bluuebunny/crossref_metadata_2025_split huggingface dataset:
Architecture and controls on Bathonian–Kimmeridgian shallow‐marine synrift wedges of the Oseberg–Brage area, northern North Sea
Authors: Ravnås R. , Bondevik K. 
Published: November 2003

The Oseberg Fault‐Block, situated along the eastern flank of the northern Viking Graben in the North Sea, was affected by Middle–Late Jurassic rifting initiated in Bajocian–Bathonian times. Temporal variations in stretching rates exerted the major control on the depositional infill patterns of the Bathonian–Kimmeridgian Heather Formation and its intercalated Middle Callovian to Early Oxfordian Fensfjord and Late Oxfordian to Kimmeridgian Sognefjord Formations. Three shallow‐marine, regressive–transgressive synrift wedges are recognized, and are interpreted in terms of discrete rift phases. The lower, regressive segments of the synrift wedges were deposited during periods of relatively low tectonic activity, whereas the upper, overall transgressive segments correspond to extensional pulses or stages during which significant fault‐related subsidence and fault‐block rotation occurred. These rotational tilt stages are further subdivided into an early, a climax and a late synrotational substage.The lower, regressive segments consist of stacked, shallowing‐upward units, which reflect the advance of wide shallow‐marine, rift‐marginal shorelines during the tectonically quiescent periods. During the intervening rotational tilt stages renewed basin floor tilting and increased basinal subsidence led to retreat of the rift‐marginal depositional systems, renewal of the half‐graben topography, formation of intrabasinal sediment sources (footwall islands) and the re‐establishment of localized footwall, hangingwall and axial depositional systems. These localized depositional systems generally have an overall forestepping‐to‐backstepping character superimposed on the larger‐scale transgressive trend. There was an associated shift from a wave‐ and storm‐dominated environment during deposition of the lower, regressive segment to a more protected, partly current‐(?tidally) influenced environment in the upper, transgressive segment. This reflects a shift from a broad open basin in tectonically quiescent periods to smaller subbasins (embayments or estuaries) during periods with increased rates of rifting.The footwall highs which formed intrabasinal sediment sources were of limited size compared with the volume of the adjacent depositional sinks. As a consequence, complete infilling of individual half‐grabens were not achieved during the synrotational stages, leaving the subbasins underfilled at the end of each successive rift phase. Mudstone drapes represent periods with deprivation of clastic material and basinal condensation during the latest synrotational to early tectonic quiescence substages, when footwall islands were small or completely submerged and there was a large distance to the (then progradational) rift‐marginal shoreline.
Plasma exchange with solvent/detergent‐treated plasma of resistant thrombotic thrombocytopenic purpura
Authors: Harrison C. N. , Lawrie A. S. , Iqbal A. , Hunter A. , Machin S. J. 
Published: November 2003

A patient with unremitting thrombotic thrombocytopenic purpura (TTP), with circulating von Willebrand factor (VWF) multimers of unusually high molecular weight, and refractory to standard plasma exchange therapy, was treated with solvent detergent (S/D) plasma. The patient achieved a sustained clinical and haematological remission, with normal VWF multimeric profile. Spontaneous remission of this patient's condition could not be excluded but would appear unlikely. S/D plasma was efficacious and potentially safe for repeated large‐volume plasma exchange with respect to viral safety and reduction of anaphylactoid reactions. We have assayed coagulation factors and physiological inhibitors of haemostasis in S/D plasma, which were comparable to normal plasma except in the distribution of VWF multimers.The use of S/D plasma, previously reported in paediatric chronic relapsing TTP, should be assessed in further cases of adult TTP in the context of a clinical trial.
In leukaemic CD5+ B cells the expression of BCL‐2 gene family is shifted toward protection from apoptosis
Authors: Gottardi D. , Alfarano A. , De Leo A. M. , Stacchini A. , Aragno M. , Rigo A. , Veneri D. , ZANOTTI R. , Pizzolo G. , Caligaris‐Cappio F. 
Published: November 2003

