bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regulation of leukemic cell adhesion, proliferation, and survival by β-catenin
Authors: Chung Eun Joo , Hwang Sang-Gu , Nguyen PhuongMai , Lee Sunmin , Kim Jung-Sik , Kim Jin Woo , Henkart Pierre A. , Bottaro Donald P. , Soon Lilian , Bonvini Paolo , Lee Su-Jae , Karp Judith E. , Oh Ho Jung , Rubin Jeffrey S. , Trepel Jane B. 
Published: October 2002

Abstract
In epithelial cells β-catenin plays a critical role as a component of the cell-cell adhesion apparatus and as a coactivator of the TCF/LEF (T-cell transcription factor/lymphoid enhancer binding factor) family of transcription factors. Deregulation of β-catenin has been implicated in the malignant transformation of cells of epithelial origin. However, a function for β-catenin in hematologic malignancies has not been reported. β-Catenin is not detectable in normal peripheral blood T cells but is expressed in T–acute lymphoblastic leukemia cells and other tumor lines of hematopoietic origin and in primary lymphoid and myeloid leukemia cells. β-Catenin function was examined in Jurkat T–acute lymphoblastic leukemia cells. Overexpression of dominant-negative β-catenin or dominant-negative TCF reduced β-catenin nuclear signaling and inhibited Jurkat proliferation and clonogenicity. Similarly, these constructs inhibited proliferation of K562 and HUT-102 cells. Reduction of β-catenin expression with β-catenin antisense down-regulated adhesion of Jurkat cells in response to phytohemagglutinin. Incubation of Jurkat cells with anti-Fas induced caspase-dependent limited proteolysis of β-catenin N- and C-terminal regions and rapid redistribution of β-catenin to the detergent-insoluble cytoskeleton, concomitant with a marked decline in nuclear β-catenin signaling. Fas-mediated apoptosis was potentiated by inhibition of β-catenin nuclear signaling. The data suggest that β-catenin can play a significant role in promoting leukemic cell proliferation, adhesion, and survival.
Receptor tyrosine kinase, EphB4 (HTK), accelerates differentiation of select human hematopoietic cells
Authors: Wang Zhengyu , Miura Nobuyuki , Bonelli Andres , Mole Pamela , Carlesso Nadia , Olson Douglas P. , Scadden David T. 
Published: October 2002

AbstractEphB4 (HTK) and its ligand, ephrinB2, are critical for angiogenesis and result in fatal abnormalities of capillary formation in null mice. EphB4 was originally identified in human bone marrow CD34+cells by us and has since been reported to be expressed in erythroid progenitors, whereas the ligand ephrinB2 is expressed in bone marrow stromal cells. Reasoning that the developmental relationship between angiogenesis and hematopoiesis implies common regulatory molecules, we assessed whether EphB4 signaling influences the function and phenotype of primitive human hematopoietic cells. Ectopically expressed EphB4 in cell lines of restricted differentiation potential promoted megakaryocytic differentiation, but not granulocytic or monocytic differentiation. Primary cord blood CD34+ cells transduced with EphB4 resulted in the elevated expression of megakaryocytic and erythroid specific markers, consistent with EphB4 selectively enhancing some lineage-committed progenitors. In less mature cells, EphB4 depleted primitive cells, as measured by long-term culture-initiating cells or CD34+CD38− cell numbers, and increased progenitor cells of multiple cell types. Effects of ectopic EphB4 expression could be abrogated by either targeted mutations of select tyrosine residues or by the tyrosine kinase inhibitor, genistein. These data indicate that EphB4 accelerates the differentiation of primitive cells in a nonlineage-restricted manner but alters only select progenitor populations, influencing lineages linked by common ancestry with endothelial cells. EphB4 enforces preferential megakaryocytic and erythroid differentiation and may be a molecular bridge between angiogenesis and hematopoiesis.
Disrupted homeostasis of Langerhans cells and interdigitating dendritic cells in monkeys with AIDS
Authors: Zimmer Michael I. , Larregina Adriana T. , Castillo Cielo M. , Capuano Saverio , Falo Louis D. , Murphey-Corb Michael , Reinhart Todd A. , Barratt-Boyes Simon M. 
Published: October 2002

