bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of plasminogen activator releasing activity in the neurohypophysis
Authors: Colucci M. , Stassen J. M. , Salwa J. , Collen D. 
Published: March 2008

SUMMARYVasopressin (AVP) and some of its synthetic analogues, for example 1 desamino 8‐D‐AVP (DDAVP), induce plasminogen activator (PA) release in vivo. It has been proposed that this occurs via the release from the central nervous system of a plasminogen activator releasing hormone (PARH). The present study shows that a crude extract of bovine posterior pituitary, but not of the anterior pituitary or of the hypothalamus, induces a marked increase of circulating PA in anaesthetized rats. PA release appears to be caused by AVP because no other PA releasing activities could be identified in or isolated from the extract. In addition, no PA‐releasing activity was found in extracts of pituitary glands of rats congenitally deficient in vasopressin. The following experiments did not reveal central nervous system involvement in the PA‐release caused by AVP or DDAVP. Perfusion of isolated organs (rat heart and rat liver) with AVP resulted in PA‐release. In squirrel monkeys, comparable PA levels were found in the venous return following intrafemoral or intracarotid injection of AVP. Moreover, when plasma obtained 2 min following AVP or DDAVP injection was transfused to a receiving animal no PA release was observed. Thus our present findings do not support the hypothesis that the fibrinolytic response to AVP is mediated by the release of a specific peptide hormone from the central nervous system.
Falsely prolonged prothrombin time due to an inhibitor to human thromboplastin
Authors: Tinegate H. N. , McArdle B. , Qureshi M. 
Published: March 2008

SummaryA patient with nephrotic syndrome of unknown aetiology was found to have a grossly prolonged prothrombin time in the absence of any other coagulation abnormality and with no clinical bleeding problem. Subsequent investigations showed his plasma contained an inhibitor‐like substance, directed against human but not animal thromboplastin.Estimation of prothrombin time using either human or rabbit brain thromboplastin is a simple and reproducible test. The standard method which has been in routine use for many years has rarely been reported to give falsely prolonged results in a properly collected blood sample, tested in parallel with a control plasma. A molecular variant of factor VII has been reported to give misleading results with animal thromboplastin (Girolami et al, 1979). We report a patient who had no clinical evidence of a bleeding tendency, and whose plasma gave grossly abnormal and inconsistent prothrombin times due to the presence of a species specific inhibitor of human thromboplastin in the plasma.
Alpha thalassaemia in Sardinian newborns
Authors: Galanello R. , Maccioni L. , Ruggeri R. , Perseu L. , Cao A. 
Published: March 2008

SUMMARYIn this study we describe the correlation between the haematological parameters (red cell indices and Hb Bart's levels) and the α‐globin genotype in Sardinian newborns. Increased Hb Bart's levels at birth always indicates α‐thalassaemia, either of the deletion or non‐deletion variety. Infants with two α‐globin genes deleted (‐α/ ‐α and ‐ ‐/act genotypes) had microcytosis, low MCH and Hb Bart's in the 2.0‐7.1% range. A minority (38.9%) of infants with the (‐α/αα) globin genotype had detectable Hb Bart's, in the 0.78‐2 '5% range, frequently associated with minimal microcytosis while the remainder (61 e l %) were completely silent. Infants carriers of a non‐deletion type of α‐thalassaemia showed Hb Bart's levels within the range found in the (‐ α/αα) genotype. The association of heterozygous Po‐thalassemia seems to have no effect on the expression of any of these α‐thalassaemia lesions at birth.
Delay in primary haemostasis produced by a fish diet without change in local thromboxane A2
Authors: Thorngren Margareta , Shafi Shahida , Born G. V. R. 
Published: March 2008