This study further investigated the mechanisms that control apoptosis in leukaemic CD5+ B cells, and focused on the Bcl‐2 gene family. The pattern of expression of Bcl‐2, Bcl‐xL, Bcl‐xS and Bax genes, selected because of their interrelated role in the control of apoptosis, was analysed in a series of CD5+ B‐cell chronic lymphoid leukaemias.Cells from 34 patients with chronic lymphoid leukaemia of B‐cell type (23 B‐chronic lymphocytic leukaemia (B‐CLL) and 11 mantle cell lymphoma (MCL) in leukaemic phase) were investigated. High levels of Bcl‐2 mRNA were observed by Northern blot and high levels of Bcl‐2 protein were detected by cytofluorograph analysis with a specific monoclonal antibody (MAb) in all cases. Strong Bax expression was detected by RT‐PCR in 20/23 B‐CLL cases; Bax was also observed in 8/11 MCL in leukaemic phase with variable degree of intensity. In both B‐CLL and MCL samples the presence of Bax protein was confirmed by cytofluorograph analysis. RT‐PCR detected high levels of Bcl‐xL in 16/23 B‐CLL and in 8/11 MCL in leukaemic phase, whereas Bcl‐xS was detectable in low to trace amounts respectively in 13/23 B‐CLL and in 6/11 MCL in leukaemic phase.According to the functional role of Bcl‐2, Bcl‐xL, Bcl‐xS and Bax, these data indicate that the pattern of Bcl‐2 family genes expression in leukaemic CD5+ B cells is skewed toward prevention of apoptosis and may thus favour the relentless accumulation of CD5+ leukaemic B cells.
Is apoptosis a massive process in myelodysplastic syndromes?
Authors: Lepelley Pascale , Campergue Laurence , Grardel Nathalie , Preudhomme Claude , Cosson Alain , Fenaux Pierre 
Published: November 2003

We looked for increased apoptosis in fresh bone marrow aspirates in 40 cases of myelodysplastic syndrome (MDS), by detection of DNA fragmentation using TdT incorporation of nucleotides on 3′ ends of DNA (TUNEL technique). No DNA laddering was seen. In six cases (15%) the TUNEL technique showed a moderate increase in the percentage of apoptotic cells (2.5–5% in comparison with <2% in controls).In seven of the 34 patients with normal findings by TUNEL analysis, apoptosis was reanalysed after short‐term (18 h) bone marrow culture without inducers of apoptosis. Increased apoptosis was shown in four of the seven cases by morphological analysis and/or the TUNEL technique. Increased apoptosis predominated on erythroblasts in three of them. The percentage of apoptotic cells, however, was <40% in all samples.Our findings suggest that increased apoptosis can be detected in one half of MDS cases after cell culture. Furthermore, the precise relationship between increased apoptosis of myeloid precursors and cytopenias will have to be more precisely explored in MDS.
Thrombomodulin activity on mesothelial cells: perspectives for mesothelial cells as an alternative for endothelial cells for cell seeding on vascular grafts
Authors: Verhagen H. J. M. , Heijnen‐Snyder G. J. , Pronk A. , Vroom Th. M. , Van Vroonhoven Th. J. M. V. , Eikelboom B. C. , Sixma J. J. , De Groot Ph. G. 
Published: November 2003

Lining the luminal surface of prosthetic small diameter bypasses with endothelial cells (EC) will lower its thrombogenicity. Unfortunately, human EC are scarce. Mesothelial cells (MC) may be a valuable alternative for EC, since they are abundantly available and have antithrombotic and fibrinolytic properties. An important anticoagulant function of EC is due to thrombomodulin (TM) on the surface. The presence of TM on omentally derived human MC is not known but would increase the chance of successful use of MC for cell seeding procedures.The expression and localization of TM on human MC was studied using monoclonal antibodies. TM activity on cultured MC, and the influence of cytokines, was measured by the gen‐eration of activated protein C (APC), and was compared to EC.TM is expressed on the surface of MC as well as intracellularly, both in vivo and in vitro. The TM‐dependent generation of APC was significantly higher on cultured MC than on cultured EC (817 ± 141 pMv 262 ± 38 pM; P<0.001); their reaction to cytokines was almost identical. Seeding the MC onto vascular prostheses did not change the TM activity.Thrombomodulin is present and highly active on cultured and seeded MC. This may have major implications for MC as a source for cell seeding on vascular prostheses.
Anaplastic large cell (CD30/Ki‐1+) lymphoma in HIV+ patients: clinical and pathological findings in a group of ten patients
Authors: Nosari Annamaria , Cantoni Silvia , Oreste Pierluigi , Schiantarelli Clara , Landonio Giuseppe , Alexiadis Spyridon , Gargantini Livio , Caggese Liliana , Gambacorta Marcello , Morra Enrica 
Published: November 2003

