bluuebunny/crossref_metadata_2025_split huggingface dataset:
Familial lupus anticoagulants
Authors: Mackie I. J. , Colaco C. B. , Machin S. J. 
Published: March 2008

SummaryThree families having more than one affected member with SLE or lupus‐like disease were investigated by global coagulation tests as well as methods based on dilute thromboplastin, Russell's viper venom and thermal stability/absorption, and by RIA for anticardiolipin (CL) antibodies. Of the 19 persons, 11 had SLE or lupus‐like disease. Eight of these 11 had a prolonged KPTT and other evidence of LA, while only 5/11 had high anticardiolipin titres. Four healthy spouses of affected females, and three asymptomatic siblings also had prolonged non‐correctable KPTTs. These persons had no bleeding or thrombotic history and normal clotting factor levels. Further clotting tests were negative, although one had raised anti‐CL antibody. Such cases may account for some of the patients one finds during routine haemostatic screening with unexplained prolonged KPTT. Although anticardiolipin levels are raised in subjects with LA, there was no close correlation between length of KPTT and anticardiolipin titre. These findings would support a hypothesis of transmissible agents or other environmental factors being involved in lupus‐like disorders.
Analysis of leucocyte differentiation antigens in blood and bone marrow from patients with Waldenström's macroglobulinaemia
Authors: Kucharska‐Pulczynska Malgorzata , Ellegaard Jørgen , Hokland Peter 
Published: March 2008

Summary. Peripheral blood and bone marrow mononuclear cells from 10 patients with newly diagnosed Waldenström's macroglobulinaemia were analysed for the presence of leucocyte differentiation antigens using flow cytometry. Most patients had circulating intracytoplasmic‐μ cells that were positive for the B‐cell specific antigens B1, B2 and B4 and for the plasma cell antigen PCA‐1. When such monoclonal cyto‐μ+ cells were purified by immune rosette depletion they were shown to express B1 to a much lesser extent than B2, B4 and PCA‐1. In bone marrow samples cells with a similar phenotype, but with higher B1 expression were found in all patients.When the serum IgM paraprotein concentrations were compared to surface markers longitudinally from presentation and during the first courses of chemotherapy, a decreased serum IgM level was accompanied by a decrease in B1 cells in peripheral blood. These data demonstrate that WM cells possess a unique phenotype with coexpression of B‐cell and plasma cell associated antigens.
Studies on the effect of heat treatment on the thrombogenicity of factor IX concentrates in dogs
Authors: Littlewood Janet D. , Dawes Joan , Smith James K. , Feldman Peter A. , Haddon Michael E. , Mcquillan Thomas A. , Foster Peter R. , Ferguson Joyce , Prowse Christopher V. 
Published: March 2008

Summary. This study examines the effects of heat treatment for 72 h at 80°C on the potential thrombogenicity of lyophilized human coagulation factor IX concentrates. Since heating generated minor amounts of thrombin, concentrate was prepared with antithrombin III addition prior to heat treatment. Changes in coagulation parameters were followed prior to and after infusion of 100 iu/kg of heated and unheated concentrates to dogs. All batches produced a transient fall in platelet count during infusion and a delayed rise in plasma fibrinopeptide A, accompanied by a minor prolongation of the activated partial thromboplastin time. Such changes were less marked for heated batches.Control infusion of a‘failed’ factor IX concentrate showed an additional fall in fibrinogen, rise in fibrin degradation products and a more rapid rise in fibrinopeptide A, while thrombin infusion caused an even more dramatic intravascular coagulation.These studies indicated no increase in the potential thrombogenicity of freeze dried factor IX concentrates as a result of heat treatment.
Utility of the FAB classification for myelodysplastic syndromes: investigation of prognostic factors in 237 cases
Authors: Kerkhofs H. , Hermans J. , Haak H. L. , Leeksma C. H. W. 
Published: March 2008

