bluuebunny/crossref_metadata_2025_split huggingface dataset:
In vivo evidence of intravascular binding sites for coagulation factor IX
Authors: Stern David M. , Knitter Glen , Kisiel Walt , Nawroth Peter P. 
Published: March 2008

SummaryPrevious studies have demonstrated that factors IX/IXa bind to specific sites on the surfaces of cultured and native endothelium in vitro and that these sites should be occupied with factor IX in homeostasis. Since factor IX of different species binds to endothelium in a similar manner, we examined if infusion of heterologous factor IX into an animal should result in displacement of host factor IX antigen from its vessel wall site. Experiments were carried out in baboons with a large excess of bovine factor IX employing species‐specific radioimmunoassays. The results indicate that infusion of bovine factor IX or active site‐blocked factor IXa, but not prothrombin, resulted in a dose‐dependent rise in the plasma level of baboon factor IX antigen. This suggested that the infused factor IX was displacing the host clotting factor from some reservoir easily accessible to the intravascular space. Consistent with this hypothesis, infusion of 125I‐factor IX demonstrated accumulation in multiple organs. Radioiodinated factor IX comigrating with the initial tracer on SDS‐PAGE could be eluted from the luminal surface of pulmonary artery and aortic segments. 125I‐factor IX was not significantly associated with cellular elements of the blood. These results suggest that there is a pool of non‐circulating factor IX which is accessible to the intravascular space, widely distributed and involves endothelium.
Dysmegakaryocytopoiesis in acute leukaemias: its predominance in myelomonocytic (M4) leukaemia and implication for poor response to chemotherapy
Authors: Jinnai Itsuro , Tomonaga Masao , Kuriyama Kazutaka , Matsuo Tatsuki , Nonaka Hiroaki , Amenomori Tatsuhiko , Yoshida Yoshiharu , Kusano Miyuki , Tagawa Masuko , Ichimaru Michito 
Published: March 2008

SummaryMegakaryocytopoiesis was morphologically investigated in 129 adults with de novo acute leukaemia. Three types were identified: type I (84 cases), no detectable megakaryocytes; type II (32 cases), quantitatively preserved megakaryocytes with normal morphology; type III (13 cases): quantitatively preserved megakaryocytes but with distinct dysplastic changes such as micromegakaryocytes and megakaryocytes with multiple small separated nuclei. Type III was found in M1 (one out of 21 cases), M2 (one out of 20 cases), M4 (eight out of 24 cases), M6 (two out of four cases) and hypoplastic leukaemia (one out of 13 cases). M3 cases were all classified into type I. Most of acute lymphoid leukaemia cases (21 cases) belonged to type II. Among AML cases, the complete remission (CR) rate by intensive chemotherapy with daunorubicin and cytosine arabinoside was significantly lower in type III (11%) than in types I (87%) and II (71%). Among M4 cases, CR rates in type III (14%) was also significantly lower than those in type I (75%) and II (100%). Thus, the present study indicates the importance of recognizing dysmegakaryocytopoiesis in AML for clariflcation of the heterogeneous biology or pathophysiology of acute leukaemias and formulation of an appropriate therapeutic strategy.
Cytogenetics of bone marrow fibroblastic cells in idiopathic chronic myelofibrosis
Authors: Greenberg Bernard R. , Woo Linda , Veomett Iris C. , Payne Claire M. , Ahmann Frederick R. 
Published: March 2008

SummaryTo determine the nature of the fibroblastic proliferation in myelofibrosis, we studied the cytogenetic composition of a pure population of in‐vitro bone marrow fibroblastic cells (FC) from a patient with idiopathic chronic myelofibrosis who had trisomy 8 in her unstimulated peripheral blood cells. This cytogenetic abnormality was absent in all the FC studied supporting the premise that in the myeloproliferative disorders the myelofibrosis represents a secondary or non‐neoplastic reaction to the clonal proliferation of haematopoietic stem cells.
Production of factor VIII deficient plasma by immunodepletion using three monoclonal antibodies
Authors: Takase Toshio , Rotblat Frances , Goodall Alison H. , Kernoff Peter B. A. , Middleton Sarah , Chand Sadhna , Denson K. W. , Austen Denis E. G. , Tuddenham Edward G. D. 
Published: March 2008

