bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differentiation of natrocarbonatite magma at Oldoinyo Lengai volcano, Tanzania
Authors: Gittins J. , Jago B. C. 
Published: July 2002

AbstractNatrocarbonatite magma, erupted as lava flows in the Tanzanian volcano Oldoinyo Lengai in June and November of 1988, has evolved chemically since its formation. The June and November flows of 1988 display increasing Cl, F, Ba, K, Mg and Mn, concomitantly with Na, Ca and P depletion. Furthermore, the June magma, at the time of eruption, had higher Cl, F, Ba and K contents and lower Ca than the November magma and evolved to higher levels of Cl, F, Ba and K content and lower Ca, Na and P. The mineralogy of the lavas reflects these trends. Crystallization of fluorite and halite–sylvite solid solution, usually as a symplectic intergrowth, occurs when Cl and F concentrations reach the critical value necessary to stabilize both minerals and explains why neither occurs as a phenocryst phase. Natrocarbonatite magma has undergone considerable and rapid magmatic evolution, probably in small and separate magma chambers. Two minerals, nyerereite and gregoryite, have dominated the crystallization history of natrocarbonatite magma, and many lavas are phenocryst-rich. However, because most of the lavas are composed principally of these two minerals, crystal accumulation has not greatly changed their composition and, consequently, we suggest that the bulk composition of the lavas closely approximates that of the parental magma.
Interleukin-6 dimers produced by endothelial cells inhibit apoptosis of B-chronic lymphocytic leukemia cells
Authors: Moreno Ana , Villar Marı́a Luisa , Cámara Carmen , Luque Rosario , Cespón Constantino , González-Porqué Pedro , Roy Garbiñe , López-Jiménez Javier , Bootello Alfredo , Santiago Ernesto Roldán 
Published: July 2002

AbstractTumoral lymphocytes from patients with B-chronic lymphocytic leukemia (B-CLL) are long-lived cells in vivo, but they die rapidly by apoptosis in vitro. Here, it is reported that endothelial cells (ECs) inhibit the apoptosis of B-CLL cells, as determined by 4 different flow cytometric methods, and that this antiapoptotic effect is mediated mainly by soluble factor(s), as can be deduced from the following findings. First, EC-conditioned medium (ECCM) inhibited the apoptotic rate in B-CLL to approximately 50% of control. Second, the antiapoptotic effect mediated by EC/B-CLL cell contact was more apparent than real; using a fluorescence-based phagocytosis assay, it was demonstrated that this effect was due to the phagocytic capacity of ECs, which internalized apoptotic cells. Third, the protective effect of ECCM was associated neither with proliferation nor differentiation signals. Fourth, the survival factor was a dimeric form of IL-6 because anti–IL-6 antibodies completely neutralized the antiapoptotic effect mediated not only by the crude ECCM but also by the 45- to 55-kd active fractions obtained after gel filtration, which contained high levels of IL-6. These IL-6 dimers (IL-6D) were noncovalently associated. Sixth, human recombinant IL-6D(hrIL-6D) inhibited B-CLL apoptosis, whereas hrIL-6 monomers (hrIL-6M) did not. Binding and functional competition experiments showed not only that monomers and dimers had similar affinity for the IL-6R, but also that hrIL-6Minhibited the antiapoptotic activity of hrIL-6D. These data suggest that IL-6D derived from ECs promote the survival of B-CLL cells.
Inhibitory effect of the mi transcription factor encoded by the mutant mi allele on GA binding protein–mediated transcript expression in mouse mast cells
Authors: Morii Eiichi , Ogihara Hideki , Oboki Keisuke , Sawa Chika , Sakuma Takahiko , Nomura Shintaro , Esko Jeffrey D. , Handa Hiroshi , Kitamura Yukihiko 
Published: July 2002

