WorldWideScience

Sample records for lymphoblastic transformation test

  1. Transformation of Myelodysplastic Syndrome to Acute Lymphoblastic Leukemia in a Child

    OpenAIRE

    2010-01-01

    Childhood myelodysplastic syndrome (MDS) is an uncommon condition. Unlike adult MDS, pediatric patients have a more progressive course and rapidly transform to acute myeloid leukemia. Evolution to acute lymphoblastic leukemia is extremely rare. We report a 5 year old female child who presented with refractory anemia with excess blasts and transformed into acute lymphoblastic leukemia 4 months after initial diagnosis.

  2. Transformer room fire tests

    Science.gov (United States)

    Fustich, C. D.

    1980-03-01

    A series of transformer room fire tests are reported to demonstate the shock hazard present when automatic sprinklers operate over energized electrical equipment. Fire protection was provided by standard 0.5 inch pendent automatic sprinklers temperature rated at 135 F and installed to give approximately 150 sq ft per head coverage. A 480 v dry transformer was used in the room to provide a three phase, four wire distribution system. It is shown that the induced currents in the test room during the various tests are relatively small and pose no appreciable personnel shock hazard.

  3. Myelodysplastic Syndrome with Myelofibrosis Transformed to a Precursor B-Cell Acute Lymphoblastic Leukemia: A Case Report with Review of the Literature

    OpenAIRE

    2012-01-01

    Myelodysplastic syndromes (MDS) comprise a group of heterogeneous clonal hematopoietic cell disorders characterized by cytopenias, bone marrow hypercellularity, and increased risk of transformation to acute leukemias. MDS usually transformed to acute myeloid leukemia, and transformation to acute lymphoblastic leukemia (ALL) is rare. Herein, we report a unique patient who presented with MDS with myelofibrosis. Two months after the initial diagnosis, she progressed to a precursor B-cell acute l...

  4. Myelodysplastic Syndrome with Myelofibrosis Transformed to a Precursor B-Cell Acute Lymphoblastic Leukemia: A Case Report with Review of the Literature

    Directory of Open Access Journals (Sweden)

    Ayed A. Algarni

    2012-01-01

    Full Text Available Myelodysplastic syndromes (MDS comprise a group of heterogeneous clonal hematopoietic cell disorders characterized by cytopenias, bone marrow hypercellularity, and increased risk of transformation to acute leukemias. MDS usually transformed to acute myeloid leukemia, and transformation to acute lymphoblastic leukemia (ALL is rare. Herein, we report a unique patient who presented with MDS with myelofibrosis. Two months after the initial diagnosis, she progressed to a precursor B-cell acute lymphoblastic leukemia. She was treated with induction therapy followed by allogenic stem cell transplantation. She was alive and doing well upon last followup. We have also reviewed the literature and discussed the clinicopathologic features of 36 MDS patients who progressed to ALL reported in the literature.

  5. Electronic Voltage and Current Transformers Testing Device

    Directory of Open Access Journals (Sweden)

    Yong Xiao

    2012-01-01

    Full Text Available A method for testing electronic instrument transformers is described, including electronic voltage and current transformers (EVTs, ECTs with both analog and digital outputs. A testing device prototype is developed. It is based on digital signal processing of the signals that are measured at the secondary outputs of the tested transformer and the reference transformer when the same excitation signal is fed to their primaries. The test that estimates the performance of the prototype has been carried out at the National Centre for High Voltage Measurement and the prototype is approved for testing transformers with precision class up to 0.2 at the industrial frequency (50 Hz or 60 Hz. The device is suitable for on-site testing due to its high accuracy, simple structure and low-cost hardware.

  6. Role of CXCR4-mediated bone marrow colonization in CNS infiltration by T cell acute lymphoblastic leukemia.

    Science.gov (United States)

    Jost, Tanja Rezzonico; Borga, Chiara; Radaelli, Enrico; Romagnani, Andrea; Perruzza, Lisa; Omodho, Lorna; Cazzaniga, Giovanni; Biondi, Andrea; Indraccolo, Stefano; Thelen, Marcus; Te Kronnie, Geertruy; Grassi, Fabio

    2016-06-01

    Infiltration of the central nervous system is a severe trait of T cell acute lymphoblastic leukemia. Inhibition of CXC chemokine receptor 4 significantly ameliorates T cell acute lymphoblastic leukemia in murine models of the disease; however, signaling by CXC chemokine receptor 4 is important in limiting the divagation of peripheral blood mononuclear cells out of the perivascular space into the central nervous system parenchyma. Therefore, Inhibition of CXC chemokine receptor 4 potentially may untangle T cell acute lymphoblastic leukemia cells from retention outside the brain. Here, we show that leukemic lymphoblasts massively infiltrate cranial bone marrow, with diffusion to the meninges without invasion of the brain parenchyma, in mice that underwent xenotransplantation with human T cell acute lymphoblastic leukemia cells or that developed leukemia from transformed hematopoietic progenitors. We tested the hypothesis that T cell acute lymphoblastic leukemia neuropathology results from meningeal infiltration through CXC chemokine receptor 4-mediated bone marrow colonization. Inhibition of leukemia engraftment in the bone marrow by pharmacologic CXC chemokine receptor 4 antagonism significantly ameliorated neuropathologic aspects of the disease. Genetic deletion of CXCR4 in murine hematopoietic progenitors abrogated leukemogenesis induced by constitutively active Notch1, whereas lack of CCR6 and CCR7, which have been shown to be involved in T cell and leukemia extravasation into the central nervous system, respectively, did not influence T cell acute lymphoblastic leukemia development. We hypothesize that lymphoblastic meningeal infiltration as a result of bone marrow colonization is responsible for the degenerative alterations of the neuroparenchyma as well as the alteration of cerebrospinal fluid drainage in T cell acute lymphoblastic leukemia xenografts. Therefore, CXC chemokine receptor 4 may constitute a pharmacologic target for T cell acute lymphoblastic

  7. Diphtheria toxin resistance in human lymphocytes and lymphoblasts in the in vivo somatic cell mutation test

    Energy Technology Data Exchange (ETDEWEB)

    Tomkins, D.J.; Wei, L.; Laurie, K.E.

    1985-01-01

    It has been shown that circulating peripheral blood lymphocytes can be used for the enumeration of 6-thioguanine-resistant cells that presumably arise by mutation in vivo. This somatic cell mutation test has been studied in lymphocytes from human populations exposed to known mutagens and/or carcinogens. The sensitivity of the test could be further enhanced by including other gene markers, since there is evidence for locus-specific differences in response to mutagens. Resistance to diphtheria toxin (Dip/sup r/) seemed like a potential marker to incorporate into the test because the mutation acts codominantly, can readily be selected in human diploid fibroblasts and Chinese hamster cells with no evidence for cell density or cross-feeding effects, and can be assayed for in nondividing cells by measuring protein synthesis inhibition. Blood samples were collected from seven individuals, and fresh, cryopreserved, or Epstein-Barr virus (EBV)-transformed lymphocytes were tested for continued DNA synthesis (TH-thymidine, autoradiography) or protein synthesis (TVS-methionine, scintillation counting). Both fresh and cryopreserved lymphocytes, stimulated to divide with phytohemagglutinin (PHA), continued to synthesize DNA in the presence of high doses of diphtheria toxin (DT). Similarly, both dividing (PHA-stimulated) and nondividing fresh lymphocytes carried on significant levels of protein synthesis even 68 hr after exposure to 100 flocculating units (LF)/ml DT. The results suggest that human T and B lymphocytes may not be as sensitive to DT protein synthesis inhibition as human fibroblast and Chinese hamster cells. For this reason, Dip/sup r/ may not be a suitable marker for the somatic cell mutation test.

  8. Modeling and testing of ethernet transformers

    Science.gov (United States)

    Bowen, David

    2011-12-01

    Twisted-pair Ethernet is now the standard home and office last-mile network technology. For decades, the IEEE standard that defines Ethernet has required electrical isolation between the twisted pair cable and the Ethernet device. So, for decades, every Ethernet interface has used magnetic core Ethernet transformers to isolate Ethernet devices and keep users safe in the event of a potentially dangerous fault on the network media. The current state-of-the-art Ethernet transformers are miniature (explored which are capable of exceptional miniaturization or on-chip fabrication. This dissertation thoroughly explores the performance of the current commercial Ethernet transformers to both increase understanding of the device's behavior and outline performance parameters for replacement devices. Lumped element and distributed circuit models are derived; testing schemes are developed and used to extract model parameters from commercial Ethernet devices. Transfer relation measurements of the commercial Ethernet transformers are compared against the model's behavior and it is found that the tuned, distributed models produce the best transfer relation match to the measured data. Process descriptions and testing results on fabricated thin-film dielectric-core toroid transformers are presented. The best results were found for a 32-turn transformer loaded with 100Ω, the impedance of twisted pair cable. This transformer gave a flat response from about 10MHz to 40MHz with a height of approximately 0.45. For the fabricated transformer structures, theoretical methods to determine resistance, capacitance and inductance are presented. A special analytical and numerical analysis of the fabricated transformer inductance is presented. Planar cuts of magnetic slope fields around the dielectric-core toroid are shown that describe the effect of core height and winding density on flux uniformity without a magnetic core.

  9. Testing Self-Similarity Through Lamperti Transformations

    KAUST Repository

    Lee, Myoungji

    2016-07-14

    Self-similar processes have been widely used in modeling real-world phenomena occurring in environmetrics, network traffic, image processing, and stock pricing, to name but a few. The estimation of the degree of self-similarity has been studied extensively, while statistical tests for self-similarity are scarce and limited to processes indexed in one dimension. This paper proposes a statistical hypothesis test procedure for self-similarity of a stochastic process indexed in one dimension and multi-self-similarity for a random field indexed in higher dimensions. If self-similarity is not rejected, our test provides a set of estimated self-similarity indexes. The key is to test stationarity of the inverse Lamperti transformations of the process. The inverse Lamperti transformation of a self-similar process is a strongly stationary process, revealing a theoretical connection between the two processes. To demonstrate the capability of our test, we test self-similarity of fractional Brownian motions and sheets, their time deformations and mixtures with Gaussian white noise, and the generalized Cauchy family. We also apply the self-similarity test to real data: annual minimum water levels of the Nile River, network traffic records, and surface heights of food wrappings. © 2016, International Biometric Society.

  10. Pharmacokinetic modeling of an induction regimen for in vivo combined testing of novel drugs against pediatric acute lymphoblastic leukemia xenografts.

    Directory of Open Access Journals (Sweden)

    Barbara Szymanska

    Full Text Available Current regimens for induction therapy of pediatric acute lymphoblastic leukemia (ALL, or for re-induction post relapse, use a combination of vincristine (VCR, a glucocorticoid, and L-asparaginase (ASP with or without an anthracycline. With cure rates now approximately 80%, robust pre-clinical models are necessary to prioritize active new drugs for clinical trials in relapsed/refractory patients, and the ability of these models to predict synergy/antagonism with established therapy is an essential attribute. In this study, we report optimization of an induction-type regimen by combining VCR, dexamethasone (DEX and ASP (VXL against ALL xenograft models established from patient biopsies in immune-deficient mice. We demonstrate that the VXL combination was synergistic in vitro against leukemia cell lines as well as in vivo against ALL xenografts. In vivo, VXL treatment caused delays in progression of individual xenografts ranging from 22 to >146 days. The median progression delay of xenografts derived from long-term surviving patients was 2-fold greater than that of xenografts derived from patients who died of their disease. Pharmacokinetic analysis revealed that systemic DEX exposure in mice increased 2-fold when administered in combination with VCR and ASP, consistent with clinical findings, which may contribute to the observed synergy between the 3 drugs. Finally, as proof-of-principle we tested the in vivo efficacy of combining VXL with either the Bcl-2/Bcl-xL/Bcl-w inhibitor, ABT-737, or arsenic trioxide to provide evidence of a robust in vivo platform to prioritize new drugs for clinical trials in children with relapsed/refractory ALL.

  11. 10 CFR 431.198 - Enforcement testing for distribution transformers.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 3 2010-01-01 2010-01-01 false Enforcement testing for distribution transformers. 431.198... COMMERCIAL AND INDUSTRIAL EQUIPMENT Distribution Transformers Compliance and Enforcement § 431.198 Enforcement testing for distribution transformers. (a) Test notice. Upon receiving information in...

  12. The Global Transformation toward Testing for Accountability

    Science.gov (United States)

    Smith, William C.

    2014-01-01

    To ensure equal access to high quality education, the global expansion of universal basic education has included accountability measures in the form of academic tests. Presently the majority of countries participate in national testing; however, the past two decades have seen a substantial shift in test characteristics and aims. This article…

  13. Test-driven verification/validation of model transformations

    Institute of Scientific and Technical Information of China (English)

    László LENGYEL; Hassan CHARAF

    2015-01-01

    Why is it important to verify/validate model transformations? The motivation is to improve the quality of the trans-formations, and therefore the quality of the generated software artifacts. Verified/validated model transformations make it possible to ensure certain properties of the generated software artifacts. In this way, verification/validation methods can guarantee different requirements stated by the actual domain against the generated/modified/optimized software products. For example, a verified/ validated model transformation can ensure the preservation of certain properties during the model-to-model transformation. This paper emphasizes the necessity of methods that make model transformation verified/validated, discusses the different scenarios of model transformation verification and validation, and introduces the principles of a novel test-driven method for verifying/ validating model transformations. We provide a solution that makes it possible to automatically generate test input models for model transformations. Furthermore, we collect and discuss the actual open issues in the field of verification/validation of model transformations.

  14. Transforming Censored Samples and Testing Fit.

    Science.gov (United States)

    2014-09-26

    Stephens (1985). In Chapter 5 it is suggested that a test that r is reasonable (r has a binomial distribution with parameters n and t) be combined with...public release; distribution unlimited. DEPARTMENT OF STATISTICS Acc;91nnl For I ITIZ CIPA&I STANFORD UNIVERSITY JD7 TA3 STANFORD, CALIFORNIA U1,anr0unved... distribution F(x), where the x-sample is type I- or type II-censored. The censoring may be done in various ways: left- or right-censoring, as is often found in

  15. A randomized controlled trial testing an adherence-optimized Vitamin D regimen to mitigate bone change in adolescents being treated for acute lymphoblastic leukemia.

    Science.gov (United States)

    Orgel, Etan; Mueske, Nicole M; Sposto, Richard; Gilsanz, Vicente; Wren, Tishya A L; Freyer, David R; Butturini, Anna M; Mittelman, Steven D

    2017-10-01

    Adolescents with acute lymphoblastic leukemia (ALL) develop osteopenia early in therapy, potentially exacerbated by high rates of concurrent Vitamin D deficiency. We conducted a randomized clinical trial testing a Vitamin D-based intervention to improve Vitamin D status and reduce bone density decline. Poor adherence to home supplementation necessitated a change to directly observed therapy (DOT) with intermittent, high-dose Vitamin D3 randomized versus standard of care (SOC). Compared to SOC, DOT Vitamin D3 successfully increased trough Vitamin 25(OH)D levels (p = .026) with no residual Vitamin D deficiency, 100% adherence to DOT Vitamin D3, and without associated toxicity. However, neither Vitamin D status nor supplementation impacted bone density. Thus, this adherence-optimized intervention is feasible and effective to correct Vitamin D deficiency in adolescents during ALL therapy. Repletion of Vitamin D and calcium alone did not mitigate osteopenia, however, and new, comprehensive approaches are needed to address treatment-associated osteopenia during ALL therapy.

  16. Implementation of an outline of transformer induced voltage tests

    Directory of Open Access Journals (Sweden)

    Orestes Hernández Areu

    2010-02-01

    Full Text Available The results of the developed work for the implementation of the induced voltage test to be applied to single phase distribution transformers in the Researches and Electroenergetic Tests Center (CIPEL of Cuba, are presented, The test outline was obtained starting from the employment of a motor - generator group, with an external voltage regulator and using a frequency converter to obtain the necessary frequency for this type of test.

  17. Transformational leadership in nursing service. A test of theory.

    Science.gov (United States)

    McDaniel, C; Wolf, G A

    1992-02-01

    What are the leadership dimensions that result in low turnover or work satisfaction? Intellectual stimulation, charisma, and individual consideration constitute aspects of transformational leadership that are suggested to enhance retention and staff satisfaction. In this study, the authors tested transformational leadership theory in one nursing department with an executive, 11 midlevel administrators, and 77 staff registered nurses. Findings support the predictions. Composed of teachable components, transformational factors are similar to leadership qualities described in magnet hospitals, offering positive implications for nursing administration and professional nursing practice.

  18. Impulse short circuit test of a 125 MVA power transformer; Stosskurzschlusspruefung eines 125-MVA-Transformators

    Energy Technology Data Exchange (ETDEWEB)

    Leibfried, T.; Kirchenmayer, E.; Knorr, W. [Siemens AG, Nuernberg (Germany)

    1998-05-04

    An impulse short circuit test was carried out on a 125 MVA, 245 kV/53 kV power transformer from the Siemens factory in Nuremberg in March 1997. This for the Swiss customer Atel manufactured and 173 t weighted transformer was transported to Arnhem (Netherlands) by ship and was tested in the Kema high power laboratory. The visual inspection of the transformer after returning to the Nuremberg factory carried out by engineers from Atel and Siemens and representatives of Kema showed no changes of the inner condition of the transformer. This successful impulse short circuit test proved the high quality standard of Siemens power transformers once again. (orig.) [Deutsch] Im Maerz 1997 wurde ein 125-MVA, 240-kV/53-kV-Leistungstransformator aus dem Siemens-Transformatorenwerk Nuernberg einer Stosskurzschlusspruefung unterzogen. Der fuer das schweizerische Energieversorgungsunternehmen Atel gebaute 173 t schwere Transformator wurde im Hochleistungslabor der Kema in Arnheim/Niederlande geprueft. Eine Inspektion des Aktivteils im Nuernberger Transformatorenwerk ergab keine Beanstandungen. Damit ist die Stosskurzschlussfestigkeit auch fuer Transformatoren dieser Leistungsklasse experimentell nachgewiesen. (orig.)

  19. Childhood Acute Lymphoblastic Leukemia

    DEFF Research Database (Denmark)

    Pui, Ching-Hon; Yang, Jun J; Hunger, Stephen P

    2015-01-01

    PURPOSE: To review the impact of collaborative studies on advances in the biology and treatment of acute lymphoblastic leukemia (ALL) in children and adolescents. METHODS: A review of English literature on childhood ALL focusing on collaborative studies was performed. The resulting article...

  20. Induced martensitic transformation during tensile test in nanostructured bainitic steels

    Energy Technology Data Exchange (ETDEWEB)

    Morales-Rivas, L. [Department of Physical Metallurgy, National Center for Metallurgical Research (CENIM-CSIC), Avda. Gregorio del Amo, 8, 28040 Madrid (Spain); University of Kaiserslautern, Materials Testing, Gottlieb - Daimler - Str., 67663 Kaiserslautern (Germany); Garcia-Mateo, C., E-mail: cgm@cenim.csic.es [Department of Physical Metallurgy, National Center for Metallurgical Research (CENIM-CSIC), Avda. Gregorio del Amo, 8, 28040 Madrid (Spain); Kuntz, Matthias [Robert Bosch GmbH, Materials and Processing Dept, P.O. Box 300240, Stuttgart (Germany); Sourmail, Thomas [Asco Industries CREAS (Research Centre) Metallurgy, BP 70045, Hagondange Cedex 57301 (France); Caballero, F.G. [Department of Physical Metallurgy, National Center for Metallurgical Research (CENIM-CSIC), Avda. Gregorio del Amo, 8, 28040 Madrid (Spain)

    2016-04-26

    Retained austenite in nanostructured bainite is able to undergo mechanically induced martensitic transformation. However, the link between transformation and deformation mechanisms involved makes difficult the understanding of the process. In this work, a model has been developed to assess the effect of the external stress itself on the martensite phase transformation. In addition, after a detailed initial microstructural characterization, the martensite fraction evolution during tensile deformation has been obtained by means of X-ray diffraction analyses after interrupted tensile tests in several nanostructured bainitic steels. Experimental results have been compared to the outputs of the model, as a reference. They suggests that stress partitioning between phases upon tensile deformation is promoted by isothermal transformation at lower temperatures.

  1. Lymphoblastic leukemia in pregnancy

    OpenAIRE

    Rojas Castrillo, Yaoska; Guevara González, José Guillermo

    2015-01-01

    Acute Leukemia occurs mainly in age groups of children under 5 years and in elderly patients, however; can also be seen in women of reproductive age. The prevalence of adult acute leukemia in young pregnant women is very rare, one case in 75,000 pregnancies and only 28% of them correspond to Lymphoblastic Leukemia occurs. The association between Acute Lymphocytic Leukemia and pregnancy poses a complex situation where you should not take or delay treatment, but the use of antineoplastic drug c...

  2. A superconducting transformer system for high current cable testing.

    Science.gov (United States)

    Godeke, A; Dietderich, D R; Joseph, J M; Lizarazo, J; Prestemon, S O; Miller, G; Weijers, H W

    2010-03-01

    This article describes the development of a direct-current (dc) superconducting transformer system for the high current test of superconducting cables. The transformer consists of a core-free 10,464 turn primary solenoid which is enclosed by a 6.5 turn secondary. The transformer is designed to deliver a 50 kA dc secondary current at a dc primary current of about 50 A. The secondary current is measured inductively using two toroidal-wound Rogowski coils. The Rogowski coil signal is digitally integrated, resulting in a voltage signal that is proportional to the secondary current. This voltage signal is used to control the secondary current using a feedback loop which automatically compensates for resistive losses in the splices to the superconducting cable samples that are connected to the secondary. The system has been commissioned up to 28 kA secondary current. The reproducibility in the secondary current measurement is better than 0.05% for the relevant current range up to 25 kA. The drift in the secondary current, which results from drift in the digital integrator, is estimated to be below 0.5 A/min. The system's performance is further demonstrated through a voltage-current measurement on a superconducting cable sample at 11 T background magnetic field. The superconducting transformer system enables fast, high resolution, economic, and safe tests of the critical current of superconducting cable samples.

  3. Adult Acute Lymphoblastic Leukemia

    Science.gov (United States)

    Faderl, Stefan; O’Brien, Susan; Pui, Ching-Hon; Stock, Wendy; Wetzler, Meir; Hoelzer, Dieter; Kantarjian, Hagop M.

    2016-01-01

    Acute lymphoblastic leukemia (ALL), a clonal expansion of hematopoietic blasts, is a highly heterogeneous disease comprising many entities for which distinct treatment strategies are pursued. Although ALL is a success story in pediatric oncology, results in adults lag behind those in children. An expansion of new drugs, more reliable immunologic and molecular techniques for the assessment of minimal residual disease, and efforts at more precise risk stratification are generating new aspects of adult ALL therapy. For this review, the authors summarized pertinent and recent literature on ALL biology and therapy, and they discuss current strategies and potential implications of novel approaches to the management of adult ALL. PMID:20101737

  4. Risk-Based Classification System of Patients With Newly Diagnosed Acute Lymphoblastic Leukemia

    Science.gov (United States)

    2016-10-24

    Adult B Acute Lymphoblastic Leukemia; Adult T Acute Lymphoblastic Leukemia; Childhood B Acute Lymphoblastic Leukemia; Childhood T Acute Lymphoblastic Leukemia; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Childhood Acute Lymphoblastic Leukemia

  5. Clinical Utility of Ammonia Concentration as a Diagnostic Test in Monitoring of the Treatment with L-Asparaginase in Children with Acute Lymphoblastic Leukemia

    Directory of Open Access Journals (Sweden)

    Małgorzata Czogała

    2014-01-01

    Full Text Available L-asparaginase (ASP is an enzyme used as one of the basic regimens in the acute lymphoblastic leukemia (ALL therapy. Because of the possibility of the enzyme inactivation by antibodies, monitoring of ASP activity is essential. The aim of the study was to examine if plasma concentration of ammonia, a direct product of the reaction catalyzed by ASP, can be used in the assessment of ASP activity. A group of 87 patients with acute lymphoblastic leukemia treated in the Department of Pediatric Oncology and Hematology in Krakow was enrolled to the study. ASP activity and ammonia concentration were measured after ASP administrations during induction. A positive correlation was found between the ammonia concentration and ASP activity (R=0.44; P<0.0001 and between the medium values of ammonia concentration and ASP activity (R=0.56; P<0.0001. The analysis of ROC curves revealed the moderate accuracy of the ammonia concentration values in the ASP activity assessment. It was also found that the medium value of ammonia concentrations can be useful in identification of the patients with low (<100 IU/L and undetectable (<30 IU/L ASP activity. The plasma ammonia concentration may reflect ASP activity and can be useful when a direct measurement of the activity is unavailable.

  6. The lymphocyte transformation test in allergic contact dermatitis: New opportunities.

    Science.gov (United States)

    Popple, Amy; Williams, Jason; Maxwell, Gavin; Gellatly, Nichola; Dearman, Rebecca J; Kimber, Ian

    2016-01-01

    Allergic contact dermatitis (ACD) is driven by the activation and proliferation of allergen-specific memory T-lymphocytes and is currently diagnosed by patch testing with a selected panel of chemical allergens. The lymphocyte transformation test (LTT) can be used to monitor ex vivo T-lymphocyte responses to antigens, including contact allergens. The LTT is not viewed as being an alternative to patch testing, but it does seek to reflect experimentally skin sensitization to specific chemicals. The LTT is based on stimulation in vitro of antigen-driven T-lymphocyte proliferation. That is, exposure in culture of primed memory T-lymphocytes to the relevant antigen delivered in an appropriate configuration will provoke a secondary response that reflects the acquisition of skin sensitization. The technical aspects of this test and the utility of the approach for investigation of immune responses to contact allergens in humans are reviewed here, with particular emphasis on further development and refinement of the protocol. An important potential application is that it may provide a basis for characterizing those aspects of T-lymphocyte responses to contact allergens that have the greatest influence on skin sensitizing potency and this will be considered in some detail.

  7. Antileukemic Efficacy of Continuous vs Discontinuous Dexamethasone in Murine Models of Acute Lymphoblastic Leukemia.

    Directory of Open Access Journals (Sweden)

    Laura B Ramsey

    Full Text Available Osteonecrosis is one of the most common, serious, toxicities resulting from the treatment of acute lymphoblastic leukemia. In recent years, pediatric acute lymphoblastic leukemia clinical trials have used discontinuous rather than continuous dosing of dexamethasone in an effort to reduce the incidence of osteonecrosis. However, it is not known whether discontinuous dosing would compromise antileukemic efficacy of glucocorticoids. Therefore, we tested the efficacy of discontinuous dexamethasone against continuous dexamethasone in murine models bearing human acute lymphoblastic leukemia xenografts (n = 8 patient samples or murine BCR-ABL+ acute lymphoblastic leukemia. Plasma dexamethasone concentrations (7.9 to 212 nM were similar to those achieved in children with acute lymphoblastic leukemia using conventional dosages. The median leukemia-free survival ranged from 16 to 59 days; dexamethasone prolonged survival from a median of 4 to 129 days in all seven dexamethasone-sensitive acute lymphoblastic leukemias. In the majority of cases (7 of 8 xenografts and the murine BCR-ABL model we demonstrated equal efficacy of the two dexamethasone dosing regimens; whereas for one acute lymphoblastic leukemia sample, the discontinuous regimen yielded inferior antileukemic efficacy (log-rank p = 0.002. Our results support the clinical practice of using discontinuous rather than continuous dexamethasone dosing in patients with acute lymphoblastic leukemia.

  8. Transformation of Follicular Lymphoma to a High-Grade B-Cell Lymphoma With MYC and BCL2 Translocations and Overlapping Features of Burkitt Lymphoma and Acute Lymphoblastic Leukemia: A Case Report and Literature Review

    Directory of Open Access Journals (Sweden)

    Alina M Bischin

    2017-02-01

    Full Text Available Most commonly, histologic transformation (HT from follicular lymphoma (FL manifests as a diffuse large B-cell lymphoma, not otherwise specified (DLBCL, NOS. Less frequently, HT may result in a high-grade B-cell lymphoma (HGBL with MYC and B-cell lymphoma protein 2 (BCL2 and/or BCL6 gene rearrangements, also known as “double-hit” or “triple-hit” lymphomas. In the 2016 revision of the World Health Organization (WHO classification of lymphoid neoplasms, the category B-cell lymphoma, unclassifiable was eliminated due to its vague criteria and limiting diagnostic benefit. Instead, the WHO introduced the HGBL category, characterized by MYC and BCL2 and/or BCL6 rearrangements. Cases that present as an intermediate phenotype of DLBCL and Burkitt lymphoma (BL will fall within this HGBL category. Very rarely, HT results in both the intermediate DLBCL and BL phenotypes and exhibits lymphoblastic features, in which case the WHO recommends that this morphologic appearance should be noted. In comparison with de novo patients with DLBCL, NOS, those with MYC and BCL2 and/or BCL6 gene rearrangements have a worse prognosis. A 63-year-old woman presented with left neck adenopathy. Laboratory assessments, including complete blood count, complete metabolic panel, serum lactate dehydrogenase, and β 2 -microglobulin, were all normal. A whole-body computerized tomographic (CT scan revealed diffuse adenopathy above and below the diaphragm. An excisional node biopsy showed grade 3A nodular FL. The Ki67 labeling index was 40% to 50%. A bone marrow biopsy showed a small focus of paratrabecular CD20+ lymphoid aggregates. She received 6 cycles of bendamustine (90 mg/m 2 on days +1 and +2 and rituximab (375 mg/m 2 on day +2, with each cycle delivered every 4 weeks. A follow-up CT scan at completion of therapy showed a partial response with resolution of axillary adenopathy and a dramatic shrinkage of the large retroperitoneal nodes. After 18 months, she had crampy

  9. 10 CFR 431.193 - Test procedures for measuring energy consumption of distribution transformers.

    Science.gov (United States)

    2010-01-01

    ... distribution transformers. 431.193 Section 431.193 Energy DEPARTMENT OF ENERGY ENERGY CONSERVATION ENERGY EFFICIENCY PROGRAM FOR CERTAIN COMMERCIAL AND INDUSTRIAL EQUIPMENT Distribution Transformers Test Procedures § 431.193 Test procedures for measuring energy consumption of distribution transformers. The...

  10. Biological Therapy in Treating Patients With Advanced Myelodysplastic Syndrome, Acute or Chronic Myeloid Leukemia, or Acute Lymphoblastic Leukemia Who Are Undergoing Stem Cell Transplantation

    Science.gov (United States)

    2017-03-27

    Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); B-cell Adult Acute Lymphoblastic Leukemia; B-cell Childhood Acute Lymphoblastic Leukemia; Childhood Chronic Myelogenous Leukemia; Childhood Myelodysplastic Syndromes; Chronic Myelomonocytic Leukemia; Essential Thrombocythemia; Polycythemia Vera; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Excess Blasts in Transformation; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; T-cell Adult Acute Lymphoblastic Leukemia; T-cell Childhood Acute Lymphoblastic Leukemia

  11. MR features of isolated uterine relapse in an adolescent with acute lymphoblastic leukaemia

    Energy Technology Data Exchange (ETDEWEB)

    Novellas, Sebastien; Fournol, Maude; Geoffray, Anne; Chevallier, Patrick [Regional Hospital Centre and University of Nice, Medical Imaging Service, Archet 2 Hospital, 151 route de Saint Antoine de Ginestiere, B.P. 3079, Nice Cedex 3 (France); Deville, Anne [Regional Hospital Centre and University of Nice, Paediatric Service, Archet 2 Hospital, Nice (France); Kurzenne, Jean-Yves [Regional Hospital Centre and University of Nice, Paediatric Surgery Service, Archet 2 Hospital, Nice (France)

    2008-03-15

    Relapses of lymphoblastic leukaemia traditionally involve the central nervous system and testes in boys. Involvement of the female pelvic organs is frequently found at autopsy; however, involvement of the cervical uterus is rare and even less commonly symptomatic. A 13-cm uterine mass was discovered in a 15-year-old adolescent with a history of lymphoblastic leukaemia during childhood. Pelvic MRI was the best tool to assess the size, characteristics and invasive nature of this lesion of the uterine cervix. To our knowledge, this is a unique case in that we describe the MRI appearance of a relapsing lymphoblastic leukaemic mass both before and after treatment. (orig.)

  12. Nivolumab and Dasatinib in Treating Patients With Relapsed or Refractory Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia

    Science.gov (United States)

    2016-08-25

    B Acute Lymphoblastic Leukemia With t(9;22)(q34;q11.2); BCR-ABL1; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Refractory Adult Acute Lymphoblastic Leukemia; Refractory Childhood Acute Lymphoblastic Leukemia

  13. Test results of a HTS power transformer connected to a power grid

    Science.gov (United States)

    Kimura, H.; Honda, K.; Hayashi, H.; Tsutsumi, K.; Iwakuma, M.; Funaki, K.; Bohno, T.; Tomioka, A.; Yagi, Y.; Maruyama, H.; Ohashi, K.

    2002-08-01

    A 22 kV/6.9 kV-1 MVA high- Tc superconducting (HTS) power transformer has been developed as a prototype with single-phase part of a 3 MVA HTS power transformer. The prototype unit is cooled by a continuous subcooled liquid nitrogen (LN 2) supply system with cryocoolers. During the field tests, the HTS transformer was connected to a distribution line at Imajuku substation (Kyushu Electric Power Co., Inc.) in Fukuoka, and inrush-current test and a long-term operation test were implemented. The test results demonstrated the HTS power transformer's applicability to a power grid.

  14. Acute Lymphoblastic Leukemia Arising in CALR Mutated Essential Thrombocythemia

    Directory of Open Access Journals (Sweden)

    Stephen E. Langabeer

    2016-01-01

    Full Text Available The development of acute lymphoblastic leukemia in an existing myeloproliferative neoplasm is rare with historical cases unable to differentiate between concomitant malignancies or leukemic transformation. Molecular studies of coexisting JAK2 V617F-positive myeloproliferative neoplasms and mature B cell malignancies indicate distinct disease entities arising in myeloid and lymphoid committed hematopoietic progenitor cells, respectively. Mutations of CALR in essential thrombocythemia appear to be associated with a distinct phenotype and a lower risk of thrombosis yet their impact on disease progression is less well defined. The as yet undescribed scenario of pro-B cell acute lymphoblastic leukemia arising in CALR mutated essential thrombocythemia is presented. Intensive treatment for the leukemia allowed for expansion of the original CALR mutated clone. Whether CALR mutations in myeloproliferative neoplasms predispose to the acquisition of additional malignancies, particularly lymphoproliferative disorders, is not yet known.

  15. DNA instability in replicating Huntington's disease lymphoblasts

    Directory of Open Access Journals (Sweden)

    Frati Luigi

    2009-02-01

    Full Text Available Abstract Background The expanded CAG repeat in the Huntington's disease (HD gene may display tissue-specific variability (e.g. triplet mosaicism in repeat length, the longest mutations involving mitotic (germ and glial cells and postmitotic (neurons cells. What contributes to the triplet mutability underlying the development of HD nevertheless remains unknown. We investigated whether, besides the increased DNA instability documented in postmitotic neurons, possible environmental and genetic mechanisms, related to cell replication, may concur to determine CAG repeat mutability. To test this hypothesis we used, as a model, cultured HD patients' lymphoblasts with various CAG repeat lengths. Results Although most lymphoblastoid cell lines (88% showed little or no repeat instability even after six or more months culture, in lymphoblasts with large expansion repeats beyond 60 CAG repeats the mutation size and triplet mosaicism always increased during replication, implying that the repeat mutability for highly expanded mutations may quantitatively depend on the triplet expansion size. None of the investigated genetic factors, potentially acting in cis to the mutation, significantly influence the repeat changes. Finally, in our experiments certain drugs controlled triplet expansion in two prone-to-expand HD cell lines carrying large CAG mutations. Conclusion Our data support quantitative evidence that the inherited CAG length of expanded alleles has a major influence on somatic repeat variation. The longest triplet expansions show wide somatic variations and may offer a mechanistic model to study triplet drug-controlled instability and genetic factors influencing it.

  16. Relationship between ABO blood group and Acute Lymphoblastic Leukemia.

    Science.gov (United States)

    Tavasolian, F; Abdollahi, E; Vakili, M; Amini, A

    2014-01-01

    Acute lymphoblastic leukemia (ALL) constitute a family of genetically heterogeneous lymphoid neoplasms derived from B- and T-lymphoid progenitors. ALL affects both children and adults. Diagnosis is based on morphologic, immunophenotypic, and genetic features that allow differentiation from normal progenitors and other hematopoietic and nonhematopoietic neoplasms. The aim of this study was to investigate the association between ALL and ABO blood group. This is a case-control study that was carried out in Amir Oncology Hospital in Shiraz during 2011 to2013. The case group consisted of 293 patients with acute lymphoblastic leukemia. And compared with 300 subject in control group ( the age in the case group was between 2-5 year, and the age in the control group was between 2-45 year) .Statistical analyzes was done performed by chi -square test. The results was considered significant when p value ABO blood group distribution was 82(A), 59 (B), 24 (AB) and 128(O) in patient with Acute Lymphoblastic Leukemia and the blood group of 300 participants in the control group include, 63% (25) A, 69% (25.6) B, 18 % 06.8) AB and 101% (42.6) O. The ABO blood group distribution showed that there is significant differences between ABO blood group and patients with acute lymphoblastic leukemia . This study showed significant association between ALL and ABO blood group and showed that blood group AB was associated with a higher risk of All (p value<0.001).

  17. Alemtuzumab and Combination Chemotherapy in Treating Patients With Untreated Acute Lymphoblastic Leukemia

    Science.gov (United States)

    2014-03-20

    Acute Undifferentiated Leukemia; B-cell Adult Acute Lymphoblastic Leukemia; B-cell Childhood Acute Lymphoblastic Leukemia; L1 Adult Acute Lymphoblastic Leukemia; L1 Childhood Acute Lymphoblastic Leukemia; L2 Adult Acute Lymphoblastic Leukemia; L2 Childhood Acute Lymphoblastic Leukemia; Philadelphia Chromosome Negative Adult Precursor Acute Lymphoblastic Leukemia; Philadelphia Chromosome Positive Adult Precursor Acute Lymphoblastic Leukemia; Philadelphia Chromosome Positive Childhood Precursor Acute Lymphoblastic Leukemia; T-cell Adult Acute Lymphoblastic Leukemia; T-cell Childhood Acute Lymphoblastic Leukemia; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Childhood Acute Lymphoblastic Leukemia

  18. APPLYING BLACK-BOX TESTING TO MODEL TRANSFORMATIONS IN THE MODEL DRIVEN ARCHITECTURE CONTEXT

    Directory of Open Access Journals (Sweden)

    Luciane Telinski Wiedermann Agner

    2014-01-01

    Full Text Available Testing model transformations has played a leading role with the dissemination of MDA in software development processes. Software testing based on black-box testing, together with the “category partitioning” method, can be efficiently used in order to conduct the verification of model transformations. This study employs software testing techniques to an ATL model transformation in the MDA context and points out their benefits. The black-box testing method was adapted to the MT-PROAPES model transformation based on profiles and platform models. The platform models define the range of input models of the MT-PROAPES and are used for the creation of the test cases. The test cases were selected so as to meet certain requirements and increase the ability to detect errors in the model transformation. This approach makes the test process more agile and does not require any abstraction of behavioral properties of the transformations. The field of transformation testing and verification still faces significant challenges and requires a lot of research. Although having some limitations, black-box testing conforms to various situations, besides allowing its integration with other test strategies.

  19. Simulation Test System of Non-Contact D-dot Voltage Transformer

    Science.gov (United States)

    Yang, Jie; Wang, Jingang; Luo, Ruixi; Gao, Can; Songnong, Li; Kongjun, Zhou

    2016-04-01

    The development trend of future voltage transformer in smart grid is non-contact measurement, miniaturization and intellectualization. This paper proposes one simulation test system of non-contact D-dot transformer for voltage measurement. This simulation test system consists of D-dot transformer, signal processing circuit and ground PC port. D-dot transformer realizes the indirect voltage measurement by measuring the change rate of electric displacement vector, a non-contact means (He et al. 2004, Principles and experiments of voltage transformer based on self-integrating D-dot probe. Proc CSEE 2014;15:2445-51). Specific to the characteristics of D-dot transformer signals, signal processing circuits with strong resistance to interference and distortion-free amplified sensor output signal are designed. WIFI wireless network is used to transmit the voltage detection to LabVIEW-based ground collection port and LabVIEW technology is adopted for signal reception, data processing and analysis and other functions. Finally, a test platform is established to simulate the performance of the whole test system of single-phase voltage transformer. Test results indicate that this voltage transformer has sound real-time performance, high accuracy and fast response speed and the simulation test system is stable and reliable and can be a new prototype of voltage transformers.

  20. TRANSFORMATION

    Energy Technology Data Exchange (ETDEWEB)

    LACKS,S.A.

    2003-10-09

    Transformation, which alters the genetic makeup of an individual, is a concept that intrigues the human imagination. In Streptococcus pneumoniae such transformation was first demonstrated. Perhaps our fascination with genetics derived from our ancestors observing their own progeny, with its retention and assortment of parental traits, but such interest must have been accelerated after the dawn of agriculture. It was in pea plants that Gregor Mendel in the late 1800s examined inherited traits and found them to be determined by physical elements, or genes, passed from parents to progeny. In our day, the material basis of these genetic determinants was revealed to be DNA by the lowly bacteria, in particular, the pneumococcus. For this species, transformation by free DNA is a sexual process that enables cells to sport new combinations of genes and traits. Genetic transformation of the type found in S. pneumoniae occurs naturally in many species of bacteria (70), but, initially only a few other transformable species were found, namely, Haemophilus influenzae, Neisseria meningitides, Neisseria gonorrheae, and Bacillus subtilis (96). Natural transformation, which requires a set of genes evolved for the purpose, contrasts with artificial transformation, which is accomplished by shocking cells either electrically, as in electroporation, or by ionic and temperature shifts. Although such artificial treatments can introduce very small amounts of DNA into virtually any type of cell, the amounts introduced by natural transformation are a million-fold greater, and S. pneumoniae can take up as much as 10% of its cellular DNA content (40).

  1. Transformation

    DEFF Research Database (Denmark)

    Peters, Terri

    2011-01-01

    Artiklen diskuterer ordet "transformation" med udgangspunkt i dels hvorledes ordet bruges i arkitektfaglig terminologi og dels med fokus på ordets potentielle indhold og egnethed i samme teminologi.......Artiklen diskuterer ordet "transformation" med udgangspunkt i dels hvorledes ordet bruges i arkitektfaglig terminologi og dels med fokus på ordets potentielle indhold og egnethed i samme teminologi....

  2. Transformation

    DEFF Research Database (Denmark)

    Peters, Terri

    2011-01-01

    Artiklen diskuterer ordet "transformation" med udgangspunkt i dels hvorledes ordet bruges i arkitektfaglig terminologi og dels med fokus på ordets potentielle indhold og egnethed i samme teminologi.......Artiklen diskuterer ordet "transformation" med udgangspunkt i dels hvorledes ordet bruges i arkitektfaglig terminologi og dels med fokus på ordets potentielle indhold og egnethed i samme teminologi....

  3. Micro/nano-mechanical test system employing tensile test holder with push-to-pull transformer

    Science.gov (United States)

    Oh, Yunje; Cyrankowski, Edward; Shan, Zhiwei; Asif, Syed Amanula Syed

    2013-05-07

    A micromachined or microelectromechanical system (MEMS) based push-to-pull mechanical transformer for tensile testing of micro-to-nanometer scale material samples including a first structure and a second structure. The second structure is coupled to the first structure by at least one flexible element that enables the second structure to be moveable relative to the first structure, wherein the second structure is disposed relative to the first structure so as to form a pulling gap between the first and second structures such that when an external pushing force is applied to and pushes the second structure in a tensile extension direction a width of the pulling gap increases so as to apply a tensile force to a test sample mounted across the pulling gap between a first sample mounting area on the first structure and a second sample mounting area on the second structure.

  4. Micro/nano-mechanical test system employing tensile test holder with push-to-pull transformer

    Energy Technology Data Exchange (ETDEWEB)

    Oh, Yunje; Cyrankowski, Edward; Shan, Zhiwei; Syed Asif, Syed Amanula

    2014-07-29

    A micromachined or microelectromechanical system (MEMS) based push-to-pull mechanical transformer for tensile testing of micro-to-nanometer scale material samples including a first structure and a second structure. The second structure is coupled to the first structure by at least one flexible element that enables the second structure to be moveable relative to the first structure, wherein the second structure is disposed relative to the first structure so as to form a pulling gap between the first and second structures such that when an external pushing force is applied to and pushes the second structure in a tensile extension direction a width of the pulling gap increases so as to apply a tensile force to a test sample mounted across the pulling gap between a first sample mounting area on the first structure and a second sample mounting area on the second structure.

  5. TRANSFORMER

    Science.gov (United States)

    Baker, W.R.

    1959-08-25

    Transformers of a type adapted for use with extreme high power vacuum tubes where current requirements may be of the order of 2,000 to 200,000 amperes are described. The transformer casing has the form of a re-entrant section being extended through an opening in one end of the cylinder to form a coaxial terminal arrangement. A toroidal multi-turn primary winding is disposed within the casing in coaxial relationship therein. In a second embodiment, means are provided for forming the casing as a multi-turn secondary. The transformer is characterized by minimized resistance heating, minimized external magnetic flux, and an economical construction.

  6. Dry type transformers: Performance tests and qualification procedures. Trasformatori a secco: prove e metodologie di collaudo

    Energy Technology Data Exchange (ETDEWEB)

    Caprio, G.; Yakov, S.

    1986-06-01

    In the performance testing of dry type transformers, not only electrical, but even environmental conditions play an important role. This is true especially with regard to dielectric stress withstand capabilities since the dielectric field is predominantly concentrated in the aerated zones where unfavourable atmospheric conditions can lead to considerable decay in dielectric rigidity. Testing procedures, normally employed for oil insulated transformers should therefore, in the case of dry type transformers, be modified to be able to ascertain compatibility between transformer type and the specific environmental conditions in which it must operate.

  7. Apoptosis induction by Maackia amurensis agglutinin in childhood acute lymphoblastic leukemic cells

    DEFF Research Database (Denmark)

    Kapoor, Sarika; Marwaha, Ram; Majumdar, Siddhartha;

    2007-01-01

    Malignant transformation is known to be associated with changes in cell surface carbohydrate-architecture, which can be detected by lectins. In the present study, Maackia amurensis agglutinin (MAA), specific for NeuNAcalpha(2-->3)Gal/GalNAc showed strong binding with lymphoblasts of children havi...

  8. Transformational Leadership and Organizational Citizenship Behavior: A Meta-Analytic Test of Underlying Mechanisms.

    Science.gov (United States)

    Nohe, Christoph; Hertel, Guido

    2017-01-01

    Based on social exchange theory, we examined and contrasted attitudinal mediators (affective organizational commitment, job satisfaction) and relational mediators (trust in leader, leader-member exchange; LMX) of the positive relationship between transformational leadership and organizational citizenship behavior (OCB). Hypotheses were tested using meta-analytic path models with correlations from published meta-analyses (761 samples with 227,419 individuals overall). When testing single-mediator models, results supported our expectations that each of the mediators explained the relationship between transformational leadership and OCB. When testing a multi-mediator model, LMX was the strongest mediator. When testing a model with a latent attitudinal mechanism and a latent relational mechanism, the relational mechanism was the stronger mediator of the relationship between transformational leadership and OCB. Our findings help to better understand the underlying mechanisms of the relationship between transformational leadership and OCB.

  9. Transformational Leadership and Organizational Citizenship Behavior: A Meta-Analytic Test of Underlying Mechanisms

    Directory of Open Access Journals (Sweden)

    Christoph Nohe

    2017-08-01

    Full Text Available Based on social exchange theory, we examined and contrasted attitudinal mediators (affective organizational commitment, job satisfaction and relational mediators (trust in leader, leader-member exchange; LMX of the positive relationship between transformational leadership and organizational citizenship behavior (OCB. Hypotheses were tested using meta-analytic path models with correlations from published meta-analyses (761 samples with 227,419 individuals overall. When testing single-mediator models, results supported our expectations that each of the mediators explained the relationship between transformational leadership and OCB. When testing a multi-mediator model, LMX was the strongest mediator. When testing a model with a latent attitudinal mechanism and a latent relational mechanism, the relational mechanism was the stronger mediator of the relationship between transformational leadership and OCB. Our findings help to better understand the underlying mechanisms of the relationship between transformational leadership and OCB.

  10. Clonal origins of ETV6-RUNX1+ acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Alpar, D.; Wren, D.; Ermini, Luca;

    2015-01-01

    Studies on twins with concordant acute lymphoblastic leukemia (ALL) have revealed that ETV6-RUNX1 gene fusion is a common, prenatal genetic event with other driver aberrations occurring subclonally and probably postnatally. The fetal cell type that is transformed by ETV6-RUNX1 is not identified...... by such studies or by the analysis of early B-cell lineage phenotype of derived progeny. Ongoing, clonal immunoglobulin (IG) and cross-lineage T-cell receptor (TCR) gene rearrangements are features of B-cell precursor leukemia and commence at the pro-B-cell stage of normal B-cell lineage development. We reasoned...

  11. Acute hepatitis A induction of precursor B-cell acute lymphoblastic leukemia: a causal relationship?

    Science.gov (United States)

    Senadhi, V; Emuron, D; Gupta, R

    2010-09-01

    Precursor B-cell acute lymphoblastic leukemia accounts for 2% of all lymphoid neoplasms in the United States and occurs most frequently in childhood, but can also occur in adults with a median age of 39 years. It is more commonly seen in males and in Caucasians. We present a case of a 51-year-old Caucasian female with the development of precursor B-cell acute lymphoblastic leukemia after suffering acute hepatitis A 4 weeks prior to her diagnosis. She presented with malaise for a month without spontaneous bruising/bleeding, infections, or B-symptoms, such as fevers, night sweats, or unintentional weight loss. Nonspecific viral transformation of bone marrow has been discussed in the literature, but we specifically describe hepatitis A-induced adult-onset precursor B-cell acute lymphoblastic leukemia, which is the first reported case in the literature.

  12. In situ measurement of solvent-mediated phase transformations during dissolution testing

    DEFF Research Database (Denmark)

    Aaltonen, Jaakko; Heinänen, Paula; Peltonen, Leena

    2006-01-01

    In this study, solvent-mediated phase transformations of theophylline (TP) and nitrofurantoin (NF) were measured in a channel flow intrinsic dissolution test system. The test set-up comprised simultaneous measurement of drug concentration in the dissolution medium (with UV-Vis spectrophotometry......). Transformation of TP anhydrate to TP monohydrate resulted in a clear decrease in the dissolution rate, while the transformation of NF anhydrate (form beta) to NF monohydrate (form II) could not be linked as clearly to changes in the dissolution rate. The transformation of TP was an order of magnitude faster than...... that of NF. The presence of a water absorbing excipient, microcrystalline cellulose, was found to delay the onset of the transformation of TP anhydrate. Combining the measurement of drug concentration in the dissolution medium with the solid phase measurement offers a deeper understanding of the solvent...

