bluuebunny/crossref_metadata_2025 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

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.
Factors affecting duration of survival after onset of blastic transformation of chronic myeloid leukemia
Authors: Wadhwa Jyoti , Szydlo Richard M. , Apperley Jane F. , Chase Andrew , Bua Marco , Marin David , Olavarria Eduardo , Kanfer Edward , Goldman John M.
Published: October 2002

We analyzed factors having an impact on response to treatment and survival in 78 consecutive patients with chronic myeloid leukemia (CML) in blastic transformation (BT) referred to the Hammersmith Hospital from January 1995 to December 2000. BT was defined as the presence of at least 30% blasts in blood or marrow or extramedullary blastic deposits. Immunophenotyping of blasts showed 57 myeloid, 19 lymphoid, and 2 biphenotypic. The median age of the patients was 39.1 years (range, 11.3-73.4 years), with 55 males and 23 females. The median survival for all patients after onset of BT was 8.2 months (95% CI, 6.4-10). Patients in lymphoid BT survived longer than those in myeloid BT (median, 11.2 months versus 6.9 months, P = .052). Initial treatment varied; 41 patients received cytotoxic drugs, 8 underwent allogeneic or autologous transplantation procedures, 21 received STI571 (imatinib mesylate, Gleevec), 1 received radiotherapy, and 7 received no therapy. Of the 25 (32%) patients who achieved a “second chronic phase” with first therapy, 6 of 21 (29%) were treated with STI571 and 19 of 50 (38%) were treated with chemotherapy, transplantation, or radiotherapy. Patients who achieved a second chronic phase survived longer than those who did not (median time from onset of BT 12.0 months versus 6.3 months, P = .0004). In multivariate analysis the finding of more than 50% blast cells in the blood and the presence of cytogenetic progression were independent adverse prognostic variables for survival. We conclude that survival after onset of BT has improved in recent years but is still unsatisfactory. We speculate that the combined use of STI571 with cytotoxic drugs may offer additional benefit.
Notch1 activation increases hematopoietic stem cell self-renewal in vivo and favors lymphoid over myeloid lineage outcome
Authors: Stier Sebastian , Cheng Tao , Dombkowski David , Carlesso Nadia , Scadden David T.
Published: October 2002

Hematopoietic stem cells sequentially pass through a series of decision points affecting self-renewal or lineage-specific differentiation. Notch1 receptor is a known modulator of lineage-specific events in hematopoiesis that we assessed in the context of in vivo stem cell kinetics. Using RAG-1−/−mouse stems cells, we documented increased stem cell numbers due to decreased differentiation and enhanced stem cell self-renewal induced by Notch1. Unexpectedly, preferential lymphoid over myeloid lineage commitment was noted when differentiation occurred. Therefore, Notch1 affects 2 decision points in stem cell regulation, favoring self-renewal over differentiation and lymphoid over myeloid lineage outcome. Notch1 offers an attractive target for stem cell manipulation strategies, particularly in the context of immunodeficiency and acquired immunodeficiency syndrome.
Vascular endothelial growth factor receptor Flt-1 negatively regulates developmental blood vessel formation by modulating endothelial cell division
Authors: Kearney Joseph B. , Ambler Carrie A. , Monaco Kelli-Ann , Johnson Natalie , Rapoport Rebecca G. , Bautch Victoria L.
Published: October 2002