We compared the clinical and pathological features of 10 HIV+ CD30+ anaplastic large cell lymphoma (ALCL) patients with 28 HIV+ CD30+ non‐Hodgkin's lymphoma (NHL) patients. The incidence of ALCL among 38 HIV+ systemic NHL patients was 26%. Clinical features were similar in all the HIV‐related NHL cases, but ALCL patients seemed to differ from HIV+ CD30− systemic NHL only in the greater frequency of lung tumours (40% v 21%) without concomitant mediastinal mass, bone marrow (75% v 18%) and gastroenteric involvement (40% v 25%). Among the HIV+ ALCL patients, histologic subtypes did not differ in frequency from ALCL in the general population. The B phenotype was predominant (50%) as in other HIV‐related NHL. EBV genoma, studied in all HIV+ ALCL patients, was present in 3/10 by in situ hybridization (ISH) and in 5/10 cases using PCR. The clinical course of lymphomas was similar in CD30 positive and negative NHL patients. Overall survival also was short in our series, particularly in HIV+ ALCL (84 v 188 d), probably because of profound immunodepression of the ALCL patients.Our findings suggest that severe immunodepression due to HIV infection determines — more than any other factor — the clinical features of HIV+ ALCL, making them very similar to those of other high‐grade systemic HIV+ NHL.
Diclofenac‐induced immune haemolytic anaemia: simultaneous occurrence of red blood cell autoantibodies and drug‐dependent antibodies
Authors: Salama Abdulgabar , Kroll Hartmut , Wittmann Georg , Mueller‐Eckhardt Christian 
Published: November 2003

During the last 5 years we have identified a total of 17 patients (nine females and eight males aged between 53 and 85 years) with immune haemolytic anaemia related to diclofenac (a nonsteroidal anti‐inflammatory drug). All patients developed acute intravascular haemolysis. Two patients died, and eight patients developed temporary renal failure that required haemodialysis. The direct antiglobulin test was positive with anti‐IgG and anti‐C3d in all cases, with anti‐IgA in 4/10 cases tested, and negative with anti‐IgM. The indirect antiglobulin test was moderately or weakly positive in 11 cases, and IgG autoantibodies could be eluted from the red blood cells (RBCs) of all patients. Initially, the diagnosis of autoimmune haemolytic anaemia of warm type was suggested in all cases. All patients had simultaneously developed autoantibodies and drug‐dependent antibodies. The majority of drug‐dependent antibodies (n=13) reacted with urine containing the drug and its metabolites (ex vivo antigen), the native drug, and diclofenac‐treated RBCs. The antibodies in the remaining four cases were detectable only in the presence of ex vivo antigen. Diclofenac appears to bind only weakly to RBCs in the absence of the drug‐dependent antibodies.We conclude that diclofenac forms neoantigens with RBCs that may stimulate the production of autoantibodies and drug‐dependent antibodies. The resulting haemolytic syndrome is very similar to autoimmune haemolytic anaemia of warm type.
EPIDEMIOLOGY OF COAGULATION FACTORS, INHIBITORS AND ACTIVATION MARKERS: THE THIRD GLASGOW MONICA SURVEY II. RELATIONSHIPS TO CARDIOVASCULAR RISK FACTORS AND PREVALENT CARDIOVASCULAR DISEASE
Authors: Woodward M. , Lowe G. D. O. , Rumley A. , Tunstall‐Pedoe H. , Philippou H. , Lane D. A. , Morrison C. E. 
Published: November 2003

Coagulation factor activity (fibrinogen, VII, VIII and IX), coagulation inhibitor activity (antithrombin, protein C, protein S), and coagulation activation markers (prothrombin fragment F1, 2; thrombin–antithrombin complexes) were measured in 746 men and 816 women aged 25–74 years, randomly sampled from the north Glasgow population in the Third MONICA Survey. After age‐adjustment, significant associations with cardiovascular risk factors were observed. Serum cholesterol and triglyceride were associated with increases in factors VII and IX, as well as antithrombin, protein C and protein S; and with increased fibrinogen and factor VIII in women. Apart from factor VIII (related to blood pressure in men, but not in women), similar associations were observed for blood pressure and body mass index. Smoking status and/or smoking markers were related to fibrinogen, factor IX, antithrombin and protein S. Alcohol intake was related to protein S, and inversely to fibrinogen and antithrombin in men. Low social class was associated with fibrinogen, factor VIII, factor IX, and with antithrombin, protein S, and low protein C in men. Serum vitamin C was associated inversely with coagulation factors and coagulation inhibitors. The only associations of activation markers were with low serum vitamin C, and with alcohol consumption and low social class in men. Prevalent cardiovascular disease was associated only with fibrinogen.These associations of coagulation factors and inhibitors with cardiovascular risk factors are plausibly relevant to thrombotic risk in cardiovascular disease. In general, ‘worse’ values of risk factors are associated with increased plasma levels of both coagulation factors and inhibitors, without significant increase in coagulation activation markers. However, the association of lower serum vitamin C with increased coagulation activation markers is of potential therapeutic interest.
Acute basophilic leukaemia and translocation t(X;6)(p11;q23)
Authors: Dastugue Nicole , Duchayne Eliane , Kuhlein Emilienne , Rubie Hervé , Demur Cécile , Aurich Joan , Robert Alain , Sie Pierre 
Published: November 2003

