bluuebunny/crossref_metadata_2025_split huggingface dataset:
The structure of hügelite, an arsenate of the phosphuranylite group, and its relationship to dumontite
Authors: Locock A. J. , Burns P. C. 
Published: January 2004

AbstractThe crystal structure of hügelite, Pb2[(UO2)3O2(AsO4)2](H2O)5, monoclinic, space group P21/m, a= 31.066(3)Å, b= 17.303(2)Å, c= 7.043(1)Å, β = 96.492(2)°, V= 3761.6(1)Å3, Z= 8, Dcalc = 5.74 g/cm3, was solved by direct methods using data from a crystal twinned by pseudo-merohedry, and was refined by full-matrix least-squares techniques on the basis of F2 to agreement indices R1 of 3.3% calculated for 5519 unique observed reflections (|Fo| 5 ≥ 4σF), and wR2 of 6.7% for all data. Intensity data were collected at room temperature using Mo-Kα radiation and a CCD-based area detector. Hügelite is a member of the phosphuranylite group and is the arsenate counterpart of dumontite. The sheets of uranyl pentagonal and hexagonal bipyramids and arsenate tetrahedra in hügelite are oriented parallel to (100), and the interlayer contains four symmetrically independent Pb atoms, each of which is coordinated by two oxygen atoms from uranyl ions, two oxygen atoms from arsenate tetrahedra, and three symmetrically distinct H2O groups. The unit-cell volume is four times larger than that previously reported for hügelite, or expected by comparison to dumontite, Pb2[(UO2)3O2(PO4)2](H2O)5; the larger cell probably results from the accommodation of the larger As atoms (relative to P) in the structure, and consequent subtle variations in the coordination geometries of the U and Pb positions.
A geochemical and Sr-Nd-O isotopic study of the Proterozoic Eriksfjord Basalts, Gardar Province, South Greenland: Reconstruction of an OIB signature in crustally contaminated rift-related basalts
Authors: R. Halama  , Wenzel T. , Upton B. G. J. , Siebel W. , Markl G. 
Published: January 2004

AbstractBasalts from the volcano-sedimentary Eriksfjord Formation (Gardar Province, South Greenland) were erupted at around 1.2 Ga into rift-related graben structures. The basalts have compositions transitional between tholeiite and alkaline basalt with MgO contents <7 wt.% and they displayLREE-enrichment relative to a chondritic source. Most of the trace element andREEcharacteristics are similar to those of basalts derived from OIB-like mantle sources. Initial87Sr/86Sr ratios of clinopyroxene separates range from 0.70278 to 0.70383 and initial ϵNdvalues vary from –3.2 to +2.1. The most unradiogenic samples overlap with the field defined by carbonatites of similar age and can be explained by mixing of isotopically depleted and enriched mantle components. Using AFC modelling equations, the Sr-Nd isotope data of the more radiogenic basalts can successfully be modelled by addition of <5% lower crustal granulite-facies gneisses as contaminants. δ18Ov-smowvalues of separated clinopyroxene range from +5.2 to +6.0% and fall within the range of typical mantle-derived rocks. However, up to 10% mixing with an average lower crustal component are permitted by the data.
Evolution of the North Qôroq centre nepheline syenites, South Greenland: alkali-mafic silicates and the role of metasomatism
Authors: Coulson I. M. 
Published: January 2004

AbstractThe North Qôroq centre comprises a series of concentric nepheline syenite intrusions and forms part of the Igaliko Nepheline Syenite Complex, in the rift-related Gardar Province of South Greenland. The North Qôroq syenites range from mildly undersaturated augite syenite to strongly peralkaline agpaitic nepheline syenite. Extensivein situfractional crystallization has been postulated for the chemical variation both within units and throughout the centre. Many of the rocks have been affected by metasomatic fluids associated with the emplacement of younger syenite units, and this complicates their interpretation. In this study, the trends and compositions exhibited by pyroxene and amphibole from North Qôroq are examined and related to either primary crystallization or metasomatic activity (e.g. controls offO2, peralkalinity). Implications thus drawn are used to interpret the chemical processes inherent in the chemical and fluid evolution of alkaline magmas, and, in particular, the transition from miaskitic to agpaitic magmatism. In general, the major phases of the North Qôroq syenites records the increasing evolution of the units by crystal fractionation, towards peralkaline compositions. The composition of olivine, in the least evolved syenites, also points to a relatively high state of fractionation of the parent magma, whilst pyroxene and amphibole record an overall decrease in Mg/Mg+Fe), and a general increase in Fe3+and alkali content, with increased fractionation. The increasing peralkalinity of the magma also governs the evolution of pyroxene and, to a lesser degree, amphibole towards higher Zr and Ti contents in the more Na-rich compositions. The trends for pyroxene from metasomatized syenite show similar patterns, but lower Fe2+enrichment, suggesting the source of the metasomatic fluids is similar to the evolving syenites. The presence of amphiboles in metasomatic rocks, and high F contents attest to the F-rich nature of the metasomatic fluids, which is in agreement with results previously reported for metasomatic fluorapatite.
Dysregulated NK receptor expression in patients with lymphoproliferative disease of granular lymphocytes
Authors: Epling-Burnette Pearlie Kay , Painter Jeffrey S. , Chaurasia Pratima , Bai Fanqi , Wei Sheng , Djeu Julie Y. , Loughran Thomas P. 
Published: January 2004