SummaryFactor VIII deficient plasma was made from pooled, HIV antibody and hepatitis B antigen screened, normal human plasma by cryoprecipitation and immunodepletion, using three different monoclonal antibodies bound to Sepharose columns, in series. These monoclonal antibodies are specific respectively for von Willebrand factor, factor VIII heavy chain and factor VIII light chain.The immunodepleted plasma contained less than 0·002 u/ml factor VIII coagulation activity (VIII:C) less than 0·0001 u/ml von Willebrand factor antigen and 1–2 g/l fibrinogen, while the levels of other clotting factors were unchanged. This immunodepleted plasma was compared with commercial factor VIII deficient plasma obtained from a severe haemophilia A patient as substrate in the one‐stage factor VIII assay. Plasmas obtained from 20 normal subjects and 28 patients with von Willebrand's disease or haemophilia A were assayed for VIII:C using the two substrates. The results were very highly correlated (r = 0·96). The columns have high capacity and can be regenerated at least 10 times. Large‐scale production of a substrate for factor VIII assays free of virus contamination is now feasible.
An abnormal antithrombin III (AT III) with low heparin affinity: AT III Clichy
Authors: Aiach M. , Franclois D. , Priollet P. , Capron L. , Roncato M. , Alhenc‐Gelas M. , Fiessinger J.‐N. 
Published: March 2008

SummaryWe have identified an inherited qualitative deficiency of antithrombin III (AT III) in a family with apparently no increased incidence of venous thrombosis. Plasma antithrombin and anti‐Xa activities were normal, but the interaction with heparin, heparan sulphate and low molecular weight heparin was uniformly decreased. An immunoblotting technique performed in plasma showed normal complex formation with thrombin. By using heparin‐Sepharose affinity chromatography and crossed immunoelectrophoresis, the variant could be separated: at least two fractions of low affinity AT III were obtained. A minor one had no antiprotease activity; the other one was further purified to homogeneity and found to have normal specific activity in absence of heparin and a 50% decreased activity in presence of heparin. We propose to call this new variant AT III Clichy.
Antithrombin III Glasgow: a variant with increased heparin affinity and reduced ability to inactivate thrombin, associated with familial thrombosis
Authors: Lane D. A. , Lowe G. D. O. , Flynn A. , Thompson E. , Ireland H. , Erdjument H. 
Published: March 2008

SummaryA functional antithrombin III (AT III) deficiency has been identified in two generations of a family with a high incidence of thrombosis. The deficiency presented as 50% reduction in heparin cofactor activity compared to its antigen concentration. No abnormality was detected by crossed immunoelectrophoresis in the presence or absence of heparin. Plasma from the propositus was precipitated with dextran sulphate, applied to heparin‐Sepharose and the AT III stepwise eluted with NaCl. The AT III had a reduced ability to inactivate thrombin, when this was monitored by substrate hydrolysis or by SDS polyacrylamide gel electrophoresis. Its mobility was normal by the latter technique using 10–20% gradient gels under reducing and non‐reducing conditions. AT III from the patient was reapplied to heparin‐Sepharose and eluted with a NaCl gradient. An active pool eluted in the same NaCl concentration range used to purify normal AT III, while predominantly inactive AT III eluted at higher NaCl concentrations. It is concluded that this variant, designated AT III Glasgow, has increased affinity for heparin but reduced ability to inactivate thrombin.
Development of the phagocytic and cidal capacity during maturation of myeloid cells: studies on cells from patients with chronic myelogenous leukaemia
Authors: Segel Erik K. , Ellegaard Jørgen , Borregaard Niels 
Published: March 2008

Summary. Myeloid cells from peripheral blood of patients with chronic myelogenous leukaemia were isolated and fractionated by density gradient centrifugation using Lymphoprep gradient followed by discontinuous Percoll gradients. Six fractions were obtained, each enriched in one of the morphologically identifiable types of myeloid cells from myeloblasts to polymorphonuclear neutrophils. Each of these cell types were functionally and biochemically characterized.The development of the capacities for phagocytosis and killing of yeast cells and the ability to generate a respiratory burst of phagocytosis correlated closely with the content of cytochrome b and vitamin B12‐binding protein, a marker of specific granules. These results support the notion that the specific granules provide the developing neutrophil with components which are essential for its microbicidal activity.
Factor XIII: a marker of mono‐ and megakaryocytopoiesis
Authors: ÁDány Róza , Kiss Attila , Muszbek László 
Published: March 2008