SummaryThe utility and prognostic significance of the FAB classification was studied in 237 patients with a myelodysplastic syndrome. No significant differences in actuarial survival and probability of transformation to acute leukaemia were found in patients with RA, AISA or CMML. The median survival time for the RA group was 50 months, for the AISA and CMML subclasses more than 60 months. The probability of transformation for the RA, AISA and CMML subgroups showed a linear trend with a probability of 25% for the RA, 16% for the AISA and of 18% for the CMML groups after a 5 year observation period. A uniformly poor prognosis was found for the RAEB and RAEB/t subgroups with median survival times of respectively 9 and 6 months.Chromosomal abnormalities were found in 68 out of 155 patients (44%). Patients with only normal metaphases or with abnormal metaphases together with karyotypic normal cells had a longer median survival time and a lower probability for transformation as compared to those with only abnormal metaphases.The most important factor in prognosis is the number of blast cells in blood and bone marrow. Age and sex, and certain quantitative and qualitative abnormalities in the peripheral blood appear of limited prognostic value for patients with RA, AISA and CMML.The longer life expectancy of 35 patients with CMML as compared to other series seems to be related to the percentage of blast cells at the time of diagnosis.
Plasma fibrinolysis during and after normal childbirth
Authors: Mackinnon S. , Walker I. D. , Davidson J. F. , Walker J. J. 
Published: March 2008

Summary.A detailed sequential study of plasma fibrinolytic components in 42 healthy women during and after childbirth showed that striking changes occurred within minutes of placental separation. Significant increases in overall fibrinolytic activity were detected 1 5 min after delivery. During this period statistically significant increases in tissue plasminogen activator levels were noted but were overshadowed by a dramatic decrease in the level of plasminogen activator inhibitor (PAI). A 10‐fold fall in PAI was noted by days 3‐5 post‐partum, suggesting that the placenta is the major source of PAI detectable at the end of pregnancy and during labour. Persisting slightly elevated levels of PAI were detected for the first few days post partum. This may be due to increased production of normal‘endothelial’PAI in response to the vascular trauma incurred by placental separation, and in response to uterine vascular changes immediately post‐partum.
Characterization of the blast cell population in two neonates with Down's syndrome and transient myeloproliferative disorder
Authors: Coulombel L. , Derycke M. , Villeval J. L. , Leonard C. , Breton‐Gorius J. , Vial M. , Bourgeois P. , Tchernia G. 
Published: March 2008

SummaryThe phenotype and in vitro growth properties of blood and marrow blast cells detected in two neonates with Down's syndrome and a transient leukaemic picture are presented. In both patients, blast cells at diagnosis were heterogeneous and expressed predominantly megakaryocyte and erythroid markers identified by membrane fluorescence using monoclonal antibodies or ultrastructural detection of platelet peroxidase and ferritin. An additional trisomy involving chromosome 22 was detected in blast cells from one patient. Blood and marrow cells colony‐assays performed at diagnosis revealed precursors with an abnormal differentiation capacity similar to those found in acute myelogenous leukaemia colony assays. However, an unusual feature was the persistence of high numbers of precursor cells (namely erythroid) following a normal differentiation pathway. Phenotypically and cytogenetically abnormal cells spontaneously disappeared by week 4‐6, but overt relapse occurred in one patient 20 months later. These results bring strong arguments in favour of the neoplastic nature of the transient leukaemic picture observed in some neonates with Down's syndrome. Furthermore, we suggest that this disorder can be individualized as a separate entity with specific phenotypic and biological properties.
Ph‐negative chronic myeloid leukaemia
Authors: Fitzgerald P. H. , Beard M. E. J. , Morris C. M. , Heaton D. C. , Reeve A. E. 
Published: March 2008

SummaryAn analysis of five patients with Philadelphia chromosome (Ph) negative chronic myeloid leukaemia (CML) revealed that two were clinically and haematologically identical to Ph‐positive CML whereas three should be reclassified as chronic myelomonocytic leukaemia (CMML). At a molecular level the first two patients showed the same juxtaposition of c‐abl and bcr genes as is seen in Ph‐positive CML. These genomic changes were not seen in the other three patients. Observations on these five patients suggest that the clinical course and prognosis of the rare patient who carries the Ph ‘molecular defect’but lacks the Philadelphia chromosome is no different from Ph‐positive CML.
A new specific chromosomal rearrangement, t(8;16) (p11;p13), in acute monocytic leukaemia
Authors: Heim Sverre , Avanzi Gian‐Carlo , Billstroum Rolf , Kristoffersson Ulf , Mandahl Nils , Bekassy Albert N. , Garwicz Stanislaw , Wiebe Thomas , Pegoraro Loigi , Falda Michele , Resegotti Luigi , Mitelman Felix 
Published: March 2008

