bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sedimentary sequences, seismofacies and evolution of depositional systems of the Oligo/Miocene Lower Freshwater Molasse Group, Switzerland
Authors: Schlunegger F. , Matter A. , Burbank D. W. , Leu W. , Mange M. , Màtyàs J. 
Published: November 2003

ABSTRACTMagnetostratigraphic chronologies, together with sedimentological, petrological, seismic and borehole data derived from the Oligo/Miocene Lower Freshwater Molasse Group of the North Alpine foreland basin enable a detailed reconstruction of alluvial architecture in relation to Alpine orogenic events. Six depositional systems are recorded in the Lower Freshwater Molasse Group. The bajada depositional system comprises 200–400‐m‐thick successions of ribbon channel conglomerates and overbank fines including mud‐ and debris‐flows which were derived from the Alpine border chain. The alluvial megafan depositional system is made up of massive pebble‐to‐cobble conglomerates up to 3 km thick which reveal a fan‐shaped geometry. This depositional environment grades downcurrent into the conglomerate channel belt depositional system, which comprises an ≈2‐km‐thick alternation of channel conglomerates and overbank fines. The sandstone channel belt depositional system is bordered by the 100–400‐m‐thick overbank fines assigned to the floodplain depositional system. At the feather edge of the basin, 50–400‐m‐thick lacustrine sediments in both clastic and carbonate facies represent the lacustrine depositional system.The spatial and temporal arrangement of these depositional systems was controlled by the geometrical evolution of the Molasse Basin. During periods of enhanced sediment supply and during phases of stable sliding of the entire wedge, >2000‐m‐thick coarsening‐and thickening‐upward megasequences comprising the conglomerate channel belt, alluvial megafan and bajada depositional systems were deposited in a narrow wedge‐shaped basin. In the distal reaches of the basin, however, no sedimentary trend developed, and the basin fill comprises a <500‐m‐thick series of sandstone meander belt, floodplain and lacustrine depositional systems. During phases of accretion at the toe of the wedge, the basin widened, and prograding systems of multistorey channel sandstones extended from the thrust front to the distal reaches of the basin.The rearrangement of the depositional systems as a function of changing orogenic conditions created discordances, which are expressed seismically by onlap and erosion of beds delimiting sedimentary sequences. Whereas stable sliding of the wedge succeeded by accretion at the toe of the wedge is recorded in the proximal Lower Freshwater Molasse by a coarsening‐and thickening‐upward megasequence followed by erosion, the opposite trend developed in the distal reaches of the Molasse. Here, fine‐grained sandstones and mudstones were deposited during periods of stable sliding, whereas phases of accretion caused a coarsening‐ and thickening‐up megasequence to form.
HIGH‐DOSE THERAPY WITH PERIPHERAL BLOOD STEM CELL TRANSPLANTATION RESULTS IN A SIGNIFICANT REDUCTION OF THE HaEMOPOIETIC PROGENITOR CELL COMPARTMENT
Authors: Voso M. T. , Murea S. , Goldschmidt H. , Hohaus S. , Haas R. 
Published: November 2003

In order to study the effect of high‐dose therapy with peripheral blood stem cell transplantation (PBSCT) on the haemopoietic reserve in man, the number and composition of bone marrow (BM) and peripheral blood (PB)‐derived progenitor cells were examined in 137 cancer patients. In 45 patients, paired samples from BM and PB were obtained before PBSC mobilization and 6–27 months after transplantation. Following PBSCT, the proportion of CD34+ cells was significantly smaller than before mobilization (BM 1.99±0.24 versus 0.8±0.09, P<0.001), and no change was observed at several follow‐up visits thereafter.The reduction was most pronounced for the primitive BM progenitor subsets such as the CD34+/DR− and CD34+/Thy‐1+ cells. The impairment of hematopoiesis was also reflected by a significant reduction in the plating efficiency of BM and PB samples.No relationship was found between the decrease in the proportion of CD34+ cells and any particular patient characteristics, kind of high‐dose therapy or the CD34+ cell content in the autograft.In conclusion, high‐dose therapy with PBSC transplantation is associated with a long‐term impairment of the haemopoietic system. The reduction in the number of haemopoietic progenitor cells is not associated with a functional deficit, as peripheral blood counts post‐transplantation were normal in the majority of patients.
Primary proliferating immature myeloid cells from CML patients are not resistant to induction of apoptosis by DNA damage and growth factor withdrawal
Authors: Albrecht Tarja , Schwab Renate , Henkes Martin , Peschel Christian , Huber Christoph , Aulitzky Walter E. 
Published: November 2003