  13. New decision support tool for acute lymphoblastic leukemia classification

    Science.gov (United States)

    Madhukar, Monica; Agaian, Sos; Chronopoulos, Anthony T.

    2012-03-01

    In this paper, we build up a new decision support tool to improve treatment intensity choice in childhood ALL. The developed system includes different methods to accurately measure furthermore cell properties in microscope blood film images. The blood images are exposed to series of pre-processing steps which include color correlation, and contrast enhancement. By performing K-means clustering on the resultant images, the nuclei of the cells under consideration are obtained. Shape features and texture features are then extracted for classification. The system is further tested on the classification of spectra measured from the cell nuclei in blood samples in order to distinguish normal cells from those affected by Acute Lymphoblastic Leukemia. The results show that the proposed system robustly segments and classifies acute lymphoblastic leukemia based on complete microscopic blood images.

  14. Item Transformation for Computer Assisted Language Testing: The Adaptation of the Spanish University Entrance Examination

    Science.gov (United States)

    Laborda, Jesus Garcia; Bakieva, Margarita; Gonzalez-Such, Jose; Pavon, Ana Sevilla

    2010-01-01

    Since the Spanish Educational system is changing and promoting the use of online tests, it was necessary to study the transformation of test items in the "Spanish University Entrance Examination" (IB P.A.U.) to diminish the effect of test delivery changes (through its computerization) in order to affect the least the current model. The…

  15. TRESK potassium channel in human T lymphoblasts

    Energy Technology Data Exchange (ETDEWEB)

    Sánchez-Miguel, Dénison Selene, E-mail: amurusk@hotmail.com [Center for Biomedical Research, University of Colima, Av. 25 de Julio 965, Villa San Sebastian, C.P. 28045 Colima (Mexico); García-Dolores, Fernando, E-mail: garciaddf@yahoo.com [Department of Pathology, Institute of Forensic Sciences, Av. Niños Héroes 130, Col. Doctores, C.P. 06720 Mexico, DF (Mexico); Rosa Flores-Márquez, María, E-mail: mariafo31@yahoo.com.mx [National Medical Center of Occident (CMNO) IMSS, Belisario Dominguez 735, Col. Independencia Oriente, C.P. 44340 Guadalajara, Jalisco (Mexico); Delgado-Enciso, Iván [University of Colima, School of Medicine, Av. Universidad 333, Col. Las Viboras, C.P. 28040 Colima (Mexico); Pottosin, Igor, E-mail: pottosin@ucol.mx [Center for Biomedical Research, University of Colima, Av. 25 de Julio 965, Villa San Sebastian, C.P. 28045 Colima (Mexico); Dobrovinskaya, Oxana, E-mail: oxana@ucol.mx [Center for Biomedical Research, University of Colima, Av. 25 de Julio 965, Villa San Sebastian, C.P. 28045 Colima (Mexico)

    2013-05-03

    Highlights: • TRESK (KCNK18) mRNA is present in different T lymphoblastic cell lines. • KCNK18 mRNA was not found in resting peripheral blood lymphocytes. • Clinical samples of T lymphoblastic leukemias and lymphomas were positive for TRESK. • TRESK in T lymphoblasts has dual localization, in plasma membrane and intracellular. -- Abstract: TRESK (TWIK-related spinal cord K{sup +}) channel, encoded by KCNK18 gene, belongs to the double-pore domain K{sup +} channel family and in normal conditions is expressed predominantly in the central nervous system. In our previous patch-clamp study on Jurkat T lymphoblasts we have characterized highly selective K{sup +} channel with pharmacological profile identical to TRESK. In the present work, the presence of KCNK18 mRNA was confirmed in T lymphoblastic cell lines (Jurkat, JCaM, H9) but not in resting peripheral blood lymphocytes of healthy donors. Positive immunostaining for TRESK was demonstrated in lymphoblastic cell lines, in germinal centers of non-tumoral lymph nodes, and in clinical samples of T acute lymphoblastic leukemias/lymphomas. Besides detection in the plasma membrane, intracellular TRESK localization was also revealed. Possible involvement of TRESK channel in lymphocyte proliferation and tumorigenesis is discussed.

  16. Effect of Taurine on Febrile Episodes in Acute Lymphoblastic Leukemia

    Directory of Open Access Journals (Sweden)

    Mina Islambulchilar

    2015-03-01

    Full Text Available Purpose: The purpose of our study was to evaluate the effect of oral taurine on the incidence of febrile episodes during chemotherapy in young adults with acute lymphoblastic leukemia. Methods: Forty young adults with acute lymphoblastic leukemia, at the beginning of maintenance course of their chemotherapy, were eligible for this study. The study population was randomized in a double blind manner to receive either taurine or placebo (2 gram per day orally. Life quality and side effects including febrile episodes were assessed using questionnaire. Data were analyzed using Pearson’s Chi square test. Results: Of total forty participants, 43.8% were female and 56.3 % were male. The mean age was 19.16±1.95 years (ranges: 16-23 years. The results indicated that the levels of white blood cells are significantly (P<0.05 increased in taurine treated group. There was no elevation in blasts count. A total of 70 febrile episodes were observed during study, febrile episodes were significantly (P<0.05 lower in taurine patients in comparison to the control ones. Conclusion: The overall incidence of febrile episodes and infectious complications in acute lymphoblastic leukemia patients receiving taurine was lower than placebo group. Taurine’s ability to increase leukocyte count may result in lower febrile episodes.

  17. Impulse tests on distribution transformers protected by means of spark gaps

    Energy Technology Data Exchange (ETDEWEB)

    Pykaelae, M.L.; Palva, V. [Helsinki Univ. of Technology, Otaniemi (Finland). High Voltage Institute; Niskanen, K. [ABB Corporate Research, Vaasa (Finland)

    1997-12-31

    Distribution transformers in rural networks have to cope with transient overvoltages, even with those caused by the direct lightning strokes to the lines. In Finland the 24 kV network conditions, such as wooden pole lines, high soil resistivity and isolated neutral network, lead into fast transient overvoltages. Impulse testing of pole-mounted distribution transformers ({<=} 200 kVA) protected by means of spark gaps were studied. Different failure detection methods were used. Results can be used as background information for standardization work dealing with distribution transformers protected by means of spark gaps. (orig.) 9 refs.

  18. Acute Lymphoblastic Leukaemia presenting as Juvenile Idiopathic ...

    African Journals Online (AJOL)

    Acute Lymphoblastic Leukaemia presenting as Juvenile Idiopathic Arthritis in a Nigerian boy. ... lead to delay in commencing appropriate treatment. ... of two months duration, had an elevated Rheumatoid factor and X-ray findings suggestive of ...

  19. Acute lymphoblastic leukemia presenting with gross hematuria

    OpenAIRE

    Kalbani, Naifain Al; Weitzman, Sheila; Abdelhaleem, Mohamed; Carcao, Manuel; Abla, Oussama

    2007-01-01

    A case of a six-year-old boy presenting with gross hematuria is reported. Investigations revealed the etiology of the hematuria to be thrombocytopenia in the setting of newly diagnosed acute lymphoblastic leukemia. The diagnosis of leukemia was confirmed by bone marrow examination. The patient’s hematuria completely resolved with platelet transfusions. Although thrombocytopenia is a very common presenting feature of acute lymphoblastic leukemia, gross hematuria is exceedingly rare. Thus, thro...

  20. The Application Wavelet Transform Algorithm in Testing ADC Effective Number of Bits

    Directory of Open Access Journals (Sweden)

    Emad A. Awada

    2013-10-01

    Full Text Available In evaluating Analog to Digital Convertors, many parameters are checked for performance and error rate.One of these parameters is the device Effective Number of Bits. In classical testing of Effective Number ofBits, testing is based on signal to noise components ratio (SNR, whose coefficients are driven viafrequency domain (Fourier Transform of ADC’s output signal. Such a technique is extremely sensitive tonoise and require large number of data samples. That is, longer and more complex testing process as thedevice under test increases in resolutions. Meanwhile, a new time – frequency domain approach (known asWavelet transform is proposed to measure and analyze Analog-to-Digital Converters parameter ofEffective Number of Bits with less complexity and fewer data samples.In this work, the algorithm of Wavelet transform was used to estimate worst case Effective Number of Bitsand compare the new testing results with classical testing methods. Such an algorithm, Wavelet transform,have shown DSP testing process improvement in terms of time and computations complexity based on itsspecial properties of multi-resolutions.

  1. Quantitative predictivity of the transformation in vitro assay compared with the Ames test. [Hamsters

    Energy Technology Data Exchange (ETDEWEB)

    Parodi, S.; Taningher, M.; Russo, P.; Pala, M.; Vecchio, D.; Fassina, G.; Santi, L.

    For 59 chemical compounds, homogeneous data on transformation in vitro, mutagenicity in the Ames test, and carcinogenicity was reviewed. The potency in inducing transformation in vitro in hamster fibroblast cells was compared with the carcinogenic potency and a modest correlation coefficient was found between the two parameters. For these same 59 compounds it was also possible to compare mutagenic potency in the Ames test with carcinogenic potency. The correlation level was very similar. The predictivity of transformation in vitro increased significantly when only compounds for which some kind of dose-response relationship was available were utilized. This result stresses the importance of the quantitative aspect of the response in predictivity studies. The present study is compared with previous studies on the quantitative predictivity of different short-term tests. The work is not definitive, but gives an idea of the possible type of approach to the problem of comparing quantitative predictivities.

  2. Reliability Analysis of Component Software in Wireless Sensor Networks Based on Transformation of Testing Data

    Directory of Open Access Journals (Sweden)

    Chunyan Hou

    2009-08-01

    Full Text Available We develop an approach of component software reliability analysis which includes the benefits of both time domain, and structure based approaches. This approach overcomes the deficiency of existing NHPP techniques that fall short of addressing repair, and internal system structures simultaneously. Our solution adopts a method of transformation of testing data to cover both methods, and is expected to improve reliability prediction. This paradigm allows component-based software testing process doesn’t meet the assumption of NHPP models, and accounts for software structures by the way of modeling the testing process. According to the testing model it builds the mapping relation from the testing profile to the operational profile which enables the transformation of the testing data to build the reliability dataset required by NHPP models. At last an example is evaluated to validate and show the effectiveness of this approach.

  3. A Study on Measurement Error during Alternating Current Induced Voltage Tests on Large Transformers

    Institute of Scientific and Technical Information of China (English)

    WANG Xuan; LI Yun-ge; CAO Xiao-long; LIU Ying

    2006-01-01

    The large transformer is pivotal equipment in an electric power supply system; Its partial discharge test and the induced voltage withstand test on large transformers are carried out at a frequency about twice the working frequency. If the magnetizing inductance cannot compensate for the stray capacitance, the test sample turns into a capacitive load and a capacitive rise exhibits in the testing circuit. For self-restoring insulation, a method has been recommended in IEC60-1 that an unapproved measuring system be calibrated by an approved system at a voltage not less than 50% of the rated testing voltage, and the result then be extrapolated linearly. It has been found that this method leads to great error due to the capacitive rise if it is not correctly used during a withstand voltage test under certain testing conditions, especially for a test on high voltage transformers with large capacity. Since the withstand voltage test is the most important means to examine the operation reliability of a transformer, and it can be destructive to the insulation, a precise measurement must be guaranteed. In this paper a factor, named as the capacitive rise factor, is introduced to assess the rise. The voltage measurement error during the calibration is determined by the parameters of the test sample and the testing facilities, as well as the measuring point. Based on theoretical analysis in this paper, a novel method is suggested and demonstrated to estimate the error by using the capacitive rise factor and other known parameters of the testing circuit.

  4. A Poisson-Fault Model for Testing Power Transformers in Service

    Directory of Open Access Journals (Sweden)

    Dengfu Zhao

    2014-01-01

    Full Text Available This paper presents a method for assessing the instant failure rate of a power transformer under different working conditions. The method can be applied to a dataset of a power transformer under periodic inspections and maintenance. We use a Poisson-fault model to describe failures of a power transformer. When investigating a Bayes estimate of the instant failure rate under the model, we find that complexities of a classical method and a Monte Carlo simulation are unacceptable. Through establishing a new filtered estimate of Poisson process observations, we propose a quick algorithm of the Bayes estimate of the instant failure rate. The proposed algorithm is tested by simulation datasets of a power transformer. For these datasets, the proposed estimators of parameters of the model have better performance than other estimators. The simulation results reveal the suggested algorithms are quickest among three candidates.

  5. Reference values for the transformed Van Lieshout hand function test for tetraplegia.

    NARCIS (Netherlands)

    Spooren, A.I.; Arnould, C.; Smeets, R.J.P.; Snoek, G.; Seelen, H.A.

    2013-01-01

    STUDY DESIGN: Longitudinal cohort study. OBJECTIVES: Previously, the Van Lieshout hand function test for tetraplegia (short form)(VLT-SF) has been transformed into an interval scale (r_VLT-SF) using the Rasch analysis, thereby fulfilling the requirements of an objective measurement. The present stud

  6. Introduction to Lean Canvas Transformation Models and Metrics in Software Testing

    Directory of Open Access Journals (Sweden)

    Nidagundi Padmaraj

    2016-05-01

    Full Text Available Software plays a key role nowadays in all fields, from simple up to cutting-edge technologies and most of technology devices now work on software. Software development verification and validation have become very important to produce the high quality software according to business stakeholder requirements. Different software development methodologies have given a new dimension for software testing. In traditional waterfall software development software testing has approached the end point and begins with resource planning, a test plan is designed and test criteria are defined for acceptance testing. In this process most of test plan is well documented and it leads towards the time-consuming processes. For the modern software development methodology such as agile where long test processes and documentations are not followed strictly due to small iteration of software development and testing, lean canvas transformation models can be a solution. This paper provides a new dimension to find out the possibilities of adopting the lean transformation models and metrics in the software test plan to simplify the test process for further use of these test metrics on canvas.

  7. A new Laplace transformation method for dynamic testing of solar collectors

    DEFF Research Database (Denmark)

    Kong, Weiqiang; Perers, Bengt; Fan, Jianhua;

    2015-01-01

    A new dynamic method for solar collector testing is developed. It is characterized by using the Laplace transformation technique to solve the differential governing equation. The new method was inspired by the so called New Dynamic Method (NDM) (Amer E. et al (1999) [1]) but totally different....... By integration of the Laplace transformation technique with the Quasi Dynamic Test (QDT) model (Fischer S. et al (2004) [2]), the Laplace – QDT (L-QDT) model is derived. Two experimental methods are then introduced. One is the shielding method which needs to shield and un-shield solar collector continuously...... and the natural experimental method. The identified collector parameters are then compared and analyzed with those obtained by the steady state test method and the QDT test method. The results comparison shows that the L-QDT method and the natural experimental method are also valid. It can be concluded...

  8. Martensitic transformation during fatigue testing of an AISI 301LN steel

    OpenAIRE

    Mateo García, Antonio Manuel; Fargas Ribas, Gemma

    2012-01-01

    The plastic deformation accumulated during fatigue testing can induce the transformation of austenite to martensite in metastable austenitic stainless steels. To analyze this issue, a metastable austenitic stainless steel grade AISI 301 LN was studied in two different conditions, i.e. annealed and cold rolled. In the first case, the steel was fully austenitic, whereas cold rolled material had almost 30% of martensite. High cycle fatigue tests at a stress ratio of 0.8 were carried out on flat ...

  9. The molecular genetic makeup of acute lymphoblastic leukemia | Office of Cancer Genomics

    Science.gov (United States)

    Abstract: Genomic profiling has transformed our understanding of the genetic basis of acute lymphoblastic leukemia (ALL). Recent years have seen a shift from microarray analysis and candidate gene sequencing to next-generation sequencing. Together, these approaches have shown that many ALL subtypes are characterized by constellations of structural rearrangements, submicroscopic DNA copy number alterations, and sequence mutations, several of which have clear implications for risk stratification and targeted therapeutic intervention.

  10. Lymphoblastic lymphoma involving multiple vertebrae.

    Science.gov (United States)

    Li, Da; Xu, Yu-Lun; Wu, Zhen

    2017-09-26

    Acute lymphoblastic lymphoma (ALL) was a malignant hematological disease in childhood but rarely, initially involved epidural compartment in adult. A 20-year-old male presented with progressive osphyalgia for 2 months and left lower motor weakness for 2 weeks with constipation. Physical examination revealed decreased muscle strength and numbness of left lower limb, and abnormal gait. Contrasted MRI showed multiple vertebrae of hypointense T1 signals (C2/C4/C7/T5/T8/T9/T12/L2/L4) and an intraspinal epidural lesion (L2-4). Subtotal resection was achieved. Histopathology suggested malignant B-cell lymphoma with Ki-67 of 90% and positivity of leukocyte common antigen (LCA). A bone marrow biopsy was unequivocally diagnostic of B-cell ALL followed by chemotherapy (Methotrexate) and partial recovery was observed. The present case was the oldest patient with epidural ALL. The radiographic changes in multiple vertebrae suggested metabolic, hematological, or granulomatous disease. The marrow biopsy was necessary if without hypercalcemia and abnormal peripheral blood examination. Accurate pathological diagnosis was essential. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Molecular diagnosis of lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    Kalal Iravathy Goud

    2013-01-01

    Full Text Available The mixed lineage leukemia (MLL gene at chromosome band 11q23 is commonly involved in reciprocal translocations that is detected in acute leukemia. The MLL gene, coomonly known as mixed lineage leukemia or myeloid lymphoid leukemia, has been independently identified and cloned from the 11q23 breakpoint of acute leukemia. We describe a patient with acute lymphoblastic leukemia whose cells had shown reciprocal translocation between short arm (p21 of chromosome 2 and long arm (q23 of chromosome number 11 [t(2;11 (p21;q23] by cytogenetic analysis. Fluorescence in situ hybridization analysis (FISH was also performed for reconfirmation with a probe for MLL which showed split signals, hybridizing to both the derivative 2 and 11 chromosomes. Our study confirmed FISH as the most suitable assay for detecting MLL rearrangements because of its sensitivity and speed. It recommended that FISH should be used as complementary to conventional cytogenetic analysis. In conclusion, evaluation of the t(2;11(p21;q23 was done by molecular clarification and flow cytometry.

  12. Gene-expression patterns in drug-resistant acute lymphoblastic leukemia cells and response to treatment

    NARCIS (Netherlands)

    A. Holleman (Amy); C. Cheng (Cheng); C.H. Pui (Ching-Hon); W.E. Evans (William); M.V. Relling (Mary); R. Pieters (Rob); G.E. Janka-Schaub (Gritta); M.H. Cheok (Meyling); M.L. den Boer (Monique); W. Yang; A.J. Veerman; K.M. Kazemier (Karin); D. Pei (Deqing)

    2004-01-01

    textabstractBACKGROUND: Childhood acute lymphoblastic leukemia (ALL) is curable with chemotherapy in approximately 80 percent of patients. However, the cause of treatment failure in the remaining 20 percent of patients is largely unknown. METHODS: We tested leukemia cells from 173

  13. Well testing applications of numerical Laplace transformation of sampled-data

    Energy Technology Data Exchange (ETDEWEB)

    Onur, M.; Reynolds, A.C.

    1996-12-31

    In recent years, the numerical Laplace transformation of sampled-data has proven to be useful for well test analysis applications. However, the success of this approach is highly dependent on the algorithms used to transform sampled-data into Laplace space and to perform the numerical inversion. In this work, we investigate several functional approximations (piecewise linear, quadratic, and log-linear) for sampled-data to achieve the {open_quotes}forward{close_quotes} Laplace transformation and present new methods to deal with the {open_quotes}tail{close_quotes} effects associated with transforming sampled-data. New algorithms that provide accurate transformation of sampled-data into Laplace space are provided. The algorithms presented can be applied to generate accurate pressure-derivatives in the time domain. Three different algorithms investigated for the numerical inversion of sampled-data. Applications of the algorithms to convolution, deconvolution, and parameter estimation in Laplace space are also presented. By using the algorithms presented here, it is shown that performing curve-fitting in the Laplace domain without numerical inversion is computationally more efficient than performing it in the time domain. Both synthetic and field examples are considered to illustrate the applicability of the proposed algorithms.

  14. Automation of the temperature elevation test in transformers with insulating oil.

    Science.gov (United States)

    Vicente, José Manuel Esteves; Rezek, Angelo José Junqueira; de Almeida, Antonio Tadeu Lyrio; Guimarães, Carlos Alberto Mohallem

    2008-01-01

    The automation of the temperature elevation test is outlined here for both the oil temperature elevation and the determination of the winding temperature elevation. While automating this test it is necessary to use four thermometers, one three-phase wattmeter, a motorized voltage variator and a Kelvin bridge to measure the resistance. All the equipments must communicate with a microcomputer, which will have the test program implemented. The system to be outlined here was initially implemented in the laboratory and, due to the good results achieved, is already in use in some transformer manufacturing plants.

  15. Transient excitation and data processing techniques employing the fast fourier transform for aeroelastic testing

    Science.gov (United States)

    Jennings, W. P.; Olsen, N. L.; Walter, M. J.

    1976-01-01

    The development of testing techniques useful in airplane ground resonance testing, wind tunnel aeroelastic model testing, and airplane flight flutter testing is presented. Included is the consideration of impulsive excitation, steady-state sinusoidal excitation, and random and pseudorandom excitation. Reasons for the selection of fast sine sweeps for transient excitation are given. The use of the fast fourier transform dynamic analyzer (HP-5451B) is presented, together with a curve fitting data process in the Laplace domain to experimentally evaluate values of generalized mass, model frequencies, dampings, and mode shapes. The effects of poor signal to noise ratios due to turbulence creating data variance are discussed. Data manipulation techniques used to overcome variance problems are also included. The experience is described that was gained by using these techniques since the early stages of the SST program. Data measured during 747 flight flutter tests, and SST, YC-14, and 727 empennage flutter model tests are included.

  16. The numerical method of inverse Laplace transform for calculation of overvoltages in power transformers and test results

    Directory of Open Access Journals (Sweden)

    Mikulović Jovan Č.

    2014-01-01

    Full Text Available A methodology for calculation of overvoltages in transformer windings, based on a numerical method of inverse Laplace transform, is presented. Mathematical model of transformer windings is described by partial differential equations corresponding to distributed parameters electrical circuits. The procedure of calculating overvoltages is applied to windings having either isolated neutral point, or grounded neutral point, or neutral point grounded through impedance. A comparative analysis of the calculation results obtained by the proposed numerical method and by analytical method of calculation of overvoltages in transformer windings is presented. The results computed by the proposed method and measured voltage distributions, when a voltage surge is applied to a three-phase 30 kVA power transformer, are compared. [Projekat Ministartsva nauke Republike Srbije, br. TR-33037 i br. TR-33020

  17. Aberrant Signaling Pathways in T-Cell Acute Lymphoblastic Leukemia

    Science.gov (United States)

    Bongiovanni, Deborah; Saccomani, Valentina

    2017-01-01

    T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive disease caused by the malignant transformation of immature progenitors primed towards T-cell development. Clinically, T-ALL patients present with diffuse infiltration of the bone marrow by immature T-cell blasts high blood cell counts, mediastinal involvement, and diffusion to the central nervous system. In the past decade, the genomic landscape of T-ALL has been the target of intense research. The identification of specific genomic alterations has contributed to identify strong oncogenic drivers and signaling pathways regulating leukemia growth. Notwithstanding, T-ALL patients are still treated with high-dose multiagent chemotherapy, potentially exposing these patients to considerable acute and long-term side effects. This review summarizes recent advances in our understanding of the signaling pathways relevant for the pathogenesis of T-ALL and the opportunities offered for targeted therapy. PMID:28872614

  18. Improved sensitivity testing of explosives using transformed Up-Down methods

    Science.gov (United States)

    Brown, Geoffrey W.

    2014-05-01

    Sensitivity tests provide data that help establish guidelines for the safe handling of explosives. Any sensitivity test is based on assumptions to simplify the method or reduce the number of individual sample evaluations. Two common assumptions that are not typically checked after testing are 1) explosive response follows a normal distribution as a function of the applied stimulus levels and 2) the chosen test level spacing is close to the standard deviation of the explosive response function (for Bruceton Up-Down testing for example). These assumptions and other limitations of traditional explosive sensitivity testing can be addressed using Transformed Up-Down (TUD) test methods. TUD methods have been developed extensively for psychometric testing over the past 50 years and generally use multiple tests at a given level to determine how to adjust the applied stimulus. In the context of explosive sensitivity we can use TUD methods that concentrate testing around useful probability levels. Here, these methods are explained and compared to Bruceton Up-Down testing using computer simulation. The results show that the TUD methods are more useful for many cases but that they do require more tests as a consequence. For non-normal distributions, however, the TUD methods may be the only accurate assessment method.

  19. Simulations and cold-test results of a prototype plane wave transformer linac structure

    Directory of Open Access Journals (Sweden)

    Arvind Kumar

    2002-03-01

    Full Text Available We have built a 4-cell prototype plane wave transformer (PWT linac structure. We discuss here details of the design and fabrication of the PWT linac structure. We present results from superfish and gdfidl simulations as well as cold tests, which are in good agreement with each other. We also present detailed tolerance maps for the PWT structure. We discuss beam dynamics simulation studies performed using parmela.

  20. Test of mode-division multiplexing and demultiplexing in free-space with diffractive transformation optics

    OpenAIRE

    Ruffato, Gianluca; Massari, Michele; Parisi, Giuseppe; Romanato, Filippo

    2016-01-01

    In recent years, mode-division multiplexing (MDM) has been proposed as a promising solution in order to increase the information capacity of optical networks both in free-space and in optical fiber transmission. Here we present the design, fabrication and test of diffractive optical elements for mode-division multiplexing based on optical transformations in the visible range. Diffractive optics have been fabricated by means of 3D high-resolution electron beam lithography on polymethylmethacry...

  1. Leader emotional intelligence, transformational leadership, trust and team commitment: Testing a model within a team context

    OpenAIRE

    Anton F. Schlechter; Jacoba J. Strauss

    2008-01-01

    This exploratory study tested a model within a team context consisting of transformational-leadership behaviour, team-leader emotional intelligence, trust (both in the team leader and in the team members) and team commitment. It was conducted within six manufacturing plants, with 25 teams participating. Of the 320 surveys distributed to these teams, 178 were received (which equals a 56% response rate). The surveys consisted of the multi-factor leadership questionnaire (MLQ), the Swinburne Uni...

  2. Design, construction, and test of a passive optical prototype high voltage instrument transformer

    DEFF Research Database (Denmark)

    Christensen, Lars Hofmann

    1995-01-01

    This paper describes an optical voltage transformer (OVT) for a 132-130 kV system based on the Pockels effect in a Bi4Ge3O12 crystal. Different from the majority of OVTs reported, this construction does not use any capacitive voltage division. To accomplish this, it was necessary to redesign...... the optical modulator. A prototype of the OVT has been constructed and tested...

  3. Development and Testing the Technology of Complex Transformation of Carbohydrates from Vegetable Raw Materials into Bioethanol

    Directory of Open Access Journals (Sweden)

    S.P. Tsygankov

    2013-07-01

    Full Text Available Results of development and testing the tentative technology of sweet sorghum and finger millet processing into bioethanol are described. The carbohydrates content and range of the studied vegetable biomass as the raw material is defined. Bioethanol potential output from sugar sorghum and finger millet carbohydrates and key technological parameters of preparation of both types of vegetable raw material for alcohol fermentation are defined. The concept of the tentative technology of bioethanol production from carbohydrate raw material of the first and second generations is offered. Testing of complex transformation of carbohydrates from vegetable raw materials into bioethanol is performed.

  4. Acute Lymphoblastic Leukaemia presenting as Juvenile Idiopathic ...

    African Journals Online (AJOL)

    PROF. EZECHUKWU

    2013-04-28

    Apr 28, 2013 ... Acute lymphoblastic leukaemia (ALL) accounts for about 77% of cases ... tosis with a White Blood Cell count (WBC) of greater than 30 x 109/L and ... tarsometatarsal, small interphalangeal joints of the feet and vertebrae.3 Our ...

  5. Childhood acute lymphoblastic leukaemia and birthweight

    DEFF Research Database (Denmark)

    Roman, Eve; Lightfoot, Tracy; Smith, Alexandra G

    2013-01-01

    BACKGROUND: Heavy birthweight is one of the few established risk factors for childhood acute lymphoblastic leukaemia (ALL). To provide new insight into this relationship, particularly at the extremes ( 4500 g), we pooled data from three of the largest childhood cancer case...

  6. High-Risk Childhood Acute Lymphoblastic Leukemia

    Science.gov (United States)

    Bhojwani, Deepa; Howard, Scott C.; Pui, Ching-Hon

    2009-01-01

    Although most children with acute lymphoblastic leukemia (ALL) are cured, certain subsets have a high risk of relapse. Relapse risk can be predicted by early response to therapy, clinical and pharmacogenetic features of the host, and genetic characteristics of leukemic cells. Though early treatment response can be assessed by the peripheral blast cell count after 1 week of single-agent glucocorticoid treatment or percent of bone marrow blasts by morphology after 1 or 2 weeks of multiagent induction treatment, determination of minimal residual disease by polymerase chain reaction (PCR) or flow cytometry after 2 to 6 weeks of induction is the most precise and useful measure. Augmented therapy has improved outcome for the poor responders to initial treatment. Infants with mixed-lineage leukemia (MLL)–rearranged ALL comprise a very poor-risk group wherein further intensification of chemotherapy causes significant toxicity. Hybrid protocols incorporating drugs effective for acute myeloid leukemia could improve survival, a strategy being tested in international trials. Studies on the biology of MLL-induced leukemogenesis have prompted the development of novel targeted agents, currently under evaluation in clinical trials. Short-term outcomes of patients with Philadelphia chromosome (Ph)–positive ALL have improved significantly by adding tyrosine kinase inhibitors to standard chemotherapy regimens. New agents and methods to overcome resistance are under investigation, and allogeneic stem cell transplantation is recommended for certain subsets of patients, for example those with Ph+ and T-cell ALL with poor early response. Genome-wide interrogation of leukemic cell genetic abnormalities and germline genetic variations promise to identify new molecular targets for therapy. PMID:19778845

  7. A retrospective evaluation method for in vitro mammalian genotoxicity tests using cytotoxicity index transformation formulae.

    Science.gov (United States)

    Fujita, Yurika; Kasamatsu, Toshio; Ikeda, Naohiro; Nishiyama, Naohiro; Honda, Hiroshi

    2016-01-15

    Although in vitro chromosomal aberration tests and micronucleus tests have been widely used for genotoxicity evaluation, false-positive results have been reported under strong cytotoxic conditions. To reduce false-positive results, the new Organization for Economic Co-operation and Development (OECD) test guideline (TG) recommends the use of a new cytotoxicity index, relative increase in cell count or relative population doubling (RICC/RPD), instead of the traditionally used index, relative cell count (RCC). Although the use of the RICC/RPD may result in different outcomes and require re-evaluation of tested substances, it is impractical to re-evaluate all existing data. Therefore, we established a method to estimate test results from existing RCC data. First, we developed formulae to estimate RICC/RPD from RCC without cell counts by considering cell doubling time and experiment time. Next, the accuracy of the cytotoxicity index transformation formulae was verified by comparing estimated RICC/RPD and measured RICC/RPD for 3 major chemicals associated with false-positive genotoxicity test results: ethyl acrylate, eugenol and p-nitrophenol. Moreover, 25 compounds with false-positive in vitro chromosomal aberration (CA) test results were re-evaluated to establish a retrospective evaluation method based on derived estimated RICC/RPD values. The estimated RICC/RPD values were in good agreement with the measured RICC/RPD values for every concentration and chemical, and the estimated RICC suggested the possibility that 12 chemicals (48%) with previously judged false-positive results in fact had negative results. Our method enables transformation of RCC data into RICC/RPD values with a high degree of accuracy and will facilitate comprehensive retrospective evaluation of test results. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. Genomic Profiling of Adult and Pediatric B-cell Acute Lymphoblastic Leukemia

    Directory of Open Access Journals (Sweden)

    Yuan-Fang Liu

    2016-06-01

    Full Text Available Genomic landscapes of 92 adult and 111 pediatric patients with B-cell acute lymphoblastic leukemia (B-ALL were investigated using next-generation sequencing and copy number alteration analysis. Recurrent gene mutations and fusions were tested in an additional 87 adult and 93 pediatric patients. Among the 29 newly identified in-frame gene fusions, those involving MEF2D and ZNF384 were clinically relevant and were demonstrated to perturb B-cell differentiation, with EP300-ZNF384 inducing leukemia in mice. Eight gene expression subgroups associated with characteristic genetic abnormalities were identified, including leukemia with MEF2D and ZNF384 fusions in two distinct clusters. In subgroup G4 which was characterized by ERG deletion, DUX4-IGH fusion was detected in most cases. This comprehensive dataset allowed us to compare the features of molecular pathogenesis between adult and pediatric B-ALL and to identify signatures possibly related to the inferior outcome of adults to that of children. We found that, besides the known discrepancies in frequencies of prognostic markers, adult patients had more cooperative mutations and greater enrichment for alterations of epigenetic modifiers and genes linked to B-cell development, suggesting difference in the target cells of transformation between adult and pediatric patients and may explain in part the disparity in their responses to treatment.

  9. Leader emotional intelligence, transformational leadership, trust and team commitment: Testing a model within a team context

    Directory of Open Access Journals (Sweden)

    Anton F. Schlechter

    2008-09-01

    Full Text Available This exploratory study tested a model within a team context consisting of transformational-leadership behaviour, team-leader emotional intelligence, trust (both in the team leader and in the team members and team commitment. It was conducted within six manufacturing plants, with 25 teams participating. Of the 320 surveys distributed to these teams, 178 were received (which equals a 56% response rate. The surveys consisted of the multi-factor leadership questionnaire (MLQ, the Swinburne University emotional intelligence test (SUEIT, the organisational-commitment scale (OCS (adapted for team commitment and the workplace trust survey (WTS. The validity of these scales was established using exploratory factor analysis (EFA and confrmatory factor analysis (CFA. The Cronbach alpha was used to assess the reliability of the scales. The model was tested using structural equation modelling (SEM; an acceptable level of model ft was found. Signifcant positive relationships were further found among all the constructs. Such an integrated model has not been tested in a team context before and the positive fndings therefore add to existing teamwork literature. The fnding that transformational leadership and leader emotional intelligence are positively related to team commitment and trust further emphasises the importance of effective leadership behaviour in team dynamics and performance.

  10. Experiences with the OECD 308 transformation test: a human pharmaceutical perspective.

    Science.gov (United States)

    Ericson, Jon F; Smith, Richard Murray; Roberts, Gary; Hannah, Bob; Hoeger, Birgit; Ryan, Jim

    2014-01-01

    The Organisation for Economic Co-operation and Development (OECD) 308 water-sediment transformation test has been routinely conducted in Phase II Tier A testing of the environmental risk assessment (ERA) for all human pharmaceutical marketing authorization applications in Europe, since finalization of Environmental Medicines Agency (EMA) ERA guidance in June 2006. In addition to the "Ready Biodegradation" test, it is the only transformation test for the aquatic/sediment compartment that supports the classification of the drug substance for its potential persistence in the environment and characterizes the fate of the test material in a water-sediment environment. Presented is an overview of 31 OECD 308 studies conducted by 4 companies with a focus on how pharmaceuticals behave in these water-sediment systems. The geometric mean (gm) parent total system half-life for the 31 pharmaceuticals was 30 days with 10th/90th percentile (10/90%ile) of 14.0/121.6 d respectively, with cationic substances having a half-life approximately 2 times that of neutral and anionic substances. The formation of nonextractable residues (NER) was considerable, with gm (10/90%ile) of 38% (20.5/81.4) of the applied radioactivity: cationic substances 50.8% (27.7/87.6), neutral substances 31.9% (15.3/52.3), and anionic substances 16.7% (9.5/30.6). In general, cationic substances had fewer transformation products and more unchanged parent remaining at day 100 of the study. A review of whether a simplified 1-point analysis could reasonably estimate the parent total system half-life showed that the total amount of parent remaining in the water and sediment extracts at day 100 followed first-order kinetics and that the theoretical half-life and the measured total system half-life values agreed to within a factor of 1.68. Recommendations from this 4-company collaboration addressed: 1) the need to develop a more relevant water-sediment transformation test reflecting the conditions of the discharge

  11. Altered brain function in new onset childhood acute lymphoblastic leukemia before chemotherapy: A resting-state fMRI study.

    Science.gov (United States)

    Hu, Zhanqi; Zou, Dongfang; Mai, Huirong; Yuan, Xiuli; Wang, Lihong; Li, Yue; Liao, Jianxiang; Liu, Liwei; Liu, Guosheng; Zeng, Hongwu; Wen, Feiqiu

    2017-10-01

    Cognitive impairments had been reported in childhood acute lymphoblastic leukemia, what caused the impairments needed to be demonstrated, chemotherapy-related or the disease itself. The primary aim of this exploratory investigation was to determine if there were changes in brain function of children with acute lymphoblastic leukemia before chemotherapy. In this study, we advanced a measure named regional homogeneity to evaluate the resting-state brain activities, intelligence quotient test was performed at same time. Using regional homogeneity, we first investigated the resting state brain function in patients with new onset childhood acute lymphoblastic leukemia before chemotherapy, healthy children as control. The decreased ReHo values were mainly founded in the default mode network and left frontal lobe, bilateral inferior parietal lobule, bilateral temporal lobe, bilateral occipital lobe, precentral gyrus, bilateral cerebellum in the newly diagnosed acute lymphoblastic leukemia patients compared with the healthy control. While in contrast, increased ReHo values were mainly shown in the right frontal lobe (language area), superior frontal gyrus-R, middle frontal gyrus-R and inferior parietal lobule-R for acute lymphoblastic leukemia patients group. There were no significant differences for intelligence quotient measurements between the acute lymphoblastic leukemia patient group and the healthy control in performance intelligence quotient, verbal intelligence quotient, total intelligence quotient. The altered brain functions are associated with cognitive change and language, it is suggested that there may be cognition impairment before the chemotherapy. Regional homogeneity by functional magnetic resonance image is a sensitive way for early detection on brain damage in childhood acute lymphoblastic leukemia. Copyright © 2017 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  12. Dexamethasone compared to prednisolone for adults with acute lymphoblastic leukemia or lymphoblastic lymphoma: final results of the ALL-4 randomized, phase III trial of the EORTC Leukemia Group

    Science.gov (United States)

    Labar, Boris; Suciu, Stefan; Willemze, Roel; Muus, Petra; Marie, Jean-Pierre; Fillet, Georges; Berneman, Zwi; Jaksic, Branimir; Feremans, Walter; Bron, Dominique; Sinnige, Harm; Mistrik, Martin; Vreugdenhil, Gerard; De Bock, Robrecht; Nemet, Damir; Gilotay, Caroline; Amadori, Sergio; de Witte, Theo

    2010-01-01

    incidences of relapse were 49.8% and 53.5% (Gray’s test: P=0.30) while the 6-year cumulative incidences of death were 18% and 9% (Gray’s test: P=0.07). Conclusions In the ALL-4 trial in adult patients with acute lymphoblastic leukemia or lymphoblastic lymphoma, treatment with dexamethasone did not show any advantage over treatment with prednisolone. PMID:20378563

  13. Testing the significance of a correlation with nonnormal data: comparison of Pearson, Spearman, transformation, and resampling approaches.

    Science.gov (United States)

    Bishara, Anthony J; Hittner, James B

    2012-09-01

    It is well known that when data are nonnormally distributed, a test of the significance of Pearson's r may inflate Type I error rates and reduce power. Statistics textbooks and the simulation literature provide several alternatives to Pearson's correlation. However, the relative performance of these alternatives has been unclear. Two simulation studies were conducted to compare 12 methods, including Pearson, Spearman's rank-order, transformation, and resampling approaches. With most sample sizes (n ≥ 20), Type I and Type II error rates were minimized by transforming the data to a normal shape prior to assessing the Pearson correlation. Among transformation approaches, a general purpose rank-based inverse normal transformation (i.e., transformation to rankit scores) was most beneficial. However, when samples were both small (n ≤ 10) and extremely nonnormal, the permutation test often outperformed other alternatives, including various bootstrap tests.

  14. [Lymphocyte transformation test following stimulation with a protein factor from neutrophilic granulocytes (PMNL) in psoriasis patients].

    Science.gov (United States)

    Ruszczak, Z; Ciborska, L; Kaszuba, A

    1988-12-01

    The lymphocyte transformation test (LTT) was given to 20 healthy subjects and 43 patients with generalized psoriasis vulgaris: it was given right after stimulation with PHA (spontaneous) and after stimulation with allogenic and autogenic protein factor (NPF). NPF was isolated from secondary lysosome granules of peripheral blood neutrophils. The results were analyzed using computer statistic tests. No distinct differences were noticed between the spontaneous transformation test in psoriatic patients compared to the controls. After stimulation with PHA, the percentage of blast cells was significantly lower in patients with psoriasis. When allogenic and autogenic NPF was used for stimulation, the LTT values were significantly higher in the psoriasis group than in the control subjects. This fact points out the increase in sensitivity of lymphocytes to NPF in active psoriasis and the possibility of abnormal neutrophil-lymphocyte interactions in vivo. This phenomenon may be intensified when under the influence of bacterial or viral agents, or medicaments; the degranulation of secondary lysosome granules of neutrophils occurs, causing the release of NPF. These investigations support our opinion that psoriasis is a systemic disease and that NPF plays a considerable role in the psoriatic reaction.

  15. Tribology of improved transformation-toughened ceramics-heat engine test

    Energy Technology Data Exchange (ETDEWEB)

    Lilley, E.; Rossi, G.A.; Pelletier, P.J. (Norton Co., Northboro, MA (United States). Advanced Ceramics Div.)

    1992-04-01

    A short term study has been carried out to evaluate the suitability as cam roller followers of three ceria zirconia toughened aluminas and two yttria stabilized tetragonal zirconias (YTZPs) previously enhanced in programs supported by ORNL. Norton Si{sub 3}N{sub 4} (NBD-100) was also included in this study as a reference material, because it was known from work at Northwestern University that Si{sub 3}N{sub 4} to experienced little or no wear in this application, and NBD-100 is currently a successful commercial bearing material. The tribological studies were subcontracted to the Torrington Company. They found that in cam roller follower simulated tests that there was essentially no wear after 1 hour and 5 hours of testing detectable by weighing and concluded that all of these ceramics are, therefore, candidate materials. Because of the minute amounts of wear it was not possible to identify the wear mechanism or to make any correlations with the other physical properties which were evaluated such as MOR, K{sub IC} hardness, density and grain size. Phase transformation during rolling has been of interest in the tribology of zirconia contain materials. The least stable of the ceria zirconia toughened aluminas resulted in as much as 33% monoclinic phase after testing whereas the yttria stabilized (TTZ) contained very little of this transformed phase. The results of this study show that oxide materials can now be considered as candidates for cam roller followers in heat engines.

  16. JAK Mutations in High-Risk Childhood Acute Lymphoblastic Leukemia

    National Research Council Canada - National Science Library

    Charles G. Mullighan; Jinghui Zhang; Richard C. Harvey; J. Racquel Collins-Underwood; Brenda A. Schulman; Letha A. Phillips; Sarah K. Tasian; Mignon L. Loh; Xiaoping Su; Wei Liu; Meenakshi Devidas; Susan R. Atlas; I-Ming Chen; Robert J. Clifford; Daniela S. Gerhard; William L. Carroll; Gregory H. Reaman; Malcolm Smith; James R. Downing; Stephen P. Hunger; Cheryl L. Willman; Janet D. Rowley

    2009-01-01

    Pediatric acute lymphoblastic leukemia (ALL) is a heterogeneous disease consisting of distinct clinical and biological subtypes that are characterized by specific chromosomal abnormalities or gene mutations...

  17. Precursor B-cell acute lymphoblastic leukemia presenting as obstructive jaundice: a case report

    Directory of Open Access Journals (Sweden)

    Awasum Michael

    2011-07-01

    Full Text Available Abstract Introduction Acute leukemias very rarely present with jaundice. Herein we report a case of precursor B-cell acute lymphoblastic leukemia that presented with jaundice in an adult. Case presentation A 44-year-old Hispanic man presented with right upper quadrant abdominal pain and jaundice. His initial blood work revealed pancytopenia and hyperbilirubinemia. Direct bilirubin was more than 50% of the total. His imaging studies were unremarkable except for hepatomegaly. All blood screening tests for various hepatocellular etiologies were normal. A diagnosis of precursor B-cell acute lymphoblastic leukemia was made upon liver biopsy. It also showed lymphocytic infiltration of the hepatic parenchyma leading to bile stasis. The diagnosis was subsequently confirmed upon bone marrow biopsy. The patient was treated with a hyperfractionated cyclophosphamide/vincristine/doxorubicin/dexamethasone regimen. Conclusion Acute lymphoblastic leukemia should be one of the differential diagnoses that should be considered when initial work-up for jaundice is inconclusive. Some cases of acute lymphoblastic leukemia have been reported in both adults and children to have presented with the initial manifestation of jaundice, but only a few had no radiographic evidence of biliary obstruction. Such presentation can pose a serious diagnostic dilemma for clinicians. This manuscript attempts to highlight it. Moreover, we believe that if acute lymphoblastic leukemia presentations similar to this case continue to be reported in adults or children, a specific immunophenotypic expression and cytogenetic abnormality may be found to be associated with hepatic infiltration by leukemia. This may substantially contribute to the further understanding of the pathophysiology of this hematologic disease.

  18. Recognition of adult and pediatric acute lymphoblastic leukemia blasts by natural killer cells.

    Science.gov (United States)

    Torelli, Giovanni F; Peragine, Nadia; Raponi, Sara; Pagliara, Daria; De Propris, Maria S; Vitale, Antonella; Bertaina, Alice; Barberi, Walter; Moretta, Lorenzo; Basso, Giuseppe; Santoni, Angela; Guarini, Anna; Locatelli, Franco; Foà, Robin

    2014-07-01

    In this study, we aimed to investigate the pathways of recognition of acute lymphoblastic leukemia blasts by natural killer cells and to verify whether differences in natural killer cell activating receptor ligand expression among groups defined by age of patients, or presence of cytogenetic/molecular aberrations correlate with the susceptibility to recognition and killing. We analyzed 103 newly diagnosed acute lymphoblastic leukemia patients: 46 adults and 57 children. Pediatric blasts showed a significantly higher expression of Nec-2 (P=0.03), ULBP-1 (P=0.01) and ULBP-3 (P=0.04) compared to adult cells. The differential expression of these ligands between adults and children was confined to B-lineage acute lymphoblastic leukemia with no known molecular alterations. Within molecularly defined subgroups of patients, a high surface expression of NKG2D and DNAM1 ligands was found on BCR-ABL(+) blasts, regardless of patient age. Accordingly, BCR-ABL(+) blasts proved to be significantly more susceptible to natural killer-dependent lysis than B-lineage blasts without molecular aberrations (P=0.03). Cytotoxic tests performed in the presence of neutralizing antibodies indicated a pathway of acute lymphoblastic leukemia cell recognition in the setting of the Nec-2/DNAM-1 interaction. These data provide a biological explanation of the different roles played by alloreactive natural killer cells in pediatric versus adult acute lymphoblastic leukemia and suggest that new natural killer-based strategies targeting specific subgroups of patients, particularly those BCR-ABL(+), are worth pursuing further. Copyright© Ferrata Storti Foundation.

  19. Martensitic Transformation during Fatigue Testing of an AISI 301LN Stainless Steel

    Science.gov (United States)

    Mateo, A.; Fargas, G.; Zapata, A.

    2012-02-01

    The plastic deformation accumulated during fatigue testing can induce the transformation of austenite to martensite in metastable austenitic stainless steels. To analyze this issue, a metastable austenitic stainless steel grade AISI 301 LN was studied in two different conditions, i.e. annealed and cold rolled. In the first case, the steel was fully austenitic, whereas cold rolled material had almost 30% of martensite. High cycle fatigue tests at a stress ratio of 0.8 were carried out on flat specimens from both steel conditions. Several characterization techniques, including optical microscopy, X-ray diffraction (XRD) and electron back scattered diffraction (EBSD), were used to detect and quantify the martensite induced by the cyclic deformation.

  20. Development and tests of fast 1-MA linear transformer driver stages

    Directory of Open Access Journals (Sweden)

    A. A. Kim

    2009-05-01

    Full Text Available In this article we present the design and test results of the most powerful, fast linear transformer driver (LTD stage developed to date. This 1-MA LTD stage consists of 40 parallel RLC (resistor R, inductor L, and capacitor C circuits called “bricks” that are triggered simultaneously; it is able to deliver ∼1  MA current pulse with a rise time of ∼100  ns into the ∼0.1-Ohm matched load. The electrical behavior of the stage can be predicted by using a simple RLC circuit, thus simplifying the designing of various LTD-based accelerators. Five 1-MA LTD stages assembled in series into a module have been successfully tested with both resistive and vacuum electron-beam diode loads.