SummaryThe translocation t(8;16) (p11;p13) was found as the sole deviation from the normal karyotype in three patients with acute monocytic leukaemia. The bone marrow morphology was strikingly similar in the two cases where smears were available for re‐evaluation: the leukaemic cells showed signs of differentiation, and active erythrophagocytosis was a particularly conspicuous feature. We suggest that t(8;16) (p11;p13) represents a new consistent abnormality in acute monocytic leukaemia, specifically associated with the differentiated subtype (M5b) and with pronounced phagocytic activity by the leukaemic monocytes.
Interleukin 3 enhances the cytotoxic activity of 1‐β‐d‐arabinofuranosylcytosine (ara‐C) on acute myeloblastic leukaemia (AML) cells
Authors: Lista Patrizia , Porcu Pierluigi , Avanzi Gian Carlo , Pegoraro Luigi 
Published: March 2008

We have evaluated the possibility of enhancing the cell killing effect of ara‐C on AML blasts by increasing their proliferative activity with haemopoietic growth factors. Leukaemic cells from 10 AML patients were incubated for 3 d in liquid culture in the presence or in the absence of the human recombinant growth factors IL‐1β (5 U/ml) and IL‐3 (3 U/ml), and subsequently exposed to ara‐C (3 μ/ml) for the last 24 h. The number of residual leukaemic stem cells was evaluated by a clonogenic assay in semisolid medium. The results showed that ara‐C exposure inhibits the proliferation of a higher proportion of clonogenic cells in cultures pretreated with growth factors than in the controls (mean inhibitory values: in the absence of growth factors = 49.8%: with IL‐1β=58.3%; with IL‐3 78.9%) The effect was statistically significant only when IL‐3 was used as a growth factor.The results suggest that haemopoietic growth factors may help to improve the therapeutic index of cytostatic agents.
Rapid and non‐radioactive prenatal diagnosis of β thalassaemia and sickle cell disease: application of the polymerase chain reaction (PCR)
Authors: Kulozik Andreas E. , Lyons John , Kohne Elisabeth , Bartram Claus R. , Kleihauer Enno 
Published: March 2008

The standard method for the prenatal diagnosis of the haemoglobinopathies is by restriction enzyme mapping of chorionic villus DNA using Southern blotting and radioactively labelled gene probes. An improvement of the procedure which involves the selective amplification of DNA fragments by the polymerase chain reaction allows one to visualize restriction fragments directly without the use of radioactivity and within 2 d after obtaining the sample.We report here the prenatal diagnosis of two pregnancies at risk for homozygous β thalassaemia and homozygous sickle cell disease using this novel approach.
Heterogeneity of CLL: high CD23 antigen and αIFN receptor expression are features of favourable disease and of cell activation
Authors: Dadmarz R. , Cawley J. C. 
Published: March 2008

Summary The relationship between α‐interferon receptor (αIFNR) numbers, B‐cell‐antigen expression and clinical stage was determined in 35 cases of typical chronic lymphocytic leukaemia (CLL). αIFNR numbers were shown to be low in patients with advanced disease and high in those with a more favourable prognosis. The B‐cell activation antigen CD 23 was similarly related to stage, being high in more favourable disease. Also, αIFNR expression was directly related to CD 23 positivity, but αIFN binding was not inhibited by CD 23 monoclonal antibody. There was no correlation between CD 19, 20, 22 and 24 antigen expression and either αIFNR numbers or clinical stage.Since CD23 antigen expression is a feature of B‐cell activation, we suggest that high CD23 and αIFNR positivity are manifestations of an activated cell phenotype and that cell activation in CLL is a feature of favourable disease.
Carrier mediated iron transport through erythroid cell membrane
Authors: Egyed A. 
Published: March 2008

Summary The transport of iron through erythroid cell membrane was studied in a model system, measuring ferrous iron uptake by reticulocytes. It was found that these cells were able to take up ferrous iron and to incorporate it into haem at a rate similar to that observed when diferric transferrin was the iron donor. No comparable iron uptake could be measured when the metal was provided as Fe3+ citrate or when reticulocytes were replaced by mature erythrocytes.The involvement of end geneous transferrin in the Fe2+ uptake by reticulocytes could be excluded, since proteolytic treatment of the cells had no significant effect on the process.Fe2+ uptake by reticulocytes followed saturation kinetics, characteristic to carrier mediated transport processes. Kinetic analysis of the data revealed the following apparent transport parameters: Km= 8.8±3.8 μm; Vmax= 1.1±0.2 ng/108 reticulocytes/ min.These results indicate that a high affinity, carrier mediated iron transport system is present in the reticulocyte membrane, ensuring the efficient translocation of the metal through the membrane barrier between the site of its release from transferrin and the site of its utilization.
Elevated red cell adenosine deaminase activity: a marker of disordered erythropoiesis in Diamond‐Blackfan anaemia and other haematologic diseases
Authors: Glader Bertil E. , Backer Karen 
Published: March 2008