AbstractThe mi transcription factor (MITF) is a basic-helix-loop-helix leucine zipper (bHLH-Zip) transcription factor that is important for the development of mast cells. Mast cells ofmi/mi genotype express normal amounts of abnormal MITF (mi-MITF), whereas mast cells of tg/tg genotype do not express any MITFs. The synthesis of heparin is abnormal in the skin mast cells of mi/mi mice. Because N-deacetylase/N-sulfotransferase 2 (NDST-2) is essential for the synthesis of heparin, the amount of NDST-2 messenger RNA (mRNA) was compared among cultured mast cells (CMCs) of +/+,mi/mi, and tg/tg genotypes. The NDST-2 mRNA was detected by in situ hybridization in the skin mast cells of +/+ andtg/tg mice, but not in the skin mast cells ofmi/mi mice. The amount of NDST-2 mRNA decreased significantly in CMCs derived from mi/mi mice when compared to the values of +/+ and tg/tg mice, suggesting that the defective form of MITF inhibited the expression of the NDST-2 transcript. The expression of NDST-2 transcript was mediated by the GGAA motif located in the 5′-untranslated region. GA binding protein (GABP) bound the GGAA motif and increased the amount of NDST-2 transcript. The mi-MITF appeared to inhibit the ability of GABP to express NDST-2 transcript by disturbing its nuclear localization. This is the first study to show that expression of an abnormal form of a bHLH-Zip transcription factor can dramatically alter the intracellular location of another DNA/RNA binding factor, which in turn brings about profound and unexpected consequences on transcript expression.
Effect of the PlA2 alloantigen on the function of β3-integrins in platelets
Authors: Bennett Joel S. , Catella-Lawson Francesca , Rut Andrew R. , Vilaire Gaston , Qi Weiwei , Kapoor Shiv C. , Murphy Scott , FitzGerald Garret A. 
Published: July 2002

AbstractThe polymorphism responsible for the PlA2 alloantigen on the β3-component of β3-containing integrins is reported to be a risk factor for coronary thrombosis. This study examined the effect of PlA2 on the function of β3-integrins using platelets from subjects homozygous and heterozygous for PlA1 and PlA2. There was overlap in the distribution of the dissociation constant (Kd) and maximum fibrinogen binding (Bmax) values for fibrinogen binding to αIIbβ3 on platelets from PlA1 and PlA2 homozygotes and PlA1/PlA2 heterozygotes. However, whereas there was no statistical difference in these values for the PlA1homozygotes and PlA2 heterozygotes, the Kd for the PlA2 homozygotes was significantly lower than that for the PlA1/PlA2 heterozygotes, but was not statistically different from that for the PlA1 homozygotes. No differences were detected in ADP sensitivity between platelets from PlA1 homozygotes and PlA1/PlA2heterozygotes, in the IC50 for RGDS inhibition of fibrinogen binding to αIIbβ3, in the αvβ3-mediated adhesion of platelets to osteopontin and vitronectin, and in the phorbol ester-stimulated adhesion to fibrinogen of B lymphocytes expressing αIIbβ3 containing either the PlA1 or the PlA2 polymorphism. Finally, no differential effects of PlA2 on turbidometric platelet aggregation, platelet secretion, or platelet thrombus formation were found as measured in the PFA-100. Because no differences were detected in the ability of β3-integrins to interact with ligands based on the presence or absence of the PlA2 polymorphism, the results suggest that factors unrelated to β3-integrin function may account for the reported association of the PlA2 allele with coronary thrombosis.
Preconditioning with fetal cord blood facilitates engraftment of primary childhood T-cell acute lymphoblastic leukemia in immunodeficient mice
Authors: Dialynas Deno P. , Lee Mi-Jeong , Gold Daniel P. , Shao Li-en , Yu Alice L. , Borowitz Michael J. , Yu John 
Published: July 2002

AbstractChildhood T-cell acute lymphoblastic leukemia (T-ALL) is one of the most common childhood cancers. It is reported that preconditioning sublethally irradiated immunodeficient NOD/SCID (nonobese diabetic/X-linked severe combined immunodeficient) mice with human cord blood mononuclear cells facilitates the engraftment, expansion, and dissemination in these mice of primary T-ALL cells obtained from patients at the time of diagnosis. Cells recovered from mouse bone marrow or spleen resembled the original leukemia cells from patients with respect to surface lineage markers and T-cell receptor Vβ gene rearrangements. Moreover, the pattern of leukemia dissemination in mouse tissues, resulting in universally fatal leukemia, is reminiscent of the human clinical disease. In addition, the fidelity of the model to the human disease is documented with regard to the presence of morphologically identifiable human leukemia cells in mouse bone marrow and blood and the maintenance of leukemia-initiating capacity within the leukemia-engrafted mouse. Therefore, several lines of independent approaches are used to suggest that the engrafted cells are of human leukemia origin and are not derived from cord blood. The in vivo model described here should enable the study of the growth properties of primary T-ALL cells obtained from patients and should prove useful in evaluating the potential efficacy of therapeutic strategies directed toward T-ALL.
Breakage and fusion of the TEL (ETV6) gene in immature B lymphocytes induced by apoptogenic signals
Authors: Eguchi-Ishimae Minenori , Eguchi Mariko , Ishii Eiichi , Miyazaki Sumio , Ueda Kazuhiro , Kamada Nanao , Mizutani Shuki 
Published: July 2002