AbstractThe natural killer (NK) type of lymphoproliferative disease of granular lymphocytes (LDGL) is associated with the expansion of CD3-, CD16+, and/or CD56+ lymphocytes. We have examined the repertoire of NK receptors expressed on these cells and delineated the functional activity. We found skewed NK receptor expression on patient NK cells. Reactivity to a single anti-killer cell immunoglobulin-like receptor (anti-KIR) antibody was noted in 7 of 13 patients. LDGL patients variably expressed NKp30, NKp44, and NKp46 RNA. In contrast, CD94 and its inhibitory heterodimerization partner NKG2A were homogenously expressed at high levels on these NK cells. Interestingly, these patients expressed a large number of activating KIR receptors by genotype analysis. Semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) demonstrated that lower than normal levels of RNA of the inhibitory KIR was present in some patients in contrast to normal NK cells. Consistent with a high level of activating receptors, we found the NK-LDGL cells have potent cytolytic function in both direct and redirected cytotoxicity assays. These results demonstrate that patients with NK-LDGL have an increased activating-to-inhibitory KIR ratio. This altered ratio might induce inappropriate lysis or cytokine production and impact the disease pathogenesis. (Blood. 2004;103:3431-3439)
Internal and external autocrine VEGF/KDR loops regulate survival of subsets of acute leukemia through distinct signaling pathways
Authors: Santos Susana Constantino Rosa , Dias Sérgio 
Published: January 2004

Abstract
Besides being expressed on endothelial cells, vascular endothelial growth factor receptors (VEGFRs) are also functional on subsets of leukemias, resulting in autocrine loops that sustain leukemia migration and proliferation. While recent evidence suggests that VEGF supports hematopoietic stem cell survival via an internal loop, the molecular mechanisms whereby autocrine stimulation of VEGFR-2 (KDR) promotes leukemia growth are not well understood. Here we show on acute myeloid primary leukemias and cell lines that VEGF/KDR autocrine loops operate both internally and externally. First, we demonstrate that KDR is constitutively phosphorylated and located at the nucleus of VEGF-producing leukemias. Treatment with anti-VEGF antibody, which acts externally, blocked KDR nuclear translocation and inhibited nuclear factor κ B (NF-κB; p65 and c-rel) activation. In contrast, a KDR-specific intracellular inhibitor failed to block KDR nuclear translocation, but inhibited the constitutive activation of mitogen activated protein kinase (MAPK)/Erk and the phosphatidylinositol 3-kinase/AKT pathways. Notably, treatment with the anti-VEGF antibody alone had little effect on cell survival, while the internal inhibitor induced leukemia apoptosis, and the 2 drugs produced synergistic effects, together and with chemotherapy, reducing cell survival to a larger extent than either agent alone. Our results demonstrate that internal and external VEGF/KDR autocrine loops regulate leukemia survival via different mechanisms, and suggest that blocking both may have therapeutic potential.
Efficacy and safety of imatinib in adult patients with c-kit–positive acute myeloid leukemia
Authors: Kindler Thomas , Breitenbuecher Frank , Marx Andreas , Beck Joachim , Hess Georg , Weinkauf Birgit , Duyster Justus , Peschel Christian , Kirkpatrick Charles J. , Theobald Matthias , Gschaidmeier Harald , Huber Christoph , Fischer Thomas 
Published: January 2004