SummaryTwelve apparently healthy male volunteers were maintained for 6 weeks on a fish diet, the haemostatic effects of which were determined as standardized skin bleeding times; thromboxane A2 formation in vivo in the bleeding time blood and in vitro in clotting venous blood; platelet aggregability; and platelet phospholipids. Within 1 week the fish diet changed the fatty acid composition of platelet membrane phospholipids, with increases in ω‐3 and decreases in ω‐6 fatty acids; decreased platelet aggregability by ADP and collagen; but the bleeding time was unchanged. Not until 6 weeks on the diet did the bleeding time increase (by 3 7%: P < 0‐01) and it was still increased 3 weeks after the end of the diet, when the fatty acid composition of the platelets had returned to normal. The effect of the diet on decreased aggregability of platelets also failed to follow the changes in their fatty acid composition and in the bleeding time. Aggregation by ADP and by the highest dose of collagen was decreased throughout the diet and for several weeks thereafter, i.e. even when the fatty acid composition had reverted to the pre‐dietary pattern and long after the normalization of the bleeding time. The diet caused no change in the in vivo appearance of thromboxane A2 in the bleeding time blood, contrasting with its effect in decreasing the in vitro formation of thromboxane A2 in clotting venous blood. These observations suggest that such fish diets do not delay haemostasis by diminishing the formation of thromboxane A2 locally nor directly by decreasing the aggregability of platelets or directly by the induced changes in their to‐3 fatty acids.
The mechanism of the anaemia in rheumatoid arthritis: effects of bone marrow adherent cells and of serum on in‐vitro erythropoiesis
Authors: Reid C. D. L. , Prouse P. J. , Baptista L. C. , GUMPEL J. M. , Chanarin I. 
Published: March 2008

SummaryClonal assays for erythroid progenitors (BFU‐e and CFU‐e) were used to study 20 patients with rheumatoid arthritis, 15 of whom had anaemia of chronic disease and five of whom were haematologically normal. The numbers of bone marrow BFU‐e and CFU‐e in the anaemic patients did not differ significantly from those in normal controls.Macrophages were removed from the bone marrow by a combination of adherence and buoyant density centrifugation over a sucrose gradient and the resulting fractions were cultured alone or together with autologous adherent cells in BFU‐e assays. Co‐culture with adherent cells significantly increased colony growth in both the controls and in seven of eight anaemic patients studied.Serum from 14 anaemic patients and from five non‐anaemic patients was added to cultures of bone marrow or to control peripheral blood ‘null’ cells. Anaemic serum uniformly either inhibited or failed to stimulate BFU‐e growth under these conditions. Serum from non‐anaemic patients and from 10 healthy controls stimulated BFU‐e growth from ‘null’ cells to an equal degree.
Assessment of the drug sensitivity of acute nonlymphocytic leukaemia using the in vitro clonogenic assay
Authors: Preisler H. D. , Azarnia N. 
Published: March 2008

SummaryThe ability of an in vitro clonogenic drug sensitivity assay to predict the outcome of therapy for acute nonlymphocytic leukaemia was evaluated using marrow cells obtained from previously untreated or first relapsed patients treated with either cytosine arabinoside/anthracycline antibiotic or high dose cytosine arabinoside remission induction therapy. While the per cent of leukaemic cells killed in vitro was correlated with the outcome of therapy, this drug sensitivity assay provided little or no clinically useful information.In 1980 we reported the results of our initial studies of an in vitro drug sensitivity assay designed to predict the response of patients with acute nonlymphocytic leukaemia (ANLL) to chemotherapy (Preisler, 198Oa). The studies described here extend our initial report and relate in vitro drug sensitivity to the biological characteristics of the leukaemic cells and to response to remission induction therapy with conventional dose cytosine arabinosidelanthracycline antibiotic therapy or ‘high dose’ cytosine arabinoside therapy.
The haemostatic plug in haemophilia A: a morphological study of haemostatic plug formation in bleeding time skin wounds of patients with severe haemophilia A
Authors: Sixma Jan J. , Van Den Berg Agnes 
Published: March 2008

SummaryHaemostatic plug formation in four patients with severe haemophilia A (VIII:C < 1%) was studied in skin biopsies taken at 3, 10 and 30 min and 2 h after a template bleeding time wound had been made. The primary haemostatic plug showed relatively minor changes, consisting of a delay in platelet degranulation and interdigitation. Some platelet aggregates not attached to vessels were encountered in the wound. Subsequently the primary haemostatic plug changed into a firm stable degranulated mass of interdigitated platelets.The major abnormality occurred during the fibrinous transformation. At 2 h many haemostatic plugs consisted of a thin peripheral layer of fibrin and platelet remnants around a central area containing red and white blood cells with a varying amount of plasma and only relatively few fibrin fibres. These observations suggest that fibrin formation in the periphery of the plug is less dependent of factor VIII than in central areas. The lack of fibrin formation in the centre of the plug compensating for the platelet lysis at 2 h may have caused the central erosion of the plug.
Platelet autoantibodies in septicaemia
Authors: Van Der Lelie J. , Dalen C. M. van der Plas‐Van , Von Dem Borne A. E. G. Kr. 
Published: March 2008