We report two infants with acute basophilic leukaemia associated with a t(X;6)(p11;q23) as the sole abnormality. Morphologic evidence of basophilic lineage was provided by light and electron microscopy. Both patients also had a similar presentation on diagnosis, characterized by clinical signs consistent with a hyperhistaminaemia syndrome, i.e. urticarian rashes and gastro‐intestinal disorders evocative of peptic ulcer. Immunophenotypes differed in the two patients, one expressing CD24, CD13 and CD33, whereas only CD117 was found in the other.Basophilic acute leukaemia, a rare group among acute leukaemias, might be nonrandomly associated with a specific chromosomal abnormality, t(X;6)(p11;q23). This new entity might also be identifiable by an uncommon clinical presentation and occurrence in infancy.
Activation during preparation of therapeutic platelets affects deterioration during storage: a comparative flow cytometric study of different production methods
Authors: METCALFE PAUL , WILLIAMSON LORNA M. , REUTELINGSPERGER CHRIS P. M. , SWANN IAN , OUWEHAND WILLEM H. , GOODALL ALISON H. 
Published: November 2003

Three different separation methods, all using centrifugation, are routinely used to prepare therapeutic platelet concentrates from human donor blood. Platelet concentrates derived from platelet‐rich plasma (PRP‐PC), buffy coat (BC‐PC) and apheresis (AP‐PC) were investigated at the end of production, and over an 8 d storage period. Change in platelet surface markers were measured by flow cytometry, using fluorescein‐conjugated antibodies to fibrinogen, P‐selectin (CD62P), GPIIb–IIIa (CD41), GPIbα (CD42b) and GPV (CD42d), and fluorescein‐conjugated Annexin V was used to measure expression of anionic phospholipid.All concentrates showed some changes during preparation but PRP‐PC underwent the greatest changes with significantly higher levels of P‐selectin (P < 0.001) and bound Annexin V (P = 0.001) than AP‐PC or BC‐PC, and lower levels of GPIbα (P = 0.002) and GPV (P < 0.001). These changes were attributable to component separation rather than venesection. These markers all continued to change on storage with a strong positive correlation between the changes seen during production and those after 5 d storage. PRP‐PC continued to show the greatest changes whereas BC‐PC showed the least. Fibrinogen was bound to 40–50% of platelets in all preparations and this did not alter significantly on storage whereas total expression of GPIIb–IIIa remained unchanged throughout.There was no evidence that the platelet surface changes were thrombin‐mediated and leucocyte depletion of BP‐PC by filtration had no effect on the changes. It is proposed that the deterioration of platelet concentrates during storage may be related to activation occurring during preparation. ‘Whole blood’ flow cytometry using a panel of fluorescein‐labelled reagents provides an informative method for evaluating platelet concentrates.
Liposomal 1,25 (OH)2 vitamin D3 compounds block proliferation and induce differentiation in myelomonocytic leukaemia cells
Authors: FRANKENBERGER MARION , HOFMANN BARBARA , EMMERICH BERTOLD , NERL CHRISTOPH , SCHWENDENER RETO A. , LÖMS ZIEGLER‐HEITBROCK H.W. 
Published: November 2003