SummaryPrevious studies have shown that human platelets, megakaryocytes and peripheral blood monocytes contain the subunit α of plasma factor XIII (FXIII) which plays a key role in fibrin stabilization. To study the expression of FXIII subunit α during differentiation of the mono‐and megakaryocytic cell lines, bone marrow smears were examined by immunomorphological methods. In addition to megakaryocytes, FXIII was detected in a large number of cells by a highly sensitive immunoperoxidase staining. Characterization of these cells was carried out by double immunofluorescent labelling in which the detection of FXIII subunit α was combined by the labelling of either Leu M3 monocyte/macrophage surface antigen or platelet factor 4 (PF4) a marker for megakaryocytic cells. On the course of differentiation from early precursors to mature megakaryocytes all phenotypic form of the megakaryocytic cell line expressed FXIII subunit α though there were considerable changes in its subcellular distribution pattern. Leu M3 positive cells of monocytopoiesis, i.e. monocytes and promonocytes and in all probability monoblasts as well, were also labelled for FXIII. On this basis FXIII subunit α could be considered as a common marker of megakaryo‐ and monocytopoiesis and its immunomorphological detection might provide a useful diagostic tool for identifying normal and perhaps also malignant differentiation forms of these cell lines.
Splenic platelet‐sequestration following routine blood transfusion is reduced by filtered/washed blood products
Authors: Bareford D. , Chandler S. T. , Hawker R. J. , Jackson N. , Smith M. , Boughton B. J. 
Published: March 2008

SummaryThe mean fall in the platelet count following 23 routine transfusions of 3–5 units packed cells for anaemia was 32.5%. This was significantly reduced to 12.5% in 15 similar transfusions through a 40 μm microaggregate filter (P<0.01) and to 4.6% following five transfusions through a polyester fibre filter (P<0.005). In 10 transfusions with frozen or polyester fibre filtered, washed red cells, the decrease in platelet count was 4.2% (P<0.001). A study of 111In‐oxine labelled autologous platelets in nine patients indicated that the fall in platelet count was due to increased splenic sequestration. Since thrombocytopenia following routine transfusion is reduced by procedures which filter the packed cells, the decrease in platelets is probably caused by their adherence to infused microaggregate debris causing their premature removal from the circulation. Patients with preexisting thrombocytopenia who receive red cell transfusions for anaemia, should therefore receive blood products depleted of microaggregate debris in order to avoid exacerbation of thrombocytopenia and haemorrhagic complications.
A new unstable haemoglobin variant: Hb Shanghai [β131 (H9)Gl→Pro] found in China
Authors: Zeng Y. T. , Ren Z. R. , Chen M. J. , Zhao J. Q. , Qiu X. K. , Huang S. Z. 
Published: March 2008

SummaryA 34–year‐old woman patient was found to have a chronic hereditary haemolytic anaemia. No abnormal haemoglobin band was detected by conventional electrophoresis, but a slow β chain could be separated on urea‐carboxymethyl cellulose chromatography. Investigations of the patient's haemoglobin revealed an unstable component. Analyses of chemical structure, including isolation and TPCK trypsin digestion of the abnormal globin chain, HPL chromatography, amino acid composition as well as sequence determination of the abnormal peptide, indicated that a glutamine was replaced by a proline at position β 131 (H9). Biosynthesis studies demonstrated a normal rate of synthesis but relatively fast degradation of the mutant β chain. The new variant is named as Hb Shanghai according to the place where it was discovered.
The purification of human basophils: their immunophenotype and cytochemistry
Authors: Bodger Michael P. , Newton Lesley A. 
Published: March 2008

SummaryAn IgM class monoclonal antibody Bsp‐1 that selectively reacts with human basophils was used to label basophils in normal and leukaemic haemopoietic samples. The immunophenotype of Bsp‐1+ basophils was determined using a panel of 21 IgG subclass monoclonal antibodies in two‐colour immunofluorescence assays. Basophils expressed the leucocyte common antigen, HLA‐ABC antigens and antigens defined by CD1 1 and CD1 3 monoclonal antibodies. Other myeloid cell (granulocyte‐monocyte) associated antigens, lymphoid cell surface determinants and HLA‐DR antigens were not detected. Basophil preparations of 95–98% purity were obtained from the peripheral blood of patients with CML and umbilical cords using fluorescence activated cell sorting techniques. Purified basophils exhibited metachromatic staining with toluidine blue, alcian blue and astra blue. PAS staining was observed in 7% of cord Bsp‐1+ cells and of 55% CML Bsp‐1+ cells. Between 5% and 10% of basophils were chloroacetate esterase‐positive which suggests that some Bsp‐1+ cells are immature basophils.
Autoantibodies against platelet GPIIb/IIIa in chronic ITP react with different epitopes*
Authors: Tsubakio T. , Tani P. , Woods V. L. , McMillan R. 
Published: March 2008