Abstract
TEL-AML1 fusion resulting from the t(12;21)(p13;q22) is one of the most common genetic abnormalities in childhood acute lymphoblastic leukemia. Recent findings that site-specific cleavage of the MLL gene can be induced by chemotherapeutic agents such as topoisomerase-II inhibitors suggest that apoptogenic agents can cause chromosomal translocations in hematopoietic cells. This study demonstrates a possible relationship between exposure to apoptogenic stimuli, TEL breaks, and the formation ofTEL-AML1 fusion in immature B lymphocytes. Short-term culture of immature B cell lines in the presence of apoptogenic stimuli such as serum starvation, etoposide, or salicylic acid induced double-strand breaks (DSBs) in intron 5 of the TEL gene and intron 1 of the AML1 gene. TEL-AML1fusion transcripts were also identified by reverse transcriptase–polymerase chain reaction (RT-PCR) analysis in cell lines treated by serum starvation or aminophylline. DSBs within theTEL gene were also associated with fusion to other unknown genes, presumably as a result of chromosomal translocation. We also examined 67 cord blood and 147 normal peripheral blood samples for the existence of in-frame TEL-AML1 fusion transcripts. One cord blood sample (1.5%) and 13 normal peripheral blood samples (8.8%) were positive as detected by nested RT-PCR. These data suggest that breakage and fusion of TEL andAML1 may be relatively common events and that sublethal apoptotic signals could play a role in initiating leukemogenesis via the promotion of DNA damage.
Stroke in hemoglobin (SD) sickle cell disease with moyamoya: successful hydroxyurea treatment after cerebrovascular bypass surgery
Authors: Schmugge Markus , Frischknecht Hannes , Yonekawa Yasuhiro , Baumgartner Ralf W. , Boltshauser Eugen , Humbert James 
Published: July 2002

Abstract
An 11-year-old boy with hemoglobin sickle disease (HbSD), bilateral stenosis of the intracranial carotid arteries, and moyamoya syndrome had recurrent ischemic strokes with aphasia and right hemiparesis. His parents (Jehovah's Witnesses) refused blood transfusions. After bilateral extracranial–intracranial (EC-IC) bypass surgery, hydroxyurea treatment increased hemoglobin F (HbF) levels to more than 30%. During a follow-up of 28 months, flow velocities in the basal cerebral arteries remained stable, neurologic sequelae regressed, and ischemic events did not recur. This is the first report of successful hydroxyurea treatment after bypass surgery for intracranial cerebral artery obstruction with moyamoya syndrome in sickle cell disease. The patient's religious background contributed to an ethically challenging therapeutic task.
Structure of a factor VIII C2 domain–immunoglobulin G4κ Fab complex: identification of an inhibitory antibody epitope on the surface of factor VIII
Authors: Spiegel Paul Clint , Jacquemin Marc , Saint-Remy Jean-Marie R. , Stoddard Barry L. , Pratt Kathleen P. 
Published: July 2002

Abstract
The development of an immune response to infused factor VIII is a complication affecting many patients with hemophilia A. Inhibitor antibodies bind to antigenic determinants on the factor VIII molecule and block its procoagulant activity. A patient-derived inhibitory immunoglobulin G4κ antibody (BO2C11) produced by an immortalized memory B-lymphocyte cell line interferes with the binding of factor VIII to phospholipid surfaces and to von Willebrand factor. The structure of a Fab fragment derived from this antibody complexed with the factor VIII C2 domain was determined at 2.0 Å resolution. The Fab interacts with solvent-exposed basic and hydrophobic side chains that form a membrane-association surface of factor VIII. This atomic resolution structure suggests a variety of amino acid substitutions in the C2 domain of factor VIII that might prevent the binding of anti-C2 inhibitor antibodies without significantly compromising the procoagulant functions of factor VIII.
Accelerated autoantibody clearance by intravenous immunoglobulin therapy: studies in experimental models to determine the magnitude and time course of the effect
Authors: Bleeker Wim K. , Teeling Jessica L. , Hack C. Erik 
Published: July 2002