Abstract
This phase 2 pilot study was conducted to determine the efficacy and safety of imatinib mesylate in patients with c-kit–positive acute myeloid leukemia (AML) refractory to or not eligible for chemotherapy. Twenty-one patients were enrolled and received imatinib 600 mg orally once daily. Five responses were seen primarily in patients, starting with relatively low blast counts in bone marrow (BM) and peripheral blood (PB): 2 patients who were considered refractory on chemotherapy on the basis of persistence of blasts in PB and BM met the criteria for complete hematologic remission, 1 patient had no evidence of leukemia, and 2 patients achieved a minor response. Treatment with imatinib demonstrated a good safety profile and was well tolerated. Western blot analysis and immunohistochemistry demonstrated c-Kit activation in primary AML cells. Further, imatinib treatment of primary AML cells inhibited c-Kit tyrosine-phosphorylation. Genomic DNA-sequencing of c-KIT showed no mutations in exons 2, 8, 10, 11, 12, and 17. Although some of the responses derived from relatively small reductions in leukemic blasts and may be attributable, in part, to prior chemotherapy, these cases suggest that imatinib has interesting clinical activity in a subset of patients with c-kit–positive AML. Further clinical trials are warranted to explore the clinical potential of imatinib in AML and to identify the underlying molecular mechanism.
Use of recombinant human growth hormone (rhGH) plus recombinant human granulocyte colony-stimulating factor (rhG-CSF) for the mobilization and collection of CD34+ cells in poor mobilizers
Authors: Carlo-Stella Carmelo , Di Nicola Massimo , Milani Raffaella , Guidetti Anna , Magni Michele , Milanesi Marco , Longoni Paolo , Matteucci Paola , Formelli Franca , Ravagnani Fernando , Corradini Paolo , Gianni Alessandro M. 
Published: January 2004

AbstractThe activity of recombinant human growth hormone (rhGH) in enhancing CD34+ cell mobilization elicited by chemotherapy plus recombinant human granulocyte colony-stimulating factor (rhG-CSF) was evaluated in 16 hard-to-mobilize patients, that is, those achieving a peak of circulating CD34+ cells 10/μL or less, or a collection of CD34+ cells equal to or less than 2 × 106/kg. Patients who had failed a first mobilization attempt with chemotherapy plus rhG-CSF (5 μg/kg/d) were remobilized with chemotherapy plus rhG-CSF and rhGH (100 μg/kg/d). As compared with rhG-CSF, the combined rhGH/rhG-CSF treatment induced significantly higher (P ≤ .05) median peak values for CD34+ cells/μL (7 versus 29), colony-forming cells (CFCs)/mL (2154 versus 28 510), and long-term culture-initiating cells (LTC-ICs)/mL (25 versus 511). Following rhG-CSF and rhGH/rhG-CSF, the median yields of CD34+ cells per leukapheresis were 1.1 × 106/kg and 2.3 × 106/kg (P ≤ .008), respectively; the median total collections of CD34+ cells were 1.1 × 106/kg and 6 × 106/kg (P ≤ .008), respectively. No specific side effect could be ascribed to rhGH, except a transient hyperglycemia occurring in 2 patients. Reinfusion of rhGH/rhG-CSF-mobilized cells following myeloablative therapy resulted in prompt hematopoietic recovery. In conclusion, our data demonstrate that in poor mobilizers addition of rhGH to rhG-CSF allows the patients to efficiently mobilize and collect CD34+ cells with maintained functional properties. (Blood. 2004;103: 3287-3295)
Congenital disorder of oxygen sensing: association of the homozygous Chuvash polycythemia VHL mutation with thrombosis and vascular abnormalities but not tumors
Authors: Gordeuk Victor R. , Sergueeva Adelina I. , Miasnikova Galina Y. , Okhotin Daniel , Voloshin Yaroslav , Choyke Peter L. , Butman John A. , Jedlickova Katerina , Prchal Josef T. , Polyakova Lydia A. 
Published: January 2004

AbstractAdaptation to hypoxia is critical for survival and regulates multiple processes, including erythropoiesis and vasculogenesis. Chuvash polycythemia is a hypoxia-sensing disorder characterized by homozygous mutation (598C&gt;T) of von Hippel-Lindau gene (VHL), a negative regulator of hypoxia sensing. Although endemic to the Chuvash population of Russia, this mutation occurs worldwide and originates from a single ancient event. That VHL 598C&gt;T homozygosity causes elevated normoxic levels of the transcription factor hypoxia inducible factor-1α (HIF-1α), serum erythropoietin and hemoglobin is known, but the disease phenotype has not been documented in a controlled manner. In this matched cohort study, VHL 598C&gt;T homozygosity was associated with vertebral hemangiomas, varicose veins, lower blood pressures, and elevated serum vascular endothelial growth factor (VEGF) concentrations (P &lt; .0005), as well as premature mortality related to cerebral vascular events and peripheral thrombosis. Spinocerebellar hemangioblastomas, renal carcinomas, and pheochromocytomas typical of classical VHL syndrome were not found, suggesting that overexpression of HIF-1α and VEGF is not sufficient for tumorigenesis. Although hemoglobin-adjusted serum erythropoietin concentrations were approximately 10-fold higher in VHL 598C&gt;T homozygotes than in controls, erythropoietin response to hypoxia was identical. Thus, Chuvash polycythemia is a distinct VHL syndrome manifested by thrombosis, vascular abnormalities, and intact hypoxic regulation despite increased basal expression of hypoxia-regulated genes.
Reversal of bone marrow angiogenesis in chronic myeloid leukemia following imatinib mesylate (STI571) therapy
Authors: Kvasnicka Hans Michael , Thiele Juergen , Staib Peter , Schmitt-Graeff Annette , Griesshammer Martin , Klose Jens , Engels Knut , Kriener Susanne 
Published: January 2004