SummaryRed‐cell adenosine deaminase (ADA) activity in children with Diamond‐Blackfan anaemia is significantly increased (1·91±0·90 U/g Hb) compared to that seen in transient erythroblastopenia of childhood (0·80±0·16 U/g Hb) or normal individuals (0·61±0·13 U/g). These data thus further support that measurement of this purine metabolic enzyme is useful in diagnosing the cause of pure RBC aplasia in children. Of interest, however, elevated RBC‐ADA activity also is seen in some children with acute leukaemia and other haematologic disorders. In children with acute lymphoblastic leukaemia (ALL), the increase in RBC‐ADA activity is proportional to the degree of anaemia. However, the elevated RBC‐ADA activity in this leukaemic population is not related to the fetal haemoglobin concentration. These data suggest increased RBC‐ADA activity may be a non‐specific manifestation of abnormal erythroid stem cell function, an alteration distinct from that seen with reactivation of fetal erythropoiesis. However, since almost all patients with Diamond‐Blackfan anaemia manifest elevated RBC‐ADA activity, this chemical alteration yet may reflect the specific erythroid differentiation lesion in this disorder.
Electron‐microscopic characterization of mixed granulated (hybridoid) leucocytes of chronic myeloid leukaemia
Authors: Schmidt U. , Mlynek M.‐L. , Leder L.‐D. 
Published: March 2008

SummaryIn chronic granulocytic leukaemia, hybridoid leucocytes can regularly be found. Light microscopically they contain a mixture of eosinophilic, basophilic and naphthol AS‐D chloroacetate esterase‐positive granules. The present study was done to clarify the ultrastructural composition of these cells. It could be clearly shown that in some leukaemic granulocytes primary and secondary eosinophilic as well as basophilic granules occur side by side. There were also basophils with additional tissue mast cell granules. Since normal mast cell granules as well as granules of normal eosinophilic promyelocytes are naphthol AS‐D chloroacetate esterase‐positive, it would appear possible that mastocytoid as well as primary eosinophilic granules within the leukaemic basophils are responsible for the atypical, granular naphthol AS‐D chloroacetate esterase‐positivity of these cells. The existence in chronic myeloid leukaemia both of mixed basophilic and eosinophilic granulated leucocytes and of mixed basophilic and mastocytoid granulated leucocytes may suggest a common myeloid precursor of eosinophils, basophils and tissue mast cells. In addition, the hybridoid granulocytes may be considered an expression of a neoplasiarelated lineage infidelity.
Allogeneic bone marrow transplantation versus intensification chemotherapy for acute myelogenous leukaemia in first remission: a prospective controlled trial
Authors: Conde E. , Iriondo A. , Rayon C. , Richard C. , Fanjul E. , Garijo J. , Hermosa V. , Coma A. , Bello C. , Carrera D. , Baro J. , Zubizarreta A. 
Published: March 2008

SummaryIn 1982 we began a prospective controlled trial to assess the effectiveness of allogeneic bone marrow transplantation and intensive post‐remission chemotherapy for patients with acute myelogenous leukaemia in first complete remission. Fourteen patients, 3–45 years of age, who had an HLA‐identical sibling donor, received bone marrow transplantation. Twenty‐five patients who either lacked an HLA‐identical sibling or were over 45 years of age received intensive consolidation chemotherapy including high‐dose cytosine arabinoside with or without adriamycin.The actuarial rate of continued complete remission (CCR) at 3 years was significantly higher in the transplantation group than in the chemotherapy group: 70% (95% confidence interval 35–91%) compared with 10% (95% confidence interval 2–30%); P = 0·01. However, the actuarial rate of CCR was not significantly different between the transplantation group and patients under 45 years in the chemotherapy group: 70% (95% confidence interval 35‐91%) compared with 17% (95% confidence interval 4–45%), 0·1>P>0·05. The actuarial probability of leukaemia relapse was significantly lower in the transplantation group than in the chemotherapy group: 10% (95% confidence interval 4–21%) compared with 88% (95% confidence interval 70–96%), 0·005 >P>0·001. There was no significant difference between both groups if we compare only the patients who died of non‐leukaemic causes: 22%, (95% confidence interval 9–42%) versus 25% (95% confidence interval 7–59%), P = NS.In summary, this study shows that allogeneic bone marrow transplantation is a better anti‐leukaemic treatment than is intensive consolidation chemotherapy in patients with AML in first complete remission.
Abnormal membrane phospholipid organization in Plasmodium falciparum‐infected human erythrocytes
Authors: Joshi P. , Gupta C. M. 
Published: March 2008