SummaryThirty‐three patients, 16 of whom had a platelet count below 100 × 109/1, were studied for the presence of platelet antibodies using the platelet suspension immunofluorescence test (PSIFT). In the acute phase platelet‐bound immunoglobulins (PBIg) were found in 62% of the thrombocytopenic patients, but also in 65% of the patients with a normal platelet count. Fourteen patients were re‐examined after successful treatment of their infection. At that time all had a normal platelet count, yet PBIg were found in 71%. In all but four patients the PBIg could be eluted with ether and were shown to bind to normal platelets but not to Glanzmann type I platelets in 11 of 12 patients tested, indicating the platelet‐specific autoantibody nature of the PBIg. Platelet autoantibodies were also demonstrated in the sera: in 38% in the acute phase and in 43% after treatment. In those patients in whom this could be tested the antibodies appeared to be strictly or partially EDTA‐dependent. It is postulated that the antibodies are mainly directed against cryptantigens, exposed in vivo only on platelets damaged by the septicaemia and in vitro in the presence of EDTA. This would also explain the lack of relationship between the platelet count and the serological findings.
Platelet fragments do not contribute to elevated levels of platelet associated IgG
Authors: Kelton John G. , Sheridan David , Neame Peter B. , Simon Gerard T. 
Published: March 2008

Summary. Most assays that measure platelet associated IgG (PAIgG) relate the IgG associated with the test platelets to the platelet count. This could lead to a systematic error if platelet fragments were present in the washed platelet sample but not counted. To address this issue, we studied platelets from patients with idiopathic thrombocytopenic purpura (ITP), thrombocytopenia complicating cardiopulmonary bypass, and laboratory synthesized platelet fragments (freezethawed) using electron microscopy. Scanning electron microscopic (SEM) examination of the platelet samples demonstrated appreciable numbers of fragments only in the freeze‐thawed specimens. Yet, ‘fragments’ could be seen in all specimens using transmission electron microscopy (TEM). Most of these ‘fragments’ proved to be artefacts: we found that the ratio of ‘fragments’ to intact platelets observed in the TEM specimens was similar to the estimated ratio of ‘fragments’ to platelets that would have been generated had the specimens been sectioned at 90° to the plane of the actual section.Platelets labelled with the membrane label 125I‐iodosulfanilic acid were fragmented by repetitive freeze‐thawing. Measurement of pellet radioactivity following washing indicated that the fragments were lost during the washing procedure.These studies indicate that elevated levels of platelet associated IgG in ITP do not represent artefacts due to contamination of the test platelets by platelet fragments.
The effect of retinoids on CFU‐GM from normal subjects and patients with myelodysplastic syndrome
Authors: Bailey‐Wood R. , May S. , Jacobs A. 
Published: March 2008

Summary. Five retinoid analogues differ in their effects on the growth of CFU‐GM from normal human marrow. At concentrations above 10−6 M all have inhibitory activity. This is maximal with 13‐cis‐retinoic acid. At lower concentrations the effect of retinoids is usually to reduce clone size rather than clone numbers though 10−8‐10−7 M etretinate increases clone size.The incubation of marrow cultures in the presence of 10−6 M all‐trans retinoic acid showed that in normal subjects colony counts are never reduced to less than 45% of the control value and total clone counts to less than 70% of the control value. In cultures from patients with myelodysplastic syndrome 20 out of 34 cases showed a greater inhibition of colony numbers than normal and 14 out of 35 cases showed a greater reduction in total clone numbers than normal. The results suggest that CFU‐GM from some patients with myelodysplastic syndrome may have a greater sensitivity than normal to the inhibitory effect of retinoic acid.
Zwa antigen distribution on the human platelet: an electron microscope study using a colloidal gold labelled marker
Authors: Saunders P. W. G. , Durack B. E. , Narang H. K. 
Published: March 2008

