bluuebunny/crossref_metadata_2025_split huggingface dataset:
Resistance of normal endothelium to damage by thrombin
Authors: Thomas D. P. , Merton Rosemary E. , Hiller K. F. , Hockley D. 
Published: March 2008

We examined the effect of locally infused thrombin on rabbit neck veins, using autologous [111In]indium‐labelled platelets as a marker of platelet deposition. Purified thrombin at concentrations which clotted the blood in isolated veins did not lead to the deposition of labelled platelets on the vessel wall. However, when the animals were pre‐treated with aspirin (10 mg/kg), there was a marked change in the ratio of radioactive counts between control and treated segments, consistent with platelet deposition on the walls of thrombin‐treated segments.Thrombin‐treated and control veins were also examined by transmission and scanning electronmicroscopy. Although occasional clumps of platelets were seen adhering to the vessel wall in both control and treated segments, the endothelium was essentially intact. There was no evidence of substantial denudation of the endothelium, and overall there was little morphological difference between control and treated segments. It is concluded that normal endothelium is not damaged by thrombin, and that venous thrombi develop by a direct effect of thrombin on platelets and fibrinogen, and not by thrombin‐mediated damage to the vein wall.
Inactivation of Kell blood group antigens by 2‐aminoethylisothiouronium bromide
Authors: Advani H. , Zamor J. , Judd W. J. , Johnson C. L. , Marsh W. L. 
Published: March 2008

Human red cells incubated with a solution containing 6% 2‐aminoethyl‐isothiouronium bromide (AET) lose activity of antigens that are part of, or related to, the Kell blood group system. However, Kx antigen is not inactivated. Studies on a wide range of other blood‐group antigens show no other evidence of changes and AET appears to react specifically with red‐cell membrane structures that have Kell activity. The AET procedure produces an artificial K0 red cell that can be used in blood group serology, and allows easy recognition of antibodies that are associated with the Kell system.AET has been used by other workers to produce a red cell that has many serological and biochemical characteristics of a PNH cell. Our studies on red cells from PNH patients have not shown any changes in Kell blood‐group antigens.
The molecular basis of alpha thalassaemia in a South African population
Authors: Mathew C. G. P. , Rousseau J. , Rees J. S. , Harley E. H. 
Published: March 2008

Summary.We have investigated the molecular basis of α thalassaemia in the so‐called ‘Cape Coloured’population of Cape Town. DNA from 17 cases was analysed by Southern blotting and hybridization with an α globin complementary DNA probe. Three types of α thalassaemia genetic determinants were detected: the 3·5 kb deletion which inactivates one α globin gene per chromosome (‐α/ haplotype), a much larger deletion which removes both α globin genes (––/ haplotype), and a non‐deletion determinant which leaves both α globin genes intact. The interaction of these determinants with each other or with the normal chromosome (αα/) produced the phenotypes α thalassaemia silent carrier, α thalassaemia trait and Hb H disease. All cases of the ‐α/ haplotype result from the rightward deletion which removes the Bgl II site between the duplicated α globin genes. The predominance of the ‐α/ haplotype (21 out of the 28 α thalassaemia determinants) over the ––/ haplotype is consistent with the low incidence of Hb H disease and the apparent absence of Hb Bart's hydrops fetalis in this population group.
ATP‐ADP compartmentation in storage pool deficient platelets: correlation between granule‐bound ADP and the bleeding time
Authors: Akkerman Jan‐Willem N. , Nieuwenhuis H. Karel , Mommersteeg‐Leautaud Marlene E. , Gorter Gertie , Sixma Jan J. 
Published: March 2008

Summary.Platelets contain two major compartments of ATP and ADP, the cytosol and the dense granules. We separated the two compartments by controlled digitonin‐induced cell lysis and measured both fractions directly in the platelets of 16 patients with storage pool deficiency. The total contents of ATP and ADP in the platelets of these patients was significantly lower than in normal controls. This was primarily caused by decreased amounts of ATP and ADP in the granule compartment, but also cytosolic ADP was low in these patients. In contrast, cytosolic ATP was not significantly decreased. The lower the amount of granule‐bound ATP and ADP, the longer was the bleeding time in these patients. The best correlation was found with granule ADP. These data may indicate that ADP stored in platelet dense granules plays a role in the arrest of bleeding.
Impaired chemiluminescence and bactericidal killing by neutrophils from patients with severe cobalamin deficiency
Authors: Skacel P.O. , Chanarin I. 
Published: March 2008