Abstract
The effect of imatinib mesylate (imatinib) therapy on angiogenesis and myelofibrosis was investigated and compared with interferon (IFN) and hydroxyurea (HU) in 98 patients with newly diagnosed Philadelphia chromosome-positive/BCR-ABL+ (Ph+/BCR-ABL+) chronic myeloid leukemia in first chronic phase and no other pretreatment. By means of immunostaining (CD34) and morphometry, a relationship between microvessel frequency and fiber density was detectable in initial bone marrow (BM) biopsies and sequential examinations after at least 8 months of therapy. First-line monotherapy with imatinib induced a significant reduction (normalization in comparison with controls) of microvessels and reticulin fibers. In most patients, decrease in BM vascularity was associated with a complete cytogenetic response. A significant anti-angiogenic effect was also observed after HU treatment, contrasting with IFN administration or combination regimens (IFN plus HU). In conclusion, our data support the anti-angiogenic capacity of imatinib by normalization of vascularity. In contrast, hematologic response following IFN treatment is independent from BM angiogenesis. (Blood. 2004;103:3549-3551)
IFNα-stimulated neutrophils and monocytes release a soluble form of TNF-related apoptosis-inducing ligand (TRAIL/Apo-2 ligand) displaying apoptotic activity on leukemic cells
Authors: Tecchio Cristina , Huber Veronica , Scapini Patrizia , Calzetti Federica , Margotto Daniela , Todeschini Giuseppe , Pilla Lorenzo , Martinelli Giovanni , Pizzolo Giovanni , Rivoltini Licia , Cassatella Marco A. 
Published: January 2004

AbstractTumor necrosis factor (TNF)–related apoptosis-inducing ligand (TRAIL) is a member of the TNF superfamily exerting cytotoxic activities toward tumor cells. Herein, we demonstrate that therapeutic concentrations of interferon α (IFNα) stimulate the expression of high levels of TRAIL mRNA and the release of elevated amounts of a soluble bioactive form of TRAIL (sTRAIL) in both human neutrophils and monocytes. Supernatants harvested from IFNα-treated neutrophils/monocytes elicited, on TRAIL-sensitive leukemic cell lines, proapoptotic activities that were significantly reduced by either a combination of TRAIL-R1/Fc and TRAIL-R2/Fc chimeras or neutralizing anti-TRAIL, anti–TRAIL-R1, and anti–TRAIL-R2 antibodies, suggesting that they were mediated by released sTRAIL acting on both TRAIL receptors. Since diseases such as chronic myeloid leukemia (CML) and melanoma are effectively treated with IFNα,we also demonstrate that CML neutrophils and peripheral blood mononuclear cells (PBMCs) cultured with IFNα at therapeutic concentrations retain the capacity of releasing sTRAIL, suggesting that CML leukocytes, in vivo, might represent an important source of sTRAIL. In this regard, we show that sTRAIL serum levels as well as leukocyte-associated TRAIL significantly increase in melanoma patients following IFNα administration. Collectively, these findings indicate that sTRAIL released by IFNα-activated neutrophils and monocytes contributes not only to the immunoregulatory actions but also to the therapeutic activities of IFNα.
Hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation: donor type matters
Authors: El-Zimaity Maha , Saliba Rima , Chan Kawah , Shahjahan Munir , Carrasco Antonio , Khorshid Ola , Caldera Humberto , Couriel Daniel , Giralt Sergio , Khouri Issa , Ippoliti Cindy , Champlin Richard , de Lima Marcos 
Published: January 2004