  1. Laboratory tests on sorption and transformation of the insecticide flubendiamide in Japanese tea field soil

    Energy Technology Data Exchange (ETDEWEB)

    Hartung, Susen [Technische Universität Braunschweig, Institute of Environmental and Sustainable Chemistry, Hagenring 30, 38106 Braunschweig (Germany); Iwasaki, Masahide; Ogawa, Naoto [Shizuoka University, Faculty of Agriculture, Department of Biological and Environmental Science, 836 Ohya, Suruga-ku, Shizuoka 422-8529 (Japan); Kreuzig, Robert, E-mail: r.kreuzig@tu-bs.de [Technische Universität Braunschweig, Institute of Environmental and Sustainable Chemistry, Hagenring 30, 38106 Braunschweig (Germany)

    2013-01-15

    Flubendiamide belongs to the modern insecticides applied in Japanese tea cultivation to control smaller tea tortrix and tea leaf roller. Since fate and behavior in soil have been only monitored sparsely and fragmentarily until today, laboratory tests were performed on sorption, leaching, biotransformation and photo-induced biotransformation of flubendiamide in two different soils. In batch equilibrium tests, K{sub d} and K{sub OC} values were 15 and 298 L kg{sup −1} for the Japanese tea field soil as well as 16 and 1610 L kg{sup −1} for the German arable field soil classifying flubendiamide to be moderately mobile and slightly mobile, respectively. The affinity to the tea field soil was additionally confirmed by soil column tests where flubendiamide was predominantly retarded in the topsoil layers resulting in a percolate contamination of only 0.002 mg L{sup −1}. In the aerobic biotransformation tests, flubendiamide did not substantially disappear within the 122-d incubation period. Due to DT{sub 50} > 122 d, flubendiamide was assessed very persistent. Supplementary, photo-induced impacts on biotransformation were studied in a special laboratory irradiation system. Despite a 14-d irradiation period, photo-induced biotransformation in the tea field soil was not identifiable, neither by HPLC/DAD nor by LC/MS/MS. 3-d irradiation tests in photosensibilizing acetone, however, showed that the primary photo-transformation product desiodo-flubendiamide was formed. How far this photochemical reaction may also occur in soil of perennial tea plant stands, however, has to be checked in field studies. - Highlights: ► Laboratory tests on sorption, leaching, microbial and photo-induced microbial transformation were performed. ► Strong sorption was revealed by batch equilibrium and column tests. ► High persistence was found in aerobic biotransformation tests. ► An enhanced biotransformation by photo-induced impacts could not be confirmed. ► Field studies are

  2. PS-341 in Treating Patients With Refractory or Relapsed Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, Chronic Myeloid Leukemia in Blast Phase, or Myelodysplastic Syndrome

    Science.gov (United States)

    2013-01-22

    Adult Acute Promyelocytic Leukemia (M3); Blastic Phase Chronic Myelogenous Leukemia; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Excess Blasts in Transformation; Relapsing Chronic Myelogenous Leukemia

  3. Acute lymphoblastic leukemia in children and adolescents: prognostic factors and analysis of survival

    Science.gov (United States)

    Lustosa de Sousa, Daniel Willian; de Almeida Ferreira, Francisco Valdeci; Cavalcante Félix, Francisco Helder; de Oliveira Lopes, Marcos Vinicios

    2015-01-01

    Objective To describe the clinical and laboratory features of children and adolescents with acute lymphoblastic leukemia treated at three referral centers in Ceará and evaluate prognostic factors for survival, including age, gender, presenting white blood cell count, immunophenotype, DNA index and early response to treatment. Methods Seventy-six under 19-year-old patients with newly diagnosed acute lymphoblastic leukemia treated with the Grupo Brasileiro de Tratamento de Leucemia da Infância – acute lymphoblastic leukemia-93 and -99 protocols between September 2007 and December 2009 were analyzed. The diagnosis was based on cytological, immunophenotypic and cytogenetic criteria. Associations between variables, prognostic factors and response to treatment were analyzed using the chi-square test and Fisher's exact test. Overall and event-free survival were estimated by Kaplan–Meier analysis and compared using the log-rank test. A Cox proportional hazards model was used to identify independent prognostic factors. Results The average age at diagnosis was 6.3 ± 0.5 years and males were predominant (65%). The most frequently observed clinical features were hepatomegaly, splenomegaly and lymphadenopathy. Central nervous system involvement and mediastinal enlargement occurred in 6.6% and 11.8%, respectively. B-acute lymphoblastic leukemia was more common (89.5%) than T-acute lymphoblastic leukemia. A DNA index >1.16 was found in 19% of patients and was associated with favorable prognosis. On Day 8 of induction therapy, 95% of the patients had lymphoblast counts <1000/μL and white blood cell counts <5.0 × 109/L. The remission induction rate was 95%, the induction mortality rate was 2.6% and overall survival was 72%. Conclusion The prognostic factors identified are compatible with the literature. The 5-year overall and event-free survival rates were lower than those reported for developed countries. As shown by the multivariate analysis, age and baseline white

  4. Acute lymphoblastic leukemia in children and adolescents: prognostic factors and analysis of survival

    Directory of Open Access Journals (Sweden)

    Daniel Willian Lustosa de Sousa

    2015-08-01

    Full Text Available OBJECTIVE: To describe the clinical and laboratory features of children and adolescents with acute lymphoblastic leukemia treated at three referral centers in Ceará and evaluate prognostic factors for survival, including age, gender, presenting white blood cell count, immunophenotype, DNA index and early response to treatment.METHODS: Seventy-six under 19-year-old patients with newly diagnosed acute lymphoblastic leukemia treated with the Grupo Brasileiro de Tratamento de Leucemia da Infância - acute lymphoblastic leukemia-93 and -99 protocols between September 2007 and December 2009 were analyzed. The diagnosis was based on cytological, immunophenotypic and cytogenetic criteria. Associations between variables, prognostic factors and response to treatment were analyzed using the chi-square test and Fisher's exact test. Overall and event-free survival were estimated by Kaplan-Meier analysis and compared using the log-rank test. A Cox proportional hazards model was used to identify independent prognostic factors.RESULTS: The average age at diagnosis was 6.3 ± 0.5 years and males were predominant (65%. The most frequently observed clinical features were hepatomegaly, splenomegaly and lymphadenopathy. Central nervous system involvement and mediastinal enlargement occurred in 6.6% and 11.8%, respectively. B-acute lymphoblastic leukemia was more common (89.5% than T-acute lymphoblastic leukemia. A DNA index >1.16 was found in 19% of patients and was associated with favorable prognosis. On Day 8 of induction therapy, 95% of the patients had lymphoblast counts <1000/µL and white blood cell counts <5.0 Ã- 109/L. The remission induction rate was 95%, the induction mortality rate was 2.6% and overall survival was 72%.CONCLUSION: The prognostic factors identified are compatible with the literature. The 5-year overall and event-free survival rates were lower than those reported for developed countries. As shown by the multivariate analysis, age

  5. Imaging findings of recurrent acute lymphoblastic leukemia in children and young adults, with emphasis on MRI

    Energy Technology Data Exchange (ETDEWEB)

    Porter, Rosalyn P. [Department of Diagnostic Imaging, St. Jude Children' s Research Hospital, 332 N. Lauderdale, Memphis, TN 38105-2794 (United States); Kaste, Sue C. [Department of Diagnostic Imaging, St. Jude Children' s Research Hospital, 332 N. Lauderdale, Memphis, TN 38105-2794 (United States); Department of Radiology, University of Tennessee, College of Medicine, Memphis, Tennessee (United States)

    2004-05-01

    Acute lymphoblastic leukemia (ALL) is the most common of all childhood malignancies. Current remission rates approach 80%. Recurrent disease can present in a wide variety of ways. MR imaging plays a crucial role in the detection of disease relapse. Because other disorders can mimic recurrence of leukemia, it is important for the radiologist to judge recurrence from non-recurrence accurately in order to avoid unnecessary testing and emotional stress on the patient and family. (orig.)

  6. Abnormal cell properties and down-regulated FAK-Src complex signaling in B lymphoblasts of autistic subjects.

    Science.gov (United States)

    Wei, Hongen; Malik, Mazhar; Sheikh, Ashfaq M; Merz, George; Ted Brown, W; Li, Xiaohong

    2011-07-01

    Recent studies suggest that one of the major pathways to the pathogenesis of autism is reduced cell migration. Focal adhesion kinase (FAK) has an important role in neural migration, dendritic morphological characteristics, axonal branching, and synapse formation. The FAK-Src complex, activated by upstream reelin and integrin β1, can initiate a cascade of phosphorylation events to trigger multiple intracellular pathways, including mitogen-activated protein kinase-extracellular signal-regulated kinase and phosphatidylinositol 3-kinase-Akt signaling. In this study, by using B lymphoblasts as a model, we tested whether integrin β1 and FAK-Src signaling are abnormally regulated in autism and whether abnormal FAK-Src signaling leads to defects in B-lymphoblast adhesion, migration, proliferation, and IgG production. To our knowledge, for the first time, we show that protein expression levels of both integrin β1 and FAK are significantly decreased in autistic lymphoblasts and that Src protein expression and the phosphorylation of an active site (Y416) are also significantly decreased. We also found that lymphoblasts from autistic subjects exhibit significantly decreased migration, increased adhesion properties, and an impaired capacity for IgG production. The overexpression of FAK in autistic lymphoblasts countered the adhesion and migration defects. In addition, we demonstrate that FAK mediates its effect through the activation of Src, phosphatidylinositol 3-kinase-Akt, and mitogen-activated protein kinase signaling cascades and that paxillin is also likely involved in the regulation of adhesion and migration in autistic lymphoblasts. Copyright © 2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  7. 10 CFR Appendix A to Subpart K of... - Uniform Test Method for Measuring the Energy Consumption of Distribution Transformers

    Science.gov (United States)

    2010-01-01

    ... CONSERVATION ENERGY EFFICIENCY PROGRAM FOR CERTAIN COMMERCIAL AND INDUSTRIAL EQUIPMENT Distribution... straps are added for the load-loss test. The measured quantities will need correction for instrumentation..., the entire instrumentation system of a three-phase test set without transformers may consist of...

  8. Transformation kinetics in controlled-power and controlled-temperature cycle testing

    Energy Technology Data Exchange (ETDEWEB)

    Robino, C.V.; Knorovsky, G.; Dykhuizen, R.C.; MacCallum, D.O.; Damkroger, B.K.

    1998-06-01

    On-heating transformation kinetics were investigated for several steels by using a Gleeble capable of programmable power input as well as programmable temperature cycling. Transformation kinetics determined in both modes are reported. The temperature cycles are significantly different between the two modes due to the latent heat associated with the phase transformations. Both diffusion rates and transformation driving force increase with temperature above the eutectoid temperature, therefore the latent heat can potentially have a significant impact on the transformation kinetics. Experiments with plain carbon steels illustrate that the latent heat of austenite formation causes an appreciable temperature arrest during transformation, and the dilatation response is similarly altered. A kinetic transformation model, based on the decomposition of pearlite and the diffusional growth of austenite, reproduced the transient dilatation data obtained from both control modes reasonably well using the same kinetic parameter values.

  9. Detecting change in biological rhythms: a multivariate permutation test approach to Fourier-transformed data.

    Science.gov (United States)

    Blackford, Jennifer Urbano; Salomon, Ronald M; Waller, Niels G

    2009-02-01

    Treatment-related changes in neurobiological rhythms are of increasing interest to psychologists, psychiatrists, and biological rhythms researchers. New methods for analyzing change in rhythms are needed, as most common methods disregard the rich complexity of biological processes. Large time series data sets reflect the intricacies of underlying neurobiological processes, but can be difficult to analyze. We propose the use of Fourier methods with multivariate permutation test (MPT) methods for analyzing change in rhythms from time series data. To validate the use of MPT for Fourier-transformed data, we performed Monte Carlo simulations and compared statistical power and family-wise error for MPT to Bonferroni-corrected and uncorrected methods. Results show that MPT provides greater statistical power than Bonferroni-corrected tests, while appropriately controlling family-wise error. We applied this method to human, pre- and post-treatment, serially-sampled neurotransmitter data to confirm the utility of this method using real data. Together, Fourier with MPT methods provides a statistically powerful approach for detecting change in biological rhythms from time series data.

  10. Treatment of Childhood Acute Lymphoblastic Leukemia Without Prophylactic Cranial Irradiation

    Science.gov (United States)

    Pui, Ching-Hon; Campana, Dario; Pei, Deqing; Bowman, W. Paul; Sandlund, John T.; Kaste, Sue C.; Ribeiro, Raul C.; Rubnitz, Jeffrey E.; Raimondi, Susana C.; Onciu, Mihaela; Coustan-Smith, Elaine; Kun, Larry E.; Jeha, Sima; Cheng, Cheng; Howard, Scott C.; Simmons, Vickey; Bayles, Amy; Metzger, Monika L.; Boyett, James M.; Leung, Wing; Handgretinger, Rupert; Downing, James R.; Evans, William E.; Relling, Mary V.

    2009-01-01

    Background We conducted a clinical trial to test whether prophylactic cranial irradiation could be omitted in all children with newly diagnosed acute lymphoblastic leukemia. Methods A total of 498 evaluable patients were enrolled. Treatment intensity was based on presenting features and the level of minimal residual disease after remission induction treatment. Continuous complete remission was compared between the 71 patients who previously would have received prophylactic cranial irradiation and the 56 historical controls who received it. Results The 5-year event-free and overall survival probabilities (95% confidence interval) for all 498 patients were 85.6% (79.9% to 91.3%) and 93.5% (89.8% to 97.2%), respectively. The 5-year cumulative risk of isolated central-nervous-system (CNS) relapse was 2.7% (1.1% to 4.2%), and that of any CNS relapse (isolated plus combined) was 3.9% (1.9% to 5.9%). The 71 patients had significantly better continuous complete remission than the 56 historical controls (P=0.04). All 11 patients with isolated CNS relapse remain in second remission for 0.4 to 5.5 years. CNS leukemia (CNS-3 status) or a traumatic lumbar puncture with blasts at diagnosis and a high level of minimal residual disease (≥ 1%) after 6 weeks of remission induction were significantly associated with poorer event-free survival. Risk factors for CNS relapse included the presence of the t(1;19)[TCF3-PBX1], any CNS involvement at diagnosis, and T-cell immunophenotype. Common adverse effects included allergic reactions to L-asparaginase, osteonecrosis, thrombosis, and disseminated fungal infection. Conclusions With effective risk-adjusted chemotherapy, prophylactic cranial irradiation can be safely omitted in the treatment of childhood acute lymphoblastic leukemia. PMID:19553647

  11. Data Transformation Technique to Improve the Outlier Detection Power of Grubbs’ Test for Data Expected to Follow Linear Relation

    Directory of Open Access Journals (Sweden)

    K. K. L. B. Adikaram

    2015-01-01

    Full Text Available Grubbs test (extreme studentized deviate test, maximum normed residual test is used in various fields to identify outliers in a data set, which are ranked in the order of x1≤x2≤x3≤⋯≤xn  (i=1,2,3,…,n. However, ranking of data eliminates the actual sequence of a data series, which is an important factor for determining outliers in some cases (e.g., time series. Thus in such a data set, Grubbs test will not identify outliers correctly. This paper introduces a technique for transforming data from sequence bound linear form to sequence unbound form (y=c. Applying Grubbs test to the new transformed data set detects outliers more accurately. In addition, the new technique improves the outlier detection capability of Grubbs test. Results show that, Grubbs test was capable of identifing outliers at significance level 0.01 after transformation, while it was unable to identify those prior to transforming at significance level 0.05.

  12. Mediastinal involvement in adults with lymphoblastic lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Schwartz, E.E.; Conroy, J.F.; Bonner, H.

    Radiologic, clinical, and pathologic findings are described in 6 young adults with lymphoblastic lymphoma (LBL), an aggressive tumor which has recently become recognized as a serious threat to adults as well as to children. Each patient presented with a mediastinal mass, three of them developing cardiac tamponade and one a superior vena cava syndrome. CT scanning and echocardiography were particularly helpful in defining the lesions. The rapid dissemination of LBL, and its early progression to a leukemic phase call for promt diagnosis and treatment.

  13. Epigenetic Modifications in Pediatric Acute Lymphoblastic Leukemia

    Directory of Open Access Journals (Sweden)

    Michael James Burke

    2014-05-01

    Full Text Available Aberrant epigenetic modifications are well-recognized drivers for oncogenesis. Pediatric acute lymphoblastic leukemia (ALL is no exception and serves as a model toward the significant impact these heritable alterations can have in leukemogenesis. In this brief review, we will focus on the main aspects of epigenetics which control leukemogenesis in pediatric ALL, mainly DNA methylation, histone modification and microRNA alterations. As we continue to gain better understanding of the driving mechanisms for pediatric ALL at both diagnosis and relapse, therapeutic interventions directed toward these pathways and mechanisms can be harnessed and introduced into clinical trials for pediatric ALL.

  14. Inflation of type I error rates by unequal variances associated with parametric, nonparametric, and Rank-Transformation Tests

    Directory of Open Access Journals (Sweden)

    Donald W. Zimmerman

    2004-01-01

    Full Text Available It is well known that the two-sample Student t test fails to maintain its significance level when the variances of treatment groups are unequal, and, at the same time, sample sizes are unequal. However, introductory textbooks in psychology and education often maintain that the test is robust to variance heterogeneity when sample sizes are equal. The present study discloses that, for a wide variety of non-normal distributions, especially skewed distributions, the Type I error probabilities of both the t test and the Wilcoxon-Mann-Whitney test are substantially inflated by heterogeneous variances, even when sample sizes are equal. The Type I error rate of the t test performed on ranks replacing the scores (rank-transformed data is inflated in the same way and always corresponds closely to that of the Wilcoxon-Mann-Whitney test. For many probability densities, the distortion of the significance level is far greater after transformation to ranks and, contrary to known asymptotic properties, the magnitude of the inflation is an increasing function of sample size. Although nonparametric tests of location also can be sensitive to differences in the shape of distributions apart from location, the Wilcoxon-Mann-Whitney test and rank-transformation tests apparently are influenced mainly by skewness that is accompanied by specious differences in the means of ranks.

  15. Herbal medicine and false-positive results on lymphocyte transformation test.

    Science.gov (United States)

    Mantani, Naoki; Sakai, Shinya; Kogure, Toshiaki; Goto, Hirozo; Shibahara, Naotoshi; Kita, Toshiaki; Shimada, Yutaka; Terasawa, Katsutoshi

    2002-06-01

    In vitro mitogenic activity of 16 herbs and 3 Kampo (herbal medicine) formulae have been reported in experimental studies. It is not known how many herbs and Kampo formulae in total have mitogenic activity. Lymphocyte transformation test (LTT) is generally utilized to diagnose drug-induced liver injury. In LTT, mitogenic activity is assessed by measuring 3H-thymidine incorporation. The objective of the present study was to determine which herbs and which Kampo formulae caused false-positivity on LTT. We examined 2496 summaries of all admission records from 1979 to 1999 in our department. We selected patients in whom liver injuries were diagnosed as definitely unrelated to Kampo medication. In these patients, LTT was performed for some herbs contained in the suspect Kampo medicines, resulting in positive LTT for 17 herbs: Evodiae Fructus (Goshuyu), Zizyphi Fructus (Taiso), Ginseng Radix (Ninjin), Zingiberis Rhizoma (Shokyo), Hoelen (Bukuryo), Aconiti Tuber (Bushi), Angelicae Radix (Toki), Cnidii Rhizoma (Senkyu), Rehmanniae Radix (Jio), Ephedrae Herba (Mao), Anemarrhenae Rhizoma (Chimo), Cinnamomi Cortex (Keihi), Bupleuri Radix (Saiko), Artemisiae Capillari Spica (Inchinko), Persicae Semen (Tonin), Moutan Cortex (Botanpi) and Paeoniae Radix (Shakuyaku). These results were considered false-positive, because the results were observed in the "definitely unrelated" patients. Mitogenic activity inherent to some herbs and Kampo formulae may sometimes cause false-positivity on LTT in clinical situations. These examples suggest that LTT for Kampo formulae may be unreliable as a diagnostic method for drug-induced liver injury.

  16. Application of Hilbert-Huang transform for defect recognition in pulsed eddy current testing

    Science.gov (United States)

    Liu, Baoling; Huang, Pingjie; Hou, Dibo; Chen, Xiao; Zhang, Guangxin

    2015-07-01

    Defect recognition plays an important role in the structure integrity and health monitor of in-service equipment. However, it is difficult to recognise deep-layer defect or small-size defect in conductive structure during pulsed eddy current (PEC) testing. Aiming at the issue, this article proposes a method based on Hilbert-Huang transform which consists of two modules: data processing and defect recognition. In the data processing module, the PEC response signal is decomposed into a few of intrinsic mode functions (IMFs) using ensemble empirical mode decomposition method. The IMFs whose variance contribution rates are bigger than 1% are chosen to reconstruct signal in order to remove noise. In the defect recognition module, the features based on specific frequency components of marginal spectrum (MS) of the reconstructed signals are extracted to discriminate those defects in surface and subsurface. Furthermore, the normalisation MS energy ratio is proposed to quantify defects which cannot be distinguished using peak value in time domain. Experiments show that the proposed method can achieve better de-noising effect and defect evaluation, which contributes to the recognition of those complicated defects such as deep-layered and small-sized defect.

  17. Opera's neutrinos and the Robertson test theory of the Lorentz transformations

    CERN Document Server

    Vargas, Jose G

    2011-01-01

    The difference in light's travel time from CERN to GPS to Gran Sasso, on the one hand, and light going the direct route in vacuum (mimicked by neutrinos), on the other hand, is analyzed with a modified Robertson test theory of the Lorentz transformations. The modification consists simply in removing the restriction of what Robertson referred to as agreement to equate the to and from speeds of light. For reasons that will be contained in a paper to soon follow, we restrict ourselves, within the new freedom, to the case of preferred frame kinematics with absolute simultaneity. At the level of not assuming any concomitant dynamical changes in this alternative, the analysis yields \\QTR{it}{zero effect}, i.e. no change with respect to special relativity (to be expected). The 60 ns would thus remain unexplained. However, a gravitation related effect that would likely accompany an alternative kinematics yields that value up to uncertainties due to the need to simplify the experimental set up for analysis. The effect...

  18. Stem cell transplantation outcomes in lymphoblastic lymphoma.

    Science.gov (United States)

    Brammer, Jonathan E; Khouri, Issa; Marin, David; Ledesma, Celina; Rondon, Gabriela; Ciurea, Stefan O; Nieto, Yago; Champlin, Richard E; Hosing, Chitra; Kebriaei, Partow

    2017-02-01

    Lymphoblastic lymphoma (LBL) is an aggressive lymphoma pathologically similar to lymphoblastic leukemia, but primarily presents with nodal or extra-medullary involvement. The aim of this study is to describe outcomes of patients undergoing stem cell transplantation (SCT) for LBL compared to historical data. Thirty-nine patients, of which 54% lacked complete remission (CR), received SCT for LBL between 1990 and 2015; 31 allogeneic and eight autologous. Overall survival (OS) and progression free survival (PFS) at three years for the entire cohort was 41%, the cumulative incidence (CI) of non-relapse mortality (NRM) was 18% at one year, and CI relapse mortality was 28% at one-year and 36% at three years; results similar to historical reports. On multivariate analysis, the use of total-body irradiation (TBI) based conditioning and transplantation in CR were independently predictive of OS and PFS. For patients requiring SCT for LBL, CR and TBI-based conditioning prior to allogeneic SCT may provide improved disease control.

  19. Complete transformation of ZnO and CuO nanoparticles in culture medium and lymphocyte cells during toxicity testing

    Science.gov (United States)

    Here, we present evidence on complete transformation of ZnO and CuO nanoparticles, which are among the most heavily studied metal oxide particles, during 24 h in vitro toxicological testing with human T-lymphocytes. Synchrotron radiation-based X-ray absorption near edge st...

  20. Laboratory diagnosis of gonorrhea by a simple transformation test with a temperature-sensitive mutant of Neisseria gonorrhoeae.

    Science.gov (United States)

    Zubrzycki, L; Weinberger, S S

    1980-01-01

    A temperature-sensitive mutant of Neisseria gonorrhoeae strain tsA-1 was used in a transformation test for the laboratory diagnosis of gonorrhea. This transformation test (C test) is based on a spotting of a DNA lysate, obtained through simple base-acid extraction of a cervical-swab specimen, onto a lawn of tsA-1, which is then incubated for one to two days at 37 C. Of 1,053 cervical-swab specimens tested, 52 contained the gonococcal DNA necessary for restoring the ability of tsA-1 to grow well at 37 C; 49 of the 52 specimens were identified as N. gonorrhoeae by routine diagnostic laboratory procedures. The time required for the C test is two to three days, which is shorter than that required for routine diagnostic laboratory tests, and the C test involves a minimum of common laboratory supplies and expertise. The discrepancies between results of the C test and routine procedures are explained as follows. In one case an isolate suspected to be N. gonorrhoeae was nonreactive in the sugar fermentation test, and in two cases the agar plates were overgrown with yeasts; neither situation affected the C test.

  1. Safety of power transformers, power supplies, reactors and similar products - Part 1: General requirements and tests

    CERN Document Server

    International Electrotechnical Commission. Geneva

    1998-01-01

    This International Standard deals with safety aspects of power transformers, power supplies, reactors and similar products such as electrical, thermal and mechanical safety. This standard covers the following types of dry-type transformers, power supplies, including switch mode power supplies, and reactors, the windings of which may be encapsulated or non-encapsulated. It has the status of a group safety publication in accordance with IEC Guide 104.

  2. Acute lymphoblastic leukemia | EU Clinical Trials Register [EU Clinical Trials Register

    Lifescience Database Archive (English)

    Full Text Available on the Trial E.1 Medical condition or disease under investigation E.1.1Medical condition(s) being investigated Acute... lymphoblastic leukemia E.1.1.1Medical condition in easily understood language Acute lymphoblastic

  3. Radiation-induced hypopituitarism in children with acute lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    Mehrdad Mirouliaei

    2013-01-01

    Full Text Available Background: Acute Lymphoblastic Leukemia (ALL is the most common malignancy among children for whom radiotherapy and chemotherapy are used for treatment. When hypothalamus-pituitary axis is exposed to radiotherapy, children′s hormone level and quality of life are influenced. The aim of this study is to determine late effects of radiotherapy on hormonal level in these patients. Materials and Methods: In this study 27 children with ALL, who have been referred to Shahid Ramezanzadeh Radiation Oncology Center in Yazd-Iran and received 18-24 Gy whole brain radiation with Cobalt 60 or 9 MV linear accelerator, were assessed. These patient′s basic weight, height and hormonal levels were measured before radiotherapy and also after different periods of time. Results: GHD (growth hormone deficiency after clonidine stimulation test was observed in 44% ( n=12 and that in 50% of them ( n=6, less than 1 year, had been passed from their radiation therapy. None of these patients demonstrated hormone deficiency in other axes. Conclusions: This study showed that even application of a 18-24 Gy radiation dose might influence growth hormone levels; therefore, we recommend reduction of radiotherapy dose in such patients whenever possible.

  4. How tests of lubricating and transformer oils became part of power plant chemistry in Denmark

    Energy Technology Data Exchange (ETDEWEB)

    Moeller, H. [I/S Nordjyllandsvaerket, Vodskov (Denmark)

    1996-12-01

    Lubricating, hydraulic and transformer oils based on refined crude oil are used in nearly all power station components, such as gear, turbines, hydraulic stations, feed pumps and transformers. The function of these components totally depends on the condition of the oils and their properties. Seen from this point one may wonder why examination and evaluation of oils did not become part of the power station chemistry within the ELSAM utility area until during the middle of the eighties. We started to examine the properties of lubricating oils at the time when several steam turbines experienced serious problems with formation of deposits in their hydraulic control circuits. This work was intensified in connection with the significant number of CHPs and wind turbines erected within the Danish electricity sector during the past 10 years or so. The majority of the CHPs are natural gas fired turbines or motors, equipment which severely stresses the lubricating oil. In collaboration with KEMA, the Netherlands, we have carried through with a large examination of lubricating oils in gas turbines and we have found suitable oil types. The objectives of our work with lubricating and transformer oils have been to link together the laboratory measurements with operational experience. Only by doing this is it possible to utilize the laboratory measurements in a correct way. It must be remembered that the main part of all oil specifications concerns the properties of new oils. Only very little is published about the requirements concerning used oils. (EG)

  5. Complete transformation of ZnO and CuO nanoparticles in culture medium and lymphocyte cells during toxicity testing.

    Science.gov (United States)

    Ivask, Angela; Scheckel, Kirk G; Kapruwan, Pankaj; Stone, Vicki; Yin, Hong; Voelcker, Nicolas H; Lombi, Enzo

    2017-03-01

    Here, we present evidence on complete transformation of ZnO and CuO nanoparticles, which are among the most heavily studied metal oxide particles, during 24 h in vitro toxicological testing with human T-lymphocytes. Synchrotron radiation-based X-ray absorption near edge structure (XANES) spectroscopy results revealed that Zn speciation profiles of 30 nm and 80 nm ZnO nanoparticles, and ZnSO4- exposed cells were almost identical with the prevailing species being Zn-cysteine. This suggests that ZnO nanoparticles are rapidly transformed during a standard in vitro toxicological assay, and are sequestered intracellularly, analogously to soluble Zn. Complete transformation of ZnO in the test conditions was further supported by almost identical Zn spectra in medium to which ZnO nanoparticles or ZnSO4 was added. Likewise, Cu XANES spectra for CuO and CuSO4-exposed cells and cell culture media were similar. These results together with our observation on similar toxicological profiles of ZnO and soluble Zn, and CuO and soluble Cu, underline the importance of dissolution and subsequent transformation of ZnO and CuO nanoparticles during toxicological testing and provide evidence that the nano-specific effect of ZnO and CuO nanoparticles is negligible in this system. We strongly suggest to account for this aspect when interpreting the toxicological results of ZnO and CuO nanoparticles.

  6. Imatinib Mesylate and Combination Chemotherapy in Treating Patients With Newly Diagnosed Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia

    Science.gov (United States)

    2016-12-28

    B Acute Lymphoblastic Leukemia With t(9;22)(q34.1;q11.2); BCR-ABL1; BCR-ABL1 Fusion Protein Expression; Minimal Residual Disease; Philadelphia Chromosome Positive; T Acute Lymphoblastic Leukemia; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Childhood Acute Lymphoblastic Leukemia

  7. Development and test in grid of 630 kVA three-phase high temperature superconducting transformer

    Institute of Scientific and Technical Information of China (English)

    Yinshun WANG; Xiang ZHAO; Junjie HAN; Huidong LI; Yin GUAN; Qing BAO; Xi XU; Shaotao DAI; Naihao SONG; Fengyuan ZHANG; Liangzhen LIN; Liye XIAO

    2009-01-01

    A 630-kVA 10.5 kV/0.4kV three-phase high temperature superconducting (HTS) power transformer was successfully developed and tested in a live grid.The windings were wound by hermetic stainless steel-reinforced multi-filamentary Bi2223/Ag tapes.The struc-tures of primary windings are solenoid with insulation and cooling path among layers,and those of secondary windings consist of double-pancakes connected in parallel.Toroidal cryostat is made from electrical insulating glass fiber reinforced plastics (GFRP) materials with room temperature bore for commercial amorphous alloy core with five limbs.Windings are laid in the toroidal cryostat so that the amorphous core operates at room temperature.An insulation technology of double-half wrapping up the Bi2223/Ag tape with Kapton film is used by a winding machine developed by the authors.Fundamental char-acteristics of the transformer are obtained by standard short-circuit and no-load tests,and it is shown that the transformer meets operating requirements in a live grid.

  8. The NOTCH signaling pathway: role in the pathogenesis of T-cell acute lymphoblastic leukemia and implication for therapy

    OpenAIRE

    2013-01-01

    T-cell acute lymphoblastic leukemia/lymphoma (T-ALL) is characterized by aberrant activation of NOTCH1 in over 60% of T-ALL cases. The high prevalence of activating NOTCH1 mutations highlights the critical role of NOTCH signaling in the pathogenesis of this disease and has prompted the development of therapeutic approaches targeting the NOTCH signaling pathway. Small molecule gamma secretase inhibitors (GSIs) can effectively inhibit oncogenic NOTCH1 and are in clinical testing for the treatme...

  9. A new Laplace transformation method for dynamic testing of solar collectors

    DEFF Research Database (Denmark)

    Kong, Weiqiang; Perers, Bengt; Fan, Jianhua

    2015-01-01

    during test period. The other is the natural test method which doesn't need any intervention. The new L-QDT model with the shielding method are tested by TRNSYS (Klein S. et al (1988) [3]) simulation. Experiments were carried out at Technical University of Denmark by using the L-QDT method...

  10. Biodegradation of sulfamethoxazole photo-transformation products in a water/sediment test.

    Science.gov (United States)

    Su, Tong; Deng, Huiping; Benskin, Jonathan P; Radke, Michael

    2016-04-01

    Occurrence of the antibiotic sulfamethoxazole (SMX) in the aquatic environment is of concern due to its potential to induce antibiotic resistance in pathogenic bacteria. While degradation of SMX can occur by numerous processes, the environmental fate of its transformation products (TPs) remains poorly understood. In the present work, biodegradation of SMX photo-TPs was investigated in a water/sediment system. Photo-TPs were produced by exposing SMX to artificial sunlight for 48 h. The resulting mixture of 8 photo-TPs was characterized using a combination of ultra-high performance liquid chromatography coupled to high-resolution mass spectrometry and tandem mass spectrometry, and then used in biodegradation experiments. Significant differences in transformation among SMX photo-TPs were observed in the water/sediment system, with four photo-TPs displaying evidence of biodegradation (dissipation half-lives [DT50] of 39.7 d for 3-amino-5-methylisoxazole, 12.7 d for 4-nitro-sulfamethxoazole, 7.6 d for an SMX isomer and 2.4 d for [C10H13N3O4S]), two displaying primarily abiotic degradation (DT50 of 31 d for sulfanilic acid and 74.9 d for 5-methylisoxazol-3-yl-sulfamate), and two photo-TPs behaving largely recalcitrantly. Remarkably, TPs previously reported to be photo-stable also were persistent in biodegradation experiments. The most surprising observation was an increase in SMX concentrations when the irradiated solution was incubated, which we attribute to back-transformation of certain photo-TPs by sediment bacteria (85% from 4-nitro-sulfamethoxazole). This process could contribute to exposure to SMX in the aquatic environment that is higher than one would expect based on the fate of SMX alone. The results highlight the importance of considering TPs along with their parent compounds when characterizing environmental risks of emerging contaminants.

  11. Treatment of adult acute lymphoblastic leukaemia.

    Science.gov (United States)

    Jacobs, P; Wood, L; Novitzky, N

    1990-01-01

    Eighty-five consecutive patients with acute lymphoblastic leukaemia (ALL), having a median age of 24 years (range 10-69 years), underwent induction and consolidation chemotherapy with weekly parenteral vincristine, Adriamycin, l-asparaginase and daily oral prednisone (VAAP), followed by standard (CNS) prophylaxis. Maintenance therapy was given for 3 years and consisted of daily 6-mercaptopurine, weekly methotrexate and monthly intrathecal therapy, with drug intensification comprising either vincristine, Adriamycin and l-asparaginase (VAA) or cyclophosphamide, vincristine, cytosine arabinoside and prednisone (COAP). Complete remission (CR) was obtained in 59 patients (69%) and only the French-American-British (FAB) L1 morphology was a significant predictive factor (P = 0.048). Twenty-three patients failed to achieve CR and of these 12 had primary drug resistance. Median follow-up is currently 260 weeks, median predicted survival of all patients is 58 weeks and for those who achieved CR it is 104 weeks. Median duration of CR is 70 weeks. Of the prognostic factors for survival, only FAB L1 subtype was significant. Bone marrow relapses occurred in 29 patients, and of these 9 (31%) achieved CR. There has been CNS relapse in two patients and both have died. Eleven patients continue in CR off therapy, with a median of 152 weeks. This regimen is effective, with acceptable toxicity, and a number of patients are potentially cured. The incidence of resistant and relapsing disease is an argument for further intensifying both induction and postinduction therapy.

  12. Childhood Acute Lymphoblastic Leukemia: Progress Through Collaboration

    Science.gov (United States)

    Yang, Jun J.; Hunger, Stephen P.; Pieters, Rob; Schrappe, Martin; Biondi, Andrea; Vora, Ajay; Baruchel, André; Silverman, Lewis B.; Schmiegelow, Kjeld; Escherich, Gabriele; Horibe, Keizo; Benoit, Yves C.M.; Izraeli, Shai; Yeoh, Allen Eng Juh; Liang, Der-Cherng; Downing, James R.; Evans, William E.; Relling, Mary V.; Mullighan, Charles G.

    2015-01-01

    Purpose To review the impact of collaborative studies on advances in the biology and treatment of acute lymphoblastic leukemia (ALL) in children and adolescents. Methods A review of English literature on childhood ALL focusing on collaborative studies was performed. The resulting article was reviewed and revised by the committee chairs of the major ALL study groups. Results With long-term survival rates for ALL approaching 90% and the advent of high-resolution genome-wide analyses, several international study groups or consortia were established to conduct collaborative research to further improve outcome. As a result, treatment strategies have been improved for several subtypes of ALL, such as infant, MLL-rearranged, Philadelphia chromosome–positive, and Philadelphia chromosome–like ALL. Many recurrent genetic abnormalities that respond to tyrosine kinase inhibitors and multiple genetic determinants of drug resistance and toxicities have been identified to help develop targeted therapy. Several genetic polymorphisms have been recognized that show susceptibility to developing ALL and that help explain the racial/ethnic differences in the incidence of ALL. Conclusion The information gained from collaborative studies has helped decipher the heterogeneity of ALL to help improve personalized treatment, which will further advance the current high cure rate and the quality of life for children and adolescents with ALL. PMID:26304874

  13. Acute lymphoblastic leukemia in adolescents and young adults in Finland.

    Science.gov (United States)

    Usvasalo, Anu; Räty, Riikka; Knuutila, Sakari; Vettenranta, Kim; Harila-Saari, Arja; Jantunen, Esa; Kauppila, Marjut; Koistinen, Pirjo; Parto, Katriina; Riikonen, Pekka; Salmi, Toivo T; Silvennoinen, Raija; Elonen, Erkki; Saarinen-Pihkala, Ulla M

    2008-08-01

    Interest has recently been paid to adolescents and young adults with acute lymphoblastic leukemia, particularly because all reports so far published indicate that these patients have a better outcome when treated with pediatric rather than adult therapeutic protocols. There are different biological subtypes of acute lymphoblastic leukemia with distinct features and prognoses; the distribution of these subtypes is not well known among adolescents. We, therefore, studied acute lymphoblastic leukemia in adolescents and young adults aged 10 to 25 years in Finland. This population-based study included 225 consecutive patients aged 10-25 years diagnosed with acute lymphoblastic leukemia during 1990-2004. One hundred and twenty-eight patients (10-16 years) were treated with pediatric Nordic (NOPHO) protocols, and 97 patients (17-25 years) with Finnish Leukemia Group National protocols. We characterized the biological subtypes, clinical features and outcome of these patients. For the whole cohort, the remission rate was 96%, 5-year event-free survival 62% and overall survival 72%. The 5-year event-free survival was 67% for the pediatric treatment group and 60% for the adult treatment group (p=n.s.). Patients with inferior outcome were those with a white blood cell count >or= 100 x 10(9)/L, the Philadelphia chromosome and MLL. Good prognostic features were TEL-AML1, hyperdiploidy, and pediatric intermediate risk stratification. Unlike all previous studies, we found that the outcome of adolescents and young adults with acute lymphoblastic leukemia treated with pediatric or adult therapeutic protocols was comparable. The success of the adult acute lymphoblastic leukemia therapy emphasizes the benefit of central referral of patients to academic centers and adherence to research protocols.

  14. Relapsed childhood acute lymphoblastic leukemia in the Nordic countries

    DEFF Research Database (Denmark)

    Oskarsson, Trausti; Söderhäll, Stefan; Arvidson, Johan

    2016-01-01

    Relapse is the main reason for treatment failure in childhood acute lymphoblastic leukemia. Despite improvements in the up-front therapy, survival after relapse is still relatively poor, especially for high-risk relapses. The aims of this study were to assess outcomes following acute lymphoblastic...... leukemia relapse after common initial Nordic Society of Paediatric Haematology and Oncology protocol treatment; to validate currently used risk stratifications, and identify additional prognostic factors for overall survival. Altogether, 516 of 2735 patients (18.9%) relapsed between 1992 and 2011 and were...

  15. Testing a measure of organizational learning capacity and readiness for transformational change in human services.

    Science.gov (United States)

    Bess, Kimberly D; Perkins, Douglas D; McCown, Diana L

    2011-01-01

    Transformative organizational change requires organizational learning capacity, which we define in terms of (1) internal and (2) external organizational systems alignment, and promoting a culture of learning, including (3) an emphasis on exploration and information, (4) open communication, (5) staff empowerment, and (6) support for professional development. We shortened and adapted Watkins and Marsick's Dimensions of Learning Organizations Questionnaire into a new 16-item Organizational Learning Capacity Scale (OLCS) geared more toward nonprofit organizations. The OLCS and its subscales measuring each of the above 6 dimensions are unusually reliable for their brevity. ANOVAs for the OLCS and subscales clearly and consistently confirmed extensive participant observations and other qualitative data from four nonprofit human service organizations and one local human service funding organization.

  16. Tribology of improved transformation-toughened ceramics-heat engine test. Final report: DOE/ORNL Ceramic Technology Project

    Energy Technology Data Exchange (ETDEWEB)

    Lilley, E.; Rossi, G.A.; Pelletier, P.J. [Norton Co., Northboro, MA (United States). Advanced Ceramics Div.

    1992-04-01

    A short term study has been carried out to evaluate the suitability as cam roller followers of three ceria zirconia toughened aluminas and two yttria stabilized tetragonal zirconias (YTZPs) previously enhanced in programs supported by ORNL. Norton Si{sub 3}N{sub 4} (NBD-100) was also included in this study as a reference material, because it was known from work at Northwestern University that Si{sub 3}N{sub 4} to experienced little or no wear in this application, and NBD-100 is currently a successful commercial bearing material. The tribological studies were subcontracted to the Torrington Company. They found that in cam roller follower simulated tests that there was essentially no wear after 1 hour and 5 hours of testing detectable by weighing and concluded that all of these ceramics are, therefore, candidate materials. Because of the minute amounts of wear it was not possible to identify the wear mechanism or to make any correlations with the other physical properties which were evaluated such as MOR, K{sub IC} hardness, density and grain size. Phase transformation during rolling has been of interest in the tribology of zirconia contain materials. The least stable of the ceria zirconia toughened aluminas resulted in as much as 33% monoclinic phase after testing whereas the yttria stabilized (TTZ) contained very little of this transformed phase. The results of this study show that oxide materials can now be considered as candidates for cam roller followers in heat engines.

  17. Targeted sequencing identifies associations between IL7R-JAK mutations and epigenetic modulators in T-cell acute lymphoblastic leukemia

    Science.gov (United States)

    Vicente, Carmen; Schwab, Claire; Broux, Michaël; Geerdens, Ellen; Degryse, Sandrine; Demeyer, Sofie; Lahortiga, Idoya; Elliott, Alannah; Chilton, Lucy; La Starza, Roberta; Mecucci, Cristina; Vandenberghe, Peter; Goulden, Nicholas; Vora, Ajay; Moorman, Anthony V.; Soulier, Jean; Harrison, Christine J.; Clappier, Emmanuelle; Cools, Jan

    2015-01-01

    T-cell acute lymphoblastic leukemia is caused by the accumulation of multiple oncogenic lesions, including chromosomal rearrangements and mutations. To determine the frequency and co-occurrence of mutations in T-cell acute lymphoblastic leukemia, we performed targeted re-sequencing of 115 genes across 155 diagnostic samples (44 adult and 111 childhood cases). NOTCH1 and CDKN2A/B were mutated/deleted in more than half of the cases, while an additional 37 genes were mutated/deleted in 4% to 20% of cases. We found that IL7R-JAK pathway genes were mutated in 27.7% of cases, with JAK3 mutations being the most frequent event in this group. Copy number variations were also detected, including deletions of CREBBP or CTCF and duplication of MYB. FLT3 mutations were rare, but a novel extracellular mutation in FLT3 was detected and confirmed to be transforming. Furthermore, we identified complex patterns of pairwise associations, including a significant association between mutations in IL7R-JAK genes and epigenetic regulators (WT1, PRC2, PHF6). Our analyses showed that IL7R-JAK genetic lesions did not confer adverse prognosis in T-cell acute lymphoblastic leukemia cases enrolled in the UK ALL2003 trial. Overall, these results identify interconnections between the T-cell acute lymphoblastic leukemia genome and disease biology, and suggest a potential clinical application for JAK inhibitors in a significant proportion of patients with T-cell acute lymphoblastic leukemia. PMID:26206799

  18. Molecular-genetic insights in paediatric T-cell acute lymphoblastic leukaemia.

    Science.gov (United States)

    Van Vlierberghe, Pieter; Pieters, Rob; Beverloo, H Berna; Meijerink, Jules P P

    2008-10-01

    Paediatric T-cell acute lymphoblastic leukaemia (T-ALL) is an aggressive malignancy of thymocytes that accounts for about 15% of ALL cases and for which treatment outcome remains inferior compared to B-lineage acute leukaemias. In T-ALL, leukemic transformation of maturating thymocytes is caused by a multistep pathogenesis involving numerous genetic abnormalities that drive normal T-cells into uncontrolled cell growth and clonal expansion. This review provides an overview of the current knowledge on onco- and tumor suppressor genes in T-ALL and suggests a classification of these genetic defects into type A and type B abnormalities. Type A abnormalities may delineate distinct molecular-cytogenetic T-ALL subgroups, whereas type B abnormalities are found in all major T-ALL subgroups and synergize with these type A mutations during T-cell pathogenesis.

  19. Treatment of acute lymphoblastic leukaemia (ALL).

    Science.gov (United States)

    Jacobs, P; Wood, L

    1992-08-01

    Forty-six consecutive patients with acute lymphoblastic leukaemia (ALL), having a median age of 23 years (range 14 to 64), underwent induction and consolidation chemotherapy with weekly parenteral vincristine, adriamycin, l-asparaginase and daily oral prednisone (VAAP), followed by standard central nervous system (CNS) prophylaxis. Maintenance therapy was given for 3 years and consisted of daily 6-mercaptopurine, weekly methotrexate, and monthly intrathecal chemotherapy, with drug intensification comprising either vincristine, adriamycin and l-asparaginase (VAA) or cyclophosphamide, vincristine, cytosine arabinoside and prednisone (COAP). Complete remission (CR) was achieved in 36 patients (78%) and only the FAB L1 morphology was a significant predictive factor (Chi-squared = 3.91: p < 0.05). Eight of the 10 non-responders had significant drug resistance and 3 deaths were associated with marrow hypoplasia. Median follow-up is 52 months. Median duration of CR is 28 months, median survival of all patients is 16 months, and for those who achieved CR is 44 months. There was no difference between the two maintenance arms. Significant prognostic factors for survival are French-American-British (FAB) subtype, in which the L1 is better than L2 (p = 0.05), and age (p = 0.035). Nineteen patients have experienced medullary relapse and 7 (37%) achieved subsequent CR; this is durable in a single patient who underwent allogeneic bone marrow transplantation. Eight patients (17%) had CNS disease at diagnosis; 5 achieved CR and 1 is alive and disease-free at 65+ months. There has been 1 CNS relapse. These results demonstrate that prolonged remissions and survival can be achieved with this protocol and many patients possibly cured. The level of toxicity is acceptable and the pattern of induction failure indicates that a margin exists for intensifying chemotherapy and thereby possibly further improving results.

  20. Comprehensive retrospective evaluation of existing in vitro chromosomal aberration test data by cytotoxicity index transformation.

    Science.gov (United States)

    Fujita, Yurika; Morita, Takeshi; Matsumura, Shoji; Kawamoto, Taisuke; Ito, Yuichi; Nishiyama, Naohiro; Honda, Hiroshi

    2016-05-01

    New OECD test guidelines have been issued, in which the cytotoxicity index relative cell count (RCC) is replaced with a new index, RICC or RPD (relative increase in cell count/relative population doubling), with the goal of reducing the high proportion of false positive results in in vitro chromosomal aberration tests. Using a mathematical approach to estimate new indices from the RCC, we constructed an evaluation flow that quantitatively estimates how often the previous test conclusions change when applying the updated cytotoxicity criteria. The new evaluation flow was applied to a retrospective evaluation of 285 chemicals in two databases. The effects of the employment of new cytotoxicity indices are investigated at a large scale. Using the new evaluation flow, 90 chemicals were estimated as positive, 39 were designated as estimated negative (13 probably negative and 26 possibly negative), and 140 were designated as negative. Moreover, we also applied a prioritization index to indicate the likelihood of a chemical being re-evaluated as negative and assigned priorities for testing. Most of the chemicals that were designated as estimated negative and had negative results in the in vivo micronucleus tests were considered as false-positives that would be correctly judged under the new test guideline. Furthermore, statistical analysis of the frequency of estimated negatives revealed that the results for Ames-positive chemicals, especially those with a strong response, are unlikely to change. Therefore, we concluded that the new indices would likely reduce the proportion of false positive results and not increase the proportion of false negative results. This study is the first report of a comprehensive re-evaluation of test results in terms of new cytotoxicity indices. The evaluation flow we have developed facilitates efficient retrospective evaluation of genotoxicity. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. NPS: A Tested Platform for Political Transformation Against Anger & Apathy in Pakistan

    Directory of Open Access Journals (Sweden)

    Allah Nawaz

    2013-07-01

    Full Text Available Political inaction is a major ‘Barrier’ to the progress of democratic values and systems in a society. It is more critical in the developing countries like Pakistan. A huge body of research on political apathy and anger in Pakistan is reporting over and over on the causes and consequences of this pathetic psychology. All that is true however, rays of hope are always there provided nations continue searching for the opportunities through scientific and rigorous research accompanied with sincerity and sense of responsibility at all the decision making levels of the state. This paper postulates a solution model for the issue in the perspectives of Pakistan by capitalizing on the role of Information and Communication Technologies (ICT in the Instant Political Transformation of the developing countries like Egypt & Lybia. The New Public Sphere (NPS is populated with Global Civil Society (GCS where International Citizens are connected together 24/7 from any corner of the Global Village and involved in use of ICT for Social Activism. Pakistan now has millions of Internet and Cell-users who are the part of GCS and waiting for a ‘Trigger’ to switch from the ‘Informal Activism to Formal & Political Activism’ through NPS.

  2. Automatic conjunctival provocation test combining Hough circle transform and self-calibrated color measurements

    Science.gov (United States)

    Bista, Suman Raj; Sárándi, István.; Dogan, Serkan; Astvatsatourov, Anatoli; Mösges, Ralph; Deserno, Thomas M.

    2013-02-01

    Computer-aided diagnosis is developed for assessment of allergic rhinitis/rhinoconjunctivitis measuring the relative redness of sclera under application of allergen solution. Images of the patient's eye are taken using a commercial digital camera. The iris is robustly localized using a gradient-based Hough circle transform. From the center of the pupil, the region of interest within the sclera is extracted using geometric anatomy-based apriori information. The red color pixels are extracted thresholding in the hue, saturation and value color space. Then, redness is measured by taking mean of saturation projected into zero hue. Evaluation is performed with 98 images taken from 14 subjects, 8 responders and 6 non-responders, which were classified according to an experienced otorhinolaryngologist. Provocation is performed with 100, 1,000 and 10,000 AU/ml allergic solution and normalized to control images without provocation. The evaluation yields relative redness of 1.01, 1.05, 1.30 and 0.95, 1.00, 0.96 for responders and non-responders, respectively. Variations in redness measurements were analyzed according to alteration of parameters of the image processing chain proving stability and robustness of our approach. The results indicate that the method improves visual inspection and may be suitable as reliable surrogate endpoint in controlled clinical trials.

  3. Fourier-transformed infrared breath testing after ingestion of technical alcohol.

    Science.gov (United States)

    Laakso, Olli; Haapala, Matti; Pennanen, Teemu; Kuitunen, Tapio; Himberg, Jaakko-Juhani

    2007-07-01

    The study aim was to evaluate the feasibility of a Fourier-transformed infrared (FT-IR) analyzer for out-of-laboratory use by screening the exhalations of inebriated individuals, and to determine analysis quality using common breath components and solvents. Each of the 35 inebriated participants gave an acceptable sample. Because of the metabolism of 2-propanol, the subjects exhaled high concentrations of acetone in addition to ethanol. Other volatile ingredients of technical ethanol products (methyl ethyl ketone, methyl isobutyl ketone, and 2-propanol) were also detected. The lower limits of quantification for the analyzed components ranged from 1.7 to 12 microg/L in simulated breath samples. The bias was +/-2% for ethanol and -11% for methanol. Within-day and between-day coefficients of variation were <1% for ethanol and <4% for methanol. The bias of ethanol and methanol analyses due to coexisting solvents ranged from -0.8 to +2.2% and from -5.6 to +2.9%, respectively. The FT-IR method proved suitable for use outside the laboratory and fulfilled the quality criteria for analysis of solvents in breath.