AbstractLangerhans cells (LCs) are immature dendritic cells (DCs) that capture antigen in peripheral tissues and migrate to draining lymph nodes, where they reside in the paracortex as interdigitating dendritic cells (IDCs). We studied the effects of simian immunodeficiency virus (SIV) on LCs and IDCs during different stages of infection in monkeys. LCs isolated from monkeys with acute SIV infection or acquired immunodeficiency syndrome (AIDS) underwent normal maturation in vitro, including a switch in chemokine receptor expression from CCR5 to CXCR4 and CCR7. LCs migrated normally from skin in response to contact sensitization in monkeys with acute SIV infection. In contrast, LC migration from skin was markedly impaired during AIDS, associated with a reduction in antigen-bearing DCs in draining lymph nodes. Lymph node IDCs were increased in proportion during acute SIV infection and had an activated phenotype, whereas during AIDS IDCs had significantly lower expression of CD40 and the activation marker CD83. IDCs from monkeys with AIDS were refractory to stimulation with CD40L, demonstrating a functional consequence of decreased CD40 expression. SIV-infected DCs were not identified in lymph nodes or skin of monkeys with AIDS, suggesting an indirect effect of infection on DC populations in vivo. These data indicate that DCs are mobilized to lymph nodes during acute SIV infection, but that during AIDS this process is suppressed, with LC migration and IDC activation being impaired. We conclude that disruption of DC homeostasis may play a role in immunopathology induced by human immunodeficiency virus and suggest that therapeutic strategies targeting DCs may have limited efficacy during AIDS.
Recurring chromosomal abnormalities in leukemia inPML-RARA transgenic mice parallel human acute promyelocytic leukemia
Authors: Le Beau Michelle M. , Bitts Sheila , Davis Elizabeth M. , Kogan Scott C. 
Published: October 2002

Abstract
Acute promyelocytic leukemia (APL) is characterized by the t(15;17)(q22;q11.2), which results in the PML-RARA fusion gene. In previous studies, we demonstrated that expression of a human PML-RARA complementary DNA in murine granulocyte precursor cells initiated the development of leukemia. However, leukemogenesis by PML-RARA required additional genetic alterations. To identify genetic changes that cooperate with PML-RARA in leukemogenesis, we performed spectral karyotyping analysis of myeloid leukemias from hMRP8-PML-RARA mice (11 cases) and from mice coexpressing PML-RARA and BCL2 (8 cases). Clonal abnormalities were detected in 18 of 19 cases (95%). Recurring numerical abnormalities identified in these murine leukemias included +15 (15 cases, 79%); loss of a sex chromosome (12 cases, 63%); +8 (10 cases, 53%); +10 (9 cases, 47%); +4, +7, or +14 (8 cases each, 42%); +16 (7 cases, 37%); and +6 (5 cases, 26%). In a series of 965 patients with APL, we identified secondary abnormalities in 368 (38%). The most common recurring abnormalities were +8 or partial trisomy of 8q (120 patients, 12.4%) and ider(17) t(15;17) (42 patients, 4.4%). The critical consequence of +8 in human leukemias appears to be the gain of 8q24, which is syntenic to mouse 15. Thus, our results suggest that PML-RARA–initiated murine leukemia is associated with a defined spectrum of genetic changes, and that these secondary mutations recapitulate, in part, the cytogenetic abnormalities found in human APL.
A novel mutation in the erythropoietin receptor gene is associated with familial erythrocytosis
Authors: Arcasoy Murat O. , Karayal Aysen F. , Segal Harvey M. , Sinning Joseph G. , Forget Bernard G. 
Published: October 2002

Abstract
Primary familial erythrocytosis (familial polycythemia) is a rare myeloproliferative disorder with an autosomal dominant mode of inheritance. We studied a new kindred with autosomal dominantly inherited familial erythrocytosis. The molecular basis for the observed phenotype of isolated erythrocytosis is heterozygosity for a novel nonsense mutation affecting codon 399 in exon 8 of the erythropoietin receptor (EPOR) gene, encoding an EpoR peptide that is truncated by 110 amino acids at its C-terminus. The newEPOR gene mutation 5881G&gt;T was found to segregate with isolated erythrocytosis in the affected family and this mutation represents the most extensive EpoR truncation reported to date, associated with familial erythrocytosis. Erythroid progenitors from an affected individual displayed Epo hypersensitivity in in vitro methylcellulose cultures, as indicated by more numerous erythroid burst-forming unit-derived colonies in low Epo concentrations compared to normal controls. Expression of mutant EpoR in interleukin 3–dependent hematopoietic cells was associated with Epo hyperresponsiveness compared to cells expressing wild-type EpoR.
Increased expression of the inflammatory chemokine CXC chemokine ligand 9/monokine induced by interferon-γ in lymphoid tissues of rhesus macaques during simian immunodeficiency virus infection and acquired immunodeficiency syndrome
Authors: Reinhart Todd A. , Fallert Beth A. , Pfeifer Melanie E. , Sanghavi Sonali , Capuano Saverio , Rajakumar Premeela , Murphey-Corb Michael , Day Richard , Fuller Craig L. , Schaefer Todd M 
Published: October 2002