Summary.Neutrophil function was examined in 24 patients with megaloblastic haemopoiesis due to vitamin B12‐or folate deficiency. Defective bactericidal activity was demonstrated in the B12‐deficient group only and was associated with normal phagocytic activity but impaired intracellular killing. Luminol amplified luminescence was consistently low in B12‐deficient subjects with RBC counts of less than 2 × 1012/1. These defects were not seen in the folate‐deficient cases although isolated abnormalities were present in those who were also alcoholic.
Papilloedema in chronic granulocytic leukaemia
Authors: Stainsby Dorothy , Elleray Evonne , Anderson J. , Hamilton P. J. , Thompson R. B. 
Published: March 2008

Summary.Five of 75 patients with chronic granulocytic leukaemia seen over a 25 year period had papilloedema at presentation. These patients had unusually high leucocyte counts and the papilloedema may be a manifestation of leucostasis. The fundal abnormalities resolved in all five patients–in four after conventional treatment with busulphan only.
Loss of promyelocytic maturation in HL60 sublines: a potential model for leukaemia progression
Authors: Fitz‐Gibbon Linda , Price Gerald B. , Sullivan Arthur K. 
Published: March 2008

Summary.The majority of cells of the human leukaemic line HL60 appear to be promyelocytes which can be stimulated to mature into functioning neutrophils. We report here the derivation of stable subclones from the parent line which differ. Two forms of variant were obtained: (1) those with a defined lesion, selected by resistance to kill by 6‐thioguanine, which matured in the presence of DMSO and retinoic acid but not in hypoxanthine. They also continued to express peroxidase and a major granulocyte antigen, and (2) those obtained by clonal growth in DMSO which did not mature in the presence of any compound tested including hypoxanthine, DMSO, retinoic acid and actinomycin D and lacked granules, peroxidase and the granulocyte antigen. The concurrent loss of the characteristic of maturability and the phenotype of myeloid commitment suggests that the control of the two phenomena may be related. These variant cell lines provide a useful model in which to study how human leukaemic cells may become arrested in less differentiated stages of development.
The relationship between human spleen and blood erythroid burstforming units (BFU‐E)
Authors: Meytes Dina , Ortega Jorge A. , Ma Andrew , Wald Barton R. , Shore Nomie A. , Dukes Peter P. 
Published: March 2008

Summary.The influence of splenectomy on erythroid burst colony formation by peripheral blood mononuclear cells from 10 patients (four with hereditary spherocytosis, two with β‐thalassaemia major, two with Hodgkin's disease and two with idiopathic thrombocytopenic purpura) was studied. In every instance splenectomy was followed by a lowering of blood BFU‐E. The post‐splenectomy levels ranged from 0 to 30% of the preoperative levels. Mononuclear cells from the spleens of eight patients were cultured and found to contain numerous BFU‐E. The total quantity of BFU‐E in the whole blood and in the spleen of the patients was generally of the same order of magnitude. The number of splenic BFU‐E did not correlate with spleen size.Splenic BFU‐E differed from peripheral blood BFU‐E in that they were more sensitive to erythropoietin (Ep) and in that they failed to respond to burst promoting activity (BPA) produced by preincubating the spleen mononuclear cells with phytohaemagglutinin M (PHA). In contrast, media conditioned by PHA‐treated spleen cells contained BPA active on peripheral blood BFU‐E from normal individuals. These data suggest that the spleen may have an influence on the numbers and functional properties of BFU‐E.
Granulocyte‐macrophage progenitor cell preservation at 4°C
Authors: Delforge Alain , Ronge‐Collard Elisabeth , Stryckmans Pierre , Spiro Théodore , Malarme Marie A. 
Published: March 2008

Summary. Eighteen bone marrows collected from patients without haematological diseases and from normal subjects were tested for the effect of 4 d storage at 4°C on CFU‐C growth. Results indicate that unfractionated bone marrow cells may be stored at 4°C for 4 d with 97%± 8 SEM recovery of the CFU‐C evaluated by the agar culture assay. On the other hand, the same preservation procedure on peripheral blood CFU‐C of 13 normal subjects yielded only 5%± 2 SEM recovery of in vitro growth capacity.The present results have practical implications. They might be exploited to preserve bone marrow CFU‐C for transplantation therapy or laboratory investigation. In contrast this single preservation procedure seems not appropriate for preserving blood CFU‐C.
Studies on the stability of factor VIII coagulant antigen (VIII: CAg) in the presence of VIII: C antibodies
Authors: Furlong R. A. , Peake I. R. 
Published: March 2008