  4. [Effects of Sam68 gene silence on proliferation of acute T lymphoblastic leukemia cell line Jurkat].

    Science.gov (United States)

    Wang, Chi-Juan; Xu, Hua; Zhang, Hai-Rui; Wang, Jian; Lin, Ya-Ni; Pang, Tian-Xiang; Li, Qing-Hua

    2014-08-01

    This study was purpose to investigate the effect of Sam68 gene silence on proliferation of human acute T lymphoblastic leukemia cell line Jurkat. The sequence of shRNA targeting the site 531-552 of Sam68 mRNA was designed and chemically synthesized, then a single-vector lentiviral, Tet-inducible shRNA-Sam68 system (pLKO-Tet-On) was constructed; next the Jurkat cells were infected with lentivirus to create stable cell clones with regulatable Sam68 gene expression. The inhibitory efficiency of Sam68 gene was assayed by Real-time PCR and Western blot; the cell activity of Jurkat cells was detected with MTT assay; the change of colony forming potential of Jurkat cells was analyzed by colony forming test; the cell cycle distribution was tested by flow cytometry. The results indicated that the expression of Sam68 in experimental cells was statistically decreased as compared with that of the control cells; the cells activity and colony forming capacity of the Jurkat cells with Sam68 gene silence were significantly inhibited; with Sam68 gene silencing, the percentage of S phase cells was significantly increased, while the percentage of G2 phase cells was significantly decreased. It is concluded that the silencing Sam68 gene using shRNA interference can effectively inhibit the proliferation of human acute T lymphoblastic leukemia cell line Jurkat.

  5. Color vision deficiency compensation for Visual Processing Disorder using Hardy-Rand-Rittler test and color transformation

    Science.gov (United States)

    Balbin, Jessie R.; Pinugu, Jasmine Nadja J.; Bautista, Joshua Ian C.; Nebres, Pauline D.; Rey Hipolito, Cipriano M.; Santella, Jose Anthony A.

    2017-06-01

    Visual processing skill is used to gather visual information from environment however, there are cases that Visual Processing Disorder (VPD) occurs. The so called visual figure-ground discrimination is a type of VPD where color is one of the factors that contributes on this type. In line with this, color plays a vital role in everyday living, but individuals that have limited and inaccurate color perception suffers from Color Vision Deficiency (CVD) and still not aware on their case. To resolve this case, this study focuses on the design of KULAY, a Head-Mounted Display (HMD) device that can assess whether a user has a CVD or not thru the standard Hardy-Rand-Rittler (HRR) test. This test uses pattern recognition in order to evaluate the user. In addition, color vision deficiency simulation and color correction thru color transformation is also a concern of this research. This will enable people with normal color vision to know how color vision deficient perceives and vice-versa. For the accuracy of the simulated HRR assessment, its results were validated thru an actual assessment done by a doctor. Moreover, for the preciseness of color transformation, Structural Similarity Index Method (SSIM) was used to compare the simulated CVD images and the color corrected images to other reference sources. The output of the simulated HRR assessment and color transformation shows very promising results indicating effectiveness and efficiency of the study. Thus, due to its form factor and portability, this device is beneficial in the field of medicine and technology.

  6. Technical protocol for laboratory tests of transformation of veterinary medicinal products and biocides in liquid manures. Version 1.0

    Energy Technology Data Exchange (ETDEWEB)

    Kreuzig, Robert [Technische Univ. Braunschweig (Germany). Inst. fuer Oekologische Chemie und Abfallanalytik

    2010-07-15

    The technical protocol under consideration describes a laboratory test method to evaluate the transformation of chemicals in liquid bovine and pig manures under anaerobic conditions and primarily is designed for veterinary medicinal products and biocides. The environmentally relevant entry routes into liquid manures occur via urine and feces of cattle and pigs in stable housings after excretion of veterinary medicinal products as parent compounds or metabolites and after the application of biocides in animal housings. Further entry routes such as solid dung application and direct dung pat deposition by production animals on pasture are not considered by this technical protocol. Thus, this technical protocol focused on the sampling of excrements from cattles and pigs kept in stables and fed under standard nutrition conditions. This approach additionally ensures that excrement samples are operationally free of any contamination by veterinary medicinal products and biocides. After the matrix characterization, reference-manure samples are prepared from the excrement samples by adding tap water to adjust defined dry substance contents typical for bovine or pig manures. This technical protocol comprehends a tiered experimental design in two parts: (a) Sampling of excrements and preparation of reference bovine and pig manures; (b) Testing of anaerobic transformation of chemicals in reference manures.

  7. Acute lymphoblastic leukemia in children with Down syndrome

    DEFF Research Database (Denmark)

    Buitenkamp, Trudy D; Izraeli, Shai; Zimmermann, Martin

    2014-01-01

    Children with Down syndrome (DS) have an increased risk of B-cell precursor (BCP) acute lymphoblastic leukemia (ALL). The prognostic factors and outcome of DS-ALL patients treated in contemporary protocols are uncertain. We studied 653 DS-ALL patients enrolled in 16 international trials from 1995...

  8. L-asparaginase treatment in acute lymphoblastic leukemia

    NARCIS (Netherlands)

    R. Pieters (Rob); S.P. Hunger (Stephen); J. Boos (Joachim); C. Rizzari (Carmelo); L.B. Silverman (Lewis); A. Baruchel (André); N. Goekbuget (Nicola); M. Schrappe (Martin); C.H. Pui (Ching-Hon)

    2011-01-01

    textabstractAsparaginases are a cornerstone of treatment protocols for acute lymphoblastic leukemia (ALL) and are used for remission induction and intensification treatment in all pediatric regimens and in the majority of adult treatment protocols. Extensive clinical data have shown that intensive a

  9. Obesity in patients with acute lymphoblastic leukemia in childhood

    Directory of Open Access Journals (Sweden)

    Iughetti Lorenzo

    2012-01-01

    Full Text Available Abstract Acute lymphoblastic leukemia is the most common malignancy in childhood. Continuous progress in risk-adapted treatment for childhood acute lymphoblastic leukemia has secured 5-year event-free survival rates of approximately 80% and 8-year survival rates approaching 90%. Almost 75% of survivors, however, have a chronic health condition negatively impacting on cardiovascular morbidity and mortality. Obesity can be considered one of the most important health chronic conditions in the general population, with an increasing incidence in patients treated for childhood cancers and especially in acute lymphoblastic leukemia survivors who are, at the same time, more at risk of experiencing precocious cardiovascular and metabolic co-morbidities. The hypothalamic-pituitary axis damage secondary to cancer therapies (cranial irradiation and chemotherapy or to primary tumor together with lifestyle modifications and genetic factors could affect long-term outcomes. Nevertheless, the etiology of obesity in acute lymphoblastic leukemia is not yet fully understood. The present review has the aim of summarizing the published data and examining the most accepted mechanisms and main predisposing factors related to weight gain in this particular population.

  10. Bone histomorphometry in children with newly diagnosed acute lymphoblastic leukemia

    NARCIS (Netherlands)

    Leeuw, JA; Koudstaal, J; Wiersema-Buist, J; Kamps, WA; Timens, W

    2003-01-01

    The objective of this study was to obtain insight into bone formation and resorption in children with newly diagnosed untreated acute lymphoblastic leukemia (ALL). In 23 consecutive children with ALL, a bone biopsy was taken from the crista iliaca posterior under ketamine anesthesia, together with t

  11. Academic career after treatment for acute lymphoblastic leukaemia

    NARCIS (Netherlands)

    Kingma, A; Rammeloo, LAJ; van der Does-van den Berg, A; Rekers-Mombarg, L; Postma, A

    2000-01-01

    Aim-To evaluate academic career in long term survivors of childhood acute lymphoblastic leukaemia (ALL), in comparison to their healthy siblings. Patients-Ninety four children treated for ALL with cranial irradiation 18 or 25 Gy and intrathecal methotrexate as CNS prophylaxis. Median age at evaluati

  12. Asparaginase-associated pancreatitis in childhood acute lymphoblastic leukaemia

    DEFF Research Database (Denmark)

    Wolthers, Benjamin O.; Frandsen, Thomas L.; Baruchel, André

    2017-01-01

    BACKGROUND: Survival for childhood acute lymphoblastic leukaemia surpasses 90% with contemporary therapy; however, patients remain burdened by the severe toxic effects of treatment, including asparaginase-associated pancreatitis. To investigate the risk of complications and risk of re-exposing pa...

  13. Epigenetics in MLL-rearranged infant Acute Lymphoblastic Leukemia

    NARCIS (Netherlands)

    D.J.P.M. Stumpel (Dominique)

    2012-01-01

    textabstractNowadays the cure rate for children diagnosed with acute lymphoblastic leukemia (ALL) has exceeded 80%. Although this is considered to be one of the major successes in pediatric oncology, the subgroup of patients that did not benefit from the improved therapeutic strategies should not be

  14. Pharmacogenetics Influence Treatment Efficacy in Childhood Acute Lymphoblastic Leukemia

    DEFF Research Database (Denmark)

    Devidsen, M.L.; Dalhoff, K.; Schmiegelow, K.

    2008-01-01

    in treatment resistance and toxic side effects. As most childhood acute lymphoblastic leukemia treatment protocols include up to 13 different chemotherapeutic agents, the impact of individual SNPs has been difficult to evaluate. So far Focus has mainly been on the widely used glucocorticosteroids, methotrexate...

  15. Neurodevelopmental Sequelae of Pediatric Acute Lymphoblastic Leukemia and Its Treatment

    Science.gov (United States)

    Janzen, Laura A.; Spiegler, Brenda J.

    2008-01-01

    This review will describe the neurocognitive outcomes associated with pediatric acute lymphoblastic leukemia (ALL) and its treatment. The literature is reviewed with the aim of addressing methodological issues, treatment factors, risks and moderators, special populations, relationship to neuroimaging findings, and directions for future research.…

  16. Etiology of common childhood acute lymphoblastic leukemia: the adrenal hypothesis

    DEFF Research Database (Denmark)

    Schmiegelow, K.; Vestergaard, T.; Nielsen, S.M.

    2008-01-01

    The pattern of infections in the first years of life modulates our immune system, and a low incidence of infections has been linked to an increased risk of common childhood acute lymphoblastic leukemia (ALL). We here present a new interpretation of these observations--the adrenal hypothesis...

  17. Pharmacogenetics influence treatment efficacy in childhood acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Davidsen, Marie Louise; Dalhoff, Kim; Schmiegelow, Kjeld

    2008-01-01

    in treatment resistance and toxic side effects. As most childhood acute lymphoblastic leukemia treatment protocols include up to 13 different chemotherapeutic agents, the impact of individual SNPs has been difficult to evaluate. So far focus has mainly been on the widely used glucocorticosteroids, methotrexate...

  18. A linear Kronig-Kramers transform test for immittance data validation

    NARCIS (Netherlands)

    Boukamp, Bernard A.

    1995-01-01

    A method is described with which immittance data can be tested for Kronig‐Kramers compliance. In contrast with other procedures, this method is linear in nature and is based on a predetermined set of relaxation times. The model contains as many parameters (or less) as there are data sets. Three mode

  19. Severe Hypertriglyceridemia During Therapy For Childhood Acute Lymphoblastic Leukemia

    Science.gov (United States)

    Bhojwani, Deepa; Darbandi, Rashid; Pei, Deqing; Ramsey, Laura B.; Chemaitilly, Wassim; Sandlund, John T.; Cheng, Cheng; Pui, Ching-Hon; Relling, Mary V.; Jeha, Sima; Metzger, Monika L.

    2014-01-01

    Background Asparaginase and steroids can cause hypertriglyceridemia in children with acute lymphoblastic leukemia (ALL). There are no guidelines for screening or management of patients with severe hypertriglyceridemia (>1000 mg/dL) during ALL therapy. Patients and Methods Fasting lipid profiles were obtained prospectively at 4 time-points for 257 children consecutively enrolled on a frontline ALL study. Risk factors were evaluated by the exact chi-square test. Details of adverse events and management of hypertriglyceridemia were extracted retrospectively. Results Eighteen of 257 (7%) patients developed severe hypertriglyceridemia. Older age and treatment with higher doses of asparaginase and steroids on the standard/high-risk arm were significant risk factors. Severe hypertriglyceridemia was not associated with pancreatitis after adjustment for age and treatment arm or with osteonecrosis after adjustment for age. However, patients with severe hypertriglyceridemia had a 2.5 to 3 times higher risk of thrombosis compared to patients without, albeit the difference was not statistical significant. Of the 30 episodes of severe hypertriglyceridemia in 18 patients, 7 were managed conservatively while the others with pharmacotherapy. Seventeen of 18 patients continued to receive asparaginase and steroids. Triglyceride levels normalized after completion of ALL therapy in all 12 patients with available measurements. Conclusion Asparaginase- and steroid-induced transient hypertriglyceridemia can be adequately managed with dietary modifications and close monitoring without altering chemotherapy. Patients with severe hypertriglyceridemia were not at increased risk of adverse events, with a possible exception of thrombosis. The benefit of pharmacotherapy in decreasing symptoms and potential complications requires further investigation. PMID:25087182

  20. [Alcaligenes xylosoxidans bacteremia in a patient with acute lymphoblastic leukemia].

    Science.gov (United States)

    Aydemir, Zeynep Alp; Ozdemir, Nihal; Celik, Nigar; Celkan, Tiraje

    2009-07-01

    Alcaligenes xylosoxidans which is an aerobic, non-fermentative gram-negative bacillus found in aqueous environments and human flora, can lead to opportunistic infections. It causes infections in elderly, immunocompromised patients, patients with chronic disorders or premature infants. In this report, a case of A. xylosoxidans bacteremia that developed in a child with acute lymphoblastic leukemia (ALL) was presented. Four-years-old male patient under ALL induction therapy was admitted with symptoms of lethargy, headache, somnolence, and fever (39 degrees C). Cerebrospinal fluid, blood, throat and urine cultures were taken from the patient and empirical treatment with sulbactam cefoperazon and amikacin was initiated. Blood cultures in BacT Alert 3D (Bio Merieux, France) revealed the growth of a gram-negative coccobacillus. The agent which was non-fermentative, indol and H2S negative, was identified as A. xylosoxidans by API 20 NE (Bio Merieux, France). Since fever continued under the current antibiotic treatment, the therapy was switched to imipenem (90 mg/kg 3x/day) and the patient's condition improved markedly after 24 hours. Disc diffusion susceptibility testing of the isolate revealed that it was resistant to ampicillin, cephalothin, cefuroxime, cefoxitin, cefotaxime, amikacin, netilmicin and gentamicin; susceptible to amoxicillin clavulanate, piperacillin tazobactam, seftazidime, cefepime, imipenem and ciprofloxacin. Following 14 days of imipenem therapy, the patient recovered and discharged from the hospital on routine follow-up. It is important to consider A. xylosoxidans as a possible causative agent particularly in the infections that develop in high risk patients at oncology, dialysis and neonatal intensive care units.

  1. Cytologic Phenotypes of B-Cell Acute Lymphoblastic Leukemia-

    Directory of Open Access Journals (Sweden)

    Ramyar Asghar

    2009-06-01

    Full Text Available Acute lymphoblastic leukemia (ALL is a malignant disorder of lymphoid precursor cells, which could be classified according to morphological and cytochemical methods as well as immunophenotyping. Twenty patients with ALL, who had been referred to the Children's Medical Center Hospital, during the year 2007, were enrolled in this study in order to evaluate the morphologic and immunophenotypic profile of these patients. Cytologic analysis of blood and bone marrow samples revealed that the frequency of ALL-L1 was 70%, followed by ALL-L2 and ALL-L3. The onset age of the patients with ALL-L1 was significantly lower than the patients with L2/L3. Severe anemia was significantly detected more in L1 group. Flow cytometic study of bone marrow showed that 10 cases had Pre-B1 ALL and 7 cases had Pre-B2 ALL, while three cases had Pro-B ALL. Comparisons of the characteristics and clinical manifestations among these groups did not show any appreciable difference. There were an increase percentage of CD20+ cells and a decrease CD10+ cells in pre-B2 group in comparison with pre-B1 group. Fifteen patients were in standard risk and five were in high risk. Although standard risk patients were more common in the group of pre-B1, this was not significant. Our results confirm the previous reports indicating heterogeneity of ALL. Immunophenotyping is not the only diagnostic test of importance, while morphological assessment still can be used in the diagnosis and classification of the disease.

  2. Fourier-transform infrared spectroscopy as a novel approach to providing effect-based endpoints in duckweed toxicity testing.

    Science.gov (United States)

    Hu, Li-Xin; Ying, Guang-Guo; Chen, Xiao-Wen; Huang, Guo-Yong; Liu, You-Sheng; Jiang, Yu-Xia; Pan, Chang-Gui; Tian, Fei; Martin, Francis L

    2017-02-01

    Traditional duckweed toxicity tests only measure plant growth inhibition as an endpoint, with limited effects-based data. The present study aimed to investigate whether Fourier-transform infrared (FTIR) spectroscopy could enhance the duckweed (Lemna minor L.) toxicity test. Four chemicals (Cu, Cd, atrazine, and acetochlor) and 4 metal-containing industrial wastewater samples were tested. After exposure of duckweed to the chemicals, standard toxicity endpoints (frond number and chlorophyll content) were determined; the fronds were also interrogated using FTIR spectroscopy under optimized test conditions. Biochemical alterations associated with each treatment were assessed and further analyzed by multivariate analysis. The results showed that comparable x% of effective concentration (ECx) values could be achieved based on FTIR spectroscopy in comparison with those based on traditional toxicity endpoints. Biochemical alterations associated with different doses of toxicant were mainly attributed to lipid, protein, nucleic acid, and carbohydrate structural changes, which helped to explain toxic mechanisms. With the help of multivariate analysis, separation of clusters related to different exposure doses could be achieved. The present study is the first to show successful application of FTIR spectroscopy in standard duckweed toxicity tests with biochemical alterations as new endpoints. Environ Toxicol Chem 2017;36:346-353. © 2016 SETAC.

  3. Nilotinib and Combination Chemotherapy in Treating Patients With Newly Diagnosed Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia or Blastic Phase Chronic Myelogenous Leukemia

    Science.gov (United States)

    2015-10-29

    B-cell Adult Acute Lymphoblastic Leukemia; Blastic Phase Chronic Myelogenous Leukemia; Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Philadelphia Chromosome Positive Adult Precursor Acute Lymphoblastic Leukemia; Untreated Adult Acute Lymphoblastic Leukemia

  4. Prognostic significance of bi/oligoclonality in childhood acute lymphoblastic leukemia as determined by polymerase chain reaction

    Directory of Open Access Journals (Sweden)

    Carlos Alberto Scrideli

    2001-09-01

    Full Text Available CONTEXT: The CDR-3 region of heavy-chain immunoglobulin has been used as a clonal marker in the study of minimal residual disease in children with acute lymphoblastic leukemia. Southern blot and polymerase chain reaction studies have demonstrated the occurrence of bi/oligoclonality in a variable number of cases of B-lineage acute lymphoblastic leukemia, a fact that may strongly interfere with the detection of minimal residual disease. Oligoclonality has also been associated with a poorer prognosis and a higher chance of relapse. OBJECTIVES: To correlate bi/oligoclonality, detected by polymerase chain reaction in Brazilian children with B-lineage acute lymphoblastic leukemia with a chance of relapse, with immunophenotype, risk group, and disease-free survival. DESIGN: Prospective study of patients’ outcome. SETTING: Pediatric Oncology Unit of the University Hospital, Faculty of Medicine of Ribeirão Preto, University of São Paulo. PARTICIPANTS: 47 children with acute lymphoblastic leukemia DIAGNOSTIC TEST: Polymerase chain reaction using consensus primers for the CDR-3 region of heavy chain immunoglobulin (FR3A, LJH and VLJH for the detection of clonality. RESULTS: Bi/oligoclonality was detected in 15 patients (31.9%. There was no significant difference between the groups with monoclonality and biclonality in terms of the occurrence of a relapse (28.1% versus 26.1%, presence of CALLA+ (81.2% versus 80% or risk group (62.5% versus 60%. Disease-free survival was similar in both groups, with no significant difference (p: 0.7695. CONCLUSIONS: We conclude that bi/oligoclonality was not associated with the factors investigated in the present study and that its detection in 31.9% of the patients may be important for the study and monitoring of minimal residual disease.

  5. Deletion of genes encoding PU.1 and Spi-B in B cells impairs differentiation and induces pre-B cell acute lymphoblastic leukemia.

    Science.gov (United States)

    Sokalski, Kristen M; Li, Stephen K H; Welch, Ian; Cadieux-Pitre, Heather-Anne T; Gruca, Marek R; DeKoter, Rodney P

    2011-09-01

    The E26 transformation-specific (Ets) transcription factor PU.1 is required to generate lymphoid progenitor cells from hematopoietic stem cells, but it is not required to generate B cells from committed B-cell lineage progenitors. We hypothesized that PU.1 function in B-cell differentiation is complemented by the related Ets transcription factor Spi-B. To test this hypothesis, mice were generated lacking both PU.1 and Spi-B in the B-cell lineage. Unlike mice lacking PU.1 or Spi-B, mice deficient in both PU.1 and Spi-B in the B-cell lineage had reduced frequencies of B cells as well as impaired B-cell differentiation. Strikingly, all PU.1 and Spi-B-deficient mice developed pre-B cell acute lymphoblastic leukemia before 30 weeks of age. Pre-B cells accumulated in the thymus resulting in massive thymic enlargement and dyspnea. These findings demonstrate that PU.1 and Spi-B are essential transcriptional regulators of B-cell differentiation as well as novel tumor suppressors in the B-cell lineage.

  6. Optimizing asparaginase therapy for acute lymphoblastic leukemia.

    Science.gov (United States)

    Rizzari, Carmelo; Conter, Valentino; Starý, Jan; Colombini, Antonella; Moericke, Anja; Schrappe, Martin

    2013-03-01

    Asparaginases are important agents used in the treatment of children with acute lymphoblastic leukemia (ALL). Three types of asparaginase are currently available: two are derived from Escherichia coli [native asparaginase and pegylated asparaginase (PEG-asparaginase)] and one from Erwinia chrysanthemi (crisantaspase). All three products share the same mechanism of action but have different pharmacokinetic properties, which do not make them easily interchangeable. Among the known toxicities and side-effects, allergic reactions and silent inactivation represent the most important limitations to the prolonged use of any asparaginase product, with associated reduced therapeutic effects and poorer outcomes. Routine real time monitoring can help to identify patients with silent inactivation and facilitate a switch to a different product to ensure continued depletion of asparagine, completion of the treatment schedule and maintenance of outcomes. However, the most appropriate second-line treatment is still a matter of debate. PEG-asparaginase has lower immunogenicity and a longer half-life than native Escherichia coli (E. coli) asparaginase, which makes it useful for both first-line and second-line use with a reduced number of doses. However, PEG-asparaginase displays cross-reactivity with native E. coli asparaginase that may harm its therapeutic effects. Crisantaspase does not display cross-reactivity to either of the E. coli-derived products, which has made crisantaspase the second-line treatment option in a number of recent protocols. As crisantaspase has a much shorter biological half-life than the E. coli-derived products, the appropriate dosage and administration schedule are of paramount importance in delivering treatment with this product. In the ongoing trial AIEOP-BFM ALL 2009 (Associazione Italiana Ematologia Oncologia Pediatrica - Berlin-Franklin-Munster), in which PEG-asparaginase is used first-line, one dose of PEG-asparaginase is substituted by seven doses

  7. Sulforaphane induces cell cycle arrest and apoptosis in acute lymphoblastic leukemia cells.

    Directory of Open Access Journals (Sweden)

    Koramit Suppipat

    Full Text Available Acute lymphoblastic leukemia (ALL is the most common hematological cancer in children. Although risk-adaptive therapy, CNS-directed chemotherapy, and supportive care have improved the survival of ALL patients, disease relapse is still the leading cause of cancer-related death in children. Therefore, new drugs are needed as frontline treatments in high-risk disease and as salvage agents in relapsed ALL. In this study, we report that purified sulforaphane, a natural isothiocyanate found in cruciferous vegetables, has anti-leukemic properties in a broad range of ALL cell lines and primary lymphoblasts from pediatric T-ALL and pre-B ALL patients. The treatment of ALL leukemic cells with sulforaphane resulted in dose-dependent apoptosis and G2/M cell cycle arrest, which was associated with the activation of caspases (3, 8, and 9, inactivation of PARP, p53-independent upregulation of p21(CIP1/WAF1, and inhibition of the Cdc2/Cyclin B1 complex. Interestingly, sulforaphane also inhibited the AKT and mTOR survival pathways in most of the tested cell lines by lowering the levels of both total and phosphorylated proteins. Finally, the administration of sulforaphane to the ALL xenograft models resulted in a reduction of tumor burden, particularly following oral administration, suggesting a potential role as an adjunctive agent to improve the therapeutic response in high-risk ALL patients with activated AKT signaling.

  8. Cannabis Extract Treatment for Terminal Acute Lymphoblastic Leukemia with a Philadelphia Chromosome Mutation

    Directory of Open Access Journals (Sweden)

    Yadvinder Singh

    2013-11-01

    Full Text Available Acute lymphoblastic leukemia (ALL is a cancer of the white blood cells and is typically well treated with combination chemotherapy, with a remission state after 5 years of 94% in children and 30-40% in adults. To establish how aggressive the disease is, further chromosome testing is required to determine whether the cancer is myeloblastic and involves neutrophils, eosinophils or basophils, or lymphoblastic involving B or T lymphocytes. This case study is on a 14-year-old patient diagnosed with a very aggressive form of ALL (positive for the Philadelphia chromosome mutation. A standard bone marrow transplant, aggressive chemotherapy and radiation therapy were revoked, with treatment being deemed a failure after 34 months. Without any other solutions provided by conventional approaches aside from palliation, the family administered cannabinoid extracts orally to the patient. Cannabinoid resin extract is used as an effective treatment for ALL with a positive Philadelphia chromosome mutation and indications of dose-dependent disease control. The clinical observation in this study revealed a rapid dose-dependent correlation.

  9. Development and testing of a fast Fourier transform high dynamic-range spectral diagnostics for millimeter wave characterization

    Energy Technology Data Exchange (ETDEWEB)

    Thoen, D. J.; Bongers, W. A.; Westerhof, E.; Baar, M. R. de; Berg, M. A. van den; Beveren, V. van; Goede, A. P. H.; Graswinckel, M. F.; Schueller, F. C. [Association EURATOM-FOM, Trilateral Euregio Cluster, FOM-Institute for Plasma Physics Rijnhuizen, P.O. Box 1207, 3430 BE Nieuwegein (Netherlands); Oosterbeek, J. W.; Buerger, A. [Association EURATOM-FZJ, Institut fuer Energieforschung-Plasmaphysik, Forschungszentrum Juelich GMBH, 52425 Juelich (Germany); Hennen, B. A. [Association EURATOM-FOM, Trilateral Euregio Cluster, FOM-Institute for Plasma Physics Rijnhuizen, P.O. Box 1207, 3430 BE Nieuwegein (Netherlands); Control Systems Technology Group, Eindhoven University of Technology, P.O. Box 513, NL-5600 MB Eindhoven (Netherlands)

    2009-10-15

    A fast Fourier transform (FFT) based wide range millimeter wave diagnostics for spectral characterization of scattered millimeter waves in plasmas has been successfully brought into operation. The scattered millimeter waves are heterodyne downconverted and directly digitized using a fast analog-digital converter and a compact peripheral component interconnect computer. Frequency spectra are obtained by FFT in the time domain of the intermediate frequency signal. The scattered millimeter waves are generated during high power electron cyclotron resonance heating experiments on the TEXTOR tokamak and demonstrate the performance of the diagnostics and, in particular, the usability of direct digitizing and Fourier transformation of millimeter wave signals. The diagnostics is able to acquire 4 GHz wide spectra of signals in the range of 136-140 GHz. The rate of spectra is tunable and has been tested between 200 000 spectra/s with a frequency resolution of 100 MHz and 120 spectra/s with a frequency resolution of 25 kHz. The respective dynamic ranges are 52 and 88 dB. Major benefits of the new diagnostics are a tunable time and frequency resolution due to postdetection, near-real time processing of the acquired data. This diagnostics has a wider application in astrophysics, earth observation, plasma physics, and molecular spectroscopy for the detection and analysis of millimeter wave radiation, providing high-resolution spectra at high temporal resolution and large dynamic range.

  10. Optimal Design of Multiple Stresses Accelerated Life Test Plan Based on Transforming the Multiple Stresses to Single Stress

    Institute of Scientific and Technical Information of China (English)

    GAO Liang; CHEN Wenhua; QIAN Ping; PAN Jun; HE Qingchuan

    2014-01-01

    For planning optimum multiple stresses accelerated life test plans, a commonly followed guiding principle is that all parameters of the life-stress relationship should be estimated, and the number of the stress level combinations must be no less than the number of parameters of the life-stress relationship. However, the general objective of an accelerated life test(ALT) is to assess thep-th quantile of the product life distribution under normal stress. For this objective,estimating all model parameters is not necessary, and this will increase the cost of test. Based on the theoretical conclusion that the stress level combinations of the optimum multiple stresses ALT plan locate on a straight line through the origin of coordinate, it is proposed that a design idea of planning the optimum multiple stresses ALT plan through transforming the problem of designing an optimum multiple stresses ALT plan to designing an optimum single stress ALT plan. Moreover, a method of planning the optimum multiple stresses ALT plan which can avoid estimating all model parameters is established. An example shows that, the proposed plan which only has two stress level combinations could achieve an accuracy no less than the traditional plan, and save the test time and cost on one stress level combination at least; when the actual product life is less than the design value, even the deviation of the model initial parameters value is up to 20%, the variance of the estimation of thep-th quantile of the proposed plan is still smaller than the traditional plans approximately 25%. A design method is provided for planning the optimum multiple stresses ALT which uses the statistical optimum degenerate test plan as the optimum multiple stresses accelerated life test plan.

  11. Decitabine in Treating Children With Relapsed or Refractory Acute Myeloid Leukemia or Acute Lymphoblastic Leukemia

    Science.gov (United States)

    2013-01-22

    Childhood Acute Myeloblastic Leukemia With Maturation (M2); Childhood Acute Promyelocytic Leukemia (M3); Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia

  12. Parameter estimation for locale long-time induction withstand voltage test and partial discharge test of transformer%变压器长时感应耐压及局部放电试验参数估算

    Institute of Scientific and Technical Information of China (English)

    马飞越; 刘威峰

    2016-01-01

    变压器长时感应耐压及局部放电试验受变压器容量、变比、联结方式等因素影响,试验频率及试验电流等参数相差较大。本文对变压器现场长时感应耐压及局部放电时的容性无功功率、试验频率、有功损耗及试验电流进行估算,简化出试验时变压器等效电容量计算公式,对比集中电容法与分布电容法估算试验参数的准确性,为现场变压器长时感应耐压及局部放电试验提供参考。%Because of long-time induction withstand voltage test and partial discharge test of transformer are affected by the factors of the transformer such as the different transformer capacity, the different transformer ratio and the connection mode, the parameter error of test frequency and test current is large. This paper estimates capacitive reactive power, test frequency, active power loss and test current for locale long-time induction withstand voltage test and partial discharge test of transformer, simplifies the transformer equivalent capacity calculation formula for test, compares the accuracy of estimating parameters between concentrated capacity method and distributed capacity method, provides reference for locale long-time induction withstand voltage and partial discharge test of transformer.

  13. Role of Ikaros in T-cell acute lymphoblastic leukemia

    Institute of Scientific and Technical Information of China (English)

    Philippe; Kastner; Susan; Chan

    2011-01-01

    Ikaros is a zinc finger transcriptional regulator encoded by the Ikzf1 gene.Ikaros displays crucial functions in the hematopoietic system and its loss of function has been linked to the development of lymphoid leukemia.In particular,Ikaros has been found in recent years to be a major tumor suppressor involved in human B-cell acute lymphoblastic leukemia.Its role in T-cell leukemia,however,has been more controversial.While Ikaros deficiency appears to be very frequent in murine T-cell leukemias,loss of Ikaros appears to be rare in human T-cell acute lymphoblastic leukemia (T-ALL).We review here the evidence linking Ikaros to T-ALL in mouse and human systems.

  14. Impaired dexamethasone-related increase of anticoagulants is associated with the development of osteonecrosis in childhood acute lymphoblastic leukemia

    NARCIS (Netherlands)

    M.L. te Winkel (Mariël Lizet); I.M. Appel (Inge); R. Pieters (Rob); M.M. van den Heuvel-Eibrink (Marry)

    2008-01-01

    textabstractCoagulation alterations may be involved in osteonecrosis in childhood acute lymphoblastic leukemia. Retrospectively, we evaluated the available coagulation parameters at diagnosis and during induction treatment of 161 acute lymphoblastic leukemia patients: 24 with symptomatic osteonecros

  15. The negative impact of being underweight and weight loss on survival of children with acute lymphoblastic leukemia

    NARCIS (Netherlands)

    den Hoed, Marissa A. H.; Pluijm, Saskia M. F.; de Groot-Kruseman, Hester A.; te Winkel, Mariel L.; Fiocco, Martha; van den Akker, Erica L. T.; Hoogerbrugge, Peter; van den Berg, Henk; Leeuw, Jan A.; Bruin, Marrie C. A.; Bresters, Dorine; Veerman, Anjo J. P.; Pieters, Rob; van den Heuvel-Eibrink, Marry M.

    2015-01-01

    Body mass index and change in body mass index during treatment may influence treatment outcome of pediatric patients with acute lymphoblastic leukemia. However, previous studies in pediatric acute lymphoblastic leukemia reported contradictory results. We prospectively collected data on body composit

  16. Acute lymphoblastic leukemia presenting with a uterine cervical mass

    Directory of Open Access Journals (Sweden)

    N Geetha

    2015-01-01

    Full Text Available Involvement of female genital tract with acute lymphoblastic leukemia (ALL is extremely rare, and it is even rarer for a patient to have symptomatic presentation. We report the case of a middle-aged lady with ALL, who presented with severe abnormal uterine bleeding and a uterine cervical mass. Biopsy of the cervical mass showed infiltration by leukemic blasts. She received chemotherapy with Berlin-Frankfurt-Munster protocol and is alive in remission after 10 years.

  17. Mercaptopurine/Methotrexate Maintenance Therapy of Childhood Acute Lymphoblastic Leukemia

    DEFF Research Database (Denmark)

    Schmiegelow, K.; Nielsen, Stine N; Frandsen, Thomas L;

    2014-01-01

    The antileukemic mechanisms of 6-mercaptopurine (6MP) and methotrexate (MTX) maintenance therapy are poorly understood, but the benefits of several years of myelosuppressive maintenance therapy for acute lymphoblastic leukemia are well proven. Currently, there is no international consensus on drug...... intensive and toxic earlier treatment phases, and often more challenging. Ongoing research address the applicability of drug metabolite measurements for dose adjustments, extensive host genome profiling to understand diversity in treatment efficacy and toxicity, and alternative thiopurine dosing regimens...

  18. Vincristine sulfate liposomal injection for acute lymphoblastic leukemia

    OpenAIRE

    Soosay Raj TA; Smith AM; Moore AS

    2013-01-01

    Trisha A Soosay Raj,1 Amanda M Smith,2 Andrew S Moore,1,21Royal Children's Hospital, Children's Health Queensland Hospital and Health Service, Brisbane, Queensland, Australia; 2Queensland Children's Medical Research Institute, The University of Queensland, Brisbane, QLD, AustraliaAbstract: Vincristine (VCR) is one of the most extensively used cytotoxic compounds in hemato-oncology. VCR is particularly important for the treatment of acute lymphoblastic leukemia (ALL), a...

  19. Optic nerve infiltration by acute lymphoblastic leukemia: MRI contribution

    Energy Technology Data Exchange (ETDEWEB)

    Soares, Maria de Fatima; Braga, Flavio Tulio [Federal University of Sao Paulo, Department of Diagnostic Imaging, Paulista School of Medicine, Sao Paulo (Brazil); Rocha, Antonio Jose da [Santa Casa de Misericordia de Sao Paulo, Servico de Diagnostico por Imagem, Sao Paulo (Brazil); Lederman, Henrique Manoel [Federal University of Sao Paulo, Division of Diagnostic Imaging in Pediatrics, Department of Diagnostic Imaging, Sao Paulo (Brazil)

    2005-08-01

    We describe the clinical presentation and imaging features of a patient with acute lymphoblastic leukemia (ALL) that was complicated by optic nerve infiltration. The clinical and diagnostic characteristics of this complication must be recognized so that optimal therapy can be started to prevent blindness. MR imaging is useful in early detection and should be performed in any leukemic patient with ocular complaints, even during remission. (orig.)

  20. Acute Central Nervous System Complications in Pediatric Acute Lymphoblastic Leukemia.

    Science.gov (United States)

    Baytan, Birol; Evim, Melike Sezgin; Güler, Salih; Güneş, Adalet Meral; Okan, Mehmet

    2015-10-01

    The outcome of childhood acute lymphoblastic leukemia has improved because of intensive chemotherapy and supportive care. The frequency of adverse events has also increased, but the data related to acute central nervous system complications during acute lymphoblastic leukemia treatment are sparse. The purpose of this study is to evaluate these complications and to determine their long term outcome. We retrospectively analyzed the hospital reports of 323 children with de novo acute lymphoblastic leukemia from a 13-year period for acute neurological complications. The central nervous system complications of leukemic involvement, peripheral neuropathy, and post-treatment late-onset encephalopathy, and neurocognitive defects were excluded. Twenty-three of 323 children (7.1%) suffered from central nervous system complications during acute lymphoblastic leukemia treatment. The majority of these complications (n = 13/23; 56.5%) developed during the induction period. The complications included posterior reversible encephalopathy (n = 6), fungal abscess (n = 5), cerebrovascular lesions (n = 5), syndrome of inappropriate secretion of antidiuretic hormone (n = 4), and methotrexate encephalopathy (n = 3). Three of these 23 children (13%) died of central nervous system complications, one from an intracranial fungal abscess and the others from intracranial thrombosis. Seven of the survivors (n = 7/20; 35%) became epileptic and three of them had also developed mental and motor retardation. Acute central neurological complications are varied and require an urgent approach for proper diagnosis and treatment. Collaboration among the hematologist, radiologist, neurologist, microbiologist, and neurosurgeon is essential to prevent fatal outcome and serious morbidity. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Inter-Platform comparability of microarrays in acute lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    Mintz Michelle

    2004-09-01

    Full Text Available Abstract Background Acute lymphoblastic leukemia (ALL is the most common pediatric malignancy and has been the poster-child for improved therapeutics in cancer, with life time disease-free survival (LTDFS rates improving from 80% today. There are numerous known genetic prognostic variables in ALL, which include T cell ALL, the hyperdiploid karyotype and the translocations: t(12;21[TEL-AML1], t(4;11[MLL-AF4], t(9;22[BCR-ABL], and t(1;19[E2A-PBX]. ALL has been studied at the molecular level through expression profiling resulting in un-validated expression correlates of these prognostic indices. To date, the great wealth of expression data, which has been generated in disparate institutions, representing an extremely large cohort of samples has not been combined to validate any of these analyses. The majority of this data has been generated on the Affymetrix platform, potentially making data integration and validation on independent sample sets a possibility. Unfortunately, because the array platform has been evolving over the past several years the arrays themselves have different probe sets, making direct comparisons difficult. To test the comparability between different array platforms, we have accumulated all Affymetrix ALL array data that is available in the public domain, as well as two sets of cDNA array data. In addition, we have supplemented this data pool by profiling additional diagnostic pediatric ALL samples in our lab. Lists of genes that are differentially expressed in the six major subclasses of ALL have previously been reported in the literature as possible predictors of the subclass. Results We validated the predictability of these gene lists on all of the independent datasets accumulated from various labs and generated on various array platforms, by blindly distinguishing the prognostic genetic variables of ALL. Cross-generation array validation was used successfully with high sensitivity and high specificity of gene predictors

  2. Hospitalisation for infection prior to diagnosis of acute lymphoblastic leukaemia in children

    DEFF Research Database (Denmark)

    Vestergaard, Therese Risom; Rostgaard, Klaus; Grau, Katrine

    2013-01-01

    . PROCEDURE: A nation-wide cohort encompassing all Danish children aged 0-14 years and born between 1977 and 2008 (N = 1,778,129) was established and followed for hospitalisations for infectious diseases and risk of childhood ALL. The exposure was lagged 1 year to limit reverse causality. In the statistical......BACKGROUND: It has been proposed that infections in infancy and early childhood are associated with a reduced risk of childhood acute lymphoblastic leukaemia (ALL). We tested this hypothesis in a register-based study of hospitalisations for infectious diseases prior to diagnosis of childhood ALL...... analyses exposure was defined as (time dependent) number of early or late (before 2 or at/after 2 years of age) hospitalisations to further explore possible age-dependent associations. RESULTS: A total of 815 children were diagnosed with ALL during follow-up. Risk of ALL was associated neither...

  3. High Risk Pediatric Acute Lymphoblastic Leukemia: To Transplant or Not to Transplant?

    Science.gov (United States)

    Pulsipher, Michael A.; Peters, Christina; Pui, Ching-Hon

    2010-01-01

    Because survival with both chemotherapy and allogeneic hematopoietic stem cell transplantation (HSCT) approaches to high risk pediatric acute lymphoblastic leukemia (ALL) generally improves through the years, regular comparisons of outcomes with either approach for a given indication are needed to decide when HSCT is indicated. Improvements in risk classification are allowing clinicians to identify patients at high risk for relapse early in their course of therapy. Whether patients defined as high risk by new methods will benefit from HSCT requires careful testing. Standardization and improvement of transplant approaches has led to equivalent survival outcomes with matched sibling and well-matched unrelated donors, however, survival using mismatched and haploidentical donors is generally worse. Trials comparing chemotherapy and HSCT must obtain sufficient data about therapy and stratify the analysis to assess the outcomes of best-chemotherapy with best-HSCT approaches. PMID:21195303

  4. Metastatic Calcinosis Cutis: A Case in a Child with Acute Pre-B Cell Lymphoblastic Leukemia

    Directory of Open Access Journals (Sweden)

    Juan Pablo Castanedo-Cázares

    2015-01-01

    Full Text Available Hypercalcemia in children with malignancy is an uncommon condition. It has been described in leukemia patients with impaired renal excretion of calcium or osteolytic lesions. Metastatic calcinosis cutis (MCC may develop if hypercalcemia persists. We report the case of a 5-year-old girl with an atypical dermatosis and unspecific gastrointestinal symptoms. Considered clinical diagnoses were xanthomas, histiocytosis, molluscum contagiosum, and nongenital warts. Cutaneous histological analysis showed amorphous basophilic deposits in the dermis suggestive of calcium deposits. Laboratory tests confirmed serum hypercalcemia. Extensive investigations such as bone marrow biopsy established the diagnosis of an acute pre-B cell lymphoblastic leukemia. Hypercalcemia in hematopoietic malignancies is unusual, especially as initial manifestation of the disease. Careful review of the literature fails to reveal previous reports of these peculiar cutaneous lesions of MCC in children with leukemia.

  5. Case report of acute lymphoblastic leukemia with multiple soft tissue mass

    Energy Technology Data Exchange (ETDEWEB)

    Jang, Jung Yong; Huh, Kyung Hoe; Yi, Won Jin; Heo, Min Suk; Lee, Sam Sun; Choi, Soon Chul [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    2005-06-15

    A 15-year-old patient, who had been diagnosed and treated as Burkitt cell type acute lymphoblastic leukemia (ALL-L3) already, visited our department. He complained of gingival enlargement and loosening teeth 1 month ago. The clinical examination revealed anterior open bite, gingival enlargement, and non tender swelling particularly in molar regions of both jaws. Deep periodontal pockets and severe mobility was shown on most of the teeth. The panoramic radiographs showed severe bone destruction and extrusion of the molars. The contrast enhanced CT showed multiple enhanced mass and bone marrow obliteration in both jaws. Chemotherapy was done the swelling was subsided at 1 month later. In conclusion, radiologic findings of leukemia with soft tissue mass, known as chloroma or granulocytic sarcoma, mimic those of lymphoma, so blood test may be needed for the final diagnosis.

  6. Acute Lymphoblastic Leukemia | EU Clinical Trials Register [EU Clinical Trials Register

    Lifescience Database Archive (English)

    Full Text Available estigation E.1.1Medical condition(s) being investigated Acute Lymphoblastic Leukemia E.1.1.1Medical conditio...E.1.2Version 18.0 E.1.2Level LLT E.1.2Classification code 10000845 E.1.2Term Acute lymphoblastic leukemia E.

  7. Nanomaterial transformation and association with fresh and freeze-dried wastewater activated sludge: implications for testing protocol and environmental fate.

    Science.gov (United States)

    Kiser, Mehlika A; Ladner, David A; Hristovski, Kiril D; Westerhoff, Paul K

    2012-07-03

    Engineered nanomaterials (ENMs) are an emerging class of contaminants entering wastewater treatment plants (WWTPs), and standardized testing protocols are needed by industry and regulators to assess the potential removal of ENMs during wastewater treatment. A United States Environmental Protection Agency (USEPA) standard method (OPPTS 835.1110) for estimating soluble pollutant removal during wastewater treatment using freeze-dried, heat-treated (FDH) activated sludge (AS) has been recently proposed for predicting ENM fate in WWTPs. This study is the first to evaluate the use of FDH AS in batch experiments for quantifying ENM removal from wastewater. While soluble pollutants sorbed equally to fresh and FDH AS, fullerene, silver, gold, and polystyrene nanoparticles' removals with FDH AS were approximately 60-100% less than their removals with fresh AS. Unlike fresh AS, FDH AS had a high concentration of proteins and other soluble organics in the liquid phase, an indication of bacterial membrane disintegration due to freeze-drying and heat exposure. This cellular matter stabilized ENMs such that they were poorly removed by FDH AS. Therefore, FDH AS is not a suitable sorbent for estimating nanoparticle removal in WWTPs, whereas fresh AS has been shown to reasonably predict full-scale performance for titanium removal. This study indicates that natural or engineered processes (e.g., anaerobic digestion, biosolids decomposition in soils) that result in cellular degradation and matrices rich in surfactant-like materials (natural organic matter, proteins, phospholipids, etc.) may transform nanoparticle surfaces and significantly alter their fate in the environment.

  8. Chemical stabilization of metals in mine wastes by transformed red mud and other iron compounds: laboratory tests.

    Science.gov (United States)

    Ardau, C; Lattanzi, P; Peretti, R; Zucca, A

    2014-01-01

    A series of static and kinetic laboratory-scale tests were designed in order to evaluate the efficacy of transformed red mud (TRM) from bauxite refining residues, commercial zero-valent iron, and synthetic iron (III) hydroxides as sorbents/reagents to minimize the generation of acid drainage and the release of toxic elements from multi-contaminant-laden mine wastes. In particular, in some column experiments the percolation of meteoric water through a waste pile, alternated with periods of dryness, was simulated. Wastes were placed in columns together with sorbents/reagents in three different set-ups: as blended amendment (mixing method), as a bed at the bottom of the column (filtration method), or as a combination of the two previous methods. The filtration methods, which simulate the creation of a permeable reactive barrier downstream of a waste pile, are the most effective, while the use of sorbents/reagents as amendments leads to unsatisfactory results, because of the selective removal of only some contaminants. The efficacy of the filtration method is not significantly affected by the periods of dryness, except for a temporary rise of metal contents in the leachates due to dissolution of soluble salts formed upon evaporation in the dry periods. These results offer original information on advantages/limits in the use of TRM for the treatment of multi-contaminant-laden mine wastes, and represent the starting point for experimentation at larger scale.

  9. Genetic risk factors for the development of osteonecrosis in children under age 10 treated for acute lymphoblastic leukemia.

    Science.gov (United States)

    Karol, Seth E; Mattano, Leonard A; Yang, Wenjian; Maloney, Kelly W; Smith, Colton; Liu, ChengCheng; Ramsey, Laura B; Fernandez, Christian A; Chang, Tamara Y; Neale, Geoffrey; Cheng, Cheng; Mardis, Elaine; Fulton, Robert; Scheet, Paul; San Lucas, F Anthony; Larsen, Eric C; Loh, Mignon L; Raetz, Elizabeth A; Hunger, Stephen P; Devidas, Meenakshi; Relling, Mary V

    2016-02-04

    Osteonecrosis is a dose-limiting toxicity in the treatment of pediatric acute lymphoblastic leukemia (ALL). Prior studies on the genetics of osteonecrosis have focused on patients ≥10 years of age, leaving the genetic risk factors for the larger group of children osteonecrosis in children osteonecrosis and 287 controls treated on Children's Oncology Group (COG) standard-risk ALL protocol AALL0331 (NCT00103285, https://clinicaltrials.gov/ct2/show/NCT00103285), with results tested for replication in 817 children osteonecrosis.

  10. Precursor T-cell acute lymphoblastic leukemia presenting with bone marrow necrosis: a case report

    Directory of Open Access Journals (Sweden)

    Khoshnaw Najmaddin SH

    2012-10-01

    transferase markers were positive and CD10, CD20 and CD79a markers were negative. Conclusion The aggressive initial clinical presentation of our patient with huge mediastinal widening, development of superior vein cava syndrome and extensive bone marrow necrosis as initial signs made the diagnosis of the case difficult. The necrotic hematopoietic cells gave inconclusive results on the initial immunohistochemistry tests. The prognosis of bone marrow necrosis is better secondary to acute lymphoblastic leukemia in the pediatric age group compared with adults and those with underlying solid tumors. Despite the aggressive behavior at initial presentation, the patient responded to chemotherapy and necrosis disappeared at day 28 after the start of the therapeutic regimen.

  11. Implementation of an automated assessment system of the Winston-Lutz test based on the transformed generalized Hough; Implementacion de un sistema de evaluacion automatizada del test de Winston-Lutz basado en la transformada generalizada de Hough

    Energy Technology Data Exchange (ETDEWEB)

    Martin-Viera Cueto, J. A.; Moreno Saiz, C.; Benitez Villegas, E. M.; Fernandez Canadillas, M. J.; Caballero Lucena, E.; Cantero Carrillo, M.

    2013-07-01

    It has implemented a software tool based on the generalized Hough transform to automate the evaluation of test WL This method provides a quantitative evaluation of the test. It also eliminates the subjectivity of the evaluator which is an uncertainty of 0.3 mm. (Author)

  12. Proteomic profile of pre - B2 lymphoblasts from children with acute lymphoblastic leukemia (ALL) in relation with the translocation (12; 21)

    National Research Council Canada - National Science Library

    Costa, Odile; Schneider, Pascale; Coquet, Laurent; Chan, Philippe; Penther, Dominique; Legrand, Elisabeth; Jouenne, Thierry; Vasse, Marc; Vannier, Jean-Pierre

    2014-01-01

    ...), indicator of good prognosis, usually.Protein expression in pre-B2 lymphoblastic cells, collected from residual bone marrow cells after diagnostic procedures, was analyzed using two dimensional gel electrophoresis protocol...