Mice lacking the vascular endothelial growth factor (VEGF) receptor flt-1 die of vascular overgrowth, and we are interested in how flt-1 normally prevents this outcome. Our results support a model whereby aberrant endothelial cell division is the cellular mechanism resulting in vascular overgrowth, and they suggest that VEGF-dependent endothelial cell division is normally finely modulated by flt-1 to produce blood vessels. Flt-1−/− embryonic stem cell cultures had a 2-fold increase in endothelial cells by day 8, and the endothelial cell mitotic index was significantly elevated before day 8. Flt-1 mutant embryos also had an increased endothelial cell mitotic index, indicating that aberrant endothelial cell division occurs in vivo in the absence of flt-1. Theflt-1 mutant vasculature of the cultures was partially rescued by mitomycin C treatment, consistent with a cell division defect in the mutant background. Analysis of cultures at earlier time points showed no significant differences until day 5, whenflt-1 mutant cultures had increased β-galactosidase+ cells, indicating that the expansion of flt-1 responsive cells occurs after day 4. Mitomycin C treatment blocked this early expansion, suggesting that aberrant division of angioblasts and/or endothelial cells is a hallmark of theflt-1 mutant phenotype throughout vascular development. Consistent with this model is the finding that expansion of platelet and endothelial cell adhesion molecule+ and VE-cadherin+ vascular cells in theflt-1 mutant background first occurs between day 5 and day 6. Taken together, these data show that flt-1 normally modulates vascular growth by controlling the rate of endothelial cell division both in vitro and in vivo.
VEGF165 promotes survival of leukemic cells by Hsp90-mediated induction of Bcl-2 expression and apoptosis inhibition
Authors: Dias Sergio , Shmelkov Sergey V. , Lam George , Rafii Shahin
Published: October 2002

Similar to endothelial cells (ECs), vascular endothelial growth factor (VEGF) induces Bcl-2 expression on VEGF receptor-positive (VEGFR+) primary leukemias and cell lines, promoting survival. We investigated the molecular pathways activated by VEGF on such leukemias, by performing a gene expression analysis of VEGF-treated and untreated HL-60 leukemic cells. One gene to increase after VEGF stimulation was heat shock protein 90 (Hsp90). This was subsequently confirmed at the protein level, on primary leukemias and leukemic cell lines. VEGF increased the expression of Hsp90 by interacting with KDR and activating the mitogen-activated protein kinase cascade. In turn, Hsp90 modulated Bcl-2 expression, as shown by a complete blockage of VEGF-induced Bcl-2 expression and binding to Hsp90 by the Hsp90-specific inhibitor geldanamycin (GA). GA also blocked the VEGF-induced Hsp90 binding to APAF-1 on leukemic cells, a mechanism shown to inhibit apoptosis. Notably, VEGF blocked the proapoptotic effects of GA, correlating with its effects at the molecular level. Earlier, we showed that in some leukemias, a VEGF/KDR autocrine loop is essential for cell survival, whereas here we identified the molecular correlates for such an effect. We also demonstrate that the generation of a VEGF/VEGFR autocrine loop on VEGFR+ cells such as ECs, also protected them from apoptosis. Infection of ECs with adenovirus-expressing VEGF resulted in elevated Hsp90 levels, increased Bcl-2 expression, and resistance to serum-free or GA-induced apoptosis. In summary, we demonstrate that Hsp90 mediates antiapoptotic and survival-promoting effects of VEGF, which may contribute to the survival advantage of VEGFR+cells such as subsets of leukemias.
Acquisition of potential N-glycosylation sites in the immunoglobulin variable region by somatic mutation is a distinctive feature of follicular lymphoma
Authors: Zhu Delin , McCarthy Helen , Ottensmeier Christian H. , Johnson Peter , Hamblin Terry J. , Stevenson Freda K.
Published: October 2002