AbstractHemorrhagic cystitis (HC) remains a common complication of allogeneic blood and marrow transplantation. Previous analyses of risk factors for this complication were performed in heterogenous populations, with dissimilar diagnosis and conditioning regimens. We postulated that HC is more prevalent in matched unrelated donor (MUD) and unrelated cord blood (UCB) transplantations than in matched related donor (MRD) transplantations. We performed a retrospective study on 105 acute lymphocytic leukemia patients treated with 12 Gy total body irradiation-based regimens and allogeneic transplants (MUD, n = 38; UCB, n = 15; mismatched related, n = 20; MRD, n = 32). HC occurred in 16% of patients receiving MRD transplants, 30% of recipients of mismatched related, and 40% of MUD or UCB transplants (hazard ratio 2.9, 95% CI 1.0-7.9 for the comparison of MRD versus MUD). The excessive rate of HC among MUD and UCB patients became evident after the first 30 days after transplantation. Recipients younger than 26 years had a significantly higher incidence of HC (HR 2.5, 95% CI 1.1-5.8). This donor type and age effect was independent of platelet engraftment, development of graft-versus-host disease (GVHD), source of stem cells, use of anti-thymocyte globulin (ATG) or cyclophosphamide in the regimen, steroid use, or stem cell source. We concluded that HC is more prevalent in MUD and UCB transplantations. (Blood. 2004;103:4674-4680)
Adult bone marrow-derived stem cells use R-cadherin to target sites of neovascularization in the developing retina
Authors: Dorrell Michael I. , Otani Atsushi , Aguilar Edith , Moreno Stacey K. , Friedlander Martin 
Published: January 2004

AbstractAdult bone marrow contains a population of hematopoietic stem cells (HSCs) that can give rise to cells capable of targeting sites of neovascularization in the peripheral or retinal vasculature. However, relatively little is known about the mechanism of targeting of these cells to sites of neovascularization. We have analyzed subpopulations of HSCs for the expression of a variety of cell surface adhesion molecules and found that R-cadherin, a calcium-dependent cell-cell adhesion molecule important for normal retinal endothelial cell guidance, was preferentially expressed by functionally targeting HSCs. Preincubation of HSCs with function-blocking anti-R-cadherin antibodies or novel R-cadherin-specific peptide antagonists effectively prevented targeting of bone marrow-derived cells to the developing retinal vasculature in vivo. Whereas control-injected HSCs targeted to all 3 normal developing retinal vascular layers, blocking R-cadherin-mediated adhesion resulted in mistargeting of the HSCs to the normally avascular outer retina. Our results suggest that vascular targeting of bone marrow-derived HSCs is dependent on mechanisms similar to those used by endogenous retinal vascular endothelial cells. Thus, R-cadherin antagonists may be useful in the treatment of neovascular diseases in which circulating HSCs contribute to abnormal angiogenesis. (Blood. 2004;103:3420-3427)
Signaling through GP Ib-IX-V activates αIIbβ3 independently of other receptors
Authors: Kasirer-Friede Ana , Cozzi Maria Rita , Mazzucato Mario , De Marco Luigi , Ruggeri Zaverio M. , Shattil Sanford J. 
Published: January 2004

AbstractPlatelet adhesion to von Willebrand factor (VWF) activates αIIbβ3, a prerequisite for thrombus formation. However, it is unclear whether the primary VWF receptor, glycoprotein (GP) Ib-IX-V, mediates αIIbβ3 activation directly or through other signaling proteins physically associated with it (eg, FcR γ-chain), possibly with the contribution of other agonist receptors and of VWF signaling through αIIbβ3. To resolve this question, human and GP Ibα transgenic mouse platelets were plated on dimeric VWF A1 domain (dA1VWF), which engages only GP Ib-IX-V, in the presence of inhibitors of other agonist receptors. Platelet adhesion to dA1VWF induced Src kinase-dependent tyrosine phosphorylation of the FcR γ-chain and the adapter molecule, ADAP, and triggered intracellular Ca2+ oscillations and αIIbβ3 activation. Inhibition of Ca2+ oscillations with BAPTA-AM prevented αIIbβ3 activation but not tyrosine phosphorylation. Pharmacologic inhibition of protein kinase C (PKC) or phosphatidylinositol 3-kinase (PI 3-kinase) prevented αIIbβ3 activation but not Ca2+ oscillations. Inhibition of Src with 2 distinct compounds blocked all responses downstream of GP Ib-IX-V under static or flow conditions. However, dA1VWF-induced responses were reduced only slightly in GP Ibα transgenic platelets lacking FcR γ-chain. These data establish that GP Ib-IX-V itself can signal to activate αIIbβ3, through sequential actions of Src kinases, Ca2+ oscillations, and PI 3-kinase/PKC. (Blood. 2004;103:3403-3411)