SummarySome patients with chronic immune thrombocytopenic purpura have autoantibodies to the platelet glycoprotein IIb/IIIa (GPIIb/IIIa) complex. To determine whether these autoantibodies are directed towards the same or different epitopes, we evaluated the ability of four murine monoclonal anti‐GPIIb/IIIa antibodies specific for different epitopes to block autoantibody binding. We noted a variation in blocking patterns among autoantibodies from patients with chronic ITP. In addition, we were able to map the relative epitope locations of both the autoantibodies and the monoclonal antibodies. These data show that the anti‐GPIIb/IIIa monoclonal autoantibodies in chronic ITP are directed towards different epitopes.
Autoimmune haemolytic anaemia in childhood associated with non‐complement binding IgM autoantibodies
Authors: Salama A. , Mueller‐Eckhardt C. 
Published: March 2008

SummaryRed cell bound IgM autoantibodies free of associated IgG autoantibodies and unable to activate complement have not yet been considered as the cause of autoimmune haemolytic anaemia (AIHA). We report on warm type AIHA resulting from the action of IgM autoantibodies on circulating RBC. Twelve children (eight of whom were infants) with relatively severe haemolytic anaemia were studied. Whereas the clinical findings and courses of all children appeared to be compatible with warm type AIHA, the serological findings during the haemolytic phase were atypical in that the direct antiglobulin test (DAT) was negative in 11, and positive in one case due to C3d only. The use of radiolabelled antihuman globulin antibodies showed, however, that the RBC of all the patients were sensitized with warm IgM antibodies. Elevated values of IgA and/or IgG immunoglobulins on the patients’ RBC were found to be present in only two cases. Complement activation by IgM autoantibodies could not be detected in all other cases neitherin vivonorin vitro.Thus, we conclude that non‐complement binding IgM autoantibodies were responsible for the AIHA in the majority of these children possibly representing an as yet unrecognized variant of warm type AIHA.
Differential pattern of oncogene and beta‐actin expression in leukaemic cells from AML patients
Authors: Blomberg J. , Andersson M. , Fäldt R. 
Published: March 2008

SummaryThe presence of mRNA hybridizing to five oncogene (fos, mos, myc, sis, abl) and a beta‐actin probe(s) was studied with a semiquantitative dot‐blot procedure in eight AML patients. Around 107 leucocytes, corresponding to 1–10 ml blood, sufficed for the analysis. Each patient, regardless of the FAB group, exhibited a distinct pattern of oncogene or beta‐actin expression. Especially strong signals were obtained with the beta‐actin probe in two patients and with the fos probe in three patients. The findings underscore the heterogeneity of AML, either present from the first step towards malignancy or arising during the progression of the disease. The pattern of oncogene expression in leukaemic cells studied in routine blood samples may become an additional means for classification and follow‐up of AML patients.
The effect of anticoagulant on platelet associated IgG
Authors: Lucas G. F. , Holburn A. M. 
Published: March 2008

SummaryBlood anticoagulated with solid K2EDTA had platelet associated IgG (PAIgG) levels five‐fold greater than citrated blood when the platelets were harvested by differential centrifugation but identical PAIgG levels when the platelets were harvested by Percoll density gradient. Furthermore, blood anticoagulated with increasing amounts of solid K2EDTA demonstrated a proportionate increase in both PAIgG and haemolysis whereas the same blood sample anticoagulated with aqueous K2EDTA exhibited neither of these effects. Coulter Counter analysis of platelet poor plasma (PPP) prepared from blood anticoagulated with solid K2EDTA revealed particles with a mean volume greater than normal RBC; such particles were not found in the PPP prepared from citrated blood. While some of these particles could be sedimented through plasma, those remaining were sufficiently buoyant to resist sedimentation unless the plasma was diluted with buffer. Studies with FITC conjugated antisera revealed that the particles could be classified into two types. Type I particles reacted strongly with a monoclonal anti‐RBC antibody, weakly with anti‐IgG antibody and had the appearance of stroma. Type II particles lacked any apparent biological structure, reacted strongly with anti‐IgG antibody but not with monoclonal anti‐RBC antibody. Thus, the buoyant IgG‐rich particles found in blood anticoagulated with solid K2EDTA appear to contribute to the high PAIgG levels associated with this anticoagulant. Consequently, solid K2EDTA should not be used to anticoagulate blood destined for PAIgG measurement.
The effect of total body irradiation and bone marrow transplantation during childhood and adolescence on growth and endocrine function
Authors: Leiper A. D. , Stanhope R. , Lau T. , Grant D. B. , Blacklock H. , Chessells J. M. , Plowman P. N. 
Published: March 2008