Most patients with follicular lymphoma (FL) have somatically mutated V genes with intraclonal variation, consistent with location in the germinal center site. Using our own and published sequences, we have investigated the frequency of potential N-glycosylation sites introduced into functional VH genes as a consequence of somatic mutation. FL cells were compared with normal memory B cells or plasma cells matched for similar levels of mutation. Strikingly, novel sites were detected in 55 of 70 (79%) patients with FL, compared to 7 of 75 (9%) in the normal B-cell population (P < .001). Diffuse large B-cell lymphoma (DLCL) showed an intermediate frequency (13 of 32 [41%] patients). Myeloma and the mutated subset of chronic lymphocytic leukemia showed frequencies similar to those of normal cells in 5 of 64 (8%) patients and 5 of 40 (13%) patients, respectively. In 3 of 3 random patients with FL, immunoglobulin was expressed as recombinant single-chain Fv inPichia pastoris, and glycosylation was demonstrated. These findings indicate that N-glycosylation of the variable region may be common in FL and in a subset of DLCL. Most novel sites are located in the complementarity-determining regions. VH sequences of nonfunctional VH genes contained few sites, arguing for positive selection in FL. One possibility is that the added carbohydrate in the variable region contributes to interaction with elements in the germinal center environment. This common feature of FL may be critical for tumor behavior.
Infusion of autologous Epstein-Barr virus (EBV)–specific cytotoxic T cells for prevention of EBV-related lymphoproliferative disorder in solid organ transplant recipients with evidence of active virus replication
Authors: Comoli Patrizia , Labirio Massimo , Basso Sabrina , Baldanti Fausto , Grossi Paolo , Furione Milena , Viganò Mario , Fiocchi Roberto , Rossi Giorgio , Ginevri Fabrizio , Gridelli Bruno , Moretta Antonia , Montagna Daniela , Locatelli Franco , Gerna Giuseppe , Maccario Rita
Published: October 2002

Epstein-Barr virus (EBV)–associated posttransplantation lymphoproliferative disorders (PTLDs) are a well-recognized complication of immunosuppression in solid organ transplant recipients. The reported therapeutic approaches are frequently complicated by rejection, toxicity, and other infectious pathologies, and overall mortality in patients with unresponsive PTLD remains high. Thus, low-toxicity treatment options or, preferably, some form of prophylactic/preemptive intervention are warranted to improve PTLD outcome in this setting. We assessed whether transfer of EBV-specific cytotoxic T lymphocytes (CTLs) generated in vitro from the peripheral blood of allograft recipients receiving immunosuppression could increase EBV-specific killing in vivo without augmenting the probability of graft rejection. Autologous EBV-specific CTLs were generated for 23 patients who were identified as being at risk of developing PTLD through the finding of elevated EBV DNA load. Of the 23 patients, 7 received 1 to 5 infusions of EBV-specific CTLs. CTL transfer was well tolerated, and none of the patients showed any evidence of rejection. An increase of the EBV-specific cytotoxicity was observed after infusion, notwithstanding continuation of immunosuppressive therapy. EBV DNA levels had a 1.5- to 3-log decrease in 5 patients, whereas in the other 2 graft recipients CTL transfer had no apparent stable effect on EBV load. Our data suggest that the infusion of autologous EBV-specific CTLs obtained from peripheral blood mononuclear cells recovered at the time of viral reactivation is able to augment virus-specific immune response and to reduce viral load in organ transplant recipients. This approach may, therefore, be safely used as prophylaxis of EBV-related lymphoproliferative disorders in these patients, following a strategy of preemptive therapy guided by EBV DNA levels.
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

EphB4 (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

Langerhans 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

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

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>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

Chemokines 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

CD4+ 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

Notch 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

Transcription 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

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.
THE AMPLITUDES OF WAVES TO BE EXPECTED IN SEISMIC PROSPECTING
Authors: Gutenberg B.
Published: October 2002

A method of calculating the amplitudes of bodily waves in earthquakes is applied to a study of the amplitudes of longitudinal waves produced by an artificial explosion. Formulae are given for calculating the energy of the reflected longitudinal wave arriving at the surface. The percentage of energy reflected at a discontinuity increases rapidly after the angle of incidence exceeds the critical refraction angle. However, no corresponding large amplitudes are recorded by the instruments. Instead, the maximum amplitudes of reflected waves are found near the shot point. This is because the ground movement is due both to the arriving wave and to the wave reflected downward from the ground. The amplitude of this movement depends, besides, on the rate of change of the angle of incidence with distance. It is pointed out that the same methods can be applied to a dipping bed, and that the amplitudes of the reflected waves are in general slightly larger in the up‐dip than in the down‐dip direction.
THE AMPLITUDE AND CHARACTER OF REFRACTION WAVES
Authors: Wolf A.
Published: October 2002

