by the PTT during this period. Nevertheless, the effect of small concentrations of heparin is observable during low‐dose prophylaxis by its prevention of the post‐operative acceleration of the PTT test. By contrast, the anti Xa test is relatively unaffected by the post‐operative acceleration and is more prolonged by the low‐dose heparin therapy.The heparin levels in 17 plasmas from gynaecological surgical patients receiving low‐dose therapy were determined by PTT, anti‐Xa and chromogenic substrate. The chromogenic substrate and anti Xa assays showed reasonably good intra‐class correlation. Heparin levels determined by the PTT test were invalidated by the post‐operative acceleration of the test. If, however, this post‐operative acceleration is of clinical significance and relates to a prethrombotic state, its detection by the PTT may be important and may be a valuable indicator for the need for an increase of the heparin dosage. Unless it is shown that the anti Xa effect of heparin is of more importance in the prevention of thrombosis than the prolongation of the PTT, the standardized PTT appears to offer a simple method of control of low‐dose heparin administration.
Cell Surface Heterogeneity of Human Blood Neutrophils and Monocytes
Authors: Barrett Sondra , Garratty Eileen , Garratty George 
Published: March 2008

Summary. Until recently, human blood neutrophils (PMN) and monocytes have been considered to be homogeneous cell populations. However, much evidence has accumulated on their functional heterogeneity. This functional heterogeneity suggests the existence of different subsets of myeloid cells analogous to T and B subsets of lymphoid cells. The goal of this study was to investigate this question of myeloid subsets by examining myeloid cells for cell surface reactivity for IgG and complement (C).Normal PMN and monocytes were examined from 60 subjects for the presence of two types of IgG‐Fc receptors and two activated C components, C3b and C3d. Most PMN and monocytes showed Fc receptor reactivity for rabbit IgG (Fc‐R). In addition, the majority of monocytes but very few PMN reacted with human IgG (anti‐Rh0) coated Rh‐positive erythrocytes (Fc‐H). Most PMN and monocytes showed C receptor reactivity for C3b, but only a minor subpopulation of both myeloid cells had C3d receptors. These data provide evidence that human blood myeloid cells may be composed of subsets with different membrane marker reactivities.
Idiopathic Neutropenia with Normocellular Bone Marrow: an Immune‐Complex Disease
Authors: Caligaris‐Cappio F. , Camussi G. , Gavosto F. 
Published: March 2008

Summary. The presence of circulating immune‐complexes (IC) and their in vivo interaction with polymorphonuclear neutrophils (PMN) have been detected in two cases of idiopathic neutropenia with normocellular bone marrow. The injection of patients' sera into New Zealand White rabbits caused a striking neutropenia due to sequestration of PMN in the vascular bed of kidneys and lungs. The kinetics of PMN disappearance from peripheral blood and the pattern of sequestration overlapped that induced by the injection of pre‐formed soluble IC. Treatment with plasmapheresis caused an early and lasting increase of PMN; rabbit PMN were almost unaffected by the injection of patient serum after the course of plasmapheresis.These data are consistent with the possibility that idiopathic neutropenia with normocellular bone marrow may be caused by persistent in vivo interaction between IC and circulating PMN.
Leukaemia Classification: a Study of the Accuracy of Diagnosis in 456 Patients
Authors: Whittaker J. A. , Withey J. , Powell D.E.B. , Parry T.E. , Khurshid M. 
Published: March 2008

Summary. A panel of five haematologists has examined, without consultation or prior knowledge of the diagnosis, blood films and bone marrow smears from 456 patients with a diagnosis of leukaemia. A diagnostic classification which recognized various subtypes of acute myelogenous leukaemia was used but no attempt was made to subdivide acute lymphoblastic leukaemia.Complete agreement with the initial diagnosis was low (56.4%) and was particularly poor (45.7%) when the patient had one of the forms of acute leukaemia. However, disagreements which would have involved the patient in a change of treatment were unusual (2.0%).We conclude that a high degree of diagnostic agreement for patients with leukaemia is unlikely from morphological classifications alone.
Stem Cell Migration Induced by Erythropoietin or Haemolytic Anaemia: the Effects of Actinomycin and Endotoxin Contamination of Erythropoietin Preparations
Authors: Quesenberry P. , Levin J. , Zuckerman K. , Rencricca N. , Sullivan R. , Tyler W. 
Published: March 2008

Summary. The injection of erythropoietin or the induction of anaemia with phenylhydrazine leads to changes in murine pluripotent and granulocyte‐macrophage stem cells indicating migration from marrow to spleen. In order to evaluate the interrelationship between erythroid differentiation and stem cell migration we have selectively suppressed erythroid differentiation with actinomycin D. Anaemia or EP injection resulted in stem cell changes consistent with migration; actinomycin blocked these changes in anaemic but not EP injected mice while blocking erythropoiesis in both groups.The erythropoietin contained from 0.01 to 1000 μg/ml of endotoxin as defined by the limulus test; it decreased marrow erythropoiesis and stimulated marrow granulopoiesis. Adsorption of the erythropoietin preparation with limulus lysate removed endotoxin without decreasing erythropoietin activity. Adsorbed erythropoietin stimulated erythropoiesis and not granulopoiesis, and stem cell changes induced by its administration were largely blocked by actinomycin, suggesting that endotoxin in the non‐adsorbed erythropoietin caused the actinomycin resistant stem cell changes.The observation that actinomycin blocks both erythroid differentiation and stem cell migration suggests that these two physiologic events are closely linked. The effects of injected erythropoietin on murine haemopoietic stem cells may, to a significant extent, be secondary to the presence of endotoxin in the erythropoietin preparations.
Abnormal Red‐Cell Metabolism of Pyridoxine Associated with β‐Thalassaemia
Authors: Anderson B. B. , Perry G. M. , Modell C. B. , Child J. A. , Mollin D. L. 
Published: March 2008

Summary. Red‐cell conversion of pyridoxine to pyridoxal phosphate was studied in control subjects, and patients with heterozygous and homozygous β‐thalassaemia. In 7% of control subjects the rate of pyridoxine conversion was well below the range found in the other control subjects (5.0–8.6%, mean 6.5%/g Hb × 10−2) but in heterozygous β‐thalassaemia was below that range in 63% of the patients. The conversion rate was also slow or borderline in the majority of patients with severe transfusion‐dependent homozygous β‐thalassaemia, in spite of the presence of some donor cells; but was normal, or fast as in other anaemias, in all but one patient with mild homozygous thalassaemia. There was a much higher incidence of a slow conversion rate in the parents of the severe homozygotes than in parents of the mild homozygotes, illustrating the familial pattern. This supports our view that the red‐cell conversion rate of pyridoxine is an inherited characteristic, independent of thalassaemia.The cause of a reduced rate of pyridoxine conversion was investigated. The increase to a normal rate following riboflavin ingestion suggests a defect in the activity of the flavin mononucleotide (FMN)‐dependent pyridoxine phosphate oxidase.