AbstractChemokines are important mediators of cell trafficking during immune inductive and effector activities, and dysregulation of their expression might contribute to the pathogenesis of human immunodeficiency virus type 1 and the related simian immunodeficiency virus (SIV). To understand better the effects of SIV infection on lymphoid tissues in rhesus macaques, we examined chemokine messenger RNA (mRNA) expression patterns by using DNA filter array hybridization. Of the 34 chemokines examined, the interferon γ (IFN-γ)–inducible chemokine CXC chemokine ligand 9/monokine induced by interferon-γ (CXCL9/Mig) was one of the most highly up-regulated chemokines in rhesus macaque spleen tissue early after infection with pathogenic SIV. The relative levels of expression of CXCL9/Mig mRNA in spleen and lymph nodes were significantly increased after infection with SIV in both quantitative image capture and analysis and real-time reverse transcriptase–polymerase chain reaction assays. In addition, in situ hybridization for CXCL9/Mig mRNA revealed that the patterns of expression were altered after SIV infection. Associated with the increased expression of CXCL9/Mig were increased numbers of IFN-γ mRNA–positive cells in tissues and reduced percentages of CXC chemokine receptor (CXCR) 3+/CD3+ and CXCR3+/CD8+ lymphocytes in peripheral blood. We propose that SIV replication in vivo initiates IFN-γ–driven positive-feedback loops in lymphoid tissues that disrupt the trafficking of effector T lymphocytes and lead to chronic local inflammation, thereby contributing to immunopathogenesis.
High frequencies of Th1-type CD4+ T cells specific to HTLV-1 Env and Tax proteins in patients with HTLV-1–associated myelopathy/tropical spastic paraparesis
Authors: Goon Peter K. C. , Hanon Emmanuel , Igakura Tadahiko , Tanaka Yuetsu , Weber Jonathan N. , Taylor Graham P. , Bangham Charles R. M. 
Published: October 2002

AbstractCD4+ T cells are critical for inducing and maintaining efficient humoral and cellular immune responses to pathogens. The CD4+ T-cell response in human T-lymphotropic virus 1 (HTLV-1) infection has not been studied in detail. However, CD4+ T cells have been shown to predominate in early lesions in HTLV-1–associated myelopathy/tropical spastic paraparesis (HAM/TSP). We present direct estimates of HTLV-1 Env- and Tax-specific CD4+ T-cell frequencies in patients infected with HTLV-1. We first showed that there was a strong bias toward the Th1 phenotype in these HTLV-1–specific CD4+ T cells in patients with HAM/TSP. We then demonstrated significantly higher frequencies of HTLV-1–specific Th1-type CD4+ T cells in HAM/TSP patients than in asymptomatic HTLV-1 carriers. The majority of these HTLV-1–specific CD4+ T cells did not express HTLV-1 Tax and were therefore unlikely to be infected by HTLV-1. High frequencies of activated HTLV-1–specific CD4+ T cells of the Th1 phenotype might contribute to the initiation or pathogenesis of HAM/TSP and other HTLV-1–associated inflammatory diseases.
Activated Notch1 signaling promotes tumor cell proliferation and survival in Hodgkin and anaplastic large cell lymphoma
Authors: Jundt Franziska , Anagnostopoulos Ioannis , Förster Reinhold , Mathas Stephan , Stein Harald , Dörken Bernd 
Published: October 2002