In seismic exploration it is assumed that elastic waves can be refracted into and out of a high speed medium at the angle of total reflection and meanwhile travel along the interface between the two media. That such a path is in agreement with the general theory of elastic waves has been proved by Muskat. The present paper is an extension of the work of Muskat, and shows in addition that the general theory can explain the low amplitude and low frequencies of these refracted waves, and is otherwise in agreement with observation. Equations are developed for the effect at any point of the low speed medium of an impulse or of a periodic disturbance initiated at any other point of the same medium. Details are worked out for the case where the recorder is so situated that the refracted wave arrives first. The direction of the arriving wave is found to be that of the angle of total reflection, and its amplitude to diminish with the square of the distance from the shot point—in agreement with Muskat. The amplitude of the refracted wave is also found to be only a small fraction of that of the direct wave, or of that of the reflected wave which arrives still later. The motion produced by the refracted wave is found to be a unidirectional pulse which lasts until the arrival of the direct wave. Finally, the appearance of a record of motion is given for certain assumed numerical data. For this case it is found that the average amplitude of the refracted wave is 8 per cent of that of the direct wave.
MOTION OF A RIGID SPHERE IN AN ACOUSTIC WAVE FIELD
Authors: Wolf Alfred
Published: October 2002

A rigid sphere in the field of plane acoustic waves in a fluid or in an elastic solid medium is subjected to harmonic forces in the direction of propagation of the waves, and proportional to their amplitude. The response curve is a function of the ratio of the circumference of the sphere to the wave length, and of the ratio of the mass of the sphere to the mass of the displaced medium. In an elastic solid, Poisson’s ratio must also be included among the variables. The response curve in fluids decreases continuously with decreasing wave length. In elastic solid media, the response curve has a maximum which is due to resonance effects. In general, the greater the mass of the sphere the smaller the response except in the neighborhood of resonance in elastic solid media. The scattering of acoustic waves by a rigid sphere is determined. The potential of scattered waves is developed in a series of spherical harmonics; it is shown that only the first order coefficients are affected by the motion of the sphere.
THE MAGNETIC FIELD OVER IGNEOUS PIPES
Authors: Blum Victor J.
Published: October 2002

In this paper a brief summary of a magnetic survey of the Canon City, Colorado, area is presented. The primary object of the article is to give the results of magnetic traverses over exposed igneous pipes which contain an appreciable amount of magnetite. These traverses reveal a magnetic low near the geometric center of the tops of the pipes. Away from the center the field increases in intensity and reaches its maximum strength along the southern edge of the intrusion. Small igneous pipes at or near the surface cause radical changes in the magnetic field within very short distances.
RECENT DEVELOPMENTS IN GEOCHEMICAL PROSPECTING FOR PETROLEUM
Authors: Horvitz Leo
Published: October 2002

A number of surveys completed during the past two years indicate that the geochemical prospecting technique can be applied successfully only when an area is explored which is sufficiently large to enable ready distinction of the anomaly from the background. Geochemical anomalies found by reconnaissance sampling have been proved to be associated with structure by the reflection seismograph. These confirmations indicate that the two methods can be used to supplement one another; one to detect the possible presence of a petroleum accumulation and the other to determine the probable depth of the accumulation. The result of a reconnaissance geochemical survey over the Heidelberg Area of Jasper County, Mississippi, are presented.
A SHOOTING METHOD FOR AREAS OF DIFFICULT DRILLING
Authors: Alcock E. D. , Waters K. H.
Published: October 2002

This paper describes an economical method for shooting in areas where shot‐hole drilling is expensive. A new computational procedure for handling the data in steep‐dip areas is derived.
REMARKS ON MULTIPLE REFLECTIONS
Authors: Gutenberg B. , Fu C. Y.
Published: October 2002