The vitamin D3 derived hormone 1,25 (OH)2 vitamin D3 (1,25 D3) is able to induce growth arrest and differentiation in myelomonocytic leukaemia cells. In order to allow for specific delivery to leukaemic cells the lipophilic compound was incorporated into the lipid membranes of liposomes. Liposomal 1,25 D3 reduced proliferation as measured by 3H‐thymidine incorporation in HL60 leukaemia cells by up to 60%. When liposomes were prepared at different concentrations of 1,25 D3 65% inhibition was achieved at 48 nM. The MC 1288 stereoisomer of 1,25 D3 was more potent and had the same activity at 48 nM.The effect of the liposomal compounds was specific to myeloid cells as they reduced proliferation in myelomonocytic HL60, monoblastic U937 and monocytic Mono Mac 6 cells but not in the T‐cell lines Jurkat and Molt 4.The antiproliferative effect of liposomal 1,25 D3 was associated with an induction of differentiation since treated HL60 cells showed a monocytic morphology, increased expression of CD14 and decreased expression of CD33.When peripheral blood leukaemic cells from M4 and M5 acute myeloid leukaemia (AML) patients were admixed with liposomal compounds an antiproliferative effect was seen in all five cases, including the two cases where free compounds led to enhanced growth. Liposomal delivery of 1,25 (OH)2 vitamin D3 may offer a novel approach to treatment of myelomonocytic leukaemia.
Interferon‐γ+ and interleukin‐2+ T cells in peripheral blood from multiple myeloma patients in relation to disease status and maintenance therapy with interferon‐α2b (intron A)
Authors: Millar Barbara C. , Millar J. L. , Powles R. L. , Catovsky D. 
Published: November 2003

Peripheral blood T cells from 83 patients with multiple myeloma (MM) were examined for the production of interferon‐γ (INFγ) and interleukin‐2 (IL‐2) using three‐colour flow cytometry. Comparisons were made between the percentage of cytokine‐positive lymphocytes in normal donors and in patients during remission or relapse. Patients were divided into those who were on maintenance therapy with interferon‐α2b (intron A) and those who had no further treatment after high‐dose melphalan (HDM) with or without autologous bone marrow (ABMR) or peripheral blood stem cell rescue (PBSCR).The percentage of INFγ+/CD3+, INFγ+/CD45R0+/CD3+ and IL‐2+/CD8+ was higher in patients on INFα2b during remission and relapse compared with normal donors (P < 0.005). During remission INFγ+/CD45R0+/CD3+ and IL‐2+/CD8+ lymphocytes were higher in patients not on INFα2b (P < 0.05 and P < 0.005, respectively). In relapsed patients INFγ+/CD3+ and INFγ+/CD45R0+/CD3+ were increased in patients not taking INFα2b (P < 0.005). There was no significant difference between the percentages of cytokine‐positive lymphocytes in patients taking or not taking INFα2b either during remission or relapse.Plasma IL‐6 levels were similar in both groups of patients during remission. The data suggest that if maintenance therapy with INFα2b induces the synthesis of INFγ and IL‐2 in vivo, the magnitude of the effect is small and may be unimportant in providing an anti‐tumour effect in the majority of patients.
Analysis of ETV6 and ETV6‐AML1 proteins in acute lymphoblastic leukaemia
Authors: AGAPE PHILIPPE , GERARD BENEDICTE , CAVE HELENE , DEVAUX ISABELLE , VILMER ETIENNE , LECOMTE MARIE‐CHRISTINE , GRANDCHAMP BERNARD 
Published: November 2003

The t(12;21) is a recurring chromosomal abnormality in acute lymphoblastic leukaemias (ALLs) which results in the production of an ETV6‐AML1 fusion gene. The association between t(12;21) and the deletion of the untranslocated allele of ETV6 is among the most frequent abnormalities observed in B‐lineage ALLs in children. In order to study the proteins encoded by ETV6ETV6‐AML1, we raised polyclonal antibodies directed against a recombinant peptide corresponding to the junctional region of ETV6‐AML1. Cell lysates from various leukaemic cell lines, and from children with B‐ and T‐lineage ALLs, were studied by Western blot.Two isoforms of ETV6 protein were detected in normal bone marrow cells and in leukaemic cells without 12p alteration: a major form (apparent m.w. 63 kD) and a minor one (apparent m.w. 53 kD).In the REH cell line, which expresses the ETV6‐AML1 fusion transcript and no normal ETV6 mRNA, the ETV6 isoforms were absent and two new bands were detected corresponding to ETV6‐AML1 protein products (apparent m.w. 95 and 105 kD). A similar pattern was obtained with blast cells from patients with a t(12;21) and a deletion of ETV6.In two patients with a t(12;21) but no deletion of ETV6, four bands were detected corresponding to both the normal ETV6 and ETV6‐AML1 proteins, suggesting that in these cases the second ETV6 allele was not inactivated.Surprisingly, the expression pattern of ETV6 differed widely from patient to patient. In three out of 13 patients without t(12;21), the relative intensity of the bands corresponding to ETV6 isoforms in blast cells from patients was completely different from normal cells, with a marked predominance of the 53 kD isoform. The pattern of ETV6 expression was normal in bone marrow from the same patients during remission. These finding suggest that ETV6 abnormalities are not restricted to patients with translocations or deletions involving this gene.