Induction of apoptosis by growth factor deprivation or gamma‐irradiation‐induced DNA damage was directly studied in proliferating primary haemopoietic cells derived from CD34‐positive cells of 13 CML patients and 12 normal controls. CD34‐positive cells were cultured in the presence of appropriate concentrations of SCF and G‐CSF for 5–7 d. After gamma irradiation with 500 rad or growth factor deprivation, the fraction of apoptotic cells was assessed by two independent methods applying either measurement of cells incorporating FITC‐labelled dUTP by terminal transferase or assessment of the fraction of cells with a less than 2N DNA content in flow cytometry.Proliferating CML cells were not resistant to the induction of apoptosis either after gamma irradiation or subsequent to growth factor deprivation. A similar fraction of normal and CML cells underwent apoptosis 48 h after withdrawal of growth factors. CML cells displayed an increased susceptibility to induction of apoptosis after DNA damage. A significantly higher proportion of apoptotic cells were detected in samples derived from CML patients after irradiation with 0.5 Gy. These results, in conjunction with conflicting observations by other investigators, on the induction of apoptosis by gamma irradiation in various bcr‐abl positive cells, suggest that bcr‐abl‐dependent effects on apoptosis strongly depend on the cells used. Our observations in CML cells derived exclusively from newly diagnosed CML patients demonstrate that bcr‐abl expression per se is not sufficient to induce resistance to apoptosis.
The triplicated α‐globin gene locus in β‐thalassaemia heterozygotes: clinical, haematological, biosynthetic and molecular studies
Authors: Traeger‐Synodinos J. , Kanavakis E. , Vrettou C. , Maragoudaki E. , Michael Th. , Metaxotou‐Mavromati A. , Kattamis C. 
Published: November 2003

Excess α‐globin chains play a major role in the pathophysiology of homozygous β‐thalassaemia. In β‐thalassaemia carriers a minor effect of α‐globin chain excess is reflected in a minimal or mild anaemia without clinical symptoms. Factors that increase α‐chain excess in heterozygotes are expected to accentuate the severity of the clinical and haematological phenotype.We report the clinical, haematological, biosynthetic and molecular data in three β‐thalassaemia heterozygotes with the rare interaction of homozygosity for α‐globin gene triplication, and in 17 heterozygotes with a single additional α‐globin gene. The three patients homozygous for the α‐globin gene locus (anti 3.7 kb arrangement) had β °‐thalassaemia mutations and a diagnosis of thalassaemia intermedia, preserving haemoglobin levels around 7–8 g/dl. Of the 17 β‐thalassaemia heterozygotes (six children and 11 adults), 16 had severe β‐thalassaemia mutations interacting with an additional α‐globin gene (13 with αααanti‐37 and four with αααanti‐42). Compared to simple β‐thalassaemia heterozygotes, they had lower haemoglobin levels and red cell indices, but higher α/β biosynthesis, HbF levels and reticulocytes.Our results suggest that homozygous α‐gene triplication interacts with a severe β‐thalassaemia mutation to cause an α‐chain excess equivalent to that observed in homozygous β‐thalassaemia intermedia. In heterozygotes for severe β‐thalassaemia mutations with one additional α‐globin gene, the α‐chain excess causes a more pronounced degree of anaemia than is usually seen in simple β‐thalassaemia heterozygotes.
Avascular necrosis of bone after allogeneic bone marrow transplantation: analysis of risk factors for 4388 patients by the Société Française de Greffe de Moëlle (SFGM)
Authors: Socié G. , Cahn J. Y. , Carmelo J. , Vernant J. P. , Jouet J. P. , Ifrah N. , Milpied N. , Michallet M. , Lioure B. , Pico J. L. , Witz F. , Molina L. , Fischer A. , Bardou V. J. , Gluckman E. , Reiffers J. 
Published: November 2003