One cannot help being impressed by the wonderful arrays of seismograms depicted in Mr. Ellsworth’s paper and in the prepared discussions. The regularity of the time intervals of successive impulses and the alternating sequence of the change of phase are readily adapted to a mechanism of multiple reflections. If the latter is accepted, the following questions seem to merit some consideration: (a) the energy concentration, (b) the positions of the reflecting surfaces, (c) the sharpness of the source‐impulse, and (d) the velocity contrast of the adjacent media.
AN INSTRUMENT FOR PLOTTING REFLECTION DATA ON THE ASSUMPTION OF LINEAR INCREASE OF VELOCITY
Authors: Daly John W.
Published: October 2002

An instrument is described by means of which reflection data may be rapidly and accurately plotted in the case that the velocity is assumed to increase linearly with depth. Lengths corresponding to the radius of the wave‐front circle and the depth of its center are obtained directly from observed reflection times by means of suitable scales attached to the device. Reflection data can be plotted either by dip units, or by the envelope method.
GEOPHYSICAL ACTIVITY IN THE OIL INDUSTRY IN THE UNITED STATES IN 1947
Authors: Eckhardt E. A.
Published: October 2002

In 1947 the oil industry of the United States produced 2.011 billion barrels of crude oil and natural‐gas liquids. The same number of barrels of new oil must be discovered in one year if the industry is to maintain its reserves. This provides a measure of the exploration job to be done.
WELL VELOCITY SHOOTING IN CALIFORNIA
Authors: Wells Robert J.
Published: October 2002

Sources of error and approximate magnitudes of errors are summarized, and the disturbing and misleading effects of impulses transmitted down the well geophone cable are discussed in detail. Several examples of the latter phenomenon in California are shown, and analyses are made indicating the probable path the energy travels from shot to the cable, and thence down the cable to the geophone. Suggested refinements to overcome this trouble are presented.
GEOPHYSICAL ACTIVITY IN 1948
Authors: Eckhardt E. A.
Published: October 2002

The expectation expressed at our convention a year ago that geophysical activity would reach a new record high in 1948, has been amply fulfilled. For the oil industry the year 1948 was record making in many respects. At its end, the reserves of the industry stood at a new all time high, in spite of their depletion by record breaking production. The over‐all exploratory effort not only replaced the oil produced but, in addition, provided a margin of over a billion barrels for the future. This report is confined to the geophysical aspects of exploration and aims to provide only a picture of its magnitude, its character and its geographic distribution.
COMPOSITE REFLECTIONS
Authors: Ricker Norman , Lynn R. D.
Published: October 2002

This paper discusses the development of a method of reflection seismic prospecting based on the use of the seismic PS phase—a disturbance which has traveled from the shot to the reflecting bed as a dilatational wave and from the reflecting bed to the earth’s free surface as a shear wave, where it is picked up by horizontal component geophones. The reflection occurs on the seismogram in the otherwise quiet region between the dilatational waves and the ground roll and thus is never obscured by the ground roll. The reflection is quite clear and capable of spot correlation from spread to spread. The use of the method in delineating the Homer and Cotton Valley structures, near Minden, Louisiana, is described in detail. The method appears to be applicable to regions where an unconsolidated subsurface extends downwards from the earth’s surface to a single hard bed serving as a reflector. Criteria for identifying the disturbance as a composite reflection are given and the advantages and limitations of the method are discussed.
PROPAGATION OF EXPLOSIVE SOUND IN A LIQUID LAYER OVERLYING A SEMI‐INFINITE ELASTIC SOLID
Authors: Press Frank , Ewing Maurice
Published: October 2002

The Pekeris theory of normal mode propagation of explosion sound in two liquid layers is extended to include the case of a solid bottom. Curves giving phase velocity, group velocity, amplitude, vertical pressure distribution as a function of frequency are presented. The relative merits of geophones and hydrophones for underwater seismology and the best depth for each type of instrument are discussed in the light of the theory. The characteristics of an incoming signal are described.
A METHOD OF ELECTRICAL PROFILING
Authors: Crumrine Kenneth C.
Published: October 2002