  13. Market transformation lessons learned from an automated demand response test in the Summer and Fall of 2003

    Energy Technology Data Exchange (ETDEWEB)

    Shockman, Christine; Piette, Mary Ann; ten Hope, Laurie

    2004-08-01

    A recent pilot test to enable an Automatic Demand Response system in California has revealed several lessons that are important to consider for a wider application of a regional or statewide Demand Response Program. The six facilities involved in the site testing were from diverse areas of our economy. The test subjects included a major retail food marketer and one of their retail grocery stores, financial services buildings for a major bank, a postal services facility, a federal government office building, a state university site, and ancillary buildings to a pharmaceutical research company. Although these organizations are all serving diverse purposes and customers, they share some underlying common characteristics that make their simultaneous study worthwhile from a market transformation perspective. These are large organizations. Energy efficiency is neither their core business nor are the decision makers who will enable this technology powerful players in their organizations. The management of buildings is perceived to be a small issue for top management and unless something goes wrong, little attention is paid to the building manager's problems. All of these organizations contract out a major part of their technical building operating systems. Control systems and energy management systems are proprietary. Their systems do not easily interact with one another. Management is, with the exception of one site, not electronically or computer literate enough to understand the full dimensions of the technology they have purchased. Despite the research team's development of a simple, straightforward method of informing them about the features of the demand response program, they had significant difficulty enabling their systems to meet the needs of the research. The research team had to step in and work directly with their vendors and contractors at all but one location. All of the participants have volunteered to participate in the study for altruistic

  14. Beyond Standardized Test Scores: An Examination of Leadership and Climate as Leading Indicators of Future Success in the Transformation of Turnaround Schools

    Science.gov (United States)

    May, Judy Jackson; Sanders, Eugene T. W.

    2013-01-01

    Districts throughout the nation are engaged in comprehensive transformation to "turn around" low performing schools. Standardized test scores are used to gauge student achievement; however, academic gains may lag behind leading indicators such as improved school climate and effective leadership. This study examines 16 underperforming…

  15. Study Of The Existence Of Neoantigens In Affected Hair Follicles Using Lymphocyte Transformation Test In Alopecia Areata And Healthy Persons

    Directory of Open Access Journals (Sweden)

    Saehi Nodeh A

    2004-07-01

    Full Text Available Background: Alopecia areata is a common, inflamatory and chronic disease of hair and nails, which in some cases result in growth inhibition and lose of hairs. Several factors such as genetic factors, autoimmunity, atopy, stress, fear etc, are known as effective factors in induction and severity of the disease, but the ethiology of this disease is not known exactly so far. Some evidences such as presence of an autoantibodies against hair follicules and infiltration of immunocompetent cells in affected areas of the disease lead that most investigators classify alopecia as autoimmune disease. In one investigation in immunology department of Tarbiat Modarres university concerning the humoral immunity in alopecia pathogenesis some evidences were found for the presences of a neoantigen in affected hair follicles. Since various studies indicates that cellular arm of the immune system is more important in alopecia areata pathogenesis, in this investigation we studied the existence of neoantigens in affected hair follicles using lymphocyte transformation test (LTT. Materials and Methods: The proliferation responses of peripheral blood mononuclear cells (MNC from alopecia patients and normal individuals were investigated against the follicular extracts of affected and normal hairs separately. Results: Our results indicate a non significant difference between proliferation responses of MNC’s from alopecia patients and normal controls against follicular extract of normal hairs. These responses were not significantly different against folliclar extracts of affected hairs as well. Regarding our results. Conclusion: We could not show the existence of a neoantigen in alopecia hair follicles, but the obtained results can not completely reject the role of a neoantigen in alopecia pathogenesis as well, because in LTT the responding cells are of memory type and these cells may be very low in peripheral blood. The immune response in this disease may be restricted

  16. Discrimination of acute lymphoblastic leukemia from systemic-onset juvenile idiopathic arthritis at disease onset

    Directory of Open Access Journals (Sweden)

    Mirian S. Tamashiro

    2011-01-01

    Full Text Available OBJECTIVE: To assess clinical and laboratory features that differentiate acute lymphoblastic leukemia from systemic juvenile idiopathic arthritis at disease onset. METHODS: Fifty-seven leukemia patients with musculoskeletal involvement, without blasts on peripheral blood and without glucocorticoid therapy at disease onset and 102 systemic juvenile idiopathic arthritis patients (International League of Associations for Rheumatology criteria were retrospectively evaluated. The following features were examined: fever, rheumatoid rash, arthritis, limb pain, hepatomegaly, splenomegaly, pericarditis, myocarditis, pleuritis, weight loss, bleeding, anemia, leukopenia, neutropenia, thrombocytopenia, erythrocyte sedimentation rate, and lactic dehydrogenase levels. RESULTS: The median age at disease onset was significantly higher in leukemia patients than in those with systemic-onset juvenile idiopathic arthritis (5.8 vs. 3.8 years. In addition, the frequencies of limb pain, hepatomegaly, weight loss and hemorrhagic manifestations were significantly higher in leukemia patients than in systemic-onset juvenile idiopathic arthritis patients (70% vs. 1%, 54% vs. 32%, 30% vs. 8%, and 9% vs. 0%, respectively. Likewise, the frequencies of anemia, leukopenia, neutropenia, thrombocytopenia and high lactic dehydrogenase levels were statistically higher in leukemia patients than in patients with systemic-onset juvenile idiopathic arthritis (88% vs. 57%, 39% vs. 1%, 60% vs. 1%, 77% vs. 1%, and 56% vs. 14%, respectively. Remarkably, multivariate analysis revealed that limb pain (OR = 553; 95% CI =46.48-6580.42 and thrombocytopenia (OR = 754.13; 95% CI =64.57-8806.72 were significant independent variables that differentiated leukemia from systemic-onset juvenile idiopathic arthritis. The R2 of the Nagelkerke test was 0.91, and the Kaplan-Meier survival curves were similar for acute lymphoblastic leukemia patients with and without limb pain. CONCLUSION: Our study

  17. Experimental Testing and Model Validation of a Decoupled-Phase On-Load Tap Changer Transformer in an Active Network

    OpenAIRE

    Zecchino, Antonio; Hu, Junjie; Coppo, Massimiliano; Marinelli, Mattia

    2016-01-01

    Due to the increasing penetration of single-phase small generation units and electric vehiclesconnected to distribution grids, system operators are facing challenges related to local unbalanced voltagerise or drop issues, which may lead to a violation of the allowed voltage band. To address this problem,distribution transformers with on-load tapping capability are under development. This paper presentsmodel and experimental validation of a 35 kVA three-phase power distribution transformer wit...

  18. Association of ARID5B gene variants with acute lymphoblastic leukemia in Yemeni children.

    Science.gov (United States)

    Al-Absi, Boshra; Noor, Suzita M; Saif-Ali, Riyadh; Salem, Sameer D; Ahmed, Radwan H; Razif, Muhammad Fm; Muniandy, Sekaran

    2017-04-01

    Studies have shown an association between ARID5B gene polymorphisms and childhood acute lymphoblastic leukemia. However, the association between ARID5B variants and acute lymphoblastic leukemia among the Arab population still needs to be studied. The aim of this study was to investigate the association between ARID5B variants with acute lymphoblastic leukemia in Yemeni children. A total of 14 ARID5B gene single nucleotide polymorphisms (SNPs) were genotyped in 289 Yemeni children, of whom 136 had acute lymphoblastic leukemia and 153 were controls, using the nanofluidic Dynamic Array (Fluidigm 192.24 Dynamic Array). Using logistic regression adjusted for age and gender, the risks of acute lymphoblastic leukemia were presented as odds ratios and 95% confidence intervals. We found that nine SNPs were associated with acute lymphoblastic leukemia under additive genetic models: rs7073837, rs10740055, rs7089424, rs10821936, rs4506592, rs10994982, rs7896246, rs10821938, and rs7923074. Furthermore, the recessive models revealed that six SNPs were risk factors for acute lymphoblastic leukemia: rs10740055, rs7089424, rs10994982, rs7896246, rs10821938, and rs7923074. The gender-specific impact of these SNPs under the recessive genetic model revealed that SNPs rs10740055, rs10994982, and rs6479779 in females, and rs10821938 and rs7923074 in males were significantly associated with acute lymphoblastic leukemia risk. Under the dominant model, SNPs rs7073837, rs10821936, rs7896246, and rs6479778 in males only showed striking association with acute lymphoblastic leukemia. The additive model revealed that SNPs with significant association with acute lymphoblastic leukemia were rs10821936 (both males and females); rs7073837, rs10740055, rs10994982, and rs4948487 (females only); and rs7089424, rs7896246, rs10821938, and rs7923074 (males only). In addition, the ARID5B haplotype block (CGAACACAA) showed a higher risk for acute lymphoblastic leukemia. The haplotype (CCCGACTGC) was

  19. Supporting Caregivers of Children With Acute Lymphoblastic Leukemia via a Smartphone App: A Pilot Study of Usability and Effectiveness.

    Science.gov (United States)

    Wang, Jingting; Yao, Nengliang; Shen, Min; Zhang, Xiaoyan; Wang, Yuanyuan; Liu, Yanyan; Geng, Zhaohui; Yuan, Changrong

    2016-11-01

    Smartphone applications are widely used for self-help interventions in adult cancer survivors. However, applications for parents of pediatric cancer patients are limited. We developed an applications to assist parents of children with acute lymphoblastic leukemia. The aim of this study is to evaluate the app's usability and effectiveness in a preliminary way. A stepwise approach and mixed methods were used. The application was initially tested by healthcare providers, and their comments and suggestions were used to develop an updated version. This version was tested by parents of children with acute lymphoblastic leukemia. Comments and nonverbal expressions of parents were recorded during a 2-week pilot test. The qualitative study was followed by a quantitative study using audit log data from the administration portal to understand how parents use the application. Six healthcare providers and 15 parents participated. Parents gained a greater knowledge of leukemia, confidence in caregiving, social support, and information on how to reduce stress. Over usability was rated as stable, useful, simple, and self-explanatory. No software failure occurred. Applications have the potential to support caregivers of pediatric cancer patients. We plan to address limitations and perform an empirical interventional study to examine its clinical effectiveness.

  20. SCENARIO OF ACUTE LYMPHOBLASTIC LEUKAEMIA IN GWALIOR REGION

    Directory of Open Access Journals (Sweden)

    Mangal

    2016-04-01

    Full Text Available BACKGROUND Leukaemia is the most prevalent childhood cancer and Acute Lymphoblastic Leukaemia (ALL constitutes about 75% of all cases. The most frequent presenting symptoms are fever, weight loss and pallor. Early diagnosis of this haematological malignancy can be helpful for prognosis of disease. AIMS AND OBJECTIVES The objectives of the present study were to assess frequency of presenting symptoms, laboratory data and prognostic factors in children with diagnosis of ALL. MATERIALS AND METHODS The present study (2014 was performed in the Department of Pathology of Gajra Raja Medical College, Gwalior, over a period of one year from October 2013 to September 2014. The blood samples were received from patients attending various Departments of Jayarogya Groups of Hospitals, a tertiary care hospital. RESULTS Out of the 37 cases diagnosed as Acute Lymphoblastic Leukaemia, 25 (67.57% were male and 12 (32.43% were female, (male:female ratio: 2.1:1; 43.35% of patients which comprises highest number of cases belonged to 11-20 years of age group. The most frequent presenting symptoms was fever (83.78% followed by weakness (70.27% and loss of appetite (27%, while most frequent presenting sign was pallor (86.48% followed by lymphadenopathy (67.57% and splenomegaly (48.65%. Complete blood cell count was abnormal in all of the patients and pancytopenia was detected in 10.81% of the patients. Of all the patients, 91.89% had abnormal White Blood Cell (WBC count at presentation with about 80% were presented with Leukocytosis. FAB L1 subtype was more common as compared to FAB L2 subtype. CONCLUSION In our study (2014, Acute Lymphoblastic Leukaemia was more prevalent in males than in females and more common in childhood than in adult. FAB L1 subtype was more common as compared to FAB L2 subtype.

  1. Prognostic significance of cell surface phenotype in acute lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    Shiek Aejaz Aziz

    2015-01-01

    Full Text Available Context: To find out the phenotypic character of lymphoblasts of acute lymphoblastic leukemia (ALL patients in our study cohort and their possible effect on the prognosis. Aims: To investigate the phenotype in ALL in our demographic population and to prognosticate various upfront current protocols employed in our hospital. Settings and Design: The study spanned over a period of 4 years with retrospective and prospective data of January 2008 through December 2011. Materials and Methods: 159 patients of all age groups were enrolled for the study, of which flow cytometry was done in 144 patients. Statistical Analysis Used: Analysis was done using the variables on SPSS (statistical package for social sciences software on computer. Survival curves were estimated by method of Kaplan-Meir. Results: Majority of the patients were of B-cell (68.1% and 30.6% patients were of T-cell lineage. Of these, 80.6% patients were having cALLa positivity. Complete remission (CR was achieved in 59.1%, 16.4% relapsed, and 20.1% patients died. Conclusions: Phenotyping has become an important and integral part of diagnosis, classification, management and prognosticating in ALL. B-cell has been found to have a better survival over T-cell lymphoblastic leukemia. cALLa antigen positivity has good impact in achieving CR in only B-cell lineage, myeloid coexpression has no significant effect on the outcome. BFM (Berlin-Frankfurt-Münster based protocols though showed a higher CR and survival vis-a-vis UKALL-XII. However, patients enrolled in former group being of low risk category and lesser in numbers cannot be compared statistically with a fair degree of confidence.

  2. Evaluation of Lymphocyte Transformation Test Results in Patients with Delayed Hypersensitivity Reactions following the Use of Anticonvulsant Drugs.

    Science.gov (United States)

    Karami, Zahra; Mesdaghi, Mehrnaz; Karimzadeh, Parvaneh; Mansouri, Mahboubeh; Taghdiri, Mohammad Mehdi; Kayhanidoost, Zarrintaj; Jebelli, Bita; Shekarriz Foumani, Reza; Babaie, Delara; Chavoshzadeh, Zahra

    2016-01-01

    Administration of the anticonvulsant drugs phenobarbital, phenytoin, carbamazepine and lamotrigine can be associated with severe hypersensitivity reactions. The lymphocyte transformation test (LTT) is a method to determine which drug has caused the hypersensitivity reaction. This study was done to evaluate the results of LTT in patients with delayed hypersensitivity reactions following the administration of anticonvulsants. Twenty-four patients with hypersensitivity reactions, e.g. drug-induced hypersensitivity syndrome/drug rash and eosinophilia with systemic symptoms (DIHS/DRESS), Stevens-Johnson syndrome (SJS) and toxic epidermal necrosis (TEN), following the administration of anticonvulsant drugs, and 24 patients who had used anticonvulsant drugs but did not have hypersensitivity reactions (the control group) were included in this study. Peripheral blood mononuclear cells were isolated. The cells were stimulated with the drugs, phytohemagglutinin as a mitogen and Candida as an antigen (positive controls). Lymphocyte proliferation was measured using the BrdU proliferation assay kit (Roche, Germany). The stimulation index was calculated as the mean ratio of the OD of stimulated cells divided by the OD of unstimulated cells. The results in the case and control groups were compared. Of 24 patients in the test group, 14 (58.3%) had positive LTT results and 10 (41.7%) had negative results. Among patients in the control group, 1 (4.2%) had a positive LTT result and 23 (95.8%) had negative results. Among the patients who had received carbamazepine and phenytoin, there was a significant difference between the results of LTT in the case and control groups (p = 0.002 and p = 0.028, respectively). Although patients receiving lamotrigine and phenobarbital had more positive LTT results in the case group than in the control group, these differences were not statistically significant. The sensitivity, specificity, positive predictive value and negative predictive value of LTT

  3. Model Transformations? Transformation Models!

    NARCIS (Netherlands)

    Bézivin, J.; Büttner, F.; Gogolla, M.; Jouault, F.; Kurtev, I.; Lindow, A.

    2006-01-01

    Much of the current work on model transformations seems essentially operational and executable in nature. Executable descriptions are necessary from the point of view of implementation. But from a conceptual point of view, transformations can also be viewed as descriptive models by stating only the

  4. CLINICOPATHOLOGICAL STUDY OF ACUTE LYMPHOBLASTIC LEUKEMIA - A MULTIPARAMETER STUDY

    Directory of Open Access Journals (Sweden)

    Jagannath

    2015-11-01

    Full Text Available BACKGROUND Acute Lymphoblastic Leukaemia (ALL, a malignancy of lymphoid lineage cells, has excellent prognosis in children. Leukemia is the most prevalent childhood cancer and Acute Lymphoblastic Leukemia (ALL constitutes 75% of all cases. The most frequent presenting symptoms are fever, weight loss and pallor. Early detection of clinical symptoms positively affects timely diagnosis. AIMS & OBJECTIVES The objectives of the present study were to assess frequency of presenting symptoms, laboratory data and prognostic factors in children with diagnosis of ALL. MATERIALS & METHODS The present study (2014 was performed in the hematology section of Department of Pathology of Gajra Raja Medical College, Gwalior over a period of 12 months from 1st October 2013 to 30th September 2014. This was a prospective study. The blood samples were received from various departments of Jayarogya hospital especially from the Pediatric and Medicine departments. RESULTS Out of the 37 cases diagnosed as Acute Lymphoblastic Leukemia, 25(67.57% were male and 12(32.43%, were female, (male:female ratio: 2.1:1. 43.35% of patients which comprises highest number of cases belonged to 11-20 years of age group. The most frequent presenting symptoms was fever (83.78% followed by weakness (70.27% and loss of appetite (27% while most frequent presenting sign was pallor (86.48% followed by lymphadenopathy (67.57% and splenomegaly (48.65%. Complete blood cell count was abnormal in all of the patients, and pancytopenia was detected in 10.81% of the patients. Of all the patients, 91.89% had abnormal white blood cell (WBC count at presentation, 10.81% had leucopenia and 80% had leucocytosis. FAB L1 subtype was more common as compared to FAB L2 subtype. CONCLUSION In our study (2014, Acute Lymphoblastic Leukemia was more prevalent in males than in females and more common in childhood than in adult. FAB L1 subtype was more common as compared to FAB L2 subtype.

  5. Oral health of children with acute lymphoblastic leukemia: A review

    Directory of Open Access Journals (Sweden)

    Kadalagere Lakshmana Girish Babu

    2016-01-01

    Full Text Available Leukemia is a malignancy of the bone marrow and blood. It is the most common childhood cancer in India. Advances in the treatment regimens have greatly increased the chances of survival. Both the disease and its treatment change the oral environment. In some cases, oral manifestations are the presenting feature of the disease and it will be the dentist′s responsibility to identify the underlying disorder and guide the diagnosis of the patient. Hence, the aim of present article is to review the literature concerning the oral health of children with acute lymphoblastic leukemia (ALL.

  6. [Disseminated fusariosis in a patient with acute lymphoblastic leukaemia

    DEFF Research Database (Denmark)

    Hermansen, N.E.; Ralfkiaer, E.M.; Kjeldsen, L.

    2008-01-01

    Invasive mould infections are a major cause of infectious mortality in highly immunosuppressed patients. Incidence in this high risk group is 10-20% with a death rate in excess of 50%. Most invasive moulds are Aspergillus spp. We present a case of a 74-year-old woman with acute lymphoblastic...... leukaemia who developed a rare disseminated mould infection with Fusarium solani during induction chemotherapy. We present the case story and discuss the pathogenesis, clinical characteristics and treatment of invasive fusariosis Udgivelsesdato: 2008/9/8...

  7. Testis Scintigraphy in a Patient with Acute Lymphoblastic Leukemia

    Directory of Open Access Journals (Sweden)

    Mine Şencan Eren

    2014-02-01

    Full Text Available Acute lymphoblastic leukemia (ALL is a pediatric malignancy associated with remissions and relapses. Common relapsing sitesare meninges, testis and ovary. Testicular scintigraphy is a highly specific modality used mainly in the differential diagnosis of testicular torsion and epidydimitis/epidydimo-orchitis. There is only one interesting image on leukemic infiltration with scrotal scintigraphy in the literature. The aim of this case presentation is to report that although the scintigraphic appearance of testicular torsion was observed in a patient with the diagnosis of ALL, testicular ALL infiltration was revealed in pathologic examination.

  8. Primary T-cell lymphoblastic lymphoma in the middle ear.

    Science.gov (United States)

    Li, Bo; Liu, Shixi; Yang, Hui; Wang, Weiya

    2016-03-01

    T-cell lymphoblastic lymphoma (T-LBL) is a highly aggressive lymphoma characterized by precursor T-cell malignancy and lymphadenopathy or mediastinal involvement. We present the case of an 11-year-old boy with a diagnosis of middle ear T-LBL, which manifested as a headache, hearing loss and peripheral facial paralysis. The child was given intensive chemotherapy and had a complete response. To our knowledge, this is the first case reported in the literature of T-LBL originating in the middle ear. This case aims to help clinicians to be vigilant about the possibility of primary lesions at atypical sites in some special diseases.

  9. Acute Lymphoblastic Leukemia Presented as Multiple Breast Masses

    Energy Technology Data Exchange (ETDEWEB)

    Bayrak, Ilkay Koray; Yalin, Turkay; Ozmen, Zafer; Aksoz, Tolga; Doughanji, Roula [Ondokuz Mayis University, Samsun (Turkmenistan)

    2009-10-15

    Breast metastases in cases leukemia are very rare and occur primarily in patients with acute myeloid leukemia. We report the involvement of breast metastases in a 30-year-old woman with acute T cell lymphoblastic leukemia. The patient's mammograms revealed an extremely dense pattern with ill-defined, denser mass-like lesions in both breasts. A bilateral breast ultrasonographic evaluation revealed lobular-shaped and partly ill-defined hypoechoic masses with a multi-septated nodular (mottled) appearance.

  10. A rare case of acute lymphoblastic leukaemia with hemophilia A

    Directory of Open Access Journals (Sweden)

    John Biju

    2009-12-01

    Full Text Available Abstract A rare case of Acute lymphoblastic leukemia with hemophillia in a 12 year old boy is presented in the article. Patient was known case of hemophillia (factor VIII deficiency. He was diagnosed as a case of ALL based on bone marrow examination and immunophenotypic study. Patient was treated as per Children Cancer group guidelines. The main aim of reporting this rare association lies in developing treatment strategies in preventing life threatening bleeding due to this rare association which though may be accidental but need further research.

  11. Second Malignant Neoplasms After Treatment of Childhood Acute Lymphoblastic Leukemia

    DEFF Research Database (Denmark)

    Schmiegelow, K.; Levinsen, Mette Frandsen; Attarbaschi, Andishe

    2013-01-01

    PURPOSE: Second malignant neoplasms (SMNs) after diagnosis of childhood acute lymphoblastic leukemia (ALL) are rare events. PATIENTS AND METHODS: We analyzed data on risk factors and outcomes of 642 children with SMNs occurring after treatment for ALL from 18 collaborative study groups between 1980...... and 2007. RESULTS: Acute myeloid leukemia (AML; n = 186), myelodysplastic syndrome (MDS; n = 69), and nonmeningioma brain tumor (n = 116) were the most common types of SMNs and had the poorest outcome (5-year survival rate, 18.1% ± 2.9%, 31.1% ± 6.2%, and 18.3% ± 3.8%, respectively). Five-year survival...

  12. Pyomyositis During Induction Chemotherapy for Acute Lymphoblastic Leukemia

    Directory of Open Access Journals (Sweden)

    Kai-Liang Kao

    2006-04-01

    Full Text Available Herein, we report on the correct diagnosis and effective treatment procedures for pyomyositis, a very rare complication that remains a diagnostic challenge in children being treated for acute lymphoblastic leukemia (ALL. We report the case of a 10-year-old girl suffering from pyomyositis with ALL. Correct diagnosis is usually delayed because the initial symptom of pyomyositis, usually local pain, is similar to the common side effect of vincristine, a drug necessary for ALL induction therapy. We summarize the procedures taken to reach a timely diagnosis and therapeutic success.

  13. Esophageal strictures during treatment for acute lymphoblastic leukemia.

    LENUS (Irish Health Repository)

    Kelly, Kevin

    2012-02-01

    Esophageal stricture is a rare complication of paediatric cancer treatment that usually occurs after esophageal exposure to radiotherapy. We describe 4 cases of esophageal stricture during chemotherapy for acute lymphoblastic leukemia. All patients presented with refractory vomiting and were diagnosed with radiologic contrast studies. None of the patients had received radiotherapy. Esophageal candidiasis was seen in 2 patients but the remaining 2 patients had earlier systemic candidiasis. High-dose dexamethasone may predispose these children to both esophageal candidiasis and peptic esophagitis. The etiology of esophageal strictures during treatment for acute leukemia is likely to be multifactorial but systemic candidiasis may play a significant role.

  14. Co-existence of PHF6 and NOTCH1 mutations in adult T-cell acute lymphoblastic leukemia.

    Science.gov (United States)

    Li, Min; Xiao, Lichan; Xu, Jingyan; Zhang, Run; Guo, Jingjing; Olson, Justin; Wu, Yujie; Li, Jianyong; Song, Chunhua; Ge, Zheng

    2016-07-01

    T-cell acute lymphoblastic leukemia (T-ALL) results from the collaboration of multiple genetic abnormalities in the transformation of T-cell progenitors. Plant homeodomain finger protein 6 (PHF6) has recently been established as a key tumor suppressor, which is mutated in T-ALL; however, the clinical significance of PHF6 mutations has not been fully determined in adult T-ALL. In the present study, amplification of the PHF6 exons was performed, followed by DNA sequencing to identify the genomic mutations and examine the expression of PHF6 in adult patients with T-ALL. The correlation between PHF6 mutations and clinical features was also analyzed using a χ(2) test, and between PHF6 mutations and survival curve using the Kaplan-Meier methods. PHF6 mutations were detected in 27.1% of the Chinese adults with T-ALL (16/59), 10 of which were found to be novel mutations. A significantly lower expression level of PHF6 was observed in T-ALL patients with PHF6 mutations compared with those without mutations. Of the observed mutations in PHF6, 6/16 were frame-shift mutations, indicating a PHF6 dysfunction in those patients. Of note, PHF6 mutations were found to be significantly associated with older age, lower hemoglobin levels, higher frequency of CD13 positivity and higher incidence of splenomegaly or lymphadenopathy. Furthermore, PHF6 mutations were found to be significantly correlated with Notch homolog 1, translocation-associated (Drosophila) (NOTCH1) mutations. The patients with T-ALL with co-existence of the two mutations had a significantly shorter event-free survival and a poor prognosis. The present results indicated that PHF6 is inactivated in adult T-ALL, due to its low expression and mutations. The present data indicated the synergistic effect of PHF6 and NOTCH1 mutations, as well as their co-existence, on the oncogenesis of adult T-ALL, and their potential as a prognostic marker for the disease.

  15. Experimental Testing and Model Validation of a Decoupled-Phase On-Load Tap Changer Transformer in an Active Network

    DEFF Research Database (Denmark)

    Zecchino, Antonio; Hu, Junjie; Coppo, Massimiliano;

    2016-01-01

    to reproduce the main feature of an unbalanced grid. The experimental activities are recreated in by carrying out dynamics simulation studies, aiming at validating the implemented models of both the transformer as well as the other grid components. Phase-neutral voltages’ deviations are limited, proving......Due to the increasing penetration of single-phase small generation units and electric vehicles connected to distribution grids, system operators are facing challenges related to local unbalanced voltage rise or drop issues, which may lead to a violation of the allowed voltage band. To address...... this problem, distribution transformers with on-load tapping capability are under development. This paper presents model and experimental validation of a 35 kVA three-phase power distribution transformer with independent on-load tap changer control capability on each phase. With the purpose of investigating...

  16. ZFX Controls Propagation and Prevents Differentiation of Acute T-Lymphoblastic and Myeloid Leukemia

    Directory of Open Access Journals (Sweden)

    Stuart P. Weisberg

    2014-02-01

    Full Text Available Tumor-propagating cells in acute leukemia maintain a stem/progenitor-like immature phenotype and proliferative capacity. Acute myeloid leukemia (AML and acute T-lymphoblastic leukemia (T-ALL originate from different lineages through distinct oncogenic events such as MLL fusions and Notch signaling, respectively. We found that Zfx, a transcription factor that controls hematopoietic stem cell self-renewal, controls the initiation and maintenance of AML caused by MLL-AF9 fusion and of T-ALL caused by Notch1 activation. In both leukemia types, Zfx prevents differentiation and activates gene sets characteristic of immature cells of the respective lineages. In addition, endogenous Zfx contributes to gene induction and transformation by Myc overexpression in myeloid progenitors. Key Zfx target genes include the mitochondrial enzymes Ptpmt1 and Idh2, whose overexpression partially rescues the propagation of Zfx-deficient AML. These results show that distinct leukemia types maintain their undifferentiated phenotype and self-renewal by exploiting a common stem-cell-related genetic regulator.

  17. ZFX controls propagation and prevents differentiation of acute T-lymphoblastic and myeloid leukemia.

    Science.gov (United States)

    Weisberg, Stuart P; Smith-Raska, Matthew R; Esquilin, Jose M; Zhang, Ji; Arenzana, Teresita L; Lau, Colleen M; Churchill, Michael; Pan, Haiyan; Klinakis, Apostolos; Dixon, Jack E; Mirny, Leonid A; Mukherjee, Siddhartha; Reizis, Boris

    2014-02-13

    Tumor-propagating cells in acute leukemia maintain a stem/progenitor-like immature phenotype and proliferative capacity. Acute myeloid leukemia (AML) and acute T-lymphoblastic leukemia (T-ALL) originate from different lineages through distinct oncogenic events such as MLL fusions and Notch signaling, respectively. We found that Zfx, a transcription factor that controls hematopoietic stem cell self-renewal, controls the initiation and maintenance of AML caused by MLL-AF9 fusion and of T-ALL caused by Notch1 activation. In both leukemia types, Zfx prevents differentiation and activates gene sets characteristic of immature cells of the respective lineages. In addition, endogenous Zfx contributes to gene induction and transformation by Myc overexpression in myeloid progenitors. Key Zfx target genes include the mitochondrial enzymes Ptpmt1 and Idh2, whose overexpression partially rescues the propagation of Zfx-deficient AML. These results show that distinct leukemia types maintain their undifferentiated phenotype and self-renewal by exploiting a common stem-cell-related genetic regulator. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  18. Genomic analyses identify recurrent MEF2D fusions in acute lymphoblastic leukaemia

    Science.gov (United States)

    Gu, Zhaohui; Churchman, Michelle; Roberts, Kathryn; Li, Yongjin; Liu, Yu; Harvey, Richard C.; McCastlain, Kelly; Reshmi, Shalini C.; Payne-Turner, Debbie; Iacobucci, Ilaria; Shao, Ying; Chen, I-Ming; Valentine, Marcus; Pei, Deqing; Mungall, Karen L.; Mungall, Andrew J.; Ma, Yussanne; Moore, Richard; Marra, Marco; Stonerock, Eileen; Gastier-Foster, Julie M.; Devidas, Meenakshi; Dai, Yunfeng; Wood, Brent; Borowitz, Michael; Larsen, Eric E.; Maloney, Kelly; Mattano Jr, Leonard A.; Angiolillo, Anne; Salzer, Wanda L.; Burke, Michael J.; Gianni, Francesca; Spinelli, Orietta; Radich, Jerald P.; Minden, Mark D.; Moorman, Anthony V.; Patel, Bella; Fielding, Adele K.; Rowe, Jacob M.; Luger, Selina M.; Bhatia, Ravi; Aldoss, Ibrahim; Forman, Stephen J.; Kohlschmidt, Jessica; Mrózek, Krzysztof; Marcucci, Guido; Bloomfield, Clara D.; Stock, Wendy; Kornblau, Steven; Kantarjian, Hagop M.; Konopleva, Marina; Paietta, Elisabeth; Willman, Cheryl L.; L. Loh, Mignon; P. Hunger, Stephen; Mullighan, Charles G.

    2016-01-01

    Chromosomal rearrangements are initiating events in acute lymphoblastic leukaemia (ALL). Here using RNA sequencing of 560 ALL cases, we identify rearrangements between MEF2D (myocyte enhancer factor 2D) and five genes (BCL9, CSF1R, DAZAP1, HNRNPUL1 and SS18) in 22 B progenitor ALL (B-ALL) cases with a distinct gene expression profile, the most common of which is MEF2D-BCL9. Examination of an extended cohort of 1,164 B-ALL cases identified 30 cases with MEF2D rearrangements, which include an additional fusion partner, FOXJ2; thus, MEF2D-rearranged cases comprise 5.3% of cases lacking recurring alterations. MEF2D-rearranged ALL is characterized by a distinct immunophenotype, DNA copy number alterations at the rearrangement sites, older diagnosis age and poor outcome. The rearrangements result in enhanced MEF2D transcriptional activity, lymphoid transformation, activation of HDAC9 expression and sensitive to histone deacetylase inhibitor treatment. Thus, MEF2D-rearranged ALL represents a distinct form of high-risk leukaemia, for which new therapeutic approaches should be considered. PMID:27824051

  19. Acute Lymphoblastic Leukemia in a Man Treated With Fingolimod for Relapsing Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Stanley Cohan MD, PhD

    2015-03-01

    Full Text Available A man with relapsing multiple sclerosis, treated with fingolimod 0.5 mg/d for 15 months, developed acute lymphoblastic leukemia and died 4 months after immune ablation and bone marrow allograft, from graft versus host disease. To our knowledge, this is the first case of acute lymphoblastic leukemia reported in a patient treated with fingolimod. Although no causal relationship can be established between fingolimod use and acute lymphoblastic leukemia risk in this single case, future surveillance for lymphatic cell malignancies in patients treated with fingolimod appears justified.

  20. A Test of Transactional and Transformational Leadership Behaviour of Salesman on Customer Relationship Marketing Behaviour: A Study of the Indian Banking Sector

    Directory of Open Access Journals (Sweden)

    Sumit Duggal

    2012-01-01

    Full Text Available The present study was aimed to test constituents as well as complete theories of Transactional and Transformational Leadership behaviour of salesman on customer relationship marketing behaviour in Indian Banking scenario. For Transactional Leadership it was hypothesized that contingency reward system and management by exception of salesperson positively affect customer trust, customer commitment and together they contribute to customer relationship behaviour .For transformational Leadership it was hypothesized that idealized influence behaviour, individualized considerate, Intellectual stimulation, Inspirational motivation behaviour of salespersons positively affect customers’ trust, customers’ commitment, customer assumptions and customers optimistic engagement. Non-Probabilistic sampling methods were used. A survey was conducted among 61 sales persons and their customers in the Indian banking sector, and the regression analysis was performed to test hypotheses. Conclusion shows that contingency reward system influence customer relationship up to a certain extent while management by exceptions is not so appropriate for maintaining the relationship with customer though it is showing correlation, while in case of transformational leadership idealized influence behaviour of salespersons positively influences customer trust, individualized consideration of salespersons, in turn influences customer commitment, Intellectual stimulation encourage creativity and changes earlier assumptions of customer and Inspirational Motivation influences optimistic engagement of customers. It was also found that the combined effect of all the constituent of Transformational Leadership theories are positively related with customers’ relationship commitment. Conclusion motivate us to think complementary nature of these theories thus points out how leadership development training can be adapted to improve relationship marketing skills of sales persons.

  1. Vincristine sulfate liposomal injection for acute lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    Soosay Raj TA

    2013-11-01

    Full Text Available Trisha A Soosay Raj,1 Amanda M Smith,2 Andrew S Moore,1,21Royal Children's Hospital, Children's Health Queensland Hospital and Health Service, Brisbane, Queensland, Australia; 2Queensland Children's Medical Research Institute, The University of Queensland, Brisbane, QLD, AustraliaAbstract: Vincristine (VCR is one of the most extensively used cytotoxic compounds in hemato-oncology. VCR is particularly important for the treatment of acute lymphoblastic leukemia (ALL, a disease that accounts for approximately one-third of all childhood cancer diagnoses. VCR's full therapeutic potential has been limited by dose-limiting neurotoxicity, classically resulting in autonomic and peripheral sensory–motor neuropathy. In the last decade, however, the discovery that liposomal encapsulation of chemotherapeutics can modulate the pharmacokinetic characteristics of a compound has stimulated much interest in liposomal VCR (vincristine sulfate liposomal injection [VSLI] formulations for the treatment of ALL and other hematological malignancies. Promising data from recent clinical trials investigating VSLI in adults with ALL resulted in US Food and Drug Administration approval for use in patients with Philadelphia chromosome (t[9;22]/BCR–ABL1 (Ph-negative (Ph- disease. Additional clinical trials of VSLI in adults and children with both Ph-positive (Ph+ and Ph- ALL are ongoing. Here we review the preclinical and clinical experience to date with VSLI for ALL.Keywords: vincristine sulfate liposomal injection, liposomes, sphingosomal vincristine, acute lymphoblastic leukemia, chemotherapy

  2. An acceptance test method of error test units in automatic verifcation system for current transformers%电流互感器自动化检定系统误差试验单元验收方法

    Institute of Scientific and Technical Information of China (English)

    周杭军; 李建

    2015-01-01

    介绍了母线式电流互感器和复匝式电流互感器进行全自动的检定试验方法.通过对误差试验单元的分析,并结合JJF 1033-2014《计量标准考核规范》的相关要求,深入探讨和研究了误差试验单元的验收方法和技术路线.%This article introduces an automatic verification test method for busbar type current transformers and the complex coil type current transformers. Through the analysis of the error test units and the relevant requirements of JJF 1033-2010"Rule for the Examination of Measurement Standard", an acceptance test method and technical route of the error test units are discussed and researched.

  3. Development and testing of a fast Fourier transform high dynamic-range spectral diagnostics for millimeter wave characterization

    NARCIS (Netherlands)

    Thoen, D. J.; Bongers, W. A.; Westerhof, E.; Oosterbeek, J. W.; M.R. de Baar,; van den Berg, M. A.; van Beveren, V.; Burger, A.; Goede, A. P. H.; Graswinckel, M. F.; Hennen, B.A.; Schüller, F. C.

    2009-01-01

    A fast Fourier transform (FFT) based wide range millimeter wave diagnostics for spectral characterization of scattered millimeter waves in plasmas has been successfully brought into operation. The scattered millimeter waves are heterodyne downconverted and directly digitized using a fast analog-digi

  4. Oxindole alkaloids from Uncaria tomentosa induce apoptosis in proliferating, G0/G1-arrested and bcl-2-expressing acute lymphoblastic leukaemia cells.

    Science.gov (United States)

    Bacher, Nicole; Tiefenthaler, Martin; Sturm, Sonja; Stuppner, Hermann; Ausserlechner, Michael J; Kofler, Reinhard; Konwalinka, Günther

    2006-03-01

    Natural products are still an untapped source of promising lead compounds for the generation of antineoplastic drugs. Here, we investigated for the first time the antiproliferative and apoptotic effects of highly purified oxindole alkaloids, namely isopteropodine (A1), pteropodine (A2), isomitraphylline (A3), uncarine F (A4) and mitraphylline (A5) obtained from Uncaria tomentosa, a South American Rubiaceae, on human lymphoblastic leukaemia T cells (CCRF-CEM-C7H2). Four of the five tested alkaloids inhibited proliferation of acute lymphoblastic leukaemia cells. Furthermore, the antiproliferative effect of the most potent alkaloids pteropodine (A2) and uncarine F (A4) correlated with induction of apoptosis. After 48 h, 100 micromol/l A2 or A4 increased apoptotic cells by 57%. CEM-C7H2 sublines with tetracycline-regulated expression of bcl-2, p16ink4A or constitutively expressing the cowpox virus protein crm-A were used for further studies of the apoptosis-inducing properties of these alkaloids. Neither overexpression of bcl-2 or crm-A nor cell-cycle arrest in G0/G1 phase by tetracycline-regulated expression of p16INK4A could prevent alkaloid-induced apoptosis. Our results show the strong apoptotic effects of pteropodine and uncarine F on acute leukaemic lymphoblasts and recommend the alkaloids for further studies in xenograft models.

  5. EFFECTS OF TEST TEMPERATURE AND STRAIN RATE ON THE MECHANICAL PROPERTIES IN AN INTERCRITICALLY HEAT-TREATED BAINITE-TRANSFORMED STEEL

    Institute of Scientific and Technical Information of China (English)

    Z. Li; D. Wu

    2004-01-01

    Larger amount of austenite could be retained in an intercritically heat-treated bainitetransformed steel. The elongation and the strength-ductility balance of the steel could be enhanced considerably due to strain-induced martensite transformation and transformationinduced plasticity (TRIP) of retained austenite. The effects of test temperature and strain rate on the mechanical properties and strain induced transformation behavior of retained austenite in the steel were investigated. Total elongation and strength-ductility balance of the specimen reached maximum when it strained at a strain rate of 2.8×10-4s-1 and at 350℃. The relation between test temperature and tensile properties showed the same tendency at three kinds of strain rates. Flow stress increased considerably with decreasing the strain rate.

  6. A DC Transformer Project

    Data.gov (United States)

    National Aeronautics and Space Administration — During the period of this project three different possible DC transformer concepts were proposed, theoretically modeled, and then experimentally tested with the...

  7. High sensitivity of flow cytometry improves detection of occult leptomeningeal disease in acute lymphoblastic leukemia and lymphoblastic lymphoma.

    Science.gov (United States)

    Del Principe, Maria Ilaria; Buccisano, Francesco; Cefalo, Mariagiovanna; Maurillo, Luca; Di Caprio, Luigi; Di Piazza, Fabio; Sarlo, Chiara; De Angelis, Gottardo; Irno Consalvo, Maria; Fraboni, Daniela; De Santis, Giovanna; Ditto, Concetta; Postorino, Massimiliano; Sconocchia, Giuseppe; Del Poeta, Giovanni; Amadori, Sergio; Venditti, Adriano

    2014-09-01

    Conventional cytology (CC) of cerebrospinal fluid (CSF) fails to demonstrate malignant cells in up to 45 % of patients with acute lymphoblastic leukemia or lymphoblastic lymphoma (ALL/LL) in whom occult leptomeningeal disease is present. Flow cytometry (FCM) is considered more sensitive than CC, but clinical implications of CC negativity/CC positivity are not yet established. CSF samples from 38 adult patients with newly diagnosed ALL/LL were examined. Five (13 %) and nine (24 %) specimens were CC positive-FC positive (FCM(pos)/CC(pos)) and CC negative-FC positive (CC(neg)/FCM(pos)), respectively. The remaining 24 (63 %) samples were double negative (CC(neg)/FCM(neg)) (p = 0.001). CC(neg)/FCM(pos) patients showed a significantly shorter overall survival (OS) compared to CC(neg)/FCM(neg) ones. In multivariate analysis, the status of single FCM positivity was demonstrated to affect independently duration of OS (p = 0.005). In conclusion, FCM significantly improves detection of leptomeningeal occult localization in ALL/LL and appears to anticipate an adverse outcome. Further prospective studies on larger series are needed to confirm this preliminary observation.

  8. What role can gender-transformative programming for men play in increasing men's HIV testing and engagement in HIV care and treatment in South Africa?

    Science.gov (United States)

    Fleming, Paul J; Colvin, Chris; Peacock, Dean; Dworkin, Shari L

    2016-11-01

    Men are less likely than women to test for HIV and engage in HIV care and treatment. We conducted in-depth interviews with men participating in One Man Can (OMC) - a rights-based gender equality and health programme intervention conducted in rural Limpopo and Eastern Cape, South Africa - to explore masculinity-related barriers to HIV testing/care/treatment and how participation in OMC impacted on these. Men who participated in OMC reported an increased capability to overcome masculinity-related barriers to testing/care/treatment. They also reported increased ability to express vulnerability and discuss HIV openly with others, which led to greater willingness to be tested for HIV and receive HIV care and treatment for those who were living with HIV. Interventions that challenge masculine norms and promote gender equality (i.e. gender-transformative interventions) represent a promising new approach to address men's barriers to testing, care and treatment.

  9. Molecular mechanisms of mistletoe plant extract-induced apoptosis in acute lymphoblastic leukemia in vivo and in vitro.

    Science.gov (United States)

    Seifert, Georg; Jesse, Patrick; Laengler, Alfred; Reindl, Tobias; Lüth, Maria; Lobitz, Stephan; Henze, Günter; Prokop, Aram; Lode, Holger N

    2008-06-18

    Viscum album (Mistletoe) is one of the most widely used alternative cancer therapies. Aqueous mistletoe extracts (MT) contain the three mistletoe lectins I, II and III as one predominant group of biologically active agents. Although MT is widely used, there is a lack of scientifically sound preclinical and clinical data. In this paper, we describe for the first time the in vivo efficacy and mechanism of action of MT in lymphoblastic leukemia. For this purpose, we first investigated both the cytotoxic effect and the mechanism of action of two standardized aqueous MTs (MT obtained from fir trees (MT-A); MT obtained from pine trees (MT-P)) in a human acute lymphoblastic leukemia (ALL) cell line (NALM-6). MT-A, MT-P and ML-I inhibited cell proliferation as determined by Casy Count analysis at very low concentrations with MT-P being the most cytotoxic extract. DNA-fragmentation assays indicated that dose-dependent induction of apoptosis was the main mechanism of cell death. Finally, we evaluated the efficacy of MT-A and MT-P in an in vivo SCID-model of pre-B ALL (NALM-6). Both MTs significantly improved survival (up to 55.4 days) at all tested concentrations in contrast to controls (34.6 days) without side effects.

  10. Inhibition of glycolysis modulates prednisolone resistance in acute lymphoblastic leukemia cells

    NARCIS (Netherlands)

    Hulleman, Esther; Kazemier, Karin M.; Holleman, Amy; VanderWeele, David J.; Rudin, Charles M.; Broekhuis, Mathilde J. C.; Evans, William E.; Pieters, Rob; Den Boer, Monique L.

    2009-01-01

    Treatment failure in pediatric acute lymphoblastic leukemia (ALL) is related to cellular resistance to glucocorticoids (eg, prednisolone). Recently, we demonstrated that genes associated with glucose metabolism are differentially expressed between prednisolone-sensitive and prednisolone-resistant pr

  11. Charcot-Marie-Tooth Disease in a Child with Acute Lymphoblastic ...

    African Journals Online (AJOL)

    ... with Acute Lymphoblastic Leukaemia: A Case Report and Review of Literature. ... vincristine treatment triggering the expression of asymptomatic CMT disease. ... Results: Facial nerve palsy, increasing lower extremities muscle weakness ...

  12. Charcot-Marie-Tooth Disease in a Child with Acute Lymphoblastic ...

    African Journals Online (AJOL)

    Alasia Datonye

    into vincristine therapy in a ten year old male on treatment for acute lymphoblastic ... diagnosis of malignancy to identify any undiagnosed neurologic deficits .... There is no cure for CMT, but physical therapy, occupational therapy, braces and ...

  13. Subdural hemorrhages in acute lymphoblastic leukemia: case report and literature review

    Institute of Scientific and Technical Information of China (English)

    Rui Yin; CaiXia Qiu; XiaoHui Dong; YeLong Chen

    2016-01-01

    Background:Acute lymphoblastic leukemia is a rare hematological malignancy.Pure subdural hemorrhages in a patient with acute lymphoblastic leukemia patient are extremely rare.Case presentation:This case presented acute spontaneous subdural hemorrhage without head trauma at first,and acute lymphoblastic leukemia was diagnosed later.The second time,the patient was admitted with multiple pure subdural hemorrhages in different locations and periods with a history of slight head trauma.Conclusions:Pure subdural hemorrhages can occur in a patient with acute lymphoblastic leukemia.More care would be needed for pure subdural hemorrhages without obvious head trauma,and patients with hematological malignancies should be protected from even mild head trauma.

  14. The controversy of varicella vaccination in children with acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Caniza, Miguela A; Hunger, Stephen P; Schrauder, Andre

    2012-01-01

    The available guidelines for varicella vaccination of susceptible children with acute lymphoblastic leukemia (ALL) have become increasingly conservative. However, vaccination of those who have remained in continuous complete remission for 1 year and are receiving chemotherapy is still considered...

  15. Hepatotoxicity During Maintenance Therapy and Prognosis in Children With Acute Lymphoblastic Leukemia

    DEFF Research Database (Denmark)

    Ebbesen, Maria S.; Nygaard, Ulrikka; Rosthøj, Susanne

    2017-01-01

    Hepatotoxicity is a known toxicity to treatment of childhood acute lymphoblastic leukemia. Hepatotoxicity occurs during maintenance therapy and is caused by metabolites of 6-Mercaptopurine (6 MP) and Methotrexate (MTX). Our objective was to investigate the association between alanine...

  16. The role of ZAP70 kinase in acute lymphoblastic leukemia infiltration into the central nervous system

    Science.gov (United States)

    Alsadeq, Ameera; Fedders, Henning; Vokuhl, Christian; Belau, Nele M.; Zimmermann, Martin; Wirbelauer, Tim; Spielberg, Steffi; Vossen-Gajcy, Michaela; Cario, Gunnar; Schrappe, Martin; Schewe, Denis M.

    2017-01-01

    Central nervous system infiltration and relapse are poorly understood in childhood acute lymphoblastic leukemia. We examined the role of zeta-chain-associated protein kinase 70 in preclinical models of central nervous system leukemia and performed correlative studies in patients. Zeta-chain-associated protein kinase 70 expression in acute lymphoblastic leukemia cells was modulated using short hairpin ribonucleic acid-mediated knockdown or ectopic expression. We show that zeta-chain-associated protein kinase 70 regulates CCR7/CXCR4 via activation of extracellular signal-regulated kinases. High expression of zeta-chain-associated protein kinase 70 in acute lymphoblastic leukemia cells resulted in a higher proportion of central nervous system leukemia in xenografts as compared to zeta-chain-associated protein kinase 70 low expressing counterparts. High zeta-chain-associated protein kinase 70 also enhanced the migration potential towards CCL19/CXCL12 gradients in vitro. CCR7 blockade almost abrogated homing of acute lymphoblastic leukemia cells to the central nervous system in xenografts. In 130 B-cell precursor acute lymphoblastic leukemia and 117 T-cell acute lymphoblastic leukemia patients, zeta-chain-associated protein kinase 70 and CCR7/CXCR4 expression levels were significantly correlated. Zeta-chain-associated protein kinase 70 expression correlated with central nervous system disease in B-cell precursor acute lymphoblastic leukemia, and CCR7/CXCR4 correlated with central nervous system involvement in T-cell acute lymphoblastic leukemia patients. In multivariate analysis, zeta-chain-associated protein kinase 70 expression levels in the upper third and fourth quartiles were associated with central nervous system involvement in B-cell precursor acute lymphoblastic leukemia (odds ratio=7.48, 95% confidence interval, 2.06–27.17; odds ratio=6.86, 95% confidence interval, 1.86–25.26, respectively). CCR7 expression in the upper fourth quartile correlated with

  17. The role of ZAP70 kinase in acute lymphoblastic leukemia infiltration into the central nervous system.

    Science.gov (United States)

    Alsadeq, Ameera; Fedders, Henning; Vokuhl, Christian; Belau, Nele M; Zimmermann, Martin; Wirbelauer, Tim; Spielberg, Steffi; Vossen-Gajcy, Michaela; Cario, Gunnar; Schrappe, Martin; Schewe, Denis M

    2017-02-01

    Central nervous system infiltration and relapse are poorly understood in childhood acute lymphoblastic leukemia. We examined the role of zeta-chain-associated protein kinase 70 in preclinical models of central nervous system leukemia and performed correlative studies in patients. Zeta-chain-associated protein kinase 70 expression in acute lymphoblastic leukemia cells was modulated using short hairpin ribonucleic acid-mediated knockdown or ectopic expression. We show that zeta-chain-associated protein kinase 70 regulates CCR7/CXCR4 via activation of extracellular signal-regulated kinases. High expression of zeta-chain-associated protein kinase 70 in acute lymphoblastic leukemia cells resulted in a higher proportion of central nervous system leukemia in xenografts as compared to zeta-chain-associated protein kinase 70 low expressing counterparts. High zeta-chain-associated protein kinase 70 also enhanced the migration potential towards CCL19/CXCL12 gradients in vitro CCR7 blockade almost abrogated homing of acute lymphoblastic leukemia cells to the central nervous system in xenografts. In 130 B-cell precursor acute lymphoblastic leukemia and 117 T-cell acute lymphoblastic leukemia patients, zeta-chain-associated protein kinase 70 and CCR7/CXCR4 expression levels were significantly correlated. Zeta-chain-associated protein kinase 70 expression correlated with central nervous system disease in B-cell precursor acute lymphoblastic leukemia, and CCR7/CXCR4 correlated with central nervous system involvement in T-cell acute lymphoblastic leukemia patients. In multivariate analysis, zeta-chain-associated protein kinase 70 expression levels in the upper third and fourth quartiles were associated with central nervous system involvement in B-cell precursor acute lymphoblastic leukemia (odds ratio=7.48, 95% confidence interval, 2.06-27.17; odds ratio=6.86, 95% confidence interval, 1.86-25.26, respectively). CCR7 expression in the upper fourth quartile correlated with central

  18. cDNA-library testing identifies transforming genes cooperating with c-myc in mouse pre-B cells.