Increasing numbers of patients are surviving after allogeneic bone marrow transplantation and are therefore at risk for developing late complications. Among these complications, avascular necrosis of bone has been reported, but only two single‐centre studies included sufficient patients to enable analysis of the risk factors for developing avascular necrosis. In this multicentre retrospective study the aim was to assess risk factors for this complication in a large number of patients.The population consisted of 4388 patients, recorded in the Société Française de Greffe de Moelle (SFGM) data base, who had undergone a single allogeneic bone marrow transplant between January 1974 and December 1993. 77 patients developed avascular necrosis leading to a 4.3% projected incidence at 5 years. Symptoms developed 2–132 months after transplantation. In these 77 patients a mean of 1.87 joints per patient were affected (range 1–7). The hip joint was the most often affected (88% of patients) and 48% of the patients required joint replacement. All but two patients received steroids for acute and/or chronic graft‐versus‐host disease (GvHD) over a mean period of 15 months. In univariate analysis, among eight factors tested as risk factors for developing avascular necrosis, six were shown to be linked to an increased risk: older age, diagnosis of aplastic anaemia or acute leukaemia, an irradiation‐based conditioning regimen, type of GvHD prophylaxis regimens, acute and chronic GvHD. In multivariate logistic regression analysis, five factors remained significantly associated with an increased risk for developing avascular necrosis: chronic GvHD (odds ratio (OR) 3.52), acute GvHD (OR 3.73), age>16 years (OR 5.81), aplastic anaemia (OR 3.90), and acute leukaemia (OR 1.72).Avascular necrosis is not a rare late complication of allogeneic bone marrow transplantation causing significant morbidity. In this study, older age, initial diagnosis, and GvHD and/or its treatment with steroids emerged as significant risk factors.
The role of immunoglobulin G and fibrinogen in platelet aggregation by Streptococcus sanguis
Authors: Ford I. , Douglas C. W. I. , Cox D. , Rees D. G. C. , Heath J. , Preston F. E. 
Published: November 2003

Previous work has shown that the type strain of Streptococcus sanguis, NCTC 7863, induces aggregation of normal platelets by a complement‐dependent mechanism. We investigated the roles of IgG and fibrinogen in the aggregation process. Plasma depleted of IgG by passage through protein A–sepharose failed to support platelet aggregation, as did plasma absorbed at 0°C with whole bacteria. However, absorption of plasma with a non‐aggregating strain of S. sanguis, SK96, did not remove aggregating activity for NCTC 7863. Supplementing 0°C‐absorbed plasma with purified IgG restored the aggregation supporting activity. A monoclonal antibody to the FcγRII receptor inhibited platelet aggregation by the bacteria, indicating a requirement for bacteria–IgG complexes interacting with the Fc receptor in platelet aggregation. There was a lag time to the onset of platelet aggregation of 7–19 min depending upon the platelet donor, but the length of this lag did not correlate with either total IgG concentration recognizing NCTC 7863 in subjects’ plasma, or the concentration any of the four IgG subclasses or with IgG avidity levels.Fibrinogen was shown to bind rapidly to the bacterial cell surface. Monclonal antibody to GPIIb/IIIa, RGDS peptide, and a specific antagonist for the platelet fibrinogen receptor, GPIIb/IIIa, FK633, inhibited platelet aggregation by NCTC 7863, indicating that platelet aggregation is fibrinogen dependent. These data suggest that platelet aggregation by some strains of S. sanguis requires multiple stimuli/agonists, including IgG–Fc receptor interaction, complement and fibrinogen.
Oral contraceptives and venous thrombosis: different sensitivities to activated protein C in women using second‐ and third‐generation oral contraceptives
Authors: Rosing J. , Tans G. , Nicolaes G. A. F. , Thomassen M. C. L. G. D. , Van Oerle R. , Van DerPloeg P. M. E. N. , Heijnen P. , Hamulyak K. , Hemker H. C. 
Published: November 2003