A method useful in electrical exploration is presented. In electrical profiling using a sensitive low frequency instrument, a considerable variety of information can be obtained at relatively small expense by making a suitable choice of electrode patterns for three measurements at each station along a profile. Apparent resistivities pertaining to relatively large electrode spreads can be computed from shorter spread measurements along a profile, and a variety, of potential drop ratios can also be computed. Suitable instrumentation should afford automatic recording of a variety of electrical functions in continuous profiling at or near the surface of the earth, and in bore holes.
GRAPHIC ADJUSTMENT BY LEAST SQUARES
Authors: Smith A. E.
Published: October 2002

The gravity meter in use today measures the differences in the acceleration of gravity between stations. When three or more gravity stations are interconnected by measured differences to form closed gravity station networks, values for the accelerations of gravity at all stations must be derived in such a manner that around all closed circuits the algebraic sum of the adjusted gravity differences is zero. Since the errors involved are assumed to be random, a solution can be obtained by the method of “least squares.” However, for large networks, the usual least squares solution is so time‐consuming that it is frequently omitted in cases where its application would be desirable. It is the purpose of this paper to describe the practical application of a more speedy method.
AN APPROXIMATE CORRECTION METHOD FOR REFRACTION IN REFLECTION SEISMIC PROSPECTING
Authors: Krey Th.
Published: October 2002

Equations are derived and discussed to compute approximate corrections which must be applied to the results obtained by the classical methods of computing and constructing data in reflection seismic prospecting, (this includes the method of construction of seismic image point and the method of seismic prospecting using zero‐spread time) to correct for refraction. In addition, the influence of refraction on the determination of average velocity as obtained by applying the time‐square distance‐square curve (Time‐Delta‐Time Velocity) is analyzed.
SUGGESTIONS OF A NEW METHOD OF MAKING UNDERGROUND OBSERVATIONS
Authors: Udden J. A.
Published: October 2002

In the north‐central part of the State of Texas, where wells are being drilled to the depth of 4,000 feet and more in order to penetrate the Bend formation (Pennsylvanian), which is the chief oil‐bearing horizon in that part of the State, it has been found that the structure of the Bend and that of the underlying Ellenburger limestone (Ordovician) is quite generally the same. The plotting of underground structure by drillers’ logs or by observations on cuttings from the Bend is very difficult, for the reason that there are small variations in the rocks of the Bend, not only vertically but also horizontally, and that these small variations lie near the limit between shale and limestone. Whether a certain part of the formation is reported as shale or as limestone will in large part depend upon the judgment and experience of the driller, or other observer. It has been exceedingly difficult to trace a definite horizon in the Bend with any considerable certainty. Exposures of the Bend indicate also that there are horizontal changes in this formation. For those who use drillers’ logs in the making of structural maps, it has been found expedient to use the contact of the Bend and the underlying Ellenburger as the key horizon. Contours are drawn on the upper surface of the Ellenburger.
THE EFFECT OF RANDOM ERRORS IN GRAVITY DATA ON SECOND DERIVATIVE VALUES
Authors: Elkins Thomas A.
Published: October 2002

Two random error grids were prepared using a set of 111 balls marked according to the Gaussian normal error law. For these grids, considered as grids of errors in gravity data, the second derivative values were computed and contoured. The resulting maps show strikingly the dangers in uncritical interpretations of second derivative maps based on insufficiently accurate data. Statistical checks were applied both to the random error grids and to the computed second derivative values. The check on the latter necessitated the development of a theory of the correlation between second derivative values which is also applicable to many other quantities, besides second derivatives, which are computed by coefficients.
GEOPHYSICAL EXPLORATION OF SOUTHWEST HUNGARY
Authors: Vajk Raoul
Published: October 2002

Geophysical exploration of an eight million acre oil concession covering southwest Hungary is discussed. During ten years of exploration (1933–1943), about 20,000 torsion balance, 12,000 gravity meter, and 15,000 magnetometer stations were made, and reflection seismograms were recorded at about 2,500 shot points. As a result of this exploration, four oil pools and a gas pool were discovered and a number of geological structures and major faults were located. Gravity, magnetic, and seismic maps showing most of the geophysical data are submitted. Interpretations of the geophysical results, geological data from subsequent drilling, and a schematic tectonic map of southwest Hungary based on the geophysical surveys are also presented.
STUDIES OF A SURFACE SEISMIC DISTURBANCE
Authors: Eisler Joseph D.
Published: October 2002