AbstractNotch signaling controls cell fate decisions of hematopoietic progenitors by inhibiting certain steps of differentiation and inducing either self-renewal or differentiation toward lymphoid or myeloid lineages. In addition, truncated Notch1 alleles could be associated with 10% of all cases of human T lymphoblastic leukemia and, when introduced into mouse bone marrow stem cells, cause T-cell neoplasms. However, functional links between the abundant expression of intact Notch1 and oncogenesis are still lacking. Here we show that Notch1 is highly expressed in B- and T-cell–derived tumor cells of Hodgkin and anaplastic large cell lymphoma. We demonstrate a novel mechanism for the oncogenic capacity of Notch1 by showing that the interaction between intact Notch1 on tumor cells and its ligand Jagged1 dramatically induces proliferation and inhibition of apoptosis in vitro. We further provide evidence that in Hodgkin and anaplastic large cell lymphoma, Jagged1 is expressed in malignant and in bystander cells colocalizing with Notch1-positive tumor cells. Notch1 signaling may therefore be activated in tumor cells by Jagged1 through homotypic or heterotypic cell–cell interactions, and it seems likely that these interactions contribute to lymphomagenesis in vivo. Thus, our data suggest that activated Notch1 signaling plays an important role in the pathobiology of Hodgkin and anaplastic large cell lymphoma and that it might be a potential new target for treatment.
Interactions of GATA-2 with the promyelocytic leukemia zinc finger (PLZF) protein, its homologue FAZF, and the t(11;17)-generated PLZF–retinoic acid receptor alpha oncoprotein
Authors: Tsuzuki Shinobu , Enver Tariq 
Published: October 2002

AbstractTranscription factor GATA-2 is implicated in the survival and growth of multipotential progenitors. Here we report that the promyelocytic leukemia zinc finger (PLZF) protein can interact with GATA-2 and can modify its transactivation capacity. Fanconi anemia zinc finger (FAZF), a PLZF-homologous protein that has been variously described as ROG (repressor of GATA), and TZFP (testis zinc finger protein) also interact with GATA-2. The zinc finger region of GATA-2 is required for binding to PLZF and FAZF, but distinct interfaces on the PLZF and FAZF molecules mediate the interaction, suggesting that GATA-2 activity is controlled by these 2 homologous proteins through distinct mechanisms. GATA-2 can also physically associate with the PLZF-RARα fusion protein generated by the t(11;17) chromosomal translocation associated with acute promyelocytic leukemia (APL). Functional experiments showed that this interaction has the capacity to render GATA-dependent transcription responsive to treatment with a combination of all-trans retinoic acid and the histone deacetylase inhibitor trichostatin A (TSA). This combination of drugs has been shown to stimulate the terminal differentiation of leukemic t(11;17)-associated APL blasts, raising the possibility that GATA target genes may be involved in the molecular pathogenesis of APL.
HLA-haploidentical blood progenitor cell transplantation in osteopetrosis
Authors: Schulz Ansgar S. , Classen Carl Friedrich , Mihatsch Walther A. , Sigl-Kraetzig Michael , Wiesneth Markus , Debatin Klaus-Michael , Friedrich Wilhelm , Müller Susanna M. 
Published: October 2002

Abstract
Infantile osteopetrosis (OP) carries an extremely poor prognosis unless treated early by hematopoietic stem cell transplantation. We explored the use of purified blood progenitor cells from HLA-haploidentical parents in 7 patients lacking suitable matched donors. Blood progenitor cells were purified by positive selection and by additional T-cell depletion using rosette formation. For conditioning, patients received busulfan, thiotepa, and either cyclophosphamide (5 patients) or fludarabine (2 patients). Stable donor engraftment developed in 6 of 7 patients. Graft-versus-host disease was not observed. Three of the 7 patients had no major complications and 4 of 7 had both veno-occlusive disease and respiratory failure. Five of 7 patients survive with complete cure of OP at a median of 4 years. Patients with OP lacking HLA-matched donors can be successfully treated by transplantation of purified blood progenitor cells from HLA-haploidentical donors.
Comparison between permeability anisotropy and elasticity anisotropy of reservoir rocks
Authors: Rasolofosaon Patrick N. J. , Zinszner Bernard E. 
Published: October 2002