    Science.gov (United States)

    Wolf, Inge; Bouquet, Corinne; Melchers, Fritz

    2016-11-01

    While c-myc often contributes to the generation of B cell transformation, its transgenic overexpression alone does not lead to full transformation of B-lineage cells. Synergistically acting second genes must cooperate. Here, we constructed doxycycline-inducible cDNA-libraries from pre-B cell mRNA. These libraries were retrovirally transduced as single copies into single cells and overexpressed in fetal-liver-derived c-myc-overexpressing pre-B cell lines. We scored transformation by survival and/or expansion of differentiating B-lineage cells in vitro and in vivo. Only one double c-myc/cDNA-library-expressing cell line was found in less than 5 × 10(6) library-transduced pre-B cells surviving and expressing a cDNA-library-derived transcript in vitro. This transcript was identified as a shortened form of the Exosc1 gene, encoding the RNA exosome complex component CSL4. Transplantations of double c-myc/Exosc1 short-form- or c-myc/Exosc1 full-length-transgenic cells into Rag1(-/-) mice resulted in survival, differentiation to CD19(+) CD93(-) sIgM(+) CD5(low/-) CD11b(+) mature B1 cells and, surprisingly, also vigorous expansion in vivo. Strikingly, after transplantations of c-myc/cDNA-library pre-BI cells the frequencies of double-transgenic pre-B cells and their differentiated progeny, expanding in vivo to heterogeneous phenotypes, was at least tenfold higher than in vitro. In a first analysis Ptprcap, Cacybp, Ndufs7, Rpl18a, and Rpl35a were identified. This suggests a strong influence of the host on B-cell transformation. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. [Tumor lysis syndrome in a pregnancy complicated with acute lymphoblastic leukemia].

    Science.gov (United States)

    Álvarez-Goris, M P; Sánchez-Zamora, R; Torres-Aguilar, A A; Briones Garduño, J C

    2016-04-01

    Acute leukemia is rare during pregnancy, affects about 1 in 75,000 pregnancies, of all leukemias diagnosed only 28% are acute lymphoblastic leukemia, this is a risk factor to develop spontaneous tumor lysis syndrome, it's a oncologic complication potentially deadly if the prophylactic treatment its avoided. Cases of acute lymphoblastic leukemia associated with pregnancy has been poorly documented in the literature the association of these two entities to pregnancy is the first report published worldwide, so the information is limited.

  20. Central nervous system involvement in acute lymphoblastic leukemia: diagnosis by immunophenotyping

    Directory of Open Access Journals (Sweden)

    Camila Silva Peres Cancela

    2013-08-01

    Full Text Available The central nervous system is the most commonly affected extramedullary site in acute lymphoblastic leukemia. Although morphologic evaluation of the cerebrospinal fluid has been traditionally used for diagnosing central nervous system involvement, it is a method of low sensitivity. The present study aimed at evaluating the use of immunophenotyping in the detection of blasts in the cerebrospinal fluid from children and adolescents with acute lymphoblastic leukemia.

  1. Post chemotherapy blood and bone marrow regenerative changes in childhood acute lymphoblastic leukemia a prospective study

    Directory of Open Access Journals (Sweden)

    Rashmi Kushwaha

    2014-01-01

    Full Text Available Context: This study was done to assess the Serial peripheral blood and bone marrow changes in patients of Acute Lymphoblastic Leukemia on chemotherapy. Aims: To assess the therapy related serial bone marrow changes in patients of Acute Lymphoblastic Leukemia. Settings and Design: Prospective study, carried out in Lymphoma- Leukemia Lab, Department of Pathology, K.G.M.U from March 2011 to March 2012. A total of 60 cases were studied Materials and Methods: History, complete hemogram, bone marrow examination at pretherapy (Day-0, intratherapy (Day-14, and end of induction chemotherapy (Day-28 were done. Peripheral blood smears were evaluated at regular interval to assess clearance of blast cells. Statistical analysis used: The statistical analysis was done using SPSS (Statistical Package for Social Sciences Version 15.0 statistical Analysis Software. The values were represented in Number (% and Mean ± SD. The following Statistical formulas were used: Mean, standard deviation, Chi square test, Paired "t" test, Student ′t′ test, Level of significance P Results: Incidence of ALL-L1 (46.7% and ALL-L2 (53.3% was equal. ALL-L2 patients had poor survival.Day 0 (D-0 bone marrow was hypercellular with flooding of marrow by leukemic cells. High levels of tumor load at D′0′ were associated with poor survival. 14 th day of Induction phase showed significant decrease in hemoglobin and TLC as compared to D ′0′ parameters. D28 showed marrow regeneration. Cellularity, Blast%, and Leukemic Index showed significant drop from day ′0′ to day 14 due to myelosupression, whereas regeneration reflected by increased cellularity as per day 28 marrow. Lymphocytosis (>20% at end of induction chemotherapy had better survival and longer remission.Risk of mortality was directly proportional to blast clearance and was a major independent prognostic factor for achievement of complete remission. Conclusions: A bone marrow examination at the end of induction

  2. Feasibility and initial effectiveness of home exercise during maintenance therapy for childhood acute lymphoblastic leukemia.

    Science.gov (United States)

    Esbenshade, Adam J; Friedman, Debra L; Smith, Webb A; Jeha, Sima; Pui, Ching-Hon; Robison, Leslie L; Ness, Kirsten K

    2014-01-01

    Children with acute lymphoblastic leukemia (ALL) are at increased risk of obesity and deconditioning from cancer therapy. This pilot study assessed feasibility/initial efficacy of an exercise intervention for patients with ALL undergoing maintenance therapy. Participants were aged 5 to 10 years, receiving maintenance therapy, in first remission. A 6-month home-based intervention, with written and video instruction, was supervised with weekly calls from an exercise coach. Pre- and poststudy testing addressed strength, flexibility, fitness, and motor function. Seventeen patients enrolled (participation 63%). Twelve (71%) finished the intervention, completing 81.7 ± 7.2% of prescribed sessions. Improvements of 5% or more occurred in 67% for knee and 75% for grip strength, 58% for hamstring/low-back and 83% for ankle flexibility, 75% for the 6-Minute Walk Test, and 33% for performance on the Bruininks-Oseretsky Test of Motor Proficiency Version 2. This pilot study demonstrated that exercise intervention during ALL therapy is feasible and has promise for efficacy.

  3. Acute lymphoblastic leukemia of childhood presenting as aplastic anemia: report of two cases

    Directory of Open Access Journals (Sweden)

    Laura Villarreal-Martínez

    2012-01-01

    Full Text Available Acute lymphoblastic leukemia is the most common malignancy in pediatric patients; its diagnosis is usually easy to establish as malignant lymphoblasts invade the bone marrow and peripheral blood. Some acute lymphoblastic leukemia patients may initially present with pancytopenia and a hypoplastic bone marrow leading to the initial diagnosis of aplastic anemia. In most of these patients clinical improvement occurs, with normalization of the complete blood count within six months, although recovery can also develop a few weeks after initiating steroid therapy. The etiologic relationship between the aplastic anemia features and the subsequent overt development of acute lymphoblastic leukemia has not been established. We describe the cases of two children who presented with severe infection and signs and symptoms of aplastic anemia confirmed by bone marrow aspirate and bone marrow biopsy that developed acute lymphoblastic leukemia thereafter. No specific therapy for aplastic anemia was administered, nevertheless a full spontaneous recovery was observed in both cases. Acute lymphoblastic leukemia was successfully treated with standard chemotherapy, both children remaining in complete remission 16 and 17 months after their initial aplastic anemia diagnosis.

  4. Experimental Testing of Nonredundant Near-Field to Far-Field Transformations with Spherical Scanning Using Flexible Modellings for Nonvolumetric Antennas

    Directory of Open Access Journals (Sweden)

    Francesco D'Agostino

    2013-01-01

    Full Text Available This paper deals with the experimental testing of effective probe compensated near-field-far-field (NF-FF transformations with spherical scanning requiring a minimum number of NF data. They rely on nonredundant sampling representations of the voltage measured by the probe, based on very flexible source modellings suitable for nonvolumetric antennas characterized by two dimensions very different from the other one. In particular, a cylinder ended in two half-spheres is adopted for modelling long antennas, whereas the quasi-planar ones are considered as enclosed in a rotational surface formed by two circular “bowls” having the same aperture diameter, but eventually different bending radii. The NF data needed to perform the classical spherical NF-FF transformation are then accurately and efficiently retrieved from the acquired nonredundant ones via optimal sampling interpolation formulas. A remarkable reduction of the number of the required NF data and, as a consequence, a significant measurement time saving can be so obtained. The experimental tests have been carried out at Antenna Characterization Lab of the University of Salerno and both the NF and FF reconstructions are resulted to be very good, thus confirming the accuracy and reliability of these NF-FF transformations from the experimental viewpoint too.

  5. Leydig cell damage after testicular irradiation for lymphoblastic leukemia

    Energy Technology Data Exchange (ETDEWEB)

    Shalet, S.M.; Horner, A.; Ahmed, S.R.; Morris-Jones, P.H.

    1985-01-01

    The effect of testicular irradiation on Leydig cell function has been studied in a group of boys irradiated between 1 and 5 years earlier for a testicular relapse of acute lymphoblastic leukemia. Six of the seven boys irradiated during prepubertal life had an absent testosterone response to HCG stimulation. Two of the four boys irradiated during puberty had an appropriate basal testosterone level, but the testosterone response to HCG stimulation was subnormal in three of the four. Abnormalities in gonadotropin secretion consistent with testicular damage were noted in nine of the 11 boys. Evidence of severe Leydig cell damage was present irrespective of whether the boys were studied within 1 year or between 3 and 5 years after irradiation, suggesting that recovery is unlikely. Androgen replacement therapy has been started in four boys and will be required by the majority of the remainder to undergo normal pubertal development.

  6. CDX2 gene expression in acute lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    Hanaa H. Arnaoaut

    2014-06-01

    Full Text Available CDX genes are classically known as regulators of axial elongation during early embryogenesis. An unsuspected role for CDX genes has been revealed during hematopoietic development. The CDX gene family member CDX2 belongs to the most frequent aberrantly expressed proto-oncogenes in human acute leukemias and is highly leukemogenic in experimental models. We used reversed transcriptase polymerase chain reaction (RT-PCR to determine the expression level of CDX2 gene in 30 pediatric patients with acute lymphoblastic leukemia (ALL at diagnosis and 30 healthy volunteers. ALL patients were followed up to detect minimal residual disease (MRD on days 15 and 42 of induction. We found that CDX2 gene was expressed in 50% of patients and not expressed in controls. Associations between gene expression and different clinical and laboratory data of patients revealed no impact on different findings. With follow up, we could not confirm that CDX2 expression had a prognostic significance.

  7. Treatment of Philadelphia chromosome-positive acute lymphoblastic leukemia.

    Science.gov (United States)

    Ottmann, Oliver G; Wassmann, Barbara

    2005-01-01

    Philadelphia chromosome positive (Ph(+)) acute lymphoblastic leukemia (ALL) includes at least one-quarter of all adults with ALL. Until recently, conventional chemotherapy programs that have been effective in other precursor B-cell ALL cases have been unable to cure patients with this diagnosis. Allogeneic stem cell transplantation early in first remission has been the recommended therapy. The availability of imatinib mesylate and other tyrosine kinase inhibitors and small molecules that affect the BCR/ABL signaling pathways may be changing the treatment paradigm and the prognosis for these patients. The results from clinical trials using imatinib in the frontline setting and in relapsed patients as well as preliminary experience treating imatinib-resistant Ph(+) ALL will be described.

  8. Immune Thrombocytopenia in a Child with T Cell Lymphoblastic Lymphoma

    Directory of Open Access Journals (Sweden)

    Kayo Tokeji

    2016-01-01

    Full Text Available We describe the case of a 13-year-old boy who presented with persistent thrombocytopenia during maintenance chemotherapy with mercaptopurine and methotrexate for T cell lymphoblastic lymphoma. He was diagnosed with immune thrombocytopenia (ITP after thorough investigations for the relapse of lymphoma and was successfully treated with immunoglobulin and steroids. ITP is known to be associated with chronic lymphocytic leukemia, Hodgkin lymphoma, and various types of non-Hodgkin lymphoma but rarely with T cell non-Hodgkin lymphoma or in children. Diagnosis of ITP with lymphoma is challenging due to the many factors affecting platelet counts, and ITP often complicates the diagnosis or treatment course of lymphoma. The underlying mechanism of ITP with NHL is still unclear. Drug-induced immunomodulation with a reduction of regulatory T cells might have contributed to the development of ITP in our case.

  9. Acute lymphoblastic leukemia: a comprehensive review and 2017 update

    Science.gov (United States)

    Terwilliger, T; Abdul-Hay, M

    2017-01-01

    Acute lymphoblastic leukemia (ALL) is the second most common acute leukemia in adults, with an incidence of over 6500 cases per year in the United States alone. The hallmark of ALL is chromosomal abnormalities and genetic alterations involved in differentiation and proliferation of lymphoid precursor cells. In adults, 75% of cases develop from precursors of the B-cell lineage, with the remainder of cases consisting of malignant T-cell precursors. Traditionally, risk stratification has been based on clinical factors such age, white blood cell count and response to chemotherapy; however, the identification of recurrent genetic alterations has helped refine individual prognosis and guide management. Despite advances in management, the backbone of therapy remains multi-agent chemotherapy with vincristine, corticosteroids and an anthracycline with allogeneic stem cell transplantation for eligible candidates. Elderly patients are often unable to tolerate such regimens and carry a particularly poor prognosis. Here, we review the major recent advances in the treatment of ALL. PMID:28665419

  10. Childhood Acute Lymphoblastic Leukemia: Integrating Genomics into Therapy

    Science.gov (United States)

    Tasian, Sarah K; Loh, Mignon L; Hunger, Stephen P

    2015-01-01

    Acute lymphoblastic leukemia (ALL), the most common malignancy of childhood, is a genetically complex entity that remains a major cause of childhood cancer-related mortality. Major advances in genomic and epigenomic profiling during the past decade have appreciably enhanced knowledge of the biology of de novo and relapsed ALL and have facilitated more precise risk stratification of patients. These achievements have also provided critical insights regarding potentially targetable lesions for development of new therapeutic approaches in the era of precision medicine. This review delineates the current genetic landscape of childhood ALL with emphasis upon patient outcomes with contemporary treatment regimens, as well as therapeutic implications of newly identified genomic alterations in specific subsets of ALL. PMID:26194091

  11. Primary orbital precursor T-cell lymphoblastic lymphoma

    DEFF Research Database (Denmark)

    Stenman, Lisa; Persson, Marta; Enlund, Fredrik

    2016-01-01

    Primary T-cell lymphoblastic lymphoma (T-LBL) in the eye region is very rare. The present study described a unique case of T-LBL involving the extraocular muscles. A 22-year-old male patient presented with a 3-week history of headache, reduced visual acuity and edema of the left eye. Clinical....... There was no involvement of the bone marrow. Based on the clinical and histopathological findings, a diagnosis of T-LBL was made. There was no evidence of NOTCH1 mutation or rearrangements of the ETV6 and MLL genes and high-resolution array-based comparative genomic hybridization (arrayCGH) analysis revealed a normal...... genomic profile. The patient received chemotherapy according to the high-risk NOPHO protocol, followed by myeloablative allogenic bone marrow transplantation. At 35 months after diagnosis, the patient remained in complete first remission, but without light perception on his left eye. To the best of our...

  12. Outcome of children and adolescents with lymphoblastic lymphoma

    Directory of Open Access Journals (Sweden)

    Maria Christina Lopes Araújo Oliveira

    2015-10-01

    Full Text Available Summary Introduction: lymphoblastic lymphoma (LBL is the second most common subtype of non-Hodgkin lymphoma in children. The aim of this study was to characterize the clinical course of children and adolescents with LBL treated at a tertiary center. Methods: this is a retrospective cohort study of 27 patients aged 16 years or younger with LBL admitted between January 1981 and December 2013. Patients were treated according to the therapy protocol used for acute lymphoblastic leucemia. Diagnosis was based on biopsy of tumor and/or cytological examination of pleural effusions. The overall survival was analyzed using the Kaplan-Meier method. Results: the median age at diagnosis was 11.6 years (interquartile range, 4.6- 13.8. LBL had T-cell origin in 16 patients (59%. The most common primary manifestation in T-cell LBL was mediastinal involvement, in 9 patients (56%. Intra-abdominal tumor was the major site of involvement in patients with precursor B-LBL. Most patients had advanced disease (18 patients – 67% at diagnosis. Twenty-four patients (89% achieved complete clinical remission. After a median follow-up of 43 months (interquartile range, 6.4-95, 22 patients (81% were alive in first complete remission. Five children (18.5% died, three of them soon after admission and two after relapsing. The probability of survival at five years for 20 patients with de novo LBL was 78% (SD 9.4. Conclusion: our findings confirm the favorable prognosis of children with LBL with an intensive chemotherapy regimen derived from ALL therapy.

  13. Listening into the Dark: An Essay Testing the Validity and Efficacy of Collaborative Developmental Action Inquiry for Describing and Encouraging Transformations of Self, Society, and Scientific Inquiry

    Directory of Open Access Journals (Sweden)

    William R. Torbert

    2013-06-01

    Full Text Available Collaborative Developmental Action Inquiry (CDAI is introduced as a meta-paradigmatic approach to social science and social action that encompasses seven other more familiar paradigms (e.g., Behaviorism, Empirical Positivism, and Postmodern Interpretivism and that triangulates among third-person, objectivity-seeking social scientific inquiry, second-person, transformational, mutuality-seeking political inquiry, and first-person, adult, spiritual inquiry and consciousness development in the emerging present. CDAI tests findings, not only against third-person criteria of validity as do quantitative, positivist studies and qualitative, interpretive studies, but also against first- and second-person criteria of validity, as well as criteria of efficacy in action. CDAI introduces the possibility of treating, not just formal third-person studies, but any and all activities in one’s daily life in an inquiring manner. The aim of this differently-scientific approach is not only theoretical, generalizable knowledge, but also knowledge that generates increasingly timely action in particular cases in the relationships that mean the most to the inquirer. To illustrate and explain why the CDAI approach can explain unusually high percentages of the variance in whether or not organizations actually transform, all three types of validity-testing are applied to a specific study of intended transformation in ten organizations. The ten organization study found that adding together the performance of each organization’s CEO and lead consultant pn a reliable, well-validated measure of developmental action-logic, predicted 59% of the variance, beyond the .01 level, in whether and how the organization transformed (as rated by three scorers who achieved between .90 and 1.0 reliability. The essay concludes with a comparison between the Empirical Positivist paradigm of inquiry and the Collaborative Developmental Action Inquiry paradigm.

  14. Hypothalamus-pituitary-adrenal axis suppression following induction chemotherapy in children with acute lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    Perdomo-Ramírez, Iván

    2016-01-01

    Full Text Available Background: Adrenal insufficiency has been reported in 46 % to 81.5 % of children receiving corticosteroids for acute lymphoblastic leukemia (ALL. Methodology: To assess the frequency of such insufficiency, 40 patients under 18 years (mean: 8.5 years with new diagnosis of ALL were studied. Base-line cortisol and adrenocorticotropin (ACTH levels were measured, and they received 5-week therapy with prednisolone. After 3 days off-steroid therapy, a stimulation test with ACTH 1 μg was done. In patients with abnormal cortisol (<18 μg/dL new ACTH tests were done and cortisol levels were determined at days 7, 14 and 30 until cortisol post-stimulation levels were normal. Results: Three days after the last steroid dose 29/40 (72.5 % had adrenal insufficiency after ACTH stimulus. At day 30 no one had abnormal cortisol levels after ACTH stimulus. All patients with adrenal suppression were over 5 years (HR 4.69; CI95 %: 1.44-15.32; p = 0.011. Conclusion: Steroids used during ALL treatment may cause adrenal insufficiency. Patients over 5 years are at high risk of developing adrenal suppression. We suggest to follow-up those patients with stress episodes after induction chemotherapy as steroid supplementation may be indicated.

  15. MLL rearrangements in pediatric acute lymphoblastic and myeloblastic leukemias: MLL specific and lineage specific signatures

    Directory of Open Access Journals (Sweden)

    te Kronnie Geertruy

    2009-06-01

    Full Text Available Abstract Background The presence of MLL rearrangements in acute leukemia results in a complex number of biological modifications that still remain largely unexplained. Armstrong et al. proposed MLL rearrangement positive ALL as a distinct subgroup, separated from acute lymphoblastic (ALL and myeloblastic leukemia (AML, with a specific gene expression profile. Here we show that MLL, from both ALL and AML origin, share a signature identified by a small set of genes suggesting a common genetic disregulation that could be at the basis of mixed lineage leukemia in both phenotypes. Methods Using Affymetrix® HG-U133 Plus 2.0 platform, gene expression data from 140 (training set + 78 (test set ALL and AML patients with (24+13 and without (116+65 MLL rearrangements have been investigated performing class comparison (SAM and class prediction (PAM analyses. Results We identified a MLL translocation-specific (379 probes signature and a phenotype-specific (622 probes signature which have been tested using unsupervised methods. A final subset of 14 genes grants the characterization of acute leukemia patients with and without MLL rearrangements. Conclusion Our study demonstrated that a small subset of genes identifies MLL-specific rearrangements and clearly separates acute leukemia samples according to lineage origin. The subset included well-known genes and newly discovered markers that identified ALL and AML subgroups, with and without MLL rearrangements.

  16. Early adolescent language development following intrathecal chemotherapy for acute lymphoblastic leukaemia.

    Science.gov (United States)

    Lewis, Fiona M; Bohan, Jaycie K

    2017-04-10

    Central nervous system (CNS) prophylaxis in the treatment of childhood acute lymphoblastic leukaemia (ALL) is routinely achieved through intrathecal chemotherapy (ITC). The presence of high level language deficits in older children who received CNS-directed ITC for ALL in early childhood is yet to be elucidated, with previous research suggesting that high level language deficits may appear later in ALL survivors' development at an age when these skills typically emerge. A test battery covering foundational language skills and higher-order language skills was administered to five participants (aged 10-15 years) with a history of ITC for ALL. Conversion of each child's language performance scores to z scores allowed for clinical interpretation of data across the language areas tested. Foundational language skills were, in general, of no clinical concern. Three of the five children presented with clinically impaired language skills in areas including resolving ambiguity, making inferences and composing novel sentences. Performance variation between the participants and within the individual participants was noted. Given the importance of early adolescent language abilities to academic and social development in late primary and secondary schooling, these preliminary findings suggest further research into emerging adolescent language abilities following ITC for ALL is warranted.

  17. Diagnosis and immunophenotype of 188 pediatric lymphoblastic lymphomas treated within a randomized prospective trial: experiences and preliminary recommendations from the European childhood lymphoma pathology panel.

    NARCIS (Netherlands)

    Oschlies, I.; Burkhardt, B.; Chassagne-Clement, C.; d'Amore, E.S.; Hansson, U.; Hebeda, K.M.; McCarthy, K.; Kodet, R.; Maldyk, J.; Mullauer, L.; Porwit, A.; Schmatz, A.I.; Tinguely, M.; Abramov, D.; Wotherspoon, A.; Zimmermann, M.; Reiter, A.; Klapper, W.

    2011-01-01

    The majority of lymphoblastic (precursor cell) neoplasms presents as leukemias. Consequently, the guidelines for lineage determination and subtyping of precursor cell neoplasms were primarily established for flow cytometry methods. Large-scale studies of nonleukemic lymphoblastic lymphomas are lacki

  18. Simultaneous UV Imaging and Raman Spectroscopy for the Measurement of Solvent-Mediated Phase Transformations During Dissolution Testing

    DEFF Research Database (Denmark)

    Ostergaard, Jesper; Wu, Jian; Naelapää, Kaisa

    2014-01-01

    The current work reports the simultaneous use of UV imaging and Raman spectroscopy for detailed characterization of drug dissolution behavior including solid-state phase transformations during dissolution. The dissolution of drug substances from compacts of sodium naproxen in 0.1 HCl as well...... as theophylline anhydrate and monohydrate in water was studied utilizing a flow-through setup. The decreases in dissolution rates with time observed by UV imaging were associated with concomitant solid form changes detected by Raman spectroscopy. Sodium naproxen and theophylline anhydrate were observed to convert...... of UV imaging and Raman spectroscopy offers a detailed characterization of drug dissolution behavior in a time-effective and sample-sparing manner. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 103:1149-1156, 2014....

  19. Effects of Scale Transformation and Test Termination Rule on the Precision of Ability Estimates in CAT. ACT Research Report Series.

    Science.gov (United States)

    Yi, Qing; Wang, Tianyou; Ban, Jae-Chun

    Error indices (bias, standard error of estimation, and root mean square error) obtained on different scales of measurement under different test termination rules in a computerized adaptive test (CAT) context were examined. Four ability estimation methods were studied: (1) maximum likelihood estimation (MLE); (2) weighted likelihood estimation…

  20. Minimal Residual Disease Evaluation in Childhood Acute Lymphoblastic Leukemia: An Economic Analysis

    Science.gov (United States)

    Gajic-Veljanoski, O.; Pham, B.; Pechlivanoglou, P.; Krahn, M.; Higgins, Caroline; Bielecki, Joanna

    2016-01-01

    Background Minimal residual disease (MRD) testing by higher performance techniques such as flow cytometry and polymerase chain reaction (PCR) can be used to detect the proportion of remaining leukemic cells in bone marrow or peripheral blood during and after the first phases of chemotherapy in children with acute lymphoblastic leukemia (ALL). The results of MRD testing are used to reclassify these patients and guide changes in treatment according to their future risk of relapse. We conducted a systematic review of the economic literature, cost-effectiveness analysis, and budget-impact analysis to ascertain the cost-effectiveness and economic impact of MRD testing by flow cytometry for management of childhood precursor B-cell ALL in Ontario. Methods A systematic literature search (1998–2014) identified studies that examined the incremental cost-effectiveness of MRD testing by either flow cytometry or PCR. We developed a lifetime state-transition (Markov) microsimulation model to quantify the cost-effectiveness of MRD testing followed by risk-directed therapy to no MRD testing and to estimate its marginal effect on health outcomes and on costs. Model input parameters were based on the literature, expert opinion, and data from the Pediatric Oncology Group of Ontario Networked Information System. Using predictions from our Markov model, we estimated the 1-year cost burden of MRD testing versus no testing and forecasted its economic impact over 3 and 5 years. Results In a base-case cost-effectiveness analysis, compared with no testing, MRD testing by flow cytometry at the end of induction and consolidation was associated with an increased discounted survival of 0.0958 quality-adjusted life-years (QALYs) and increased discounted costs of $4,180, yielding an incremental cost-effectiveness ratio (ICER) of $43,613/QALY gained. After accounting for parameter uncertainty, incremental cost-effectiveness of MRD testing was associated with an ICER of $50,249/QALY gained. In

  1. Testicular relapse in childhood acute lymphoblastic leukemia: The challenges and lessons

    Directory of Open Access Journals (Sweden)

    K P Kulkarni

    2010-01-01

    Full Text Available Background : Relapse of disease is documented in 15-20% of children with acute lymphoblastic leukemia (ALL. Although testicular relapse is rare with modern risk-adapted treatment protocols, earlier, the testes were a frequently encountered site of relapse and were designated as "drug sanctuaries". Purpose : This descriptive study was designed to assess the pattern of testicular relapse and to identify high-risk factors. Materials and Methods : Data obtained from case records of 407 boys with ALL were analyzed. Fine needle aspiration cytology was carried out in children presenting with painless enlargement of testi(es. Bone marrow aspiration and cerebrospinal fluid examination were performed concomitantly to confirm or exclude disease at these sites. Results : Testicular relapse was documented in 30 boys. It was isolated in 17 patients and associated with bone marrow and/or central nervous system relapse in 13. At relapse, nine boys were over the age of 10 years. The majority were very early and early relapsers. Hyperleucocytosis was documented in five of 30 and seven of 137 relapsers and nonrelapsers, respectively (P = 0.04. Twelve of the 30 boys with testicular relapse were treated with testicular irradiation, reinduction and maintenance therapy. The estimated median overall survival was 33 months. Conclusion : Testicular relapse, which depends on the therapy administered, may manifest several months/years after completion of treatment. The high incidence of testicular relapse in our series implicates the need of revaluation of our protocol and incorporation of high/intermediate dose methotrexate therapy upfront.

  2. Prognostic value of cytogenetics in adult patients with Philadelphia-negative acute lymphoblastic leukemia.

    Science.gov (United States)

    Gómez-Seguí, Inés; Cervera, Jose; Such, Esperanza; Martínez-Cuadrón, David; Luna, Irene; Ibáñez, Mariam; López-Pavía, María; Gascón, Adriana; Roig, Mónica; Martínez, Jesús; Sanz, Jaime; Montesinos, Pau; Martín-Aragonés, Guillermo; Lorenzo, Ignacio; Senent, Leonor; Barragán, Eva; Cordón, Lourdes; Sempere, Amparo; Sanz, Guillermo F; Sanz, Miguel Angel

    2012-01-01

    The prognostic value of cytogenetics in adult acute lymphoblastic leukemia (ALL) is not as established as in childhood ALL. We have analyzed the outcome and prognostic value of karyotype in 84 adults diagnosed with Philadelphia-negative ALL from a single institution that received induction chemotherapy and had successful karyotype performed. The most frequent finding was normal karyotype in 35 (42%) cases, followed by aneuploidies in 20 cases (24%) and t(4;11)(q21;q23)/MLL/AF4 in 5 (6%), and the remaining 24(27%) cases carried miscellaneous clonal abnormalities. The group of patients with t(4;11)(q21;q23)/MLL/AF4, hypodiploidy and low hyperdiploidy (less than 50 chromosomes) showed a worse outcome than those with normal karyotype and miscellaneous abnormalities in terms of overall survival (OS) (3 years OS; 47% vs. 13%, p = 0.014) and relapse-free survival (RFS) (3 years RFS; 44% vs. 27%, p = 0.005). Other cytogenetic prognostic classifications reported to date were tested in our series, but any was fully reproducible. In conclusion, karyotype is a useful tool for risk assessment in adult ALL. We have confirmed the bad prognosis of t(4;11)(q21;q23)/MLL/AF4 and hypodiploidy. Besides, low hyperdiploidy could also define a high-risk group of patients who might be candidates for more intensive treatment.

  3. Isolated testicular relapse in acute lymphoblastic leukemia - Effective treatment with the modified CCG-112 protocol

    Directory of Open Access Journals (Sweden)

    Shama Goyal

    2005-01-01

    Full Text Available BACKGROUND: The testes have been considered a sanctuary site for leukemic cells and testicular relapses used to account for a major proportion of the poor outcome of boys with acute lymphoblastic leukemia. With use of aggressive chemotherapy which includes intermediate or high dose methotrexate, the incidence of testicular relapses has declined. However once these patients have received cranial irradiation as a part of the front line protocol, high dose methotrexate needs to be avoided because of risk of developing leucoencephalopathy. AIM: To study the use of non cross resistant chemotherapeutic agents along with a regimen containing lower doses of methotrexate in patients of isolated testicular relapse (ITR. MATERIALS AND METHODS: This is a retrospective analysis of 12 consecutive patients with ITR treated with modified version of the CCG-112 protocol which consists of intensive systemic chemotherapy, cranial chemoprophylaxis along with testicular irradiation. RESULTS: One patient died of regimen related toxicity. Two patients relapsed in the bone marrow during maintenance. Of the nine patients who completed treatment, eight are alive and in remission. One patient had a bone marrow relapse two months after completing treatment. The Kaplan Meier estimates give us an Event Free Survival (EFS of 66.7% at 10 yrs. CONCLUSIONS: Thus, though the incidence is very low, patients with ITR should be treated aggressively since they have an excellent chance of achieving a long term EFS.

  4. Reduced cardiorespiratory fitness in adult survivors of childhood acute lymphoblastic leukemia.

    Science.gov (United States)

    Tonorezos, Emily S; Snell, Peter G; Moskowitz, Chaya S; Eshelman-Kent, Debra A; Liu, Jennifer E; Chou, Joanne F; Smith, Stephanie M; Dunn, Andrea L; Church, Timothy S; Oeffinger, Kevin C

    2013-08-01

    Adult survivors of childhood acute lymphoblastic leukemia (ALL) are at increased cardiovascular risk. Studies of factors including treatment exposures that may modify risk of low cardiorespiratory fitness in this population have been limited. To assess cardiorespiratory fitness, maximal oxygen uptake (VO2 max) was measured in 115 ALL survivors (median age, 23.5 years; range 18-37). We compared VO2 max measurements for ALL survivors to those estimated from submaximal testing in a frequency-matched (age, gender, race/ethnicity) 2003-2004 National Health and Nutritional Examination Survey (NHANES) cohort. Multivariable linear regression models were constructed to evaluate the association between therapeutic exposures and outcomes of interest. Compared to NHANES participants, ALL survivors had a substantially lower VO2 max (mean 30.7 vs. 39.9 ml/kg/min; adjusted P VO2 max than NHANES participants. For key treatment exposure groups (cranial radiotherapy [CRT], anthracycline chemotherapy, or neither), ALL survivors had substantially lower VO2 max compared with NHANES participants (all comparisons, P VO2 max. Among females, CRT was associated with low VO2 max (P = 0.02), but anthracycline exposure was not (P = 0.58). In contrast, among males, anthracycline exposure ≥ 100 mg/m(2) was associated with low VO2 max (P = 0.03), but CRT was not (P = 0.54). Adult survivors of childhood ALL have substantially lower levels of cardiorespiratory fitness compared with a similarly aged non-cancer population. Copyright © 2013 Wiley Periodicals, Inc.

  5. Medical neglect death due to acute lymphoblastic leukaemia: an autopsy case report.

    Science.gov (United States)

    Usumoto, Yosuke; Sameshima, Naomi; Tsuji, Akiko; Kudo, Keiko; Nishida, Naoki; Ikeda, Noriaki

    2014-12-01

    We report the case of 2-year-old girl who died of precursor B-cell acute lymphoblastic leukaemia (ALL), the most common cancer in children. She had no remarkable medical history. She was transferred to a hospital because of respiratory distress and died 4 hours after arrival. Two weeks before death, she had a fever of 39 degrees C, which subsided after the administration of a naturopathic herbal remedy. She developed jaundice 1 week before death, and her condition worsened on the day of death. Laboratory test results on admission showed a markedly elevated white blood cell count. Accordingly, the cause of death was suspected to be acute leukaemia. Forensic autopsy revealed the cause of death to be precursor B-cell ALL. With advancements in medical technology, the 5-year survival rate of children with ALL is nearly 90%. However, in this case, the deceased's parents preferred complementary and alternative medicine (i.e., naturopathy) to evidence-based medicine and had not taken her to a hospital for a medical check-up or immunisation since she was an infant. Thus, if she had received routine medical care, she would have a more than 60% chance of being alive 5 years after diagnosis. Therefore, we conclude that the parents should be accused of medical neglect regardless of their motives.

  6. Acute lymphoblastic leukemia masquerading as juvenile rheumatoid arthritis: diagnostic pitfall and association with survival.

    Science.gov (United States)

    Marwaha, Ram Kumar; Kulkarni, Ketan Prasad; Bansal, Deepak; Trehan, Amita

    2010-03-01

    Acute lymphoblastic leukemia (ALL) often presents with osteoarthritic manifestations which may lead to misdiagnosis with juvenile rheumatoid arthritis (JRA). This study was designed to identify ALL patients with initial diagnosis of JRA, compare their clinicolaboratory characteristics and outcome with other ALL patients treated at our center. Case records of 762 patients with ALL were analyzed. Information regarding the clinical-demographic profile, therapy and outcome were recorded. Of the children, 49 (6.4%) had initial presentation mimicking JRA. Asymmetric oligoarthritis was the most common pattern of joint involvement. Majority presented with fever, pallor, arthritis, night pain, and bone pain. None of the routine prognostic factors including age, gender, lymphadenopathy, hepatosplenomegaly, total leukocytes count (TLC), and platelet count were significantly associated with relapse/death. The mean symptom-presentation interval (SPI), hemoglobin was significantly higher whilst the TLC was significantly lower in these patients compared to other ALL patients. The 5 year overall-survival was better than other patients with ALL (p = 0.06, by logrank test). Significantly longer SPI in these patients underscores the need for prompt and early investigations to rule out ALL in patients of JRA with atypical features and pointers of ALL. Children with ALL-mimicking JRA may belong to a subgroup of ALL with a better prognosis.

  7. Developing "Care Assistant": A smartphone application to support caregivers of children with acute lymphoblastic leukaemia.

    Science.gov (United States)

    Wang, Jingting; Yao, Nengliang; Wang, Yuanyuan; Zhou, Fen; Liu, Yanyan; Geng, Zhaohui; Yuan, Changrong

    2016-04-01

    Acute lymphoblastic leukaemia (ALL) is the most common childhood malignancy. Caring for children with ALL is an uncommon experience for parents without medical training. They urgently need professional assistance when their children are recovering at home. This paper documents the process of developing an Android application (app) "Care Assistant" for family caregivers of children with ALL. Key informant interviews and focus group studies were used before programming the app. The key informants and focus group members included: caregivers of children with ALL, cancer care physicians and nurses, and software engineers. We found several major challenges faced by caregivers: limited access to evidence-based clinic information, lack of financial and social assistance, deficient communications with doctors or nurses, lack of disease-related knowledge, and inconvenience of tracking treatments and testing results. This feedback was used to develop "Care Assistant". This app has eight modules: personal information, treatment tracking, family care, financial and social assistance, knowledge centre, self-assessment questionnaires, interactive platform, and reminders. We have also developed a web-based administration portal to manage the app. The usability and effectiveness of "Care Assistant" will be evaluated in future studies. © The Author(s) 2015.

  8. Skeletal, neuromuscular and fitness impairments among children with newly diagnosed acute lymphoblastic leukemia

    Science.gov (United States)

    Ness, Kirsten K.; Kaste, Sue C.; Zhu, Liang; Pui, Ching-Hon; Jeha, Sima; Nathan, Paul C.; Inaba, Hiroto; Wasilewski-Masker, Karen; Shah, Durga; Wells, Robert J.; Karlage, Robyn E.; Robison, Leslie L.; Cox, Cheryl L.

    2014-01-01

    This study describes skeletal, neuromuscular and fitness impairments among 109 children (median age 10 (range 4–18) years, 65.1% male, 63.3% white) with acute lymphoblastic leukemia (ALL), enrolled on a physical activity trial from 2009 to 2013. Outcomes were measured 7-10 days after diagnosis and compared to age- and sex-specific expected values. Associations between function and HRQL were evaluated with logistic regression. Children low values for BMD z-scores/height (mean±standard error: −0.53±0.16 vs. 0.00±0.14, p <0.01), body mass index percentile (57.6±3.15 vs. 50.0±3.27%, p=0.02), quadriceps strength (201.9±8.3 vs. 236.1±5.4 Newtons, p<0.01), six minute walk distance (385.0±13.1 vs. 628.2±7.1 meters, p < 0.001), and Bruininks-Oseretsky Test of Motor Proficiency (23±2.5 vs. 50±3.4%, p < 0.001). Quadriceps weakness was associated with a 20.9-fold (95% CI 2.5–173.3) increase in poor physical HRQL. Children with newly diagnosed ALL have weakness and poor endurance and may benefit from early rehabilitation that includes strengthening and aerobic conditioning. PMID:25030039

  9. A reliable Raman-spectroscopy-based approach for diagnosis, classification and follow-up of B-cell acute lymphoblastic leukemia

    Science.gov (United States)

    Managò, Stefano; Valente, Carmen; Mirabelli, Peppino; Circolo, Diego; Basile, Filomena; Corda, Daniela; de Luca, Anna Chiara

    2016-04-01

    Acute lymphoblastic leukemia type B (B-ALL) is a neoplastic disorder that shows high mortality rates due to immature lymphocyte B-cell proliferation. B-ALL diagnosis requires identification and classification of the leukemia cells. Here, we demonstrate the use of Raman spectroscopy to discriminate normal lymphocytic B-cells from three different B-leukemia transformed cell lines (i.e., RS4;11, REH, MN60 cells) based on their biochemical features. In combination with immunofluorescence and Western blotting, we show that these Raman markers reflect the relative changes in the potential biological markers from cell surface antigens, cytoplasmic proteins, and DNA content and correlate with the lymphoblastic B-cell maturation/differentiation stages. Our study demonstrates the potential of this technique for classification of B-leukemia cells into the different differentiation/maturation stages, as well as for the identification of key biochemical changes under chemotherapeutic treatments. Finally, preliminary results from clinical samples indicate high consistency of, and potential applications for, this Raman spectroscopy approach.

  10. Simultaneous UV imaging and raman spectroscopy for the measurement of solvent-mediated phase transformations during dissolution testing.

    Science.gov (United States)

    Østergaard, Jesper; Wu, Jian X; Naelapää, Kaisa; Boetker, Johan P; Jensen, Henrik; Rantanen, Jukka

    2014-04-01

    The current work reports the simultaneous use of UV imaging and Raman spectroscopy for detailed characterization of drug dissolution behavior including solid-state phase transformations during dissolution. The dissolution of drug substances from compacts of sodium naproxen in 0.1 HCl as well as theophylline anhydrate and monohydrate in water was studied utilizing a flow-through setup. The decreases in dissolution rates with time observed by UV imaging were associated with concomitant solid form changes detected by Raman spectroscopy. Sodium naproxen and theophylline anhydrate were observed to convert to the more stable forms (naproxen, and theophylline monohydrate) within approximately 5 min. Interestingly, the new approach revealed that three intermediate forms are involved in the dissolution process prior to the appearance of the neutral naproxen during dissolution in an acidic medium. The combination of UV imaging and Raman spectroscopy offers a detailed characterization of drug dissolution behavior in a time-effective and sample-sparing manner. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

  11. Bladder cancer diagnosis from bladder wash by Fourier transform infrared spectroscopy as a novel test for tumor recurrence.

    Science.gov (United States)

    Gok, Seher; Aydin, Ozge Z; Sural, Yavuz S; Zorlu, Ferruh; Bayol, Umit; Severcan, Feride

    2016-09-01

    This study proposes Fourier Transform Infrared (FTIR) spectroscopy as a more sensitive, rapid, non-destructive and operator-independent analytical diagnostic method for bladder cancer recurrence from bladder wash than other routinely used urine cytology and cystoscopy methods. A total of 136 patients were recruited. FTIR spectroscopic experiments were carried out as a blind study, the classification results of which were then compared with those of cytology and cystoscopy. Firstly, 71 samples (n = 37; bladder cancer and n = 34; control) were studied with transmittance FTIR spectroscopy. After achieving successful differentiation of the groups, to develop a more rapid diagnostic tool and check the reproducibility of the results, the work was continued with different samples (n = 65 as n = 44; bladder cancer and n = 21; control), using the reflection mode (ATR) of FTIR spectroscopy by a different operator. The results revealed significant alterations in moleculer content in the cancer group. Based on the spectral differences, using transmittance FTIR spectroscopy coupled with chemometrics, the diseased group was successfully differentiated from the control. When only carcinoma group was taken into consideration a sensitivity value of 100% was achieved. Similar results were also obtained by ATR-FTIR spectroscopy. This study shows the power of infrared spectroscopy in the diagnosis of bladder cancer.

  12. Language skills in a child with Leber hereditary optic neuropathy following intrathecal chemotherapy for acute lymphoblastic leukemia.

    Science.gov (United States)

    Lewis, Fiona M; Coman, David J; Murdoch, Bruce E

    2010-11-01

    The language skills of a male child with Leber hereditary optic neuropathy (LHON) and coincidentally treated for acute lymphoblastic leukemia (ALL) with intrathecal chemotherapy at the age of 3 years 8 months were comprehensively evaluated twice over a 6-month period approximately 5½ years after diagnosis of ALL. Despite marked chemotherapy-related leukoencephalopathic changes documented on magnetic resonance imaging, the child presented with stable language skills, which were generally average to above-average based on the normative data from a comprehensive language test battery. In light of the coincidental presentation in the child of a diagnosis of LHON, which may lead to serious vision impairment and increased vulnerability to drug neurotoxicity, coupled with a history of central nervous system (CNS)-directed treatment for ALL resulting in progressive white matter pathology, the study highlights the importance of ongoing monitoring of the child's language development throughout his adolescent years.

  13. Targeted Resequencing of 9p in Acute Lymphoblastic Leukemia Yields Concordant Results with Array CGH and Reveals Novel Genomic Alterations

    NARCIS (Netherlands)

    Sarhadi, V.K.; Lahti, L.M.; Scheinin, I.; Tyybäkinoja, A.; Savola, S.; Usvasalo, A.; Räty, R.; Elonen, E.; Saarinen-Pihkala, U.M.; Knuutila, S.

    2013-01-01

    Genetic alterations of the short arm of chromosome 9 are frequent in acute lymphoblastic leukemia. We performed targeted sequencing of 9p region in 35 adolescent and adult acute lymphoblastic leukemia patients and sought to investigate the sensitivity of detecting copy number alterations in comparis

  14. The use of optical microscope equipped with multispectral detector to distinguish different types of acute lymphoblastic leukemia

    Science.gov (United States)

    Pronichev, A. N.; Polyakov, E. V.; Tupitsyn, N. N.; Frenkel, M. A.; Mozhenkova, A. V.

    2017-01-01

    The article describes the use of a computer optical microscopy with multispectral camera to characterize the texture of blasts bone marrow of patients with different variants of acute lymphoblastic leukemia: B- and T- types. Specific characteristics of the chromatin of the nuclei of blasts for different types of acute lymphoblastic leukemia were obtained.

  15. Time trends in the incidence of acute lymphoblastic leukemia among children 1976-2002: a population-based Nordic study

    DEFF Research Database (Denmark)

    Svendsen, Anne Louise; Feychting, Maria; Klaeboe, Lars

    2007-01-01

    We studied the incidence of childhood acute lymphoblastic leukemia in Denmark, Finland, Norway, and Sweden during 1976-2002, on the basis of data from national cancer registries. The incidence of acute lymphoblastic leukemia increased with the calendar period until 1983, and with the birth cohort...

  16. Assessing Compliance With Mercaptopurine Treatment in Younger Patients With Acute Lymphoblastic Leukemia in First Remission | Division of Cancer Prevention

    Science.gov (United States)

    This randomized phase III trial studies compliance to a mercaptopurine treatment intervention compared to standard of care in younger patients with acute lymphoblastic leukemia in remission. Assessing ways to help patients who have acute lymphoblastic leukemia to take their medications as prescribed may help them in taking their medications more consistently and may improve treatment outcomes. |

  17. Miniaturization of cytotoxicity tests for concentration range-finding studies prior to conducting the pH 6.7 Syrian hamster embryo cell-transformation assay.

    Science.gov (United States)

    Plöttner, Sabine; Käfferlein, Heiko U; Brüning, Thomas

    2013-08-15

    The Syrian hamster embryo (SHE) cell-transformation assay (SHE assay) is a promising alternative method to animal testing for the identification of potential carcinogens in vitro. Prior to conducting the SHE assay the appropriate concentration range for each test chemical must be established, with a maximum concentration causing approximately 50% cytotoxicity. Concentration range-finding is done in separate experiments, which are similar to the final SHE assay but with less replicates and more concentrations. Here we present an alternative for the cytotoxicity testing by miniaturization of the test procedure by use of 24-well plates and surpluses from feeder-cell preparations as target cells. In addition, we integrated the photometry-based neutral red (NR) assay. For validation of the assay, incubations with dimethyl sulf-oxide, p-phenylenediamine-2HCl, aniline, o-toluidine-HCl, 2,4-diaminotoluene, and 2-naphthylamine were carried out in the miniaturized approach and compared with the standard procedure in terms of calculating the relative plating efficiencies (RPEs). To directly compare both methods, concentrations that produced 50% cytotoxicity (IC50) were calculated. Excellent associations were observed between the number of colonies and NR uptake. For all test substances a concentration-dependent, concomitant decrease of NR uptake in the miniaturized approach and RPEs in the standard test was observed after a 7-day incubation. The results from both test setups showed a comparable order of magnitude and the IC50 values differed by a factor cytotoxicity testing in the SHE assay, as it saves valuable SHE cells and speeds-up the time, to obtain test results more rapidly. Copyright © 2013 Elsevier B.V. All rights reserved.

  18. Epidemiologic study on survival of chronic myeloid leukemia and Ph(+) acute lymphoblastic leukemia patients with BCR-ABL T315I mutation

    DEFF Research Database (Denmark)

    Nicolini, Franck E; Mauro, Michael J; Martinelli, Giovanni

    2009-01-01

    ), or blastic-phase (BP) and Philadelphia chromosome-positive (Ph)(+) acute lymphoblastic leukemia (ALL) patients with T315I mutation. Medical records of 222 patients from 9 countries were reviewed; data were analyzed using log-rank tests and Cox proportional hazard models. Median age at T315I mutation......The BCR-ABL T315I mutation represents a major mechanism of resistance to tyrosine kinase inhibitors (TKIs). The objectives of this retrospective observational study were to estimate overall and progression-free survival for chronic myeloid leukemia in chronic-phase (CP), accelerated-phase (AP...