SummaryWe present the application of a new technique for visualizing surface antigen distribution patterns on intact platelets, treated with anti Zwa antibody, using colloidal gold labelled anti‐human immunoglobulin as a marker. Platelets from Zwa negative and from both heterozygous and homozygous Zwa positive individuals were examined for surface Zwa antigen distribution. Platelets fixed with paraformaldehyde show an even distribution of gold particles with a well‐developed reticular pattern over their surfaces. Platelets heterozygous for Zwa shows considerable antigen variation, some platelets having similar quantities of antigen to, others much less than, homozygotes. The importance of platelet fixation prior to antigen demonstration by anti Zwa antibody and immunogold visualization is seen by the redistribution of antigen on unfixed platelets. It is suggested that this technique could be exploited to investigate the relationship between platelet surface antigens or structures and their functions.
Purification of antithrombin ‘Vicenza’: a molecule with normal heparin affinity and impaired reactivity to thrombin
Authors: Finazzi G. , Tran T. H. , Barbui T. , Duckert F. 
Published: March 2008

SummaryAntithrombin III (AT) ‘Vicenza’, a previously described dysfunctional AT associated with familial thrombosis, has been isolated by heparin affinity chromatography. The purified molecule has been investigated by SDS‐polyacrylamide gel electrophoresis and crossed immunoelectrophoresis after incubation with different amounts of thrombin. A normal affinity for heparin has been demonstrated. However, evidence is produced that AT ‘Vicenza’ poorly inhibits thrombin. Present data suggest that AT ‘Vicenza’ consists of a population of two molecules, half of which does not form a complex with thrombin however and loses its heparin affinity upon thrombin treatment.
Pathogenesis of hepatic fibrosis in experimental iron overload
Authors: Weintraub Lewis R. , Goral Anthony , Grasso Joseph , Franzblau Carl , And Albert Sullivan , Sullivan Susanne 
Published: March 2008

SummarySignificant increases in prolyl hydroxylase activity, a key enzyme in the collagen biosynthetic pathway, were noted in the hepatic homogenates of iron‐loaded animals as compared to controls. The increase in prolyl hydroxylase activity was seen without any light microscopic histologic evidence of cell necrosis or accumulation of collagen in the livers from the iron‐loaded animals. However, utilizing electron microscopy, collagen fibrils were demonstrated immediately adjacent to the hepatocytes in the iron‐loaded animals but not the controls. No fibroblasts or inflammatory cells were noted in this area. There was no evidence of damage to the subcellular organelles of the iron‐loaded hepatocytes. The hydroxy‐proline content of the iron‐loaded livers was also shown to be increased. These experimental studies in conjunction with clinical observations described below suggest that in vivo iron overload may have a primary effect on stimulating collagen synthesis by hepatocytes.
Myelodysplastic syndromes: a scoring system with prognostic significance
Authors: Mufti G. J. , Stevens J. R. , Oscier D. G. , Hamblin T. J. , Machin D. 
Published: March 2008

Summary 141 patients with MDS were classified according to the FAB criteria and followed up for a period of 4–192 months. It was recognized that patients with RAEBT had a uniformly poor prognosis. However, there was a wide variation in survival among the other subgroups. A score of 1 was assigned to each of the following presenting haematological features: bone marrow blasts ≤ 5%, platelets ≤ 100 × 109/1, neutrophils ≤ 2.5 × 109/1 and Hb ≤ 10.0 g/dl. Therefore the score for each patient ranged between 0 and 4. There were no statistically significant differences between those patients who scored 0 or 1, or between those who scored 2 and 3. Therefore patients were put into three groups: Group A (score 0 or 1), Group B (score 2 or 3), Group C (score 4). The differences in survival between each of the three groups are highly significant (P<0.00001). This system further separates patients with RA, RAS, RAEB into good and bad prognostic groups.This study also confirms that deaths due to cytopenias are more common than those due to transformation to AML. The use of this scoring system in conjunction with the FAB criteria for MDS should serve as a prognostic tool on which to base treatment.
Differentiation of patients with subtype IIb‐like von Willebrand's disease by means of perfusion experiments with reconstituted blood
Authors: Sakariassen Kjell S. , Nieuwenhuis H. Karel , Sixma Jan J. 
Published: March 2008