We developed new experimental and theoretical tools for the measurement and the characterization of arbitrary elasticity tensors and permeability tensors in rocks. They include an experimental technique for the 3‐D visualization of hydraulic invasion fronts in rock samples by monitoring the injection of salt solutions by X‐ray tomography, and a technique for inverting the complete set of the six coefficients of the permeability tensor from invasion front images. In addition, a technique for measuring the complete set of the 21 elastic coefficients, a technique allowing the identification and the orientation in the 3‐D space of the symmetry elements (planes, axes), and a technique for approximating the considered elastic tensor by a tensor of simpler symmetry with the quantification of the error induced by such an approximation have been developed. We apply these tools to various types of reservoir rocks and observed quite contrasted behaviors. In some rocks, the elastic anisotropy and the hydraulic anisotropy are closely correlated, for instance in terms of the symmetry directions. This is the case when elastic anisotropy and hydraulic anisotropy share the same cause (e.g., layering, fractures). In contrast, in some other rocks, hydraulic properties and elastic properties are clearly uncorrelated. These results highlight the challenge we have to face in order to estimate the rock permeability and to monitor the fluid flow from seismic measurements in the field.
The boundary element method for 3‐D dc resistivity modeling in layered earth
Authors: Ma Qinzhong 
Published: October 2002

The integral equation for dc resistivity modeling of 3‐D inhomogeneous bodies buried in a layered earth is derived by using Green's theorem. The main features of this method are (1) the layers above and below the 3‐D object can be included, (2) multiple subsurface inhomogeneous bodies can be embedded in the different layers, and (3) the boundary element method (BEM) is used to solve the integral equation using triangular surface elements. Linear variation of the electrical properties is assumed within each element. The potential on the ground surface is obtained by solving the linear equation system with Gaussian elimination. Model calculations demonstrate that the results obtained by this method compare well with the analytical solution of a sphere in a uniform half‐space and the asymptotic behavior for the solution of a buried body beneath a surficial layer as the layer resistivity approaches that of the half‐space. A comparison of responses over elongate 3‐D bodies with responses over 2‐D bodies of identical cross‐section also shows satisfactory agreement.
Assessment criteria in a large-scale writing test: what do they really mean to the raters?
Authors: Lumley Tom 
Published: October 2002

The process of rating written language performance is still not well understood, despite a body of work investigating this issue over the last decade or so (e.g., Cumming, 1990; Huot, 1990; Vaughan, 1991; Weigle, 1994a; Milanovic et al., 1996). The purpose of this study is to investigate the process by which raters of texts written by ESL learners make their scoring decisions using an analytic rating scale designed for multiple test forms. The context is the Special Test of English Proficiency ( step), which is used by the Australian government to assist in immigration decisions. Four trained, experienced and reliable step raters took part in the study, providing scores for two sets of 24 texts. The first set was scored as in an operational rating session. Raters then provided think-aloud protocols describing the rating process as they rated the second set. A coding scheme developed to describe the think-aloud data allowed analysis of the sequence of rating, the interpretations the raters made of the scoring categories in the analytic rating scale, and the difficulties raters faced in rating.Data show that although raters follow a fundamentally similar rating process in three stages, the relationship between scale contents and text quality remains obscure. The study demonstrates that the task raters face is to reconcile their impression of the text, the specific features of the text, and the wordings of the rating scale, thereby producing a set of scores. The rules and the scale do not cover all eventualities, forcing the raters to develop various strategies to help them cope with problematic aspects of the rating process. In doing this they try to remain close to the scale, but are also heavily influenced by the complex intuitive impression of the text obtained when they first read it. This sets up a tension between the rules and the intuitive impression, which raters resolve by what is ultimately a somewhat indeterminate process. In spite of this tension and indeterminacy, rating can succeed in yielding consistent scores provided raters are supported by adequate training, with additional guidelines to assist them in dealing with problems. Rating requires such constraining procedures to produce reliable measurement.
Depression in palliative care: a systematic review. Part 2. Treatment
Authors: Ly Kelly Lan , Chidgey Jayne , Addington-Hall Julia , Hotopf Matthew 
Published: October 2002

Objective: To summarize available literature containing data on the treatment of depression in palliative care patients. Methods: A systematic review was conducted using extensive electronic databases and hand searches. All randomized controlled trials (RCTs) of interventions for depression in patients with advanced disease were eligible. Results: Three RCTs assessed pharmacological treatments. Of these, two were placebo controlled and assessed mianserin and thioridazine. The third compared two antidepressants. There were no RCTs that specifically assessed psychotherapy for patients with depression. Conclusion: There are too few adequate studies to draw clear conclusions about management of depression in this setting. The treatment of depression in patients with advanced disease must, for now, be informed by the larger body of evidence on effective treatments for depression in patients with either no physical illness or less severe medical conditions.