Summary. The stability of factor VIII coagulant antigens (VIII:CAg) at 56°C was investigated using an immunoradiometric assay for VIII: CAg. In normal or CRM+ haemophilic plasmas VIII: CAg was rapidly inactivated at 56°C. VIII: CAg in spontaneous VIII: C inhibitor plasmas and in post‐treatment samples from haemophiliacs with VIII: C inhibitor was resistant to inactivation at 56°C, indicating the presence of heat stable VIII: CAg‐anti VIII: CAg complexes. In vitro VIII: CAg‐anti VIII: CAg complexes were formed by incubation of diluted VIII: C antibodies and normal plasma and the stability of these complexes at 56°C was studied. Haemophilic VIII: CAg antibodies formed heat stable immune complexes over a narrow range of inhibitor dilutions whilst some spontaneous VIII: CAg antibodies formed these stable complexes over a much wider range of dilutions emphasizing the difference in the properties of these antibodies.
Acquired haemostatic defects in the ill newborn
Authors: Feusner James H. , Slichter Sherrill J. , Harker Laurence A. 
Published: March 2008

Summary. The kinetics and function of platelets and fibrinogen were studied in 22 ill newborns. Overall 51Cr‐platelet survival was considerably shortened (patients 2·6 d ± 1·7, adult normal 9·5 d ± 0·6, P < 0·001) while 125I‐fibrinogen surival was less severely decreased (patients 2·1 d ± 0·8, adult normal 5·1 d ± 0·4, P < 0·05).Three patients with bacterial sepsis and one with disseminated herpes simplex had the most severely reduced platelet survival times (1·3 d ± 0·9), causing thrombocytopenia (62 ±32 × 109/l) despite production rates averaging 2 1/2 times normal. Although fibrinogen survival times were comparably reduced in these patients to 1·4 d ± 0·4, fibrinogen concentrations were normal because of compensatory increased production.In three patients with necrotizing enterocolitis platelet and fibrinogen survival times were similarly reduced (platelets 1·6 d ± 0·6, fibrinogen 1·6 d ± 0·6) with platelet counts of 69 ± 27 × 109/l and platelet production rates of twice normal. Since their fibrinogen production was not increased, they had decreased fibrinogen concentration (1·0 ± 0·19 g/l).In six patients with respiratory distress syndrome the kinetic results were more variable. Platelet survival was less severely affected than in the other groups and production was approximately twice normal; hence, the platelet count was maintained (177 ± 107 × 109/l). Fibrinogen in this group was slightly reduced because of decreased production in the presence of mildly decreased survival (2·7 d ± 0·7).The two patients with cytomegalovirus infection had severe thrombocytopenia (23 × 109/l) due to a combination of decreased platelet survival (3·6 d), increased splenic pooling and no compensatory increase in marrow platelet production. Fibrinogen production was normal but its plasma concentration was moderately reduced because of a decrease in fibrinogen survival.In many of these patients, fibrinogen dysfunction was suggested by a prolonged thrombin time and a discrepancy between fibrinogen concentration as determined by a time dependent assay and an equilibrium total clottable protein assay. Likewise, platelet dysfunction, evidenced as a prolonged bleeding time, was found in patients with RDS; some of these infants had otherwise unexplained bleeding.
Regeneration of peripheral blood cells following ABO incompatible allogeneic bone marrow transplantation for severe aplastic anaemia
Authors: Hows J. M. , Chipping P.M. , Palmer S. , Gordon‐Smith E. C 
Published: March 2008

Summary. The regeneration of peripheral blood cells in six patients receiving ABO incompatible bone marrow transplants for severe aplastic anaemia has been studied. The results are compared with those of 18 similar aplastic patients treated with ABO compatible transplants. Reticulocyte recovery in the ABO incompatible cases was significantly delayed (P < 0·01) and associated with greatly prolonged red cell transfusion requirements (P < 0·01).Peripheral blood regeneration of neutrophils, lymphocytes and platelets was also significantly delayed (P < 0·01). Platelet support was required for longer in the ABO incompatible cases (P < 0·01) but there was no increase in the incidence or severity of infections in the post transplant period.
Studies on the partition of transferrin‐donated iron in rabbit reticulocytes
Authors: Egyed A. 
Published: March 2008