Epidemiological studies have shown that women who use third‐generation oral contraceptives (OC) containing desogestrel, gestodene or norgestimate have a higher risk of venous thrombosis than women who use second‐generation OC containing levonorgestrel. It is also known that a mutation in factor V (factor VLeiden), which results in resistance to activated protein C (APC) and which is the most common cause of hereditary thrombophilia, potentiates the prothrombotic effect of OC.Effects of APC on thrombin generation in the plasma of women using OC were compared to the response to APC in non‐OC users and in individuals that were hetero‐zygous or homozygous for factor VLeiden. The response towards APC was evaluated on basis of the ratio (APC‐sr) of the time integrals of thrombin formation determined in the presence and absence of APC.Compared with women not using OC, women who used OC exhibited a significantly decreased sensitivity to APC (P < 0.001), independent of the kind of OC used. Women who used third‐generation monophasic OC were significantly less sensitive to APC than women using second‐generation OC (P < 0.001) and had APC‐sr that did not significantly differ from heterozygous female carriers of factor VLeiden who did not use OC. Women who were heterozygous for factor VLeiden and used OC had APC‐sr in the range of homozygous carriers of factor VLeiden. Two women who started OC therapy had significantly elevated APC‐sr within 3 d.Acquired APC resistance may explain the epidemiol‐ogical observation of increased risk for venous thrombosis in OC users, especially in women using third‐generation OC.
A variant of the EPB3 gene of the anti‐Lepore type in hereditary spherocytosis
Authors: Bianchi Paola , Zanella Alberto , Alloisio Nicole , Barosi Giovanni , Bredi Elena , Pelissero Giovanni , Zappa Manuela , Vercellati Cristina , Baronciani Luciano , Delaunay Jean , Sirchia Girolamo 
Published: November 2003

The EPB3 gene encodes band 3 (anion exchanger 1) of the red cell membrane. A subset of hereditary spherocytosis (HS) is associated with EPB3 gene mutations and band 3 deficiency. We report a large Italian family in which 10 of the 27 members investigated displayed an autosomal dominant HS. SDS‐PAGE revealed a reduction in band 3 in the patients. Screening of the Pst I polymorphic site confirmed the linkage of HS with the EPB3 gene. Analysis of complementary and genomic DNA showed a large additional segment. Nucleotide sequencing disclosed an in‐frame duplication of 69 nucleotides (nt) including a triplet of intronic origin and a genuine exonic duplication of 66 nt. Two CCTGC sequences occurred close to one another, one near the intron 12 acceptor splice site (nt −7 to −3), and the other within exon 13 (nt 1494–1498). We assumed that the abnormal allele arose from an unequal recombination event of the anti‐Lepore type between the two CCTGC sequences.At the level of the mutated protein, termed band 3 Milano, the additional segment (Gln plus duplication of residues 478–499) corresponded to the last part of the third transmembrane domain (TM3), the entire second outer loop and part of TM4 as it is currently defined in hydropathy analysis. After deglycosylation of band 3, only the normal band was detected, supporting the view that band 3 Milano is probably not incorporated into the membrane.
Two new mutations of the glucose‐6‐phospate dehydrogenase (G6PD) gene associated with haemolytic anaemia: clinical, biochemical and molecular relationships
Authors: Zarza R. , Pujades A. , Rovira A. , Saavedra R. , Fernandez J. , Aymerich M. , Vives Corrons J. Ll. 
Published: November 2003

In two unrelated Spanish males with glucose‐6‐phosphate dehydrogenase (G6PD) deficiency and haemolytic anaemia, and two different novel point mutations in the G6PD gene, have been identified. A C to T transition at nucleotide 406 resulting in a (136) Arg to Cys substitution and a C to G transition at nucleotide 1155 resulting in a (385) Cys to Trp substitution. These two molecular defects have not been described before and are designated G6PD Valladolid406 C→T and G6PD Madrid1155 C→G . In vitro biochemical characterization of both mutant enzymes showed important differences in their molecular properties according to their different clinical behaviour. In G6PD Valladolid, the mutation of which is located in exon 5, the normal in vitro heat stability may explain its mild clinical expression (low‐grade haemolysis interrupted by an acute haemolytic crisis at age 70). In G6PD Madrid, the mutation, located in exon 10, results in a deficient variant associated with neonatal jaundice and life‐long chronic nonspherocytic haemolytic anaemia (CNSHA). This finding further emphasizes the importance of this specific region of the G6PD gene in the stabilization of the G6PD molecule. Putative relationships between these single point mutations and the molecular properties of the mutant enzymes are also discussed.
An erythroid and megakaryocytic common precursor cell line (B1647) expressing both c‐mpl and erythropoietin receptor (Epo‐R) proliferates and modifies globin chain synthesis in response to megakaryocyte growth and development factor (MGDF) but not to erythropoietin (Epo)
Authors: Bonsi Laura , Grossi Alberto , Strippoli Pierluigi , Tumietto Fabio , Tonelli Roberto , Vannucchi Alessandro M. , Ronchi Antonella , Ottolenghi Sergio , Visconti Giovannella , Avanzi Gian Carlo , Pegoraro Luigi , Paolo Bagnara Gian 
Published: November 2003