AbstractRecently, it has been postulated that the beneficial effect of intravenous immunoglobulins (IVIGs) in antibody-mediated autoimmune disorders is based on accelerated catabolism of autoantibodies. In the current study, in vivo experiments were performed with mice in which autoantibody production was mimicked by continuous infusion of monoclonal antibodies. In this model, a single dose of IVIG reduced the plasma concentrations of the infused immunoglobulin (Ig)G1 monoclonal antibody (mAb) by approximately 40% after 3 days, whereas the concentration of an IgA mAb was not affected. To extrapolate these findings to humans, a computational model for IgG clearance was established that accurately predicted the time course and magnitude of the decrease in IgG plasma levels observed in mice. Adapted for humans, this model predicted a gradually occurring decrease in autoantibody levels after IVIG administration (2 g/kg), with a maximum reduction of approximately 25% after 3 to 4 weeks and a continued decrease of several months. In conclusion, a single high dose of IVIG induces a relatively small but long-lasting reduction of autoantibody levels by accelerated IgG clearance. This mechanism has clinical relevance in the sense that it can fully explain, as the sole mechanism, the gradual decrease in autoantibody levels observed in several patient studies. However, in some clinical studies, larger or more rapid effects have been observed that cannot be explained by accelerated clearance. Hence, IVIG can also reduce autoantibody levels through mechanisms such as down-regulation of antibody production or neutralization by anti-idiotypic antibodies.
CD20 levels determine the in vitro susceptibility to rituximab and complement of B-cell chronic lymphocytic leukemia: further regulation by CD55 and CD59
Authors: Golay Josée , Lazzari Manuela , Facchinetti Valeria , Bernasconi Sergio , Borleri Gianmaria , Barbui Tiziano , Rambaldi Alessandro , Introna Martino 
Published: July 2002

Abstract
Complement-dependent cytotoxicity is thought to be an important mechanism of action of the anti-CD20 monoclonal antibody rituximab. This study investigates the sensitivity of freshly isolated cells obtained from 33 patients with B-cell chronic lymphocytic leukemia (B-CLL), 5 patients with prolymphocytic leukemia (PLL), and 6 patients with mantle cell lymphoma (MCL) to be lysed by rituximab and complement in vitro. The results showed that in B-CLL and PLL, the levels of CD20, measured by standard immunofluorescence or using calibrated beads, correlated linearly with the lytic response (coefficient greater than or equal to 0.9;P &lt; .0001). Furthermore, the correlation remained highly significant when the 6 patients with MCL were included in the analysis (coefficient 0.91; P &lt; .0001), which suggests that CD20 levels primarily determine lysis regardless of diagnostic group. The role of the complement inhibitors CD46, CD55, and CD59 was also investigated. All B-CLL and PLL cells expressed these molecules, but at different levels. CD46 was relatively weak on all samples (mean fluorescence intensity less than 100), whereas CD55 and CD59 showed variability of expression (mean fluorescence intensity 20-1200 and 20-250, respectively). Although CD55 and CD59 levels did not permit prediction of complement susceptibility, the functional block of these inhibitors demonstrated that they play an important role in regulating complement-dependent cytotoxicity. Thus, lysis of poorly responding B-CLL samples was increased 5- to 6-fold after blocking both CD55 and CD59, whereas that of high responders was essentially complete in the presence of a single blocking antibody. These data demonstrate that CD20, CD55, and CD59 are important factors determining the in vitro response to rituximab and complement and indicate potential strategies to improve the clinical response to this biologic therapy.
Rhenium 188–labeled anti-CD66 (a, b, c, e) monoclonal antibody to intensify the conditioning regimen prior to stem cell transplantation for patients with high-risk acute myeloid leukemia or myelodysplastic syndrome: results of a phase I-II study
Authors: Bunjes Donald , Buchmann Inga , Duncker Christian , Seitz Ulrike , Kotzerke Jörg , Wiesneth Markus , Dohr Dagmar , Stefanic Martin , Buck Andreas , Harsdorf Stefanie V. , Glatting Gerhard , Grimminger Wolfgang , Karakas Tunca , Munzert Gerd , Döhner Hartmut , Bergmann Lothar , Reske Sven N. 
Published: July 2002