Summary. Reticulocytes with high cytosolic non‐haem radioiron content were prepared by adding metabolic inhibitors. The cells were then reincubated without the inhibitors for various periods of time. Cytosol was prepared from the labelled cells and fractionated on a Sephadex G‐100 column on which four main non‐haem radioiron containing peaks could be distinguished. During reincubation the 59Fe content of these cytosol fractions changed in different ways.The high molecular weight fraction showed little metabolic activity, indicating that this fraction is not utilized for haem synthesis when iron is in excess in the cytosol. The second non‐haem radioiron containing peak eluted with the haemoglobin moiety. This non‐haem iron binding substance proved to be rather stable: 1 mM EDTA could not remove a significant amount of iron from it. During reincubation its radiorion content decreased almost linearly with time. Two further peaks eluted in the low molecular weight region. Their kinetics during reincubation suggest that these peaks represent those non‐haem iron components of the cytosol which can reversibly move from the cytosol into the stroma compartment.
Antibodies against platelet membrane glycoproteins
Authors: Jenkins C. S. P. , Clemetson K. J. , Ali‐Briggs Elizabeth F. 
Published: March 2008

Summary. Glycocalicin has been proposed as the common platelet receptor for both ristocetin‐human VIIIR:WF and thrombin‐induced platelet aggregation. Platelets which have lost glycocalicin do not respond to either ristocetin‐human VIIIR:WF or bovine VIIIR:WF. Using antibodies to the platelet membrane glycoproteins la and lb, lib and Ilia, and glycocalicin we show that the Fab'fragments of anti‐glycoproteins la and lb and anti‐glycocalicin IgG totally inhibited bovine VIIIR:WF‐induced platelet aggregation, while those from anti‐glycoproteins lib and Ilia IgG were without effect. Thrombin‐induced platelet aggregation was strongly inhibited by the Fab'fragments of anti‐glycoproteins la and lb IgG and anti‐glycocalicin IgG, indicating that these glycoproteins play a major role in thrombin‐platelet interaction. Fab'fragments of antiglycoproteins lib and Ilia IgG inhibited thrombin‐induced platelet aggregation to a lesser extent implying that these glycoproteins are also somehow involved in the platelet response to thrombin perhaps as fibrinogen receptors.The data presented here give further support to the proposal that ristocetin‐human VIIIR:WF and bovine VIIIR:WF share a common receptor on the platelet surface and indicate that this structure plays an important role in thrombin‐induced platelet responses.
Colchicine ultrasensitivity of lymphocytes in chronic lymphocytic leukaemia
Authors: Wetherley‐Mein G. , Thomson A. E. R. , O'Connor T. W. E. , Peel W. E. , Singh A. K. 
Published: March 2008

Summary. It has been previously reported that, in comparison with normal lymphocytes, the lymphocytes in chronic lymphocytic leukaemia (CLL) are ultrasensitive in culture to the cytocidal action of colchicine. In this report the results of 240 colchicine studies in 87 patients with CLL are presented and analysed in terms of the diagnostic, clinical and haematological significance of colchicine ultrasensitivity (CUS) in CLL.All patients with CLL showed very significantly increased CUS of lymphocytes. The CUS did not vary with clinical and haematological status or time and only very rarely with treatment. There was no correlation between % CUS and subsequent course or survival. The results in CLL and in other forms of lymphocytosis and in non‐Hodgkin's lymphoma are compared.It is concluded that the test is of considerable diagnostic value, particularly in identifying low‐count and treated CLL and in the exclusion of non‐CLL lymphocytosis. It appears to have no prognostic value but may have future application in monitoring treatment which selectively eliminates the abnormal cell population.
Defective spectrin dimer–dimer association in a family with transfusion dependent homozygous hereditary elliptocytosis
Authors: Evans J. P. M. , Baines A. J. , Hann I. M. , Al‐Hakim I. , Knowles S. M. , Hoffbrand A. V. 
Published: March 2008