Summary. Seventeen children (11 M, 6 F) with acute leukaemia and myeloproliferative disorders were investigated for growth and endocrine dysfunction. All had undergone bone marrow transplantation prepared with cyclophos‐phamide and single fraction total body irradiation (900–1000 cGy) between 1.5 and 3.8 (mean 2.2) years previously. The majority of children exhibited growth failure, which was of multiple aetiology. Ten patients, of whom eight had had previous prophylactic cranial irradiation, had evidence of growth hormone deficiency based on the reduced growth hormone response to insulin induced hypoglycaemia. Three patients had evidence of hypothalamic damage as shown by their growth hormone response to 200μg GHRH (1–29) NH2 intravenously. Gonadal failure was common, assessed clinically, and biochemically by basal gonadotrophin and sex steroid concentrations. All four girls of adolescent age (10.6–14.1 years) had ovarian failure requiring sex steroid replacement. Of the eight boys of adolescent age (12.3–18.3 years), two had testicular failure requiring sex steroid supplements. Both of these had had previous testicular irradiation. Five others had compensated gonadal failure, and one had normal Leydig cell function.Abnormalities of the TSH response to TRH occurred in 10 patients but only three had overt hypothyroidism. Unlike growth hormone deficiency, gonadal and thyroid dysfunction showed no correlation with previous cranial radiotherapy.
Functional analysis of a clonal expansion of Leu 11 positive NK active lymphoid cells
Authors: Hart D. N. J. , Leahy M. F. , McKenzie J. L. , Furley A. J. , Carter J. , Beard M. E. J. 
Published: March 2008

Summary.A female patient with an unusual lymphoproliferative disease associated with marked neutropenia has been observed for 36 months. The expanded cell population consists of large lymphocytes, many of which contain large azurophilic granules with acid phosphatase activity. These cells were T3, T8, Tl1 and Leu 11 positive but lacked the Ml, T10, IL‐2 receptor and HLA.DR antigens. The majority of these cells (60‐70%) were also Leu 7 (HNK‐1) positive. Strong natural killer (NK) activity was found in both the Leu 7 positive and negative cell populations. This cytotoxic activity was inhibited by monoclonal antibodies known to inhibit NK activity but was unaffected by antibodies which block T cell and T/NK cell cytotoxicity. Further functional analysis indicated that these cells suppressed normal T cell responses to mitogens, MLC responses and PWM induced B cell immunoglobulin synthesis. No effect on bone marrow progenitor cell growth was demonstrated. Antibody dependent cellular cytotoxic (ADCC) activity was barely detectable despite the presence of the Leu 11 antigen. Southern blot DNA analysis demonstrated clonal rearrangement of the T cell receptor β gene thereby confirming that this variant of Ty lymphoproliferative disease was a neoplastic condition.
The placental transport of [3H] vitamin K1 in rats
Authors: Hamulyák Karly , De Boervanden Berg Marian A. G , Thijssen Henk H. W. , Hemker H. Coenraad , Vermeer Cees 
Published: March 2008

Summary.In this paper we describe the placental transport of [3H]vitamin K1 in pregnant rats during the first 24 h after the oral administration of the vitamin. Vitamin K1 in the fetal livers ranged from 0.13% (3 h) to 2% (24 h) of the values found in the corresponding maternal livers. In spite of the low placental transfer of vitamin K, we found no accumulation of coagulation factor precursors in the fetal rat liver microsomes as could be expected in vitamin K deficiency. Moreover, we could not demonstrate any difference between adult and fetal rat liver microsomes with regard to the sensitivity for warfarin. From these results we conclude that a substantial placental barrier exists for the transport of pharmacological amounts of vitamin K1 but that under physiological conditions sufficient vitamin K1 appears to be present in the fetal liver to ensure a full carboxylation reaction. The vitamin K‐dependent carboxylase activity rate of adult and fetal rat liver microsomes was comparable, indicating that the newborn rat has an adequate carboxylating system.