  19. ETV6-RUNX1 (+) Acute Lymphoblastic Leukaemia in Identical Twins.

    Science.gov (United States)

    Ford, Anthony M; Greaves, Mel

    2017-01-01

    Acute leukaemia is the major subtype of paediatric cancer with a cumulative risk of 1 in 2000 for children up to the age of 15 years. Childhood acute lymphoblastic leukaemia (ALL) is a biologically and clinically diverse disease with distinctive subtypes; multiple chromosomal translocations exist within the subtypes and each carries its own prognostic relevance. The most common chromosome translocation observed is the t(12;21) that results in an in-frame fusion between the first five exons of ETV6 (TEL) and almost the entire coding region of RUNX1 (AML1).The natural history of childhood ALL is almost entirely clinically silent and is well advanced at the point of diagnosis. It has, however, been possible to backtrack this process through molecular analysis of appropriate clinical samples: (i) leukaemic clones in monozygotic twins that are either concordant or discordant for ALL; (ii) archived neonatal blood spots or Guthrie cards from individuals who later developed leukaemia; and (iii) stored, viable cord blood cells.Here, we outline our studies on the aetiology and pathology of childhood ALL that provide molecular evidence for a monoclonal, prenatal origin of ETV6-RUNX1+ leukaemia in monozygotic identical twins. We provide mechanistic support for the concept that altered patterns of infection during early childhood can deliver the necessary promotional drive for the progression of ETV6-RUNX1+ pre-leukaemic cells into a postnatal overt leukaemia.

  20. Runx1 deficiency predisposes mice to T-lymphoblastic lymphoma

    Science.gov (United States)

    Kundu, Mondira; Compton, Sheila; Garrett-Beal, Lisa; Stacy, Terryl; Starost, Matthew F.; Eckhaus, Michael; Speck, Nancy A.; Liu, P. Paul

    2005-01-01

    Chromosomal rearrangements affecting RUNX1 and CBFB are common in acute leukemias. These mutations result in the expression of fusion proteins that act dominant-negatively to suppress the normal function of the Runt-related transcription factor 1 (RUNX)/core binding factor β (CBFβ) complexes. In addition, loss-of-function mutations in Runt-related transcription factor 1 (RUNX1) have been identified in sporadic cases of acute myeloid leukemia (AML) and in association with the familial platelet disorder with propensity to develop AML (FPD/AML). In order to examine the hypothesis that decreased gene dosage of RUNX1 may be a critical event in the development of leukemia, we treated chimeric mice generated from Runx1lacZ/lacZ embryonic stem (ES) cells that have homozygous disruption of the Runx1 gene with N-ethyl-N-nitrosourea (ENU). We observed an increased incidence of T-lymphoblastic lymphoma in Runx1lacZ/lacZ compared with wild-type chimeras and confirmed that the tumors were of ES-cell origin. Our results therefore suggest that deficiency of Runx1 can indeed predispose mice to hematopoietic malignancies. PMID:16051740

  1. The mystery of electroencephalography in acute lymphoblastic leukemia.

    Science.gov (United States)

    Goldberg-Stern, Hadassa; Cohen, Rony; Pollak, Lea; Kivity, Sara; Eidlitz-Markus, Tal; Stark, Batya; Yaniv, Isaac; Shuper, Avinoam

    2011-04-01

    The aim of the study was to evaluate changes in electroencephalogram (EEG) recordings during the course of acute lymphoblastic leukemia (ALL) in children. The study group consisted of 48 children with ALL who underwent a total of 72 EEGs at various stages of the disease. The medical files were reviewed for pertinent clinical data, and the EEGs were evaluated for changes in brain activity. Abnormal background activity was noted in 52.2% of the EEGs done at 1-10 days of therapy, in 43.5% of those done at 10-60 days, and only 4.3% of those done at later stages (p=0.037). These findings, together with earlier reports, suggest that early-stage ALL, even before treatment, may be associated with excessive slow EEG activity, which improves over time. The EEG changes, by themselves, are not an indication of central nervous system leukemia or a predictor of later seizures or other central nervous system involvement.

  2. Management of Philadelphia chromosome-positive acute lymphoblastic leukemia.

    Science.gov (United States)

    Ottmann, O G

    2012-08-01

    Tyrosine kinase inhibitors (TKIs) directed against the ABL kinase are now used routinely during frontline therapy for Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) and result in hematologic remission rates exceeding 90%. Minimal residual disease levels are generally lower when TKIs are used in combination with chemotherapy rather than as monotherapy. Although outcome has improved substantially with TKI-based regimens compared with historic controls, allogeneic stem cell transplantation (SCT) in first remission provides the best chance of cure for the majority of patients eligible for SCT. Administration of imatinib after SCT further reduces molecular recurrence and is associated with greatly improved relapse-free and overall survival. The high relapse rate in non-transplanted patients is largely attributable to the emergence of leukemic clones with mutations in the tyrosine kinase domain of BCR-ABL. Ongoing studies with newer TKIs will determine whether these more potent agents are able to sustain remissions without SCT. Assessment of minimal residual disease has become an integral part of the management of Ph+ALL, as it has prognostic importance and is used to guide therapeutic intervention. Novel immunotherapeutic interventions and combinations of TKIs are currently being investigated in clinical trials and may further improve the prognosis of patients with Ph+ALL.

  3. Acute Lymphoblastic Leukemia with Eosinophilia and Strongyloides Stercoralis Hyperinfection

    Directory of Open Access Journals (Sweden)

    Yadollah Zahedpasha

    2011-12-01

    Full Text Available Background: Acute lymphoblastic leukemia (ALL is the most common malignancy in children. Bone pain is an important symptom that can be severe. Eosinophilia without any other abnormal laboratory findings is rare in ALL. Strongyloides stercoralis in ALL causes disseminated fatal disease.Case Presentation: This 9-year-old girl presented with bone pain in lumbar region. Bone pain was the only symptom. The patient didnt have organomegaly. The BM samples were studied by flow cytometry, which showed pre-B cell ALL. Larva of Strongyloides stercoralis was found in fecal examination. Plain chest x ray showed bilateral para-cardiac infiltration. Strongyloidiasis was treated before starting chemotherapy. After two days treatment with Mebendazol the patient developed cough, dyspnea, respiratory distress and fever. The treatment changed to Ivermectin for 2 days. Chemotherapy started five days after diagnosis of leukemia.Conclusion: The patient complained merely of bone pain in lumbar region without any other signs and symptoms. Peripheral blood smear showed eosinophilia without any other abnormality. Stool examination showed Strongyloides stercoralis larvae. We suggest that all patients diagnosed as ALL in tropical and subtropical regions should be evaluated for parasitic infection especially with Strongyloides stercoralis.

  4. Vincristine sulfate liposomal injection for acute lymphoblastic leukemia.

    Science.gov (United States)

    Raj, Trisha A Soosay; Smith, Amanda M; Moore, Andrew S

    2013-01-01

    Vincristine (VCR) is one of the most extensively used cytotoxic compounds in hemato-oncology. VCR is particularly important for the treatment of acute lymphoblastic leukemia (ALL), a disease that accounts for approximately one-third of all childhood cancer diagnoses. VCR's full therapeutic potential has been limited by dose-limiting neurotoxicity, classically resulting in autonomic and peripheral sensory-motor neuropathy. In the last decade, however, the discovery that liposomal encapsulation of chemotherapeutics can modulate the pharmacokinetic characteristics of a compound has stimulated much interest in liposomal VCR (vincristine sulfate liposomal injection [VSLI]) formulations for the treatment of ALL and other hematological malignancies. Promising data from recent clinical trials investigating VSLI in adults with ALL resulted in US Food and Drug Administration approval for use in patients with Philadelphia chromosome (t[9;22]/BCR-ABL1) (Ph)-negative (Ph-) disease. Additional clinical trials of VSLI in adults and children with both Ph-positive (Ph+) and Ph- ALL are ongoing. Here we review the preclinical and clinical experience to date with VSLI for ALL.

  5. Transplant Outcomes for Children with Hypodiploid Acute Lymphoblastic Leukemia

    Science.gov (United States)

    Mehta, Parinda A.; Zhang, Mei-Jie; Eapen, Mary; He, Wensheng; Seber, Adriana; Gibson, Brenda; Camitta, Bruce M.; Kitko, Carrie L.; Dvorak, Christopher C.; Nemecek, Eneida R.; Frangoul, Haydar A.; Abdel-Azim, Hisham; Kasow, Kimberly A.; Lehmann, Leslie; Vicent, Marta Gonzalez; Diaz Pérez, Miguel A.; Ayas, Mouhab; Qayed, Muna; Carpenter, Paul A.; Jodele, Sonata; Lund, Troy C.; Leung, Wing H.; Davies, Stella M.

    2015-01-01

    Children with hypodiploid acute lymphoblastic leukemia (ALL) have inferior outcomes despite intensive risk adapted chemotherapy regimens. We describe 78 children with hypodiploid ALL who underwent hematopoietic stem cell transplant (HSCT) between 1990 and 2010. Thirty nine (50%) patients had ≤ 43 chromosomes, 12 (15%) had 44 chromosomes and 27 (35%) had 45 chromosomes. Forty three (55%) patients were transplanted in first remission (CR1) while 35 (45%) were transplanted in ≥CR2. Twenty nine patients (37%) received a graft from a related donor and 49 (63%) from an unrelated donor. All patients received a myeloablative conditioning regimen. The 5-year probabilities of leukemia-free survival (LFS), overall survival (OS), relapse, and treatment related mortality (TRM) for the entire cohort were 51%, 56%, 27% and 22% respectively. Multivariate analysis confirmed that mortality risks were higher for patients transplanted in CR2 (HR 2.16, p=0.05), with chromosome number ≤43 (HR 2.15, p=0.05) and for those transplanted in the first decade of the study period (HR 2.60, p=0.01). Similarly, treatment failure risks were higher with chromosome number ≤43 (HR 2.28, p=0.04) and the earlier transplant period (HR 2.51, p=0.01). Although survival is better with advances in donor selection and supportive care, disease-related risk factors significantly influence transplantation outcomes. PMID:25865650

  6. Molecular mechanisms involved in chemoresistance in paediatric acute lymphoblastic leukaemia

    Directory of Open Access Journals (Sweden)

    Stanković Tatjana

    2008-01-01

    Full Text Available Acute lymphoblastic leukaemia (ALL is the most common paediatric cancer. Despite cure rates approaching 80%, resistance to treatment and disease relapse remain a significant clinical problem. Identification of the genes and biological pathways responsible for chemoresistance is therefore crucial for the design of novel therapeutic approaches aiming to improve patient survival. Mutations in the membrane transporter P-glycoprotein genes, genetic variations in drug-metabolising enzymes and defects in apoptotic pathways are mechanisms of chemoresistance common to a wide spectrum of cancers and also play a role in paediatric ALL. In addition, several recent microarray studies have identified transcriptional profiles specifically associated with chemoresistance and pointed to a number of potentially novel therapeutic targets. These microarray studies have shown that genes discriminating between clinically responsive and resistant leukaemias tend to be involved in cellular processes such as regulation of cell cycle, proliferation, and DNA repair. Here we review the outcomes of these microarray studies and also present our own investigations into apoptotic resistance to DNA double strand breaks (DSBs in paediatric ALL. We present stratification of paediatric ALL by the profile of DNA damage response following ionising radiation (IR in vitro. This approach allows classification of ALL tumours at presentation into IR-apoptotic sensitive and IR-apoptotic resistant. Furthermore, apoptotic resistant leukaemias exhibit abnormal response of NFkB pathway following irradiation and inhibition of this pathway can sensitise leukaemic cells to IR-induced DSBs.

  7. Infant acute lymphoblastic leukemia: a 20-year children's hospital experience.

    Science.gov (United States)

    Murray, Rebecca A F; Thom, Giddel; Gardner, Renee V; Craver, Randall D

    2008-01-01

    We reviewed our 20-year experience with infant acute lymphoblastic leukemia (ALL). Nine infants (4.2% of all ALL) were identified; all were < 6 months of age. White blood cell counts ranged from 42,000-1.6 million/microL, 6 of 8 had hepatosplenomegaly, and 6 of 9 (66.6%) had central nervous system disease. Of 7 with cytogenetic information, 6 (85.7%) had diploidy; the remaining child was 47, XY,+8,del(21)(q22). Four had the MLL-11q23 abnormality. All received chemotherapy. Four underwent stem cell transplantation. Survival was 67%, (15 months-21 years). Deaths occurred at 9 months, 15 months (graft vs. host), and 7 years (complications of small bowel transplantation). Only 1 undergoing stem cell transplantation died. There were no late recurrences or second malignancies. Despite extensive disease and age < 6 months at diagnosis (a poor prognostic feature), for ALL patients our 67% survival is at least as good as reported, although it is less favorable than childhood ALL.

  8. The genomic landscape of hypodiploid acute lymphoblastic leukemia.

    Science.gov (United States)

    Holmfeldt, Linda; Wei, Lei; Diaz-Flores, Ernesto; Walsh, Michael; Zhang, Jinghui; Ding, Li; Payne-Turner, Debbie; Churchman, Michelle; Andersson, Anna; Chen, Shann-Ching; McCastlain, Kelly; Becksfort, Jared; Ma, Jing; Wu, Gang; Patel, Samir N; Heatley, Susan L; Phillips, Letha A; Song, Guangchun; Easton, John; Parker, Matthew; Chen, Xiang; Rusch, Michael; Boggs, Kristy; Vadodaria, Bhavin; Hedlund, Erin; Drenberg, Christina; Baker, Sharyn; Pei, Deqing; Cheng, Cheng; Huether, Robert; Lu, Charles; Fulton, Robert S; Fulton, Lucinda L; Tabib, Yashodhan; Dooling, David J; Ochoa, Kerri; Minden, Mark; Lewis, Ian D; To, L Bik; Marlton, Paula; Roberts, Andrew W; Raca, Gordana; Stock, Wendy; Neale, Geoffrey; Drexler, Hans G; Dickins, Ross A; Ellison, David W; Shurtleff, Sheila A; Pui, Ching-Hon; Ribeiro, Raul C; Devidas, Meenakshi; Carroll, Andrew J; Heerema, Nyla A; Wood, Brent; Borowitz, Michael J; Gastier-Foster, Julie M; Raimondi, Susana C; Mardis, Elaine R; Wilson, Richard K; Downing, James R; Hunger, Stephen P; Loh, Mignon L; Mullighan, Charles G

    2013-03-01

    The genetic basis of hypodiploid acute lymphoblastic leukemia (ALL), a subtype of ALL characterized by aneuploidy and poor outcome, is unknown. Genomic profiling of 124 hypodiploid ALL cases, including whole-genome and exome sequencing of 40 cases, identified two subtypes that differ in the severity of aneuploidy, transcriptional profiles and submicroscopic genetic alterations. Near-haploid ALL with 24-31 chromosomes harbor alterations targeting receptor tyrosine kinase signaling and Ras signaling (71%) and the lymphoid transcription factor gene IKZF3 (encoding AIOLOS; 13%). In contrast, low-hypodiploid ALL with 32-39 chromosomes are characterized by alterations in TP53 (91.2%) that are commonly present in nontumor cells, IKZF2 (encoding HELIOS; 53%) and RB1 (41%). Both near-haploid and low-hypodiploid leukemic cells show activation of Ras-signaling and phosphoinositide 3-kinase (PI3K)-signaling pathways and are sensitive to PI3K inhibitors, indicating that these drugs should be explored as a new therapeutic strategy for this aggressive form of leukemia.

  9. Suppressed neutrophil function in children with acute lymphoblastic leukemia.

    Science.gov (United States)

    Tanaka, Fumiko; Goto, Hiroaki; Yokosuka, Tomoko; Yanagimachi, Masakatsu; Kajiwara, Ryosuke; Naruto, Takuya; Nishimaki, Shigeru; Yokota, Shumpei

    2009-10-01

    Infection is a major obstacle in cancer chemotherapy. Neutropenia has been considered to be the most important risk factor for severe infection; however, other factors, such as impaired neutrophil function, may be involved in susceptibility to infection in patients undergoing chemotherapy. In this study, we analyzed neutrophil function in children with acute lymphoblastic leukemia (ALL). Whole blood samples were obtained from 16 children with ALL at diagnosis, after induction chemotherapy, and after consolidation chemotherapy. Oxidative burst and phagocytic activity of neutrophils were analyzed by flow cytometry. Oxidative burst of neutrophils was impaired in ALL patients. The percentage of neutrophils with normal oxidative burst after PMA stimulation was 59.0 +/- 13.2 or 70.0 +/- 21.0% at diagnosis or after induction chemotherapy, respectively, which was significantly lower compared with 93.8 +/- 6.1% in healthy control subjects (P = 0.00004, or 0.002, respectively); however, this value was normal after consolidation chemotherapy. No significant differences were noted in phagocytic activity in children with ALL compared with healthy control subjects. Impaired oxidative burst of neutrophils may be one risk factor for infections in children with ALL, especially in the initial periods of treatment.

  10. Is this acute lymphoblastic leukaemia or juvenile rheumatoid arthritis.

    Science.gov (United States)

    Kirubakaran, Chellam; Scott, Julius Xavier; Ebenezer, Sam

    2011-08-01

    Arthritis could be a presenting feature of acute lymphoblastic leukaemia (ALL) and could be wrongly diagnosed as juvenile rheumatoid arthritis (JRA). Clinical and laboratory parameters might differentiate ALL and JRA in children who present with arthritis. Out of a total of 250 children of ALL, 10 were referred to the department of child health and paediatric haemato-oncology of Christian Medical College, Vellore during 1990-2002. They were compared with 10 age-matched children who had systematic onset of JRA. The age groups in ALL and JRA were 6.05 +/- 2.45 years and 5.47 +/- 4.4 years respectively. Severe pain as evidenced by inability to walk was found in children but one child with JRA was unable to walk (p JRA group. ESR was elevated in all cases in both the groups. One case in each group had antinuclear antibody positivity. It can be concluded that ALL can masquerade as systematic onset of JRA. So paediatricians should be careful enough while diagnosing the disease process.

  11. TREATMENT OF ADOLESCENT AND YOUNG ADULTS WITH ACUTE LYMPHOBLASTIC LEUKEMIA

    Directory of Open Access Journals (Sweden)

    Josep-Maria Ribera

    2014-07-01

    Full Text Available The primary objective of this review was to update and discuss the current concepts andthe results of the treatment of acute lymphoblastic leukemia (ALL in adolescents and young adults(AYA. After a brief consideration of the epidemiologic and clinicobiologic characteristics of ALLin the AYA population, the main retrospective comparative studies stating the superiority ofpediatric over adult-based protocols were reviewed. The most important prospective studies inyoung adults using pediatric inspired or pediatric unmodified protocols were also reviewedemphasizing their feasibility at least up to the age of 40 yr and their promising results, with eventfreesurvival rates of 60-65% or greater. Results of trials from pediatric groups have shown that theunfavourable prognosis of adolescents is no more adequate. The majority of the older adolescentswith ALL can be cured with risk-adjusted and minimal residual disease-guided intensivechemotherapy, without stem cell transplantation. However, some specific subgroups, which aremore frequent in adolescents than in children (e.g., early pre-T, iAMP21, and BCR-ABL-like,deserve particular attention. In summary, the advances in treatment of ALL in adolescents havebeen translated to young adults, and that explains the significant improvement in survival of thesepatients in recent years.

  12. A 50-Year Journey to Cure Childhood Acute Lymphoblastic Leukemia

    Science.gov (United States)

    Pui, Ching-Hon; Evans, William E.

    2013-01-01

    The 50th anniversary of Seminars in Hematology coincides with the 50th of St. Jude Children’s Research Hospital, and both milestones are inexorably linked to studies contributing to the cure of childhood acute lymphoblastic leukemia (ALL). We thought it fitting, therefore, to mark these events by traveling back in time to point out some of the achievements, institutions, study groups and individuals that have made cure of childhood ALL a reality. In many instances, progress was driven by new ideas, while in others it was driven by new experimental tools that allowed more precise assessment of the biology of leukemic blasts and their utility in selecting therapy. We also discuss a number of contemporary advances that point the way to exciting future directions. Whatever pathways are taken, a clear challenge will be to use emerging genome-based or immunologic-based treatment options in ways that will enhance, rather than duplicate or compromise, recent gains in outcome with classic cytotoxic chemotherapy. The theme of this journey serves as a reminder of the chief ingredient of any research directed to a catastrophic disease such as ALL. It is the audacity of a small group of investigators who confronted a childhood cancer with the goal of cure, not palliation, as their mindset. PMID:23953334

  13. Invasive Pulmonary Aspergillosis in a Patient with Acute Lymphoblastic Leukemia

    Directory of Open Access Journals (Sweden)

    Orhan Ayyıldız

    2004-01-01

    Full Text Available Fungal infections are common and life-threatening among immunosupressive patients.Invasive pulmonar aspergilloz (IPA generally occurs when Aspergillus inhaled, but rarelywith the hematogen spread of dermal or gastrointestinal Aspergillus. We present here, IPA ina 58 year-old male patient with acute lymphoblastic leukemia (ALL. He was admitted to ourclinic with fatigue, weakness, pansitopenia, and with petechia. Supportive treatment,vincristine and prednisone was initiated. Chest roentgenogram was normal. Dyspnea andfever (39.5’C were seen after 1 month of therapy. Thorax high resolution computerizedtomography was obtained and cavitary lesion was seen in the left upper-anterior segment oflung. Sputum and blood culture were negative. In spite of the empiric use of Meropenem 3gr/d, Vancomycin 2 gr/d and fluconazole 200 mg/d, fever was not turned to normal andclinical symptoms were not healed. On the fifth days of therapy amphotericin-B was initiatedand the other antibiotics were stopped after 3 days. General symptoms were healed on the 8thdays. Radiologic findings were improved partially after 20 days. The patient clinically is welland remains in remission and radiologic findings were turn to near normal after 10 monthsof treatment. We aimed to emphasis about treatment of empirical Amphotericin-B incritically ill patient with ALL.

  14. Unilateral Exudative Retinal Detachment as the Sole Presentation of Relapsing Acute Lymphoblastic Leukemia

    Directory of Open Access Journals (Sweden)

    Fatih Mehmet Azık

    2012-06-01

    Full Text Available Ocular findings are rarely the initial symptom of leukemia, although up to 90% of all leukemia patients have fundus changes during the course of the disease. Herein we report a relapsing acute lymphoblastic leukemia patient with the sole presentation of sudden visual loss and exudative retinal detachment. An 8-year-old boy with acute lymphoblastic leukemia developed sudden visual loss during his first remission period. Bullous retinal detachment with total afferent pupillary defect was observed. Orbital magnetic resonance imaging revealed an intraocular mass lesion; simultaneously obtained bone marrow and cerebrospinal fluid samples showed no evidence of leukemic cells. Following local irradiation, and systemic and intrathecal chemotherapy the mass disappeared. Local irradiation, and systemic and intrathecal chemotherapy effectively controlled the isolated ocular relapse of acute lymphoblastic leukemia and eliminated the need for enucleation.

  15. Consensus definitions of 14 severe acute toxic effects for childhood lymphoblastic leukaemia treatment

    DEFF Research Database (Denmark)

    Schmiegelow, Kjeld; Attarbaschi, Andishe; Barzilai, Shlomit

    2016-01-01

    Although there are high survival rates for children with acute lymphoblastic leukaemia, their outcome is often counterbalanced by the burden of toxic effects. This is because reported frequencies vary widely across studies, partly because of diverse definitions of toxic effects. Using the Delphi...... method, 15 international childhood acute lymphoblastic leukaemia study groups assessed acute lymphoblastic leukaemia protocols to address toxic effects that were to be considered by the Ponte di Legno working group. 14 acute toxic effects (hypersensitivity to asparaginase, hyperlipidaemia, osteonecrosis......, thromboembolism, and Pneumocystis jirovecii pneumonia) that are serious but too rare to be addressed comprehensively within any single group, or are deemed to need consensus definitions for reliable incidence comparisons, were selected for assessment. Our results showed that none of the protocols addressed all 14...

  16. The importance of immunophenotyping by flow cytometry in distinction between hematogones and B lymphoblasts

    Directory of Open Access Journals (Sweden)

    Aline B. Wohlfahrt

    2015-02-01

    Full Text Available Hematogones are normal B-lineage lymphoid precursors in the bone marrow. B lymphoblasts are immature neoplastic cells present in patients with precursor B-cell acute lymphoblastic leukemia (B-ALL. Hematogones and B lymphoblasts share characteristics, such as morphological similarity often indistinct and expression of the same antigens in immunophenotypic analysis. Increased numbers of hematogones in patients with B-ALL during regeneration of bone marrow after treatment for leukemia, in cases of disease relapse or marrow transplantation, may be subject to questions about the nature and prognosis of this immature cell. This article presents information about the morphological and immunophenotypic characteristics of B lymphoid precursors and verifies the relevance of immunophenotyping by flow cytometry (FC in the distinction between those cells. This differentiation is essential to establish a correct prognosis and assist in medical decision about the most appropriate therapeutic scheme.

  17. Integral transformational coaching

    NARCIS (Netherlands)

    Keizer, W.A.J.; Nandram, S.S.

    2009-01-01

    In Chap. 12, Keizer and Nandram present the concept of Integral Transformational Coaching based on the concept of Flow and its effects on work performance. Integral Transformational Coaching is a method that prevents and cures unhealthy stress and burnout. They draw on some tried and tested spiritua

  18. Integral transformational coaching

    NARCIS (Netherlands)

    Keizer, W.A.J.; Nandram, S.S.

    2009-01-01

    In Chap. 12, Keizer and Nandram present the concept of Integral Transformational Coaching based on the concept of Flow and its effects on work performance. Integral Transformational Coaching is a method that prevents and cures unhealthy stress and burnout. They draw on some tried and tested

  19. The amoeba-to-flagellate transformation test is not reliable for the diagnosis of the genus Naegleria. Description of three new Naegleria spp.

    Science.gov (United States)

    De Jonckheere, J F; Brown, S; Dobson, P J; Robinson, B S; Pernin, P

    2001-07-01

    Trophozoites of several isolates from one location in Australia have failed consistently to transform into flagellates, although they display all other characteristics of the genus Naegleria. When changing the standard transformation test, flagellates were produced. In phylogenetic trees derived from partial small subunit ribosomal DNA (SSUrDNA) sequences, one of these strains branches close to a cluster comprising N. clarki, N. australiensis, N. italica and N. jadini. It is proposed that these Australian isolates represent a new species, named N. fultoni (strain NG885). Failing to form flagellates since their isolation, even when different transformation procedures are used, are two Naegleria strains from Chile and Indonesia. In SSUrDNA-based phylogenetic trees the Chilean strain clusters with N. pussardi and the Indonesian strain clusters with N. galeacystis, but the degree of sequence difference from these described species (3.5% and 2.2%, respectively) is sufficient to propose that both of the strains represent new species, named N. chilensis (strain NG946) and N. indonesiensis (strain NG945), respectively. The close relationships between each of the new species and the Naegleria species with which they cluster in SSUrDNA-based trees were confirmed by ribosomal internal transcribed spacer region (ITS) sequence comparisons. In France, several non-flagellating N. fowleri strains were isolated from one location. ITS rDNA sequence comparisons indicated that they correspond to a 'type' of N. fowleri found in both Europe and the USA. A redefinition of the genus Naegleria is proposed as a consequence of these and previous findings.

  20. Test up to 80 kA of an Al-Stabilized NbTi Cable With the Upgraded Saclay Superconducting Transformer

    CERN Document Server

    Berriaud, C; Donati, A; Gharib, A; Peiro, G; Willering, G

    2014-01-01

    An ATLAS Barrel Toroid conductor was tested in the Saclay High Current Test Facility. The conductor is a Nb-Ti Rutherford cable imbedded in a high purity aluminum stabilizer. The conductor's width was reduced from 57 mm to 30 mm in order to be able to use an existing sample holder. We tried to measure the critical current in background fields of up to 3 T. The field was produced by a 0.8 m long superconducting dipole magnet. The test station was equipped with a superconducting transformer transferring maximum primary and secondary currents of respectively 174 A and 80 kA. The secondary current was measured with flux coils and with a superconducting Direct Control Current Transducer (DCCT), a modified version of the ``Macc+{''} 600 A commercial DCCT from Hitec, which was operated at currents of up to 57 kA. This paper reports on the performance of the test station, on the results of the quench current measurements performed on the stabilized ATLAS conductor and on the difficulties to measure the critical curre...

  1. Thinking about Transformer Water Spray System Test%变压器水喷雾系统试验的思考

    Institute of Scientific and Technical Information of China (English)

    赵国刚; 王强

    2012-01-01

    Transformer water spray system has protective functions toward the transformer including: fire-fighting, fire-suppression, preventing fire from spreading, prevention of fire, etc. Starting from the importance of water spray system test, and combining with the practical experiences, this article analyses, thinks, puts forward problems and gives concrete measurements toward the following three fields of launch conditions, fire pipes, and water from fire service.%变压器水喷雾系统对变压器的防护能起到灭火、抑制火灾、防止火灾蔓延、预防着火的作用。从水喷雾系统试验的重要性着手,结合实际经验,从启动条件、消防管道、消防用水三方面进行分析、思考,提出问题,并给出具体的措施。

  2. Acute lymphoblastic leukemia | EU Clinical Trials Register [EU Clinical Trials Register

    Lifescience Database Archive (English)

    Full Text Available of the trial TropicALL study; Thromboprophylaxis in Children treated for Acute Lymphoblastic Leukemia with L...oprofylaxe in kinderen behandeld voor Acute lymfatische leukemie met laag-moleculair-gewicht heparine: een g...dition or disease under investigation E.1.1Medical condition(s) being investigated Acute lymphoblastic leukemia Acute... Medical condition or disease under investigation E.1.2Version 17.1 E.1.2Level LLT E.1.2Classification code 10000845 E.1.2Term Acute

  3. UNUSUAL CLINICAL PRESENTATION OF RELAPSE IN PATIENT WITH ACUTE LYMPHOBLASTIC LEUKEMIA.

    Directory of Open Access Journals (Sweden)

    Vanya Slavcheva

    2015-04-01

    Full Text Available Acute lymphoblastic leukemia is a disease, which is more common in children. We report a clinical case of a patient aged 25. Thirty-two months before his last admission in Hematology clinic, acute pre- B lymphoblastic leukemia had been diagnosed and treated till March 2012. In September 2013 after bone marrow aspiration, flow cytometric analysis, trepan biopsy and biopsy of the kidney had been carried out, the patient was diagnosed with first late relapse, involving bone marrow and kidney. A second remission was achieved using Berlin- Frankfurt– Munster chemotherapy [BFM] and allogenic stem cell transplantation was performed.

  4. Aplastic anaemia preceding acute lymphoblastic leukaemia in an adult with isolated deletion of chromosome 9q.

    LENUS (Irish Health Repository)

    Kelly, Kevin

    2008-12-01

    Aplastic anaemia (AA) can precede acute lymphoblastic leukaemia (ALL) in 2% of children but this is rarely reported to occur in adults. A 21-year-old male presented with bone marrow failure and bone marrow biopsy showed a profoundly hypocellular marrow. He recovered spontaneously but represented 2 months later when he was diagnosed with pre-B acute lymphoblastic leukaemia. Chromosomal examination revealed 46,XY,del(9)(q13q34). To the best of our knowledge this is the first case to be reported of aplasia preceding ALL with 9q minus as the sole chromosomal abnormality.

  5. Primary lymphoblastic B-cell lymphoma of the stomach: A case report

    Institute of Scientific and Technical Information of China (English)

    Miao-Xia He; Ming-Hua Zhu; Wei-Qiang Liu; Li-Li Wu; Xiong-Zeng Zhu

    2008-01-01

    Primary stomach lymphoblastic B-cell lymphoma (B-LBL) is a rare tumor. We describe a primary stomach B-LBL in a 38 years old female who presented with nonspecific complaints of fatigue and vomiting for 2 mo.Gastrofiberscopy revealed a large gastric ulcer, which was successfully resected. Pathology showed a lymphoblastic cell lymphoma arising from the stomach, and there was no evidence of disease at any extrastomach site.Immunohistochemical staining and gene rearrangement studies supported that the stomach tumor was a clonal B-cell lymphoma. Therefore, the diagnosis of B-LBL was made based on the stomach specimen.

  6. Cytosine arabinoside-metabolizing enzyme genes are underexpressed in children with MLL gene-rearranged acute lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    J.F. Mata

    2006-11-01

    Full Text Available Infant acute lymphoblastic leukemia (IALL is characterized by mixed lineage leukemia (MLL gene rearrangements, unique gene expression profiles, poor prognosis, and drug resistance. One exception is cytosine arabinoside (Ara-C to which IALL cells seem to be more sensitive. We quantified mRNA expression of Ara-C key enzymes in leukemic lymphoblasts from 64 Brazilian ALL children, 15 of them presenting MLL gene rearrangement, and correlated it with clinical and biological features. The diagnosis was based on morphological criteria and immunophenotyping using monoclonal antibodies. MLL gene rearrangements were detected by conventional cytogenetic analysis, RT-PCR and/or fluorescence in situ hybridization. The DCK and HENT1 expression levels were determined by real-time quantitative PCR using SYBR Green I. Relative quantification was made by the standard curve method. The results were analyzed by Mann-Whitney and Fisher exact tests. A P value of £0.05 was considered to be statistically significant. DCK and HENT1 expression levels were significantly lower in children with MLL gene-rearranged ALL compared to children with MLL germ line ALL (P = 0.0003 and 0.03, respectively. Our results differ from previous ones concerning HENT1 mRNA expression that observed a higher expression level in MLL gene-rearranged leukemias. In conclusion, the expression of the genes related to Ara-C metabolism was lower in MLL-positive children in the sample studied, suggesting the presence of population differences in the expression profile of these genes especially for HENT1.

  7. I. Effect of Trichinella spiralis infection on the migration of mesenteric lymphoblasts and mesenteric T lymphoblasts in syngeneic mice.

    Science.gov (United States)

    Rose, M L; Parrott, D M; Bruce, R G

    1976-11-01

    The migration of [125I]UdR-labelled mesenteric lymph node cells in NIH strain mice at various times after inis produced an enhanced accumulation of mesenteric immunoblasts in the small intestine at 2 and 4 days after infection but not at later times. The enhanced migration occurred when using cells from both uninfected and infected donors, denoting an absence of antigenic specificity. This effect is not secondary to a reduced arrival of cells at sites away from the gut in infected mice, but to a primary increase of the arrival in the small intestine. Mesenteric T lymphoblasts (separated on a nylon-wool column) migrated to the small intestine of uninfected recipients and appear to be a major portion of the population which migrate to the gut of infected recipients. Our results were confirmed using 51Cr to label mesenteric cells. We conclude that the parasite causes the small intestine to become more attractive or retentive for mesenteric blast cells early during infection.

  8. Follow-up strategies after treatment (large loop excision of the transformation zone (LLETZ)) for cervical intraepithelial neoplasia (CIN): Impact of human papillomavirus (HPV) test.

    Science.gov (United States)

    van der Heijden, Esther; Lopes, Alberto D; Bryant, Andrew; Bekkers, Ruud; Galaal, Khadra

    2015-01-06

    Development of cancer of the cervix is a multi-step process as before cervical cancer develops, cervical cells undergo changes and become abnormal. These abnormalities are called cervical intraepithelial neoplasia (CIN) and are associated with increased risk of subsequent invasive cancer of the cervix. Oncogenic high-risk human papillomavirus (hrHPV), the causative agent of cervical cancer and its precursor lesions, is present in up to one-third of women following large loop excision of the transformation zone (LLETZ) treatment and is associated with increased risk of residual disease and disease recurrence. HPV testing may serve as a surveillance tool for identifying women at higher risk of recurrence. High-risk human papillomavirus testing will enable us to identify women at increased risk of residual or recurrent CIN and therefore will allow us to offer closer surveillance and early treatment, when indicated. • To evaluate the effectiveness and safety of hrHPV testing after large loop excision of the transformation zone (LLETZ) treatment• To determine optimal follow-up management strategies following LLETZ treatment according to hrHPV status We searched the Cochrane Gynacological Cancer Review Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), PubMed and PsycINFO up to August 2013. We searched registers of clinical trials, abstracts of scientific meetings and reference lists of included studies, and we contacted experts in the field. We searched for randomised control trials (RCTs) that compared follow-up management strategies following LLETZ treatment for CIN. Two review authors independently assessed whether potentially relevant studies met the inclusion criteria. No trials were found; therefore no data were analysed. The search identified 813 references on MEDLINE, 418 on EMBASE, 22 on CINAHL, 666 on PubMed, 291 on PsycINFO and

  9. No effects of power line frequency extremely low frequency electromagnetic field exposure on selected neurobehavior tests of workers inspecting transformers and distribution line stations versus controls.

    Science.gov (United States)

    Li, Li; Xiong, De-fu; Liu, Jia-wen; Li, Zi-xin; Zeng, Guang-cheng; Li, Hua-liang

    2014-03-01

    We aimed to evaluate the interference of 50 Hz extremely low frequency electromagnetic field (ELF-EMF) occupational exposure on the neurobehavior tests of workers performing tour-inspection close to transformers and distribution power lines. Occupational short-term "spot" measurements were carried out. 310 inspection workers and 300 logistics staff were selected as exposure and control. The neurobehavior tests were performed through computer-based neurobehavior evaluation system, including mental arithmetic, curve coincide, simple visual reaction time, visual retention, auditory digit span and pursuit aiming. In 500 kV areas electric field intensity at 71.98% of total measured 590 spots were above 5 kV/m (national occupational standard), while in 220 kV areas electric field intensity at 15.69% of total 701 spots were above 5 kV/m. Magnetic field flux density at all the spots was below 1,000 μT (ICNIRP occupational standard). The neurobehavior score changes showed no statistical significance. Results of neurobehavior tests among different age, seniority groups showed no significant changes. Neurobehavior changes caused by daily repeated ELF-EMF exposure were not observed in the current study.

  10. Temporal lobe epilepsy with hippocampal sclerosis in acute lymphoblastic leukemia.

    Science.gov (United States)

    Kasai-Yoshida, Emi; Ogihara, Masaaki; Ozawa, Miwa; Nozaki, Taiki; Morino, Michiharu; Manabe, Atsushi; Hosoya, Ryota

    2013-07-01

    Of 71 acute lymphoblastic leukemia survivors at our hospital over the past 10 years, 2 children developed mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS). This is the first report to describe the clinical course of MTLE-HS observed longitudinally by EEG and MRI. Patient 1 experienced a seizure during chemotherapy involving intrathecal methotrexate. Postseizure MRI suggested methotrexate encephalopathy or leukemic invasion. Anticonvulsant therapy was initiated; subsequent EEGs and MRIs revealed normal results. Three years after chemotherapy, a diffuse, irregular spike-and-wave pattern was observed on interictal EEG. Five years after chemotherapy, the patient developed MTLE-HS comprising complex partial seizures, typical temporal spikes on EEG, and hippocampal sclerosis (HS). Patient 2 did not experience seizures during chemotherapy. Four years later, the patient started experiencing complex partial seizures, and a diffuse, irregular spike-and-wave pattern was observed on interictal EEG. A clinical picture of MTLE-HS developed 2 years later. In both patients, nonspecific EEG abnormalities (ie, diffuse, irregular spike-and-wave activity) preceded the appearance of HS on MRI by 2 years, suggesting an insidious advance of HS during the latent period. Such atypical EEG findings may indicate MTLE-HS during follow-up of leukemia patients. MTLE-HS develops several years after an initial precipitating incident such as prolonged seizures, central nervous system infection, and brain trauma. In our cases, the initial precipitating incident may have been chemotherapy and/or prolonged seizures. Thus, MTLE-HS associated with leukemia may not be as rare as generally believed. A large cohort study of late neurologic complications is warranted.

  11. Improved Prognosis for Older Adolescents With Acute Lymphoblastic Leukemia

    Science.gov (United States)

    Pui, Ching-Hon; Pei, Deqing; Campana, Dario; Bowman, W. Paul; Sandlund, John T.; Kaste, Sue C.; Ribeiro, Raul C.; Rubnitz, Jeffrey E.; Coustan-Smith, Elaine; Jeha, Sima; Cheng, Cheng; Metzger, Monika L.; Bhojwani, Deepa; Inaba, Hiroto; Raimondi, Susana C.; Onciu, Mihaela; Howard, Scott C.; Leung, Wing; Downing, James R.; Evans, William E.; Relling, Mary V.

    2011-01-01

    Purpose The prognosis for older adolescents and young adults with acute lymphoblastic leukemia (ALL) has been historically much worse than that for younger patients. We reviewed the outcome of older adolescents (age 15 to 18 years) treated in four consecutive Total Therapy studies to determine if recent improved treatment extended to this high-risk group. Patients and Methods Between 1991 and 2007, 963 pediatric patients, including 89 older adolescents, were enrolled on Total Therapy studies XIIIA, XIIIB, XIV, and XV. In the first three studies, treatment selection was based on presenting clinical features and leukemic cell genetics. In study XV, the level of residual disease was used to guide treatment, which featured intensive methotrexate, glucocorticoid, vincristine, and asparaginase, as well as early triple intrathecal therapy for higher-risk ALL. Results The 89 older adolescents were significantly more likely to have T-cell ALL, the t(4;11)(MLL-AF4), and detectable minimal residual disease during or at the end of remission induction; they were less likely to have the t(12;21)(ETV6-RUNX1) compared with younger patients. In the first three studies, the 44 older adolescents had significantly poorer event-free survival and overall survival than the 403 younger patients. This gap in prognosis was abolished in study XV: event-free survival rates at 5 years were 86.4% ± 5.2% (standard error) for the 45 older adolescents and 87.4% ± 1.7% for the 453 younger patients; overall survival rates were 87.9% ± 5.1% versus 94.1% ± 1.2%, respectively. Conclusion Most older adolescents with ALL can be cured with risk-adjusted intensive chemotherapy without stem-cell transplantation. PMID:21172890

  12. Nanoparticle targeted therapy against childhood acute lymphoblastic leukemia

    Science.gov (United States)

    Satake, Noriko; Lee, Joyce; Xiao, Kai; Luo, Juntao; Sarangi, Susmita; Chang, Astra; McLaughlin, Bridget; Zhou, Ping; Kenney, Elaina; Kraynov, Liliya; Arnott, Sarah; McGee, Jeannine; Nolta, Jan; Lam, Kit

    2011-06-01

    The goal of our project is to develop a unique ligand-conjugated nanoparticle (NP) therapy against childhood acute lymphoblastic leukemia (ALL). LLP2A, discovered by Dr. Kit Lam, is a high-affinity and high-specificity peptidomimetic ligand against an activated α4β1 integrin. Our study using 11 fresh primary ALL samples (10 precursor B ALL and 1 T ALL) showed that childhood ALL cells expressed activated α4β1 integrin and bound to LLP2A. Normal hematopoietic cells such as activated lymphocytes and monocytes expressed activated α4β1 integrin; however, normal hematopoietic stem cells showed low expression of α4β1 integrin. Therefore, we believe that LLP2A can be used as a targeted therapy for childhood ALL. The Lam lab has developed novel telodendrimer-based nanoparticles (NPs) which can carry drugs efficiently. We have also developed a human leukemia mouse model using immunodeficient NOD/SCID/IL2Rγ null mice engrafted with primary childhood ALL cells from our patients. LLP2A-conjugated NPs will be evaluated both in vitro and in vivo using primary leukemia cells and this mouse model. NPs will be loaded first with DiD near infra-red dye, and then with the chemotherapeutic agents daunorubicin or vincristine. Both drugs are mainstays of current chemotherapy for childhood ALL. Targeting properties of LLP2A-conjugated NPs will be evaluated by fluorescent microscopy, flow cytometry, MTS assay, and mouse survival after treatment. We expect that LLP2A-conjugated NPs will be preferentially delivered and endocytosed to leukemia cells as an effective targeted therapy.

  13. The transfer function method for the evaluation of short-circuit tests and on-site diagnostics of power transformers; Die Uebertragungsfunktion als Methode zur Beurteilung der Stosskurzschlusspruefung und Vor-Ort-Isolationsdiagnose

    Energy Technology Data Exchange (ETDEWEB)

    Christian, J.; Feser, K. [Stuttgart Univ. (Germany). Inst. fuer Energieuebertragung und Hochspannungstechnik; Leibfried, T. [Siemens AG, Nuernberg (Germany). Geschaeftsgebiet Leistungstransformatoren; Jaeggi, F. [Aare-Tessin AG fuer Elektrizitaet, Olten (Switzerland)

    1999-03-22

    A short circuit test according to IEC 76-5 was performed on a 125 MVA, 245 kV/53 kV power transformer from the Siemens factory in Nuremberg at the Kema high power laboratory (Arnhem, Netherlands) in March 1997. Thereby, the transfer function method was examined as an additional method for evaluating the short-circuit test. The visual inspection of the transformer after returning to the Nuremberg factory carried out by engineers from Atel and Siemens and representatives of Kema showed no changes of the core and coil assembly. At the Flumenthal substation a second transformer of the same type was installed. Before commissioning, the transfer functions of both transformers have been measured. These measurements provide essential information concerning the comparability of measurements from different transformers and are the basis for measurements to be carried out in the future. (orig.) [Deutsch] Im Maerz 1997 wurde ein 125-MVA-Leistungstranformator aus dem Siemens Transformatorenwerk Nuernberg im Hochleistungslabor der Kema, Arnheim einer Stosskurzschlusspruefung unterzogen. Dabei wurde die Analyse der Uebertragungsfunktion des Transformators als zusaetzliche Methode zur Beurteilung der Stosskurzschlusspruefung untersucht. Der Aktivteil wurde danach im Herstellerwerk begutachtet. Dabei ergaben sich keine Beanstandungen. Im Umspannwerk Flumenthal wurde ein zweiter baugleicher Transformator installiert. Vor der Inbetriebnahme wurden zusaetzliche Vergleichsmessungen an den zwei baugleichen Transformatoren durchgefuehrt. (orig.)

  14. EBV, HCMV, HHV6, and HHV7 Screening in Bone Marrow Samples from Children with Acute Lymphoblastic Leukemia

    Science.gov (United States)

    Morales-Sánchez, A.; Pompa-Mera, E. N.; Fajardo-Gutiérrez, A.; Alvarez-Rodríguez, F. J.; Bekker-Méndez, V. C.; Flores-Chapa, J. de Diego; Flores-Lujano, J.; Jiménez-Hernández, E.; Peñaloza-González, J. G.; Rodríguez-Zepeda, M. C.; Torres-Nava, J. R.; Velázquez-Aviña, M. M.; Amador-Sánchez, R.; Alvarado-Ibarra, M.; Reyes-Zepeda, N.; Espinosa-Elizondo, R. M.; Pérez-Saldivar, M. L.; Núñez-Enríquez, J. C.; Mejía-Aranguré, J. M.; Fuentes-Pananá, E. M.

    2014-01-01

    Acute lymphoblastic leukemia (ALL) is the most common cancer in childhood worldwide and Mexico has reported one of the highest incidence rates. An infectious etiology has been suggested and supported by epidemiological evidences; however, the identity of the involved agent(s) is not known. We considered that early transmitted lymphotropic herpes viruses were good candidates, since transforming mechanisms have been described for them and some are already associated with human cancers. In this study we interrogated the direct role of EBV, HCMV, HHV6, and HHV7 human herpes viruses in childhood ALL. Viral genomes were screened in 70 bone marrow samples from ALL patients through standard and a more sensitive nested PCR. Positive samples were detected only by nested PCR indicating a low level of infection. Our result argues that viral genomes were not present in all leukemic cells, and, hence, infection most likely was not part of the initial genetic lesions leading to ALL. The high statistical power of the study suggested that these agents are not involved in the genesis of ALL in Mexican children. Additional analysis showed that detected infections or coinfections were not associated with prognosis. PMID:25309913

  15. EBV, HCMV, HHV6, and HHV7 Screening in Bone Marrow Samples from Children with Acute Lymphoblastic Leukemia

    Directory of Open Access Journals (Sweden)

    A. Morales-Sánchez

    2014-01-01

    Full Text Available Acute lymphoblastic leukemia (ALL is the most common cancer in childhood worldwide and Mexico has reported one of the highest incidence rates. An infectious etiology has been suggested and supported by epidemiological evidences; however, the identity of the involved agent(s is not known. We considered that early transmitted lymphotropic herpes viruses were good candidates, since transforming mechanisms have been described for them and some are already associated with human cancers. In this study we interrogated the direct role of EBV, HCMV, HHV6, and HHV7 human herpes viruses in childhood ALL. Viral genomes were screened in 70 bone marrow samples from ALL patients through standard and a more sensitive nested PCR. Positive samples were detected only by nested PCR indicating a low level of infection. Our result argues that viral genomes were not present in all leukemic cells, and, hence, infection most likely was not part of the initial genetic lesions leading to ALL. The high statistical power of the study suggested that these agents are not involved in the genesis of ALL in Mexican children. Additional analysis showed that detected infections or coinfections were not associated with prognosis.

  16. Wntless (GPR177) expression correlates with poor prognosis in B-cell precursor acute lymphoblastic leukemia via Wnt signaling.

    Science.gov (United States)

    Chiou, Shyh-Shin; Wang, Li-Ting; Huang, Shih-Bo; Chai, Chee-Yin; Wang, Shen-Nien; Liao, Yu-Mei; Lin, Pei-Chin; Liu, Kwei-Yan; Hsu, Shih-Hsien

    2014-10-01

    B-cell precursor acute lymphoblastic leukemia (BCP ALL) is the most common childhood leukemia, with a cure rate of 80%. Nevertheless, disease relapse is the most important prognostic factor for the disease outcome. We aimed to elucidate the role of Wnt secretion-regulating protein, Wntless (Wls)/GPR177, on disease outcome in pediatric patients with BCP ALL, and assess its pathogenetic role in the regulation of the disease. Wls expression was characterized and correlated with Wnt pathway signaling in the bone marrow leukemia cells isolated from 44 pediatric patients with BCP ALL. The overexpression of Wls was detected in leukemia cells and was significantly correlated with the disease relapse and poor survival in the patients. The high expression of Wls also correlated with the Wnt expression and consequent downstream signaling activation, which was shown to provide essential proliferation, transformation and anti-apoptotic activity during leukemogenesis. These results indicated that Wls played an essential role in disease relapse and poor survival in patients with BCP ALL. Therefore, Wls may provide a potential future therapeutic target, particularly for patients who do not respond to existing therapies and suffer relapse.

  17. Somatic inactivation of ATM in hematopoietic cells predisposes mice to cyclin D3 dependent T cell acute lymphoblastic leukemia.