Summary Four unrelated patients with a bleeding diathesis (bleeding time longer than 30 min), some spontaneous platelet aggregation, thrombocytopenia and large platelets, had decreased levels of factor VIII‐von Willebrand factor (FVIII‐VWF) related properties and impaired platelet adherence to human artery subendothelium. The largest multimers of plasma FVIII‐VWF were absent and enhanced ristocetin induced platelet aggregation in platelet‐rich plasma was observed.‘Pseudo‐von Willebrand's disease’ was excluded, because FVIII‐VWF from normal subjects did not initiate platelet aggregation. Perfusion studies with reconstituted blood, consisting of respectively patient platelets in normal plasma or normal platelets in patient plasma, yielded evidence for an intrinsic platelet abnormality in two out of the four patients and a plasma defect in the other two patients. Similar experiments with platelets and plasma from four patients with von Willebrand's disease (VWD) subtype I and four patients with VWD subtype IIa showed that the impaired platelet adherence in blood from these patients was caused by a plasma defect.These experiments indicate that patients with laboratory findings in many respects similar to those originally reported for patients with VWD subtype IIb may represent a heterogeneous group of individuals. The data derived from our study imply that perfusion experiments with reconstituted blood offer a new approach in characterization of these patients, which may be more relevant for the treatment of the patients than characterization by ristocetin induced adsorption of FVIII‐VWF to platelets.
Red cell kinetics in thalassaemia intermedia: its use for a prospective prognosis
Authors: Najean Y. , Deschryver F. , Henni T. , Girot R. 
Published: March 2008

Summary A kinetic study of erythroid cell production and destruction (radioactive iron incorporation, red blood cell survival time, bone marrow scintigraphy) was performed in 12 cases of thalassaemia intermedia (six adults and six children), classified retrospectively, and compared to that performed in 17 cases of Cooley's anaemia.Our results confirm the genetic heterogeneity of these cases, the level of Hb F varies from 30% to 100% and the non α/α chain synthesis is only statistically superior to that seen in Cooley's disease. On the other hand, the kinetic study clearly separates the cases who are, or will be, clinically intermediate, showing a higher radioactive iron medullary uptake, a less ineffective erythropoiesis than that seen in Cooley's disease, and a greater peripheral haemolysis. In our study, no overlap was seen between the two groups.Iron kinetic study is then of prognostic interest and may help in therapy decisions, transfusion regimen and iron chelation, and splenectomy.
Control of lysozyme gene expression in differentiating HL‐60 cells
Authors: Polansky Daniel A. , Yang Angela , Brader Kevin , Miller D. M. 
Published: March 2008

SummaryWe have investigated the control of lysozyme gene expression in HL‐60 cells induced to differentiate into macrophage‐like cells with phorbol myristate acetate (PMA). Differentiation, as evidenced by cellular adherence, and morphological changes corresponded temporally to an increase in nonspecific esterase activity. The lysozyme concentration in the medium of uninduced HL‐60 cells was 10 μg/107 cells. increasing to a maximum of 46 μg/107 cells after 48 h incubation with PMA (16 nm). At 72 h the lysozyme concentration decreased to 16 μg/107 cells. Intracellular lysozyme activity remained constant throughout differentiation. If HL‐60 cells were exposed to PMA for 24 h, washed, then maintained in normal medium, they differentiated normally, confirming their irreversible commitment to differentiate. The increase in lysozyme secretion by these cells, however, is markedly blunted suggesting that continued PMA treatment of differentiated cells is required for their secretion of lysozyme. There is no change in the rate of extracellular degradation of lysozyme during differentiation. The level of lysozyme mRNA does not correlate directly with the amount of lysozyme secreted into the medium. Hybridization of uninduced HL‐60 cell RNA with a chicken lysozyme cDNA probe demonstrates moderate hybridization. There is a modest (five‐fold) increase in lysozyme mRNA between 0 and 36 h of exposure to PMA, corresponding to the burst of lysozyme secretion by these cells. The lysozyme mRNA decreases to a level which is lower than the original baseline by 72 h, when the cells are still secreting substantial amounts of lysozyme. These data suggest that both transcriptional and post‐transcriptional controls are operative in the control of lysozyme gene expression during the differentiation of HL‐60 cells. They also imply that lysozyme secretion is not a necessary component in the macrophage‐monocyte differentiation of these cells.