A human megakaryocyte cell line (B1647) has been established from bone marrow cells obtained from a patient with acute myelogenous leukaemia (FAB M2). The cells were CD34−, CD33+, HLA‐DR+, CD38+, and expressed the immunophenotypic markers of the megakaryocyte lineage (CD41 and von Willebrand factor). Moreover the cells expressed the c‐mpl (thrombopoietin receptor) mRNA and protein. On the other hand, the B1647 cells also possessed erythroid lineage characteristics: the vast majority of cells were glycophorin positive, and about 10% of unstimulated cells stained with an anti‐globin γ chain MoAb. In addition, S1 protection analysis demonstrated expression of β‐globin mRNA, and Epo receptor (Epo‐R) protein was detected by cytofluorimetric assay. Several growth factors, when tested alone or in combination, failed to influence the B1647 cell growth. A significant increase of cell proliferation was observed only after the addition, in serum‐free culture, of recombinant human megakaryocyte growth development factor (MGDF), a recombinant c‐mpl ligand encompassing the receptor‐binding domain and identical to thrombopoietin (TPO), at concentrations ranging from 0.01 to 1 ng/ml. Interestingly, MGDF failed to induce megakaryocytic differentiation of the B1647 cells, but significantly increased the synthesis of the globin γ‐chain.B1647 cells could be a useful model for studying the biological effect of TPO on common megakaryocyte and erythroid progenitors.
Polymorphism of the tumour necrosis factor‐alpha and lymphotoxin‐alpha genes in chronic lymphocytic leukaemia
Authors: Demeter Judith , Porzsolt Franz , Rämisch Stephanie , Schmidt Dorothee , Schmid Mathias , Messer Gerald 
Published: November 2003

The neoplastic cells of CLL are able to produce TNF which is known to stimulate the proliferation of CLL cells in an autocrine and paracrine manner. Genetic polymorphism of molecules of the TNF ligand superfamily has been described and certain alleles were suspected to predispose to variant biological responses. Previously, the rare allele TNFB*1 of the TNF‐β/lymphotoxin (LT)‐α gene (NcoI, asparagine at amino acid position 26) was found to be associated with a stronger LT‐α response of PBMC in vitro.We now report on a significant increase of the allele TNF1 (TNFA −308 G) of the TNF‐α promoter/enhancer polymorphism in a group of 73 CLL patients when compared to healthy individuals (RR=3.18, 95% confidence interval 1.57–8.3; P=0.006). The allelic distribution of the TNF‐β/LT‐α NcoI polymorphism did not differ significantly from randomized healthy controls. On the other hand, the frequency of the allele TNFB*2 was increased in CLL patients with advanced clinical stage (P=0.0004). These findings indicate immunogenetic associations involving polymorphisms of cytokine genes serving as paracrine and autocrine growth factors, which thus can contribute to the pathogenesis of the TNF/LT‐sensitive haematological malignancy CLL.
Reliability of delayed INR determination: implications for decentralized anticoagulant care with off‐site blood sampling
Authors: Baglin Trevor , Luddington Roger 
Published: November 2003

In order to develop decentralized anticoagulant care by off‐site blood sampling and transport of samples to a centralized laboratory for International Normalized Ratio (INR) determination we have performed a direct comparative study of INR stability. Analysis was performed daily for 5 d using nine thromboplastins. The overall mean difference of INR after 3 d was only 0.05 INR units for samples with a therapeutic INR. After 5 d there was a mean difference of 0.11 INR units with ‘non‐Manchester’ reagents and 0.44 INR units with ‘Manchester’ reagents. With over‐anticoagulated samples mean differences of 0.55–0.72 INR units were observed after 3 d and 1.16–2.46 INR units after 5 d. Although there was some variation in stability of results with different thromboplastins, the difference over time with each thromboplastin was much less than the difference between thromboplastins.In conclusion, there is no clinically significant change in INR when analysis is delayed for up to 3 d. Off‐site blood sampling can accommodate a large increase in patient workload without a major revenue increase in primary care and with continued total quality management and central expert advice.