SummaryThe membrane phospholipid organization in Plasmodium falciparum‐infected human erythrocytes was analysed by employing phospholipase A2 and Merocyanine 540 as external membrane probes. Both bee venom and pancreatic phospholipases A2 failed to hydrolyse phosphatidylserine in uninfected human red cells isolated from in vitro P. falciparum cultures. However, these enzymes under identical conditions readily degraded this aminophospholipid in P. falciparium‐infected erythrocytes. Phosphatidylethanolamine hydrolysis also increased in parasitized cells. The degree to which these aminophospholipids were cleaved by the enzymes in intact infected cells depended on the developmental stage of the intracellular parasite, and was maximum at the schizont stage. This was consistent with the finding that the ‘fluid‐sensing’ fluorescent dye, Merocyanine 540, readily labelled both the schizont and trophozoite‐infected cells but not the fresh, uninfected or ring‐infected erythrocytes. These results demonstrate that P. falciparum produces stage‐dependent changes in the membrane phospholipid organization of its host erythrocyte.
Comparison of the in vitro characteristics of von Willebrand factor in British and commercial factor VIII concentrates
Authors: Lawrie A. S. , Harrison P. , Armstrong A. L. , Wilbourn B. R. , Dalton R. G. , Savidge G. F. 
Published: March 2008

Summary. Qualitative/quantitative analysis of von Willebrand factor antigen (vWf:Ag) in either heat or solvent/detergent treated factor VIII concentrates, used for haemophilia replacement therapy, was undertaken to assess their suitability for the treatment of vWD. For the first time immunoaffinity purified vWf:Ag (Monoclate by‐product) was also evaluated by in vitro assessment.Potencies of vWf: Ag varied considerably but were consistently higher (28.9–420.5 iu/ml) than factor VIII:C (one‐stage) activity (8.13–42.44 iu/ml). The functional activity of vWf was assessed by either Ristocetin Cofactor (vWf:RCo) or collagen binding methods (vWf:CBA) with typical vWf:RCo/vWf:Ag ratios ranging from 0.08 to 0.94. Multimeric analysis confirmed that in vitro biological activity was dependent on the presence of the high molecular weight forms of vWf: Ag. A significant correlation (r=0.95) between vWf:RCo activity and collagen binding was observed in all of the concentrates with the exception of the immunopurified product.The data suggest that either NHS 8Y (mean vWfRCo/vWf:Ag=0.94), Haemate P (mean vWf:RCo/vWf:Ag=0.69) and high purity Octapharma V.I (vWf:RCo/vWf:Ag=0.82) which contain medium/high MW vWf:Ag multimers are likely to be most cost‐effective in the treatment of symptomatic severe vWD patients than other currently available concentrates.
The use of DNA probes to monitor minimal residual disease in childhood acute lymphoblastic leukaemia
Authors: Katz Fay , Ball Lynne , Gibbons Barbara , Chessells Judith 
Published: March 2008

SummaryDNA probes to both the joining region (JH) of the immunoglobulin heavy chain gene (IgH) and to the β chain of the T‐cell antigen receptor complex (TCR) have been used as tumour‐specific markers to monitor the rearrangements of the IgH chain gene and the TCR β gene in the blast cells of children presenting with acute lymphoblastic leukaemia (ALL) of B or T cell origin. Blast cells from 68 children with early B cell ALL and eight with T‐ALL were examined at presentation, at day 28 after commencement of therapy and at varying times thereafter. An additional 43 patients (42 with B cell ALL, one with T‐ALL) were studied both at presentation, at completion of their 2‐year treatment course and 3 months later. Twelve patients, drawn from both these groups, were studied at relapse as were a further eight patients in whom an extramedullary relapse had occurred. Persistence of clonally‐derived cells as a predictor of early relapse was seen in the day 28 bone marrows of 11/76 newly‐diagnosed children (nine early B and two T‐ALL) followed by rapid, overt relapse in four of the early B ALL cases. No minimal residual disease (MRD) was detected in bone marrows from any of the 43 patients completing their 2‐year treatment course, but six of these subsequently relapsed at varying time periods thereafter. Identical patterns of rearrangement at both presentation and relapse were seen in most cases. Oligoclonality, or multiple IgH chain gene rearrangements was seen in the blast cells of 15% of patients with early B cell ALL. No correlation between oligoclonality, high white count, unfavourable phenotype, or abnormal karyotype could, however, be ascertained.