Seismic studies in a caliche covered area revealed existence of a prominent surface wave group. The dispersive characteristics of this wave group and the existence of retrograde elliptical particle motion place it in a class of Rayleigh waves. Examples of vertical as well as two‐component motion are presented.
THE DEVELOPMENT OF A NEW METHOD OF SEISMIC VELOCITY DETERMINATION
Authors: Kokesh F. P.
Published: October 2002

The conventional method of making velocity surveys in bore holes is inherently expensive, time consuming, and inconvenient, and has a tendency towards non‐uniformity of results. With increasing recognition of the importance of seismic velocity information in the evaluation of seismograph data, the attention of geophysicists is turning towards means of overcoming the obstacles standing in the way of obtaining velocity information in greater volume. Considerable interest has recently been aroused in a new method of measuring seismic velocities wherein the explosive charge is placed in the hole and the seismic energy is picked up with multiple detector groups placed on the surface. Experimentation carried on during the past year indicates that the new method is quite workable. Casing perforator guns of the conventional bullet type have given results to depths exceeding 8,000 ft. with complete safety. Some experimentation with primacord as the explosive has given encouragement as a means of increasing the depth at which the method may be used. Substantial improvements have been made in the manner of obtaining the time break. This paper attempts to outline the basic problems of velocities and their measurement and describes the preliminary development that has been done thus far on the new method of velocity measurement.
A SEISMIC VELOCITY LOGGING METHOD
Authors: Vogel C. B.
Published: October 2002

A well logging method is described which measures seismic velocity as a function of depth. The method uses a transient sound pulse, thus making possible the resolution of shear waves. Various systems of sources and receivers for minimizing bore hole errors are discussed. With the most elaborate system considerable accuracy is obtainable in the face of large bore hole diameter variations.
THE SIGNIFICANCE OF DIFFRACTION IN THE INVESTIGATION OF FAULTS
Authors: Krey Theodor
Published: October 2002

Seismic reflection records taken across faults frequently show an overlapping of reflections from the displaced blocks. It is demonstrated that diffraction of seismic waves is a cause and the effect may be used in interpretation. Overlapping is increased if a seismic profile crosses a fault at an acute angle. Plotted dips will be inaccurate unless diffraction is taken into account. Further, the diffraction oscillation pattern will also be obtained if a reflection horizon terminates for a reason other than faulting, for example, at a wedgeout or reef edge, or at a sudden change of facies. The facts developed are demonstrated by practical examples in which attention is directed to the approximations involved in plotting the boundaries of discontinuities.
THE EFFECT OF VARIATIONS IN CHEMICAL COMPOSITION ON THE VELOCITY OF SEISMIC WAVES IN CARBONATE ROCKS
Authors: Kisslinger Carl
Published: October 2002

The variations of velocity in limestones have not fallen into as definite a pattern as have those in sandstones and shales. Although it is conceded generally that textural characteristics are more important than mineral content in determining the velocity in sandstones and shales, the possibility that the concentration of magnesium carbonate may appreciably alter the velocity in a limestone is investigated. It is found that dolomitization can be expected to have an effect on the velocity, but that effect is not certain, in that it depends on the nature of the dolomitization process. A volume for volume replacement of calcite by dolomite tends to increase the velocity, but dolomitization giving rise to local porosity, whether the resulting interstices are empty or filled by non‐carbonate material, tends to decrease the velocity.
TRANSIENT COUPLING IN GROUNDED CIRCUITS
Authors: Wait James R.
Published: October 2002

Transient coupling between insulated circuits of finite length grounded at their end points in an infinite homogeneous and conducting medium is investigated. The general result is specialized to the case of a typical electrodal array as used in electrical resistivity logging in wells or drill holes. A graphical example shows how the voltages build up to their static value due to a suddenly applied current.