Summary. Red cell membrane proteins have been examined in a family in which three children have severe transfusion‐dependent homozygous hereditary elliptocytosis. The membranes in all three show a considerable excess of spectrin dimers over tetramers in spectrin extracts. The red cell membranes of their parents with heterozygous hereditary elliptocytosis show a lesser but significant increase in spectrin dimers. Some of the family members also have an α‐globin gene deletion and haemoglobin D trait.The present results are the first demonstration of a defect of spectrin dimer–dimer association in homozygous elliptocytosis and provide strong support for the concept that this defect is the primary cause of the red cell abnormality in at least some families of hereditary elliptocytosis.
Acquired von Willebrand's disease: demonstration of a circulating inhibitor to the factor VIII complex in four cases
Authors: Sampson Barbara M. , Greaves M. , Malia R. G. , Preston F. E. 
Published: March 2008

Summary. We have studied four patients suffering from acquired von Willebrand's disease. All patients had a severe bleeding diathesis with recurrent life‐threatening haemorrhages. Three of the patients had a monoclonal gammopathy and one of these developed multiple myeloma. In three patients tested, a plasma inhibitor to ristocetin cofactor activity was detected. In each case this was localized to the IgG fraction of plasma. In addition, VIII:C activity was found to be associated with the IgG fraction of patients’ plasma and altered mobility of VIII: C was detected on Laurell immunoelectrophoresis. Furthermore, plasma from all four patients and the IgG fraction therefrom resulted in a dissociation of normal VIII:C into two components separable by gel‐filtration on Sepharose 6B. Finally, the circulating half‐life of the three factor VIII activities was found to be markedly reduced in the patients with acquired von Willebrand's disease.We conclude that in the patients studied the coagulation defect was related to the presence of a circulating inhibitor to the factor VIII complex and that this inhibitor was associated with the IgG fraction of plasma.
Haemopoietic stimulators and inhibitors in aplastic anaemia serum
Authors: Nissen Catherine , Moser Yolanda , Speck Bruno , Bendy Johanna 
Published: March 2008

Summary. Normal serum and serum from four patients with severe aplastic anaemia was fractionated by Sephadex G‐150 gel filtration. Fractions were tested for direct haemopoietic activity on colony forming cells in methylcellulose cultures, and for their indirect influence on haemopoiesis via CSA‐ and BPA‐producing cells. All aplastic anaemia sera contained abnormal inhibitors and stimulators. An inhibitor acting on both haemopoietic and factor producing cells, eluting with the IgM fraction was found in all, variable inhibitors of lower molecular weight in single patients. Stimulatory activity of 10000–50000 MW acting on factor producing cells, but not on colony forming cells directly, was found in all, a variable stimulator eluting with the very high MW fraction in single patients.In two patients who achieved complete autologous bone marrow remission after treatment with high dose immunosuppression, Sephadex fractions of serum before treatment and remission serum were simultaneously tested on autologous bone marrow in remission. Inhibitors were detected before treatment and disappeared in remission, stimulators were not detectable before treatment but became strong in remission. It is concluded that the effect of aplastic anaemia serum on haemopoiesis in culture is determined by the balance of inhibitors and stimulators on both haemopoietic and CSA/BPA producing cells.
Serum beta2microglobulin and survival duration in multiple myeloma: a simple reliable marker for staging.
Authors: Bataille Regis , Durie Brian G. M. , Grenierj Jean 
Published: March 2008

Summary.Previous reports have shown serum beta2microglobulin (SB2M) to be a reliable marker for evaluation of presenting tumour mass, response to chemotherapy and prognosis of patients with multiple myeloma (MM). In the current study, SB2M was evaluated and correlated by bivariate and multivariate regression analyses with the main presenting clinical features, response to chemotherapy and survival duration of 115 untreated myeloma patients.In the bivariate analysis, there was a clear correlation between SB2M and myeloma stage (P= 0·002). Other interesting correlations were between SB2M and creatinine values (P< 0·001), SB2M and the likelihood of having lambda subtype (P< 0·001), high SB2M and high uric acid (P< 0·036), high SB2M and a low haemoglobin (P< 0·001). In the multivariate regression analyses, SB2M alone completely substituted for the effect of initial staging and gave a very reliable fit for survival prediction. Particularly noteworthy was the dramatic difference in survival duration observed between patients with a high pre‐treatment SB2M (> 6 μg/ml) and those with low SB2M: 26 months versus 52 months (P< 0·0001).We conclude that SB2M is the major determinant of survival in MM and can be used alone for effective pretreatment stratification of myeloma patients.