Abstract
The conditioning regimen prior to stem cell transplantation in 36 patients with high-risk acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) was intensified by treating patients with a rhenium 188–labeled anti-CD66 monoclonal antibody. Dosimetry was performed prior to therapy, and a favorable dosimetry was observed in all cases. Radioimmunotherapy with the labeled antibody provided a mean of 15.3 Gy of additional radiation to the marrow; the kidney was the normal organ receiving the highest dose of supplemental radiation (mean 7.4 Gy). Radioimmunotherapy was followed by standard full-dose conditioning with total body irradiation (12 Gy) or busulfan and high-dose cyclophosphamide with or without thiotepa. Patients subsequently received a T-cell–depleted allogeneic graft from a HLA-identical family donor (n = 15) or an alternative donor (n = 17). In 4 patients without an allogeneic donor, an unmanipulated autologous graft was used. Infusion-related toxicity due to the labeled antibody was minimal, and no increase in treatment-related mortality due to the radioimmunoconjugate was observed. Day +30 and day +100 mortalities were 3% and 6%, respectively, and after a median follow-up of 18 months treatment-related mortality was 22%. Late renal toxicity was observed in 17% of patients. The relapse rate of 15 patients undergoing transplantation in first CR (complete remission) or second CR was 20%; 21 patients not in remission at the time of transplantation had a 30% relapse rate.
Chronic myelogenous leukemia blast cell proliferation is inhibited by peptides that disrupt Grb2-SoS complexes
Authors: Kardinal Christian , Konkol Birgit , Lin Hui , Eulitz Manfred , Schmidt Enrico K. , Estrov Zeev , Talpaz Moshe , Arlinghaus Ralph B. , Feller Stephan M. 
Published: July 2002

Abstract
Chronic myelogenous leukemia (CML) is commonly characterized by the presence of the p210Bcr-Abl oncoprotein. Many downstream effectors of Bcr-Abl have been described, including activation of the Grb2-SoS-Ras–MAP kinase (Erk) pathway. The precise contributions of these signal-transduction proteins in CML blast cells in human patients are not yet well defined. To gain further insight into the importance of Grb2 for CML, peptides that disrupt Grb2-SoS complexes were tested. These high-affinityGrb2-binding peptides (HAGBPs) can autonomously shuttle into cells and function by binding to the N-terminal SH3 domain of Grb2. The HAGBPs were analyzed for their effects on Bcr-Abl–expressing cell lines and freshly isolated CML blast cells from patients. They induced a dramatic decrease in the proliferation of CML cell lines. This was not observed with point-mutated control peptides with abolished Grb2SH3(N) binding. As expected, Grb2-SoS complexes were greatly diminished in the HAGBP-treated cells, and MAP kinase activity was significantly reduced as determined by an activation-specific phospho-MAPK antibody. Furthermore, cell fractions that are enriched for blast cells from CML patients with active disease were also incubated with the Grb2 blocker peptides. The HAGBPs led to a significant proliferation reduction of these cells in the majority of the isolates, but not in all patients' cells. These results show that, in addition to the direct targeting of Bcr-Abl, selective inhibition of Grb2 protein complexes may be a therapeutic option for a significant number of CML patients.
Peripheral blood dendritic cells in children with acute Plasmodium falciparum malaria
Authors: Urban Britta C. , Mwangi Tabitha , Ross Amanda , Kinyanjui Samson , Mosobo Moses , Kai Oscar , Lowe Brett , Marsh Kevin , Roberts David J. 
Published: July 2002

AbstractThe importance of dendritic cells (DCs) for the initiation and regulation of immune responses not only to foreign organisms but also to the self has raised considerable interest in the qualitative and quantitative analysis of these cells in various human diseases.Plasmodium falciparum malaria is characterized by the poor induction of long-lasting protective immune responses. This study, therefore, investigated the percentage of peripheral blood DCs as lineage marker–negative and HLA-DR+ or CD83+cells in healthy children and in children suffering from acute malaria in Kilifi, Kenya. Comparable percentages of CD83+ DCs were found in peripheral blood of healthy children and children with malaria. However, the percentage of HLA-DR+ peripheral blood DCs was significantly reduced in children with malaria. The results suggest that a proportion of peripheral blood DCs may be functionally impaired due to the low expression of HLA-DR on their surface.