    Science.gov (United States)

    Ehrlich, Lori A; Yang-Iott, Katherine; DeMicco, Amy; Bassing, Craig H

    2015-01-01

    T-cell acute lymphoblastic leukemia (T-ALL) is a cancer of immature T cells that exhibits heterogeneity of oncogenic lesions, providing an obstacle for development of more effective and less toxic therapies. Inherited deficiency of ATM, a regulator of the cellular DNA damage response, predisposes young humans and mice to T-ALLs with clonal chromosome translocations. While acquired ATM mutation or deletion occurs in pediatric T-ALLs, the role of somatic ATM alterations in T-ALL pathogenesis remains unknown. We demonstrate here that somatic Atm inactivation in haematopoietic cells starting as these cells differentiate in utero predisposes mice to T-ALL at similar young ages and harboring analogous translocations as germline Atm-deficient mice. However, some T-ALLs from haematopoietic cell specific deletion of Atm were of more mature thymocytes, revealing that the developmental timing and celluar origin of Atm inactivation influences the phenotype of ATM-deficient T-ALLs. Although it has been hypothesized that ATM suppresses cancer by preventing deletion and inactivation of TP53, we find that Atm inhibits T-ALL independent of Tp53 deletion. Finally, we demonstrate that the Cyclin D3 protein that drives immature T cell proliferation is essential for transformation of Atm-deficient thymocytes. Our study establishes a pre-clinical model for pediatric T-ALLs with acquired ATM inactivation and identifies the cell cycle machinery as a therapeutic target for this aggressive childhood T-ALL subtype.

  18. Acute kidney injury and bilateral symmetrical enlargement of the kidneys as first presentation of B-cell lymphoblastic lymphoma.

    Science.gov (United States)

    Shi, Su-fang; Zhou, Fu-de; Zou, Wan-zhong; Wang, Hai-yan

    2012-12-01

    Lymphoblastic lymphoma is an uncommon subtype of lymphoid neoplasm in adults. Acute kidney injury at initial presentation due to lymphoblastic lymphoma infiltration of the kidneys has rarely been described. We report a 19-year-old woman who presented with acute kidney injury due to massive lymphomatous infiltration of the kidneys. The diagnosis of B-cell lymphoblastic lymphoma was established by immunohistochemical study of the biopsied kidney. The patient had an excellent response to the VDCLP protocol (vincristine, daunomycin, cyclophosphamide, asparaginase, and dexamethasone) with sustained remission. We recommend that lymphomatous infiltration be considered in patients presenting with unexplained acute kidney injury and enlarged kidneys.

  19. The landscape of somatic mutations in infant MLL-rearranged acute lymphoblastic leukemias

    DEFF Research Database (Denmark)

    Andersson, Anna K; Ma, Jing; Wang, Jianmin

    2015-01-01

    Infant acute lymphoblastic leukemia (ALL) with MLL rearrangements (MLL-R) represents a distinct leukemia with a poor prognosis. To define its mutational landscape, we performed whole-genome, exome, RNA and targeted DNA sequencing on 65 infants (47 MLL-R and 18 non-MLL-R cases) and 20 older childr...

  20. Acute lymphoblastic leukaemia after treatment of nephrotic syndrome with immunosuppressive drugs.

    Science.gov (United States)

    Kuis, W; de Kraker, J; Kuijten, R H; Donckerwolcke, R A; Voûte, P A

    1976-06-01

    The authors present a 4-year-old girl with nephrotic syndrome who developed actue lymphoblastic leukaemia 5 months after the start of a combined treatment of alternate day prednisone and daily cyclophosphamide during 3 months. The nephrotic syndrome was due to focal segmental glomerulosclerosis. The occurrence of leukaemia might be related to the preceeding treatment with cyclophosphamide.

  1. Hypothalamic-pituitary-adrenal axis function in survivors of childhood acute lymphoblastic leukemia and healthy controls.

    NARCIS (Netherlands)

    Gordijn, M.S.; Litsenburg, R.R. van; Gemke, R.J.; Bierings, M.B.; Hoogerbrugge, P.M.; Ven, P.M. van de; Heijnen, C.J.; Kaspers, G.J.L.

    2012-01-01

    Of all malignancies in children, acute lymphoblastic leukemia (ALL) is the most common type. Since survival significantly improves over time, treatment-related side effects become increasingly important. Glucocorticoids play an important role in the treatment of ALL, but they may suppress the hypoth

  2. Fatal Aspergillus rhinosinusitis during induction chemotherapy in a child with acute lymphoblastic leukemia.

    NARCIS (Netherlands)

    Vlaardingerbroek, H.; Flier, M. van der; Borgstein, J.A.; Lequin, M.H.; Sluis, I.M. van der

    2009-01-01

    Invasive fungal infections are a major problem in patients treated for hematologic malignancies. We report a 3-year-old girl who suffered from febrile neutropenia during induction therapy for acute lymphoblastic leukemia. Initial chest computed tomography revealed no evidence of intrapulmonary funga

  3. Reduced folate carrier mutations are not the mechanism underlying methotrexate resistance in childhood acute lymphoblastic leukemia.

    NARCIS (Netherlands)

    Kaufman, Y; Drori, S.; Cole, PD; Kamen, BA; Sirota, J; Ifergan, I; Arush, MW; Elhasid, R; Sahar, D; Kaspers, G.J.L.; Jansen, G.; Matherly, LH; Rechavi, G; Toren, A; Assaraf, Y.G.

    2004-01-01

    BACKGROUND: Although the majority of children with acute lymphoblastic leukemia (ALL) are cured with combination chemotherapy containing methotrexate (MTX), drug resistance contributes to treatment failure for a substantial fraction of patients. The primary transporter for folates and MTX is the red

  4. Treatment of Philadelphia chromosome-positive acute lymphoblastic leukemia in pregnancy.

    Science.gov (United States)

    Mainor, Candace B; Duffy, Alison P; Atkins, Kristin L; Kimball, Amy S; Baer, Maria R

    2016-04-01

    BCR-ABL inhibitors administered in conjunction with chemotherapy have significantly improved outcomes in Philadelphia chromosome-positive acute lymphoblastic leukemia but, for patients diagnosed during pregnancy, data on risks to the fetus are limited. We report a woman treated with chemotherapy and imatinib mesylate who delivered a healthy baby at 30 weeks, and we discuss available data.

  5. Endocrine Effects of the Treatment for Acute Lymphoblastic Leukemia and Hodgkin’s Lymphoma in Childhood

    NARCIS (Netherlands)

    R.D. van Beek (Robert Diederik)

    2010-01-01

    textabstractOne quarter of all cases of pediatric malignancies is acute Lymphoblastic leukemia (ALL). Per year approximately 4 in 100.000 children are diagnosed with ALL. The disease has a peak incidence between the third and sixth year of life. Predisposing factors for ALL are Down syndrome, Fancon

  6. Delayed Neurotoxicity Associated with Therapy for Children with Acute Lymphoblastic Leukemia

    Science.gov (United States)

    Cole, Peter D.; Kamen, Barton A.

    2006-01-01

    Most children diagnosed today with acute lymphoblastic leukemia (ALL) will be cured. However, treatment entails risk of neurotoxicity, causing deficits in neurocognitive function that can persist in the years after treatment is completed. Many of the components of leukemia therapy can contribute to adverse neurologic sequelae, including…

  7. Fatal Ophiostoma piceae infection in a patient with acute lymphoblastic leukemia

    NARCIS (Netherlands)

    Bommer, M.; Hütter, M.L.; Stilgenbauer, S.; de Hoog, G.S.; de Beer, Z.W.; Wellinghausen, N.

    2009-01-01

    We report to our knowledge the first case of human infection with Ophiostoma piceae. This Sporothrix schenckii-related fungus caused disseminated infection involving the lung and the brain in a patient with lymphoblastic lymphoma. The case emphasizes the significance of molecular techniques for iden

  8. Fatal Ophiostoma piceae infection in a patient with acute lymphoblastic leukaemia

    NARCIS (Netherlands)

    Bommer, M.; Hutter, M.L.; Stilgenbauer, S.; de Hoog, G.S.; de Beer, Z.W.; Wellinghausen, N.

    2009-01-01

    We report to our knowledge the first case of human infection with Ophiostoma piceae. This Sporothrix schenckii-related fungus caused disseminated infection involving the lung and the brain in a patient with lymphoblastic lymphoma. The case emphasizes the significance of molecular techniques for iden

  9. Analysis of handwriting of children during treatment for acute lymphoblastic leukemia

    NARCIS (Netherlands)

    Reinders-Messelink, H.A.; Schoemaker, M.M.; Göeken, L.N.H.; Bökkerink, J.P.M.; Kamps, W.A.

    2001-01-01

    Background. Children treated for acute lymphoblastic leukemia (ALL) often complain about handwriting problems. Procedure. Using a computerized writing task, we have prospectively studied the processes necessary for the production of handwriting movements in I I children (5-12 years old) during treat

  10. Chemotherapy-Related Side Effects in Childhood Acute Lymphoblastic Leukemia in Indonesia: Parental Perceptions

    NARCIS (Netherlands)

    Sitaresmi, M.N.; Mostert, S.; Purwanto, I.; Gundy, C.; Sutaryo, N.N.; Veerman, A.J.P.

    2009-01-01

    Noncompliance with prescribed medication has been associated with increased chance of relapse and poor outcome. Side effects may be an important cause of noncompliance. Fifty-one parents of children with acute lymphoblastic leukemia in a tertiary care hospital in Indonesia were interviewed about the

  11. Clinical and genetic features of pediatric acute lymphoblastic leukemia in Down syndrome in the Nordic countries

    DEFF Research Database (Denmark)

    Lundin, Catarina; Forestier, Erik; Klarskov Andersen, Mette

    2014-01-01

    BACKGROUND: Children with Down syndrome (DS) have an increased risk for acute lymphoblastic leukemia (ALL). Although previous studies have shown that DS-ALL differs clinically and genetically from non-DS-ALL, much remains to be elucidated as regards genetic and prognostic factors in DS-ALL. METHODS...

  12. High frequency of BTG1 deletions in acute lymphoblastic leukemia in children with down syndrome

    DEFF Research Database (Denmark)

    Lundin, Catarina; Hjorth, Lars; Behrendtz, Mikael

    2012-01-01

    Previous cytogenetic studies of myeloid and acute lymphoblastic leukemias in children with Down syndrome (ML-DS and DS-ALL) have revealed significant differences in abnormality patterns between such cases and acute leukemias in general. Also, certain molecular genetic aberrations characterize DS...

  13. Physicians compliance during maintenance therapy in children with Down syndrome and acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Bohnstedt, C; Levinsen, M; Rosthøj, S

    2013-01-01

    Children with Down syndrome (DS) and acute lymphoblastic leukemia (ALL) have an inferior prognosis compared with non-DS ALL patients. We reviewed methotrexate (MTX)/mercaptopurine (6MP) maintenance therapy data for children with DS treated according to the Nordic Society of Pediatric Hematology...

  14. High white blood cell count at diagnosis of childhood acute lymphoblastic leukaemia

    DEFF Research Database (Denmark)

    Vaitkeviciene, Goda; Forestier, Erik; Hellebostad, Marit;

    2011-01-01

    Prognostic impact of peripheral blood white blood cell count (WBC) at the diagnosis of childhood acute lymphoblastic leukaemia (ALL) was evaluated in a population-based consecutive series of 2666 children aged 1-15 treated for ALL between 1992 and 2008 in the five Nordic countries (Denmark, Finland...

  15. Vincristine pharmacokinetics is related to clinical outcome in children with standard risk acute lymphoblastic leukemia

    NARCIS (Netherlands)

    Loennerholm, Gudmar; Frost, Britt-Marie; Abrahamsson, Jonas; Behrendtz, Mikael; Castor, Anders; Forestier, Erik; Heyman, Mats; Uges, Donald R. A.; de Graaf, Siebold S. N.

    2008-01-01

    Vincristine is a key drug in the treatment of childhood and adult acute lymphoblastic leukemia (ALL), and many other childhood malignancies. Despite decades of wide clinical use, no data on the correlation between vincristine pharmacokinetics and long-term clinical outcome have been published. We he

  16. Chemotherapy-Related Side Effects in Childhood Acute Lymphoblastic Leukemia in Indonesia: Parental Perceptions

    NARCIS (Netherlands)

    Sitaresmi, M.N.; Mostert, S.; Purwanto, I.; Gundy, C.; Sutaryo, N.N.; Veerman, A.J.P.

    2009-01-01

    Noncompliance with prescribed medication has been associated with increased chance of relapse and poor outcome. Side effects may be an important cause of noncompliance. Fifty-one parents of children with acute lymphoblastic leukemia in a tertiary care hospital in Indonesia were interviewed about the

  17. Erroneous exchange of asparaginase forms in the treatment of acute lymphoblastic leukemia

    NARCIS (Netherlands)

    Cheung, K.C.; Bemt, P.M. van den; Torringa, M.L.; Tamminga, R.Y.; Pieters, R.; Smet, P.A. de

    2011-01-01

    For the treatment of children with acute lymphoblastic leukemia (ALL), Dutch pediatric oncologists use the Dutch Childhood Oncology Group ALL 10 protocol. This protocol is complex, as it comprises many different drug regimens. One of the drugs is asparaginase which is available in different forms wi

  18. Erroneous Exchange of Asparaginase Forms in the Treatment of Acute Lymphoblastic Leukemia

    NARCIS (Netherlands)

    Cheung, Ka-Chun; van den Bemt, Patricia M. L. A.; Torringa, Maarten L. J.; Tamminga, Rienk Y. J.; Pieters, Rob; de Smet, Peter A. G. M.

    2011-01-01

    For the treatment of children with acute lymphoblastic leukemia (ALL), Dutch pediatric oncologists use the Dutch Childhood Oncology Group ALL 10 protocol. This protocol is complex, as it comprises many different drug regimens. One of the drugs is asparaginase which is available in different forms wi

  19. Improved flow cytometric detection of minimal residual disease in childhood acute lymphoblastic leukemia

    NARCIS (Netherlands)

    Denys, B.; van der Sluijs-Gelling, A. J.; Homburg, C.; van der Schoot, C. E.; de Haas, V.; Philippe, J.; Pieters, R.; van Dongen, J. J. M.; van der Velden, V. H. J.

    2013-01-01

    Most current treatment protocols for acute lymphoblastic leukemia (ALL) include minimal residual disease (MRD) diagnostics, generally based on PCR analysis of rearranged antigen receptor genes. Although flow cytometry (FCM) can be used for MRD detection as well, discordant FCM and PCR results are ob

  20. LONGITUDINAL-STUDY OF BONE-AGE IN ACUTE LYMPHOBLASTIC-LEUKEMIA

    NARCIS (Netherlands)

    TAMMINGA, RYJ; ZWEENS, M; KAMPS, W; DRAYER, N

    1993-01-01

    Bone age was assessed in children with acute lymphoblastic leukaemia (ALL) using the Tanner-Whitehouse II method. X-rays of the left hand (wrist) were made at diagnosis and annually until 5 years after diagnosis. A total of 164 X-rays from 40 patients was available. During treatment bone age develop

  1. The significance of change of Th22 cells in patients with acute lymphoblastic leukemia

    Institute of Scientific and Technical Information of China (English)

    刘立民

    2013-01-01

    Objective To investigate the proportion of Th22 cells in peripheral blood of patients with acute lympho-blastic leukemia(ALL) and evaluate its significance.Methods The proportions of Th22 cells in peripheral blood of B-ALL and T-ALL patients before therapy(group 1),

  2. Acute lymphoblastic leukemia and obesity : increased energy intake or decreased physical activity?

    NARCIS (Netherlands)

    Jansen, H.; Postma, A.; Stolk, R. P.; Kamps, W. A.

    2009-01-01

    Background Obesity is a well-known problem in children with acute lymphoblastic leukemia ( ALL), and it might be the result of an excess in energy intake, reduced energy expenditure, or both. The aim of this study is to describe energy intake and physical activity during treatment for ALL with inter

  3. A recurrent germline PAX5 mutation confers susceptibility to pre-B cell acute lymphoblastic leukemia

    NARCIS (Netherlands)

    Shah, S.; Schrader, K.A.; Waanders, E.; Timms, A.E.; Vijai, J.; Miething, C.; Wechsler, J.; Yang, J.; Hayes, J.; Klein, R.J.; Zhang, Jinghui; Wei, L.; Wu, G.; Rusch, M.; Nagahawatte, P.; Ma, J; Chen, S.C.; Song, G.; Cheng, J.; Meyers, P.; Bhojwani, D.; Jhanwar, S.; Maslak, P.; Fleisher, M.; Littman, J.; Offit, L.; Rau-Murthy, R.; Fleischut, M.H.; Corines, M.; Murali, R.; Gao, X.; Manschreck, C.; Kitzing, T.; Murty, V.V.; Raimondi, S.C.; Kuiper, R.P.; Simons, A.; Schiffman, J.D.; Onel, K.; Plon, S.E.; Wheeler, D.A.; Ritter, D.; Ziegler, D.S.; Tucker, K.; Sutton, R.; Chenevix-Trench, G.; Li, J.; Huntsman, D.G.; Hansford, S.; Senz, J.; Walsh, T.; Lee, M. van der; Hahn, C.N.; Roberts, K.G.; King, M.C.; Lo, S.M.; Levine, R.L.; Viale, A.; Socci, N.D.; Nathanson, K.L.; Scott, H.S.; Daly, M.; Lipkin, S.M.; Lowe, S.W.; Downing, J.R.; Altshuler, D.; Sandlund, J.T.; Horwitz, M.S.; Mullighan, C.G.; Offit, K.

    2013-01-01

    Somatic alterations of the lymphoid transcription factor gene PAX5 (also known as BSAP) are a hallmark of B cell precursor acute lymphoblastic leukemia (B-ALL), but inherited mutations of PAX5 have not previously been described. Here we report a new heterozygous germline variant, c.547G>A (p.Gly1

  4. Unravelling Pathobiological Molecular Mechanisms of T-Cell Acute Lymphoblastic Leukemia

    NARCIS (Netherlands)

    R.D. Mendes (Rui Daniel)

    2016-01-01

    markdownabstractT-cell acute lymphoblastic leukemia (T-ALL) represents 10-15% of pediatric acute leukemias. Despite major therapeutic improvements due to treatment intensification and refined risk-adapted stratification during the past decade, ~30% of T-ALL cases relapse with very poor prognosis.

  5. Management and treatment of osteonecrosis in children and adolescents with acute lymphoblastic leukemia

    NARCIS (Netherlands)

    M.L. te Winkel (Mariël Lizet); R. Pieters (Rob); E.-J.D. Wind (Ernst-Jan); J.H.J.M. Bessems (Gert); M.M. van den Heuvel-Eibrink (Marry)

    2014-01-01

    textabstractThere is no consensus regarding how to manage osteonecrosis in pediatric acute lymphoblastic leukemia patients. Therefore, we performed a quality assessment of the literature with the result of a search strategy using the MESH terms osteonecrosis, children, childhood cancer, surgery,

  6. Sleep, fatigue, depression, and quality of life in survivors of childhood acute lymphoblastic leukemia.

    NARCIS (Netherlands)

    Gordijn, M.S.; Litsenburg, R.R. van; Gemke, R.J.; Huisman, J.; Bierings, M.B.; Hoogerbrugge, P.M.; Kaspers, G.J.L.

    2013-01-01

    BACKGROUND: With the improved survival of childhood acute lymphoblastic leukemia (ALL), the effect of treatment on psychosocial well-being becomes increasingly relevant. Literature on sleep and fatigue during treatment is emerging. However, information on these subjects after treatment is sparse. Th

  7. Sleep, fatigue, depression, and quality of life in survivors of childhood acute lymphoblastic leukemia.

    NARCIS (Netherlands)

    Gordijn, M.S.; Litsenburg, R.R. van; Gemke, R.J.; Huisman, J.; Bierings, M.B.; Hoogerbrugge, P.M.; Kaspers, G.J.L.

    2013-01-01

    BACKGROUND: With the improved survival of childhood acute lymphoblastic leukemia (ALL), the effect of treatment on psychosocial well-being becomes increasingly relevant. Literature on sleep and fatigue during treatment is emerging. However, information on these subjects after treatment is sparse.

  8. Prognosis in childhood and adult acute lymphoblastic leukaemia : a question of maturation?

    NARCIS (Netherlands)

    Plasschaert, SLA; Kamps, WA; Vellenga, E; de Vries, EGE; de Bont, ESJM

    2004-01-01

    Acute lymphoblastic leukaemia (ALL) is a disease diagnosed in children as well as adults. Progress in the treatment of ALL has led to better survival rates, however, children have benefited more from improved treatment modalities than adults. Recent evidence has underscored that the difference in ch

  9. Expression of multidrug resistance-associated proteins predicts prognosis in childhood and adult acute lymphoblastic leukemia

    NARCIS (Netherlands)

    Plasschaert, SLA; de Bont, ESJM; Boezen, M; vander Kolk, DM; Daenen, SMJG; Faber, KN; Kamps, WA; de Vries, EGE; Vellenga, E

    2005-01-01

    PURPOSE: Patients with acute lymphoblastic leukemia (ALL) are treated with a variety of chemotherapeutic drugs, which can be transported by six multidrug resistance-associated proteins (MRP). These MRPs have strongly overlapping functional activities. The aim of this study was to investigate the exp

  10. MicroRNA characterize genetic diversity and drug resistance in pediatric acute lymphoblastic leukemia

    NARCIS (Netherlands)

    D. Schotte (Diana); R.X. de Menezes (Renee); F. Akbari Moqadam (Farhad); L.M. Khankahdani (Leila Mohammadi); E.A.M. Lange-Turenhout (Ellen); C. Chen (Caifu); R. Pieters (Rob); M.L. den Boer (Monique)

    2011-01-01

    textabstractBackground MicroRNA regulate the activity of protein-coding genes including those involved in hematopoietic cancers. The aim of the current study was to explore which microRNA are unique for seven different subtypes of pediatric acute lymphoblastic leukemia. Design and Methods Expression

  11. Venous thromboembolism in adults treated for acute lymphoblastic leukaemia: Effect of fresh frozen plasma supplementation

    NARCIS (Netherlands)

    I. Lauw (Ivoune); B. van der Holt (Bronno); S. Middeldorp (Saskia); J.C.M. Meijers; J.J. Cornelissen (Jan); B.J. Biemond (Bart)

    2013-01-01

    textabstractTreatment of acute lymphoblastic leukaemia (ALL) is frequently complicated by venous thromboembolism (VTE). The efficacy and optimal approach of VTE prevention are unclear, particularly in adult patients. We assessed the effect of thromboprophylaxis on symptomatic VTE incidence in cycle

  12. In childhood acute lymphoblastic leukemia, blasts at different stages of immunophenotypic maturation have stem cell properties

    NARCIS (Netherlands)

    le Viseur, Christoph; Hotfilder, Marc; Bomken, Simon; Wilson, Kerrie; Roettgers, Silja; Schrauder, Andre; Rosemann, Annegret; Irving, Julie; Stam, Ronald W.; Shultz, Leonard D.; Harbott, Jochen; Juergens, Heribert; Schrappe, Martin; Pieters, Rob; Vormoor, Josef

    We examined the leukemic stem cell potential of blasts at different stages of maturation in childhood acute lymphoblastic leukemia (ALL). Human leukemic bone marrow was transplanted intrafemorally into NOD/scid mice. Cells sorted using the B precursor differentiation markers CD19, CD20, and CD34

  13. Genornewide identification of prednisolone-responsive genes in acute lymphoblastic leukemia cells

    NARCIS (Netherlands)

    Tissing, Wirn J. E.; den Boer, Monique L.; Meijerink, Jules P. P.; Menezes, Renee X.; Swagemakers, Sigrid; van der Spek, Peter J.; Sallan, Stephen E.; Armstrong, Scott A.; Pieters, Rob

    2007-01-01

    Glucocorticoids are keystone drugs in the treatment of childhood acute lymphoblastic leukemia (ALL). To get more insight in signal transduction pathways involved in glucocorticoid-induced apoptosis, Affymetrix U133A GeneChips were used to identify transcriptionally regulated genes on 3 and 8 hours

  14. Neuropsychological outcome in chemotherapy-only-treated children with acute lymphoblastic leukemia

    NARCIS (Netherlands)

    Jansen, Nathalie C. A. J.; Kingma, Annette; Schuitema, Arnout; Bouma, Anke; Veerman, Anjo J. P.; Kamps, Willem A.

    2008-01-01

    Purpose To evaluate neuropsychological functioning over time in children treated for acute lymphoblastic leukemia (ALL) with chemotherapy only. Patients and Methods Forty-nine consecutive patients (median age at first assessment, 6.8 years; range, 4.0 to 11.8 years) treated with intrathecal and syst

  15. Sleep, fatigue, depression, and quality of life in survivors of childhood acute lymphoblastic leukemia.

    NARCIS (Netherlands)

    Gordijn, M.S.; Litsenburg, R.R. van; Gemke, R.J.; Huisman, J.; Bierings, M.B.; Hoogerbrugge, P.M.; Kaspers, G.J.L.

    2013-01-01

    BACKGROUND: With the improved survival of childhood acute lymphoblastic leukemia (ALL), the effect of treatment on psychosocial well-being becomes increasingly relevant. Literature on sleep and fatigue during treatment is emerging. However, information on these subjects after treatment is sparse. Th

  16. Glioblastoma multiforme in a child with acute lymphoblastic leukemia: Case report and review of literature

    Directory of Open Access Journals (Sweden)

    Shah Kirit

    2004-07-01

    Full Text Available An 11-year-old boy with acute lymphoblastic leukemia had received prophylactic cranial irradiation (1800 cGy /10 fractions and intrathecal methotrexate. Five years later, he developed a glioblastoma multiforme in the right frontal region while the leukemia was in remission. It is possible that the glioma may have been induced by radiation and /or chemotherapy.

  17. Pharmacogenetic risk factors for altered bone mineral density and body composition in pediatric acute lymphoblastic leukemia

    NARCIS (Netherlands)

    M.L. te Winkel (Mariël Lizet); R.D. van Beek (Robert Diederik); S.M.P.F. de Muinck Keizer-Schrama (Sabine); A.G. Uitterlinden (André); W.C.J. Hop (Wim); R. Pieters (Rob); M.M. van den Heuvel-Eibrink (Marry)

    2010-01-01

    textabstractBackground This study investigates pharmacogenetic risk factors for bone mineral (apparent) density (BM(A)D) and body composition in pediatric acute lymphoblastic leukemia Design and Methods We determined the influence of SNPs in 4 genes (vitamin-D receptor (VDR: BsmI/ApaI/TaqI and Cdx-2

  18. Management and treatment of osteonecrosis in children and adolescents with acute lymphoblastic leukemia.

    Science.gov (United States)

    Te Winkel, Mariël L; Pieters, Rob; Wind, Ernst-Jan D; Bessems, J H J M Gert; van den Heuvel-Eibrink, Marry M

    2014-03-01

    There is no consensus regarding how to manage osteonecrosis in pediatric acute lymphoblastic leukemia patients. Therefore, we performed a quality assessment of the literature with the result of a search strategy using the MESH terms osteonecrosis, children, childhood cancer, surgery, bisphosphonates, 6 hydroxymethyl-glutaryl CoA reductase inhibitors, anticoagulants and hyperbaric oxygen, and terms related to these MESH terms. A randomized controlled trial showed that osteonecrosis can be prevented by intermittent, instead of continuous, corticosteroid administration. The studies on interventions after onset of osteonecrosis were of low-quality evidence. Seven pediatric acute lymphoblastic leukemia studies described non-surgical interventions; bisphosphonates (n=5), hyperbaric oxygen therapy (n=1), or prostacyclin analogs (n=1). Safety and efficacy studies are lacking. Five studies focused on surgical interventions; none was of sufficient quality to draw definite conclusions. In conclusion, preventing osteonecrosis is feasible in a proportion of the pediatric acute lymphoblastic leukemia patients by discontinuous, instead of continuous, steroid scheduling. The questions as to how to treat childhood acute lymphoblastic leukemia patients with osteonecrosis cannot be answered as good-quality studies are lacking.

  19. Aggravated bone density decline following symptomatic osteonecrosis in children with acute lymphoblastic leukemia

    NARCIS (Netherlands)

    den Hoed, Marissa A. H.; Pluijm, Saskia M. F.; te Winkel, Mariel L.; de Groot-Kruseman, Hester A.; Fiocco, Martha; Hoogerbrugge, Peter; Leeuw, Jan; Bruin, Marrie C. A.; van der Sluis, Inge M.; Bresters, Dorien; Lequin, Maarten H.; Roos, Jan C.; Veerman, Anjo J. P.; Pieters, Rob; van den Heuvel-Eibrink, Marry M.

    2015-01-01

    Osteonecrosis and decline of bone density are serious side effects during and after treatment of childhood acute lymphoblastic leukemia. It is unknown whether osteonecrosis and low bone density occur together in the same patients, or whether these two osteogenic side-effects can mutually influence e

  20. Management and treatment of osteonecrosis in children and adolescents with acute lymphoblastic leukemia

    NARCIS (Netherlands)

    M.L. te Winkel (Mariël Lizet); R. Pieters (Rob); E.-J.D. Wind (Ernst-Jan); J.H.J.M. Bessems (Gert); M.M. van den Heuvel-Eibrink (Marry)

    2014-01-01

    textabstractThere is no consensus regarding how to manage osteonecrosis in pediatric acute lymphoblastic leukemia patients. Therefore, we performed a quality assessment of the literature with the result of a search strategy using the MESH terms osteonecrosis, children, childhood cancer, surgery, bis

  1. Free Air Intraperitoneally During Chemotherapy for Acute Lymphoblastic Leukemia : Consider Pneumatosis Cystoides Intestinalis

    NARCIS (Netherlands)

    Groninger, Ellis; Hulscher, Jan B. F.; Timmer, Bert; Tamminga, Rienk Y. J.; Broens, Paul M. A.

    2010-01-01

    Intraperitoneal free air in a child with acute lymphoblastic leukemia (ALL) treated with induction chemotherapy is an ominous sign suspective of gastrointestinal perforation. We report a case of pneumatosis cystoides intestinalis (PCI) with free intraperitoneal air without bowel perforation in a chi

  2. Endocrine Effects of the Treatment for Acute Lymphoblastic Leukemia and Hodgkin’s Lymphoma in Childhood

    NARCIS (Netherlands)

    R.D. van Beek (Robert Diederik)

    2010-01-01

    textabstractOne quarter of all cases of pediatric malignancies is acute Lymphoblastic leukemia (ALL). Per year approximately 4 in 100.000 children are diagnosed with ALL. The disease has a peak incidence between the third and sixth year of life. Predisposing factors for ALL are Down syndrome, Fancon

  3. LAF4, an AF4-related gene, is fused to MLL in infant acute lymphoblastic leukemia

    NARCIS (Netherlands)

    von Bergh, ARM; Beverloo, HB; Rombout, P; van Wering, ER; van Weel, MH; Beverstock, GC; Kluin, PM; Slater, RM; Schuuring, E

    2002-01-01

    Infant acute lymphoblastic leukemia (ALL) with MLL gene rearrangements is characterized by a proB phenotype and a poor clinical outcome. We analyzed an infant proB ALL with t(2; 11)(p 15;p 14) and an MLL rearrangement on Southern blot analysis, Rapid amplification of cDNA ends-polymerase chain react

  4. Minimal residual disease diagnostics in acute lymphoblastic leukemia: Need for sensitive, fast, and standardized technologies

    NARCIS (Netherlands)

    J.J.M. van Dongen (Jacques); V.H.J. van der Velden (Vincent); M. Brüggemann (Monika); A. Orfao (Alberto)

    2015-01-01

    textabstractMonitoring of minimal residual disease (MRD) has become routine clinical practice in frontline treatment of virtually all childhood acute lymphoblastic leukemia (ALL) and in many adult ALL patients. MRD diagnostics has proven to be the strongest prognostic factor, allowing for risk group

  5. LONGITUDINAL-STUDY OF BONE-AGE IN ACUTE LYMPHOBLASTIC-LEUKEMIA

    NARCIS (Netherlands)

    TAMMINGA, RYJ; ZWEENS, M; KAMPS, W; DRAYER, N

    1993-01-01

    Bone age was assessed in children with acute lymphoblastic leukaemia (ALL) using the Tanner-Whitehouse II method. X-rays of the left hand (wrist) were made at diagnosis and annually until 5 years after diagnosis. A total of 164 X-rays from 40 patients was available. During treatment bone age

  6. Genornewide identification of prednisolone-responsive genes in acute lymphoblastic leukemia cells

    NARCIS (Netherlands)

    Tissing, Wirn J. E.; den Boer, Monique L.; Meijerink, Jules P. P.; Menezes, Renee X.; Swagemakers, Sigrid; van der Spek, Peter J.; Sallan, Stephen E.; Armstrong, Scott A.; Pieters, Rob

    2007-01-01

    Glucocorticoids are keystone drugs in the treatment of childhood acute lymphoblastic leukemia (ALL). To get more insight in signal transduction pathways involved in glucocorticoid-induced apoptosis, Affymetrix U133A GeneChips were used to identify transcriptionally regulated genes on 3 and 8 hours o

  7. Prediction of immunophenotype, treatment response, and relapse in childhood acute lymphoblastic leukemia using DNA microarrays

    DEFF Research Database (Denmark)

    Willenbrock, Hanni; Juncker, Agnieszka; Schmiegelow, K.

    2004-01-01

    Gene expression profiling is a promising tool for classification of pediatric acute lymphoblastic leukemia ( ALL). We analyzed the gene expression at the time of diagnosis for 45 Danish children with ALL. The prediction of 5-year event-free survival or relapse after treatment by NOPHO-ALL92 or 2000...

  8. Measures of 6-mercaptopurine and methotrexate maintenance therapy intensity in childhood acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Nielsen, Stine Nygaard; Grell, Kathrine; Nersting, Jacob

    2016-01-01

    PURPOSE: Normal white blood cell counts (WBC) are unknown in children with acute lymphoblastic leukemia (ALL). Accordingly, 6-mercaptopurine (6MP) and methotrexate (MTX) maintenance therapy is adjusted by a common WBC target of 1.5-3.0 × 10(9)/L. Consequently, the absolute degree...

  9. Central Venous Catheters and Bloodstream Infection During Induction Therapy in Children With Acute Lymphoblastic Leukemia

    DEFF Research Database (Denmark)

    Bergmann, Kristin; Hasle, Henrik; Asdahl, Peter

    2016-01-01

    The purpose of the study was to assess the risk of firsttime bloodstream infection (BSI) according to type of central venous catheter (CVC) during induction therapy in children with acute lymphoblastic leukemia (ALL). Patients eligible for our analysis were all newly diagnosed children with ALL...

  10. Chemotherapeutic treatment reduces circulating levels of surfactant protein-D in children with acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Rathe, Mathias; Sorensen, Grith L.; Wehner, Peder S.

    2017-01-01

    with acute lymphoblastic leukemia (ALL). PROCEDURE: In a prospective study, 43 children receiving treatment for ALL were monitored for mucosal toxicity from diagnosis through the induction phase of treatment. Serial blood draws were taken to determine the levels of SP-D, interleukin-6 (IL-6), C...

  11. Late cardiac effects of anthracycline containing therapy for childhood acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Rathe, Mathias; Carlsen, Niels L T; Oxhøj, Henrik

    2007-01-01

    At present about 80% of children with acute lymphoblastic leukemia (ALL) will be cured following treatment with multi-drug chemotherapy. A major concern for this growing number of survivors is the risk of late effects of treatment. The aim of this study was to determine whether signs...

  12. Free Air Intraperitoneally During Chemotherapy for Acute Lymphoblastic Leukemia : Consider Pneumatosis Cystoides Intestinalis

    NARCIS (Netherlands)

    Groninger, Ellis; Hulscher, Jan B. F.; Timmer, Bert; Tamminga, Rienk Y. J.; Broens, Paul M. A.

    Intraperitoneal free air in a child with acute lymphoblastic leukemia (ALL) treated with induction chemotherapy is an ominous sign suspective of gastrointestinal perforation. We report a case of pneumatosis cystoides intestinalis (PCI) with free intraperitoneal air without bowel perforation in a

  13. Genome-wide signatures of differential DNA methylation in pediatric acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Nordlund, Jessica; Bäcklin, Christofer L; Wahlberg, Per

    2013-01-01

    BACKGROUND: Although aberrant DNA methylation has been observed previously in acute lymphoblastic leukemia (ALL), the patterns of differential methylation have not been comprehensively determined in all subtypes of ALL on a genome-wide scale. The relationship between DNA methylation, cytogenetic...

  14. Fine motor and handwriting problems after treatment for childhood acute lymphoblastic leukemia

    NARCIS (Netherlands)

    ReindersMesselink, HA; Schoemaker, MM; Hofte, M; Goeken, LNH; Kingma, A; vandenBriel, MM; Kamps, WA

    1996-01-01

    Motor skills were investigated in 18 children 2 years after treatment for acute lymphoblastic leukemia (ALL). Cross and fine motor functioning were examined with the Movement Assessment Battery for Children. Handwriting as a specific fine motor skill was studied with a computerized writing task. We

  15. Serial Ultrasound Monitoring for Early Recognition of Asparaginase Associated Pancreatitis in Children With Acute Lymphoblastic Leukemia

    DEFF Research Database (Denmark)

    Raja, Raheel Altaf; Schmiegelow, K.; Henriksen, Birthe Merete

    2015-01-01

    BACKGROUND: Acute lymphoblastic leukemia (ALL) is the most common cancer in children and L-asparaginase is an essential component of the treatment. Cessation of L-asparaginase decreases event free survival. Acute pancreatitis is the toxicity that most commonly results in cessation of L...

  16. Tracheoesophageal fistula resulting from invasive aspergillosis in acute lymphoblastic leukemia: a case report

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Si Won [Daejeon St. Mary' s Hospital, College of Medicine, Catholic University, Daejeon (Korea, Republic of)

    2006-04-15

    Tracheoesophageal fistula (TEF) in adult patients is an uncommon complication in leukemia. We present here on a case of TEF in a 46-year-old woman with ALL. The patient was asymptomatic and TEF is resulted from aspergillus bronchitis during the chemotherapy for acute lymphoblastic leukemia (ALL)

  17. DNA methylation-based subtype prediction for pediatric acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Nordlund, Jessica; Bäcklin, Christofer L; Zachariadis, Vasilios

    2015-01-01

    BACKGROUND: We present a method that utilizes DNA methylation profiling for prediction of the cytogenetic subtypes of acute lymphoblastic leukemia (ALL) cells from pediatric ALL patients. The primary aim of our study was to improve risk stratification of ALL patients into treatment groups using DNA...

  18. High concordance of subtypes of childhood acute lymphoblastic leukemia within families

    DEFF Research Database (Denmark)

    Schmiegelow, K.; Thomsen, U Lautsen; Baruchel, A

    2012-01-01

    Polymorphic genes have been linked to the risk of acute lymphoblastic leukemia (ALL). Surrogate markers for a low burden of early childhood infections are also related to increased risk for developing childhood ALL. It remains uncertain, whether siblings of children with ALL have an increased risk...

  19. Extremely low-frequency magnetic fields and survival from childhood acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Schüz, J; Grell, K; Kinsey, S

    2012-01-01

    A previous US study reported poorer survival in children with acute lymphoblastic leukemia (ALL) exposed to extremely low-frequency magnetic fields (ELF-MF) above 0.3 μT, but based on small numbers. Data from 3073 cases of childhood ALL were pooled from prospective studies conducted in Canada...

  20. Combining Push Pull Tracer Tests and Microbial DNA and mRNA Analysis to Assess In-Situ Groundwater Nitrate Transformations

    Science.gov (United States)

    Henson, W.; Graham, W. D.; Huang, L.; Ogram, A.

    2015-12-01

    Nitrogen transformation mechanisms in the Upper Floridan Aquifer (UFA) are still poorly understood because of karst aquifer complexity and spatiotemporal variability in nitrate and carbon loading. Transformation rates have not been directly measured in the aquifer. This study quantifies nitrate-nitrogen transformation potential in the UFA using single well push-pull tracer injection (PPT) experiments combined with microbial characterization of extracted water via qPCR and RT-qPCR of selected nitrate reduction genes. Tracer tests with chloride and nitrate ± carbon were executed in two wells representing anoxic and oxic geochemical end members in a spring groundwater contributing area. A significant increase in number of microbes with carbon addition suggests stimulated growth. Increases in the activities of denitrification genes (nirK and nirS) as measured by RT-qPCR were not observed. However, only microbes suspended in the tracer were obtained, ignoring effects of aquifer material biofilms. Increases in nrfA mRNA and ammonia concentrations were observed, supporting Dissimilatory Reduction of Nitrate to Ammonia (DNRA) as a reduction mechanism. In the oxic aquifer, zero order nitrate loss rates ranged from 32 to 89 nmol /L*hr with no added carbon and 90 to 240 nmol /L*hr with carbon. In the anoxic aquifer, rates ranged from 18 to 95 nmol /L*hr with no added carbon and 34 to 207 nmol /L*hr with carbon. These loss rates are low; 13 orders of magnitude less than the loads applied in the contributing area each year, however they do indicate that losses can occur in oxic and anoxic aquifers with and without carbon. These rates may include, ammonia adsorption, uptake, or denitrification in aquifer material biofilms. Rates with and without carbon addition for both aquifers were similar, suggesting aquifer redox state and carbon availability alone are insufficient to predict response to nutrient additions without characterization of microbial response. Surprisingly, these

  1. Combining the least correlation design, wavelet packet transform and correlation coefficient test to reduce the size of calibration set for NIR quantitative analysis in multi-component systems.

    Science.gov (United States)

    Cai, Chen-Bo; Xu, Lu; Han, Qing-Juan; Wu, Hai-Long; Nie, Jin-Fang; Fu, Hai-Yan; Yu, Ru-Qin

    2010-05-15

    The paper focuses on solving a common and important problem of NIR quantitative analysis in multi-component systems: how to significantly reduce the size of the calibration set while not impairing the predictive precision. To cope with the problem orthogonal discrete wavelet packet transform (WPT), the least correlation design and correlation coefficient test (r-test) have been combined together. As three examples, a two-component carbon tetrachloride system with 21 calibration samples, a two-component aqueous system with 21 calibration samples, and a two-component aqueous system with 41 calibration samples have been treated with the proposed strategy, respectively. In comparison with some previous methods based on much more calibration samples, the results out of the strategy showed that the predictive ability was not obviously decreased for the first system while being clearly strengthened for the second one, and the predictive precision out of the third one was even satisfactory enough for most cases of quantitative analysis. In addition, all important factors and parameters related to our strategy are discussed in detail.

  2. Endocrinological and Cardiological Late Effects Among Survivors of Childhood Acute Lymphoblastic Leukemia

    Directory of Open Access Journals (Sweden)

    Hale Ören

    2013-09-01

    Full Text Available Objective: Survival rates for childhood acute lymphoblastic leukemia (ALL have significantly improved and late effects of therapy have been important in the follow-up of survivors. The objective of this study is to identify the endocrinological and cardiological late effects of ALL patients treated in our pediatric hematology unit. Materials and Methods: Patients treated for ALL with BFM protocols after at least 5 years of diagnosis and not relapsed were included in the study. Endocrinological late effects (growth failure, obesity, insulin resistance, dyslipidemia, thyroid gland disorders, osteopenia/osteoporosis, and pubertal disorders and cardiological late effects were evaluated. The study group was evaluated with anthropometric measurements, body mass index, and laboratory testing of fasting glucose, insulin, serum lipids, thyroid functions, and bone mineral densities. Echocardiography and pulsed wave Doppler imaging were performed for analysis of cardiac functions. Results: Of the 38 ALL survivors, at least 1 adverse event occurred in 23 (60%, with 8 of them (21% having multiple problems. Six (16% of the survivors were obese and 8 (21% of them were overweight. Subjects who were overweight or obese at the time of diagnosis were more likely to be overweight or obese at last follow-up. Obesity was more frequently determined in patients who were younger than 6 years of age at the time of diagnosis. Insulin resistance was observed in 8 (21% subjects. Insulin resistance was more frequently seen in subjects who had family history of type 2 diabetes mellitus. Hyperlipidemia was detected in 8 (21% patients. Hypothyroidism or premature thelarche were detected in 2 children. Two survivors had osteopenia. Cardiovascular abnormalities occurred in one of the subjects with hypertension and cardiac diastolic dysfunction. Conclusion: We point out the necessity of follow-up of these patients for endocrinological and cardiological late effects, since at least

  3. Validation of a mouse xenograft model system for gene expression analysis of human acute lymphoblastic leukaemia

    Directory of Open Access Journals (Sweden)

    Francis Richard W

    2010-04-01

    Full Text Available Abstract Background Pre-clinical models that effectively recapitulate human disease are critical for expanding our knowledge of cancer biology and drug resistance mechanisms. For haematological malignancies, the non-obese diabetic/severe combined immunodeficient (NOD/SCID mouse is one of the most successful models to study paediatric acute lymphoblastic leukaemia (ALL. However, for this model to be effective for studying engraftment and therapy responses at the whole genome level, careful molecular characterisation is essential. Results Here, we sought to validate species-specific gene expression profiling in the high engraftment continuous ALL NOD/SCID xenograft. Using the human Affymetrix whole transcript platform we analysed transcriptional profiles from engrafted tissues without prior cell separation of mouse cells and found it to return highly reproducible profiles in xenografts from individual mice. The model was further tested with experimental mixtures of human and mouse cells, demonstrating that the presence of mouse cells does not significantly skew expression profiles when xenografts contain 90% or more human cells. In addition, we present a novel in silico and experimental masking approach to identify probes and transcript clusters susceptible to cross-species hybridisation. Conclusions We demonstrate species-specific transcriptional profiles can be obtained from xenografts when high levels of engraftment are achieved or with the application of transcript cluster masks. Importantly, this masking approach can be applied and adapted to other xenograft models where human tissue infiltration is lower. This model provides a powerful platform for identifying genes and pathways associated with ALL disease progression and response to therapy in vivo.

  4. Are parenting behaviors associated with child sleep problems during treatment for acute lymphoblastic leukemia?

    Science.gov (United States)

    McCarthy, Maria C; Bastiani, Jessica; Williams, Lauren K

    2016-07-01

    Sleep disturbance is a recognized common side effect in children treated for acute lymphoblastic leukemia (ALL). Although associated with treatment factors such as hospitalization and corticosteroids, sleep problems may also be influenced by modifiable environmental factors such as parenting behaviors. The purpose of this study was to examine sleep problems in children undergoing treatment for ALL compared to healthy children and whether parenting practices are associated with sleep difficulties. Parents of 73 children aged 2-6 years who were (1) in the maintenance phase of ALL treatment (ALL group, n = 43) or (2) had no major medical illness (healthy control group, n = 30) participated in the study. Parents completed questionnaires measuring their child's sleep behavior and their own parenting practices. Parents of children undergoing ALL treatment reported significantly more child sleep problems; 48% of children with ALL compared to 23% of healthy children had clinical levels of sleep disturbance. Parents of the ALL group also reported significantly more lax parenting practices and strategies associated with their child's sleep including co-sleeping, comforting activities, and offering food and drink in the bedroom. Results of multivariate regression analysis indicated that, after controlling for illness status, parent-child co-sleeping was significantly associated with child sleep difficulties. Strategies employed by parents during ALL treatment may be a potential modifiable intervention target that could result in improved child sleep behaviors. Future research aimed at developing and testing parenting interventions aimed to improve child sleep in the context of oncology treatment is warranted.

  5. Activity of the Aurora kinase inhibitor VX-680 against Bcr/Abl-positive acute lymphoblastic leukemias.

    Science.gov (United States)

    Fei, Fei; Stoddart, Sonia; Groffen, John; Heisterkamp, Nora

    2010-05-01

    The emergence of resistance to tyrosine kinase inhibitors due to point mutations in Bcr/Abl is a challenging problem for Philadelphia chromosome-positive (Ph-positive) acute lymphoblastic leukemia (ALL) patients, especially for those with the T315I mutation, against which neither nilotinib or dasatinib shows significant activity. VX-680 is a pan-Aurora kinase inhibitor active against all Bcr/Abl proteins but has not been extensively examined in preclinical models of Ph-positive ALL. Here, we have tested VX-680 for the treatment of Bcr/Abl-positive ALL when leukemic cells are protected by the presence of stroma. Under these conditions, VX-680 showed significant effects on primary human Ph-positive ALL cells both with and without the T315I mutation, including ablation of tyrosine phosphorylation downstream of Bcr/Abl, decreased viability, and induction of apoptosis. However, drug treatment of human Ph-positive ALL cells for 3 days followed by drug removal allowed the outgrowth of abnormal cells 21 days later, and on culture of mouse Bcr/Abl ALL cells on stroma with lower concentrations of VX-680, drug-resistant cells emerged. Combined treatment of human ALL cells lacking the T315I mutation with both VX-680 and dasatinib caused significantly more cytotoxicity than each drug alone. We suggest that use of VX-680 together with a second effective drug as first-line treatment for Ph-positive ALL is likely to be safer and more useful than second-line treatment with VX-680 as monotherapy for drug-resistant T315I Ph-positive ALL.

  6. Identification of germline susceptibility loci in ETV6-RUNX1-rearranged childhood acute lymphoblastic leukemia

    Science.gov (United States)

    Ellinghaus, E; Stanulla, M; Richter, G; Ellinghaus, D; te Kronnie, G; Cario, G; Cazzaniga, G; Horstmann, M; Panzer Grümayer, R; Cavé, H; Trka, J; Cinek, O; Teigler-Schlegel, A; ElSharawy, A; Häsler, R; Nebel, A; Meissner, B; Bartram, T; Lescai, F; Franceschi, C; Giordan, M; Nürnberg, P; Heinzow, B; Zimmermann, M; Schreiber, S; Schrappe, M; Franke, A

    2012-01-01

    Acute lymphoblastic leukemia (ALL) is a malignant disease of the white blood cells. The etiology of ALL is believed to be multifactorial and likely to involve an interplay of environmental and genetic variables. We performed a genome-wide association study of 355 750 single-nucleotide polymorphisms (SNPs) in 474 controls and 419 childhood ALL cases characterized by a t(12;21)(p13;q22) — the most common chromosomal translocation observed in childhood ALL — which leads to an ETV6–RUNX1 gene fusion. The eight most strongly associated SNPs were followed-up in 951 ETV6-RUNX1-positive cases and 3061 controls from Germany/Austria and Italy, respectively. We identified a novel, genome-wide significant risk locus at 3q28 (TP63, rs17505102, PCMH=8.94 × 10−9, OR=0.65). The separate analysis of the combined German/Austrian sample only, revealed additional genome-wide significant associations at 11q11 (OR8U8, rs1945213, P=9.14 × 10−11, OR=0.69) and 8p21.3 (near INTS10, rs920590, P=6.12 × 10−9, OR=1.36). These associations and another association at 11p11.2 (PTPRJ, rs3942852, P=4.95 × 10−7, OR=0.72) remained significant in the German/Austrian replication panel after correction for multiple testing. Our findings demonstrate that germline genetic variation can specifically contribute to the risk of ETV6–RUNX1-positive childhood ALL. The identification of TP63 and PTPRJ as susceptibility genes emphasize the role of the TP53 gene family and the importance of proteins regulating cellular processes in connection with tumorigenesis. PMID:22076464

  7. Current Concepts in Pediatric Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia

    Science.gov (United States)

    Bernt, Kathrin M.; Hunger, Stephen P.

    2014-01-01

    The t(9;22)(q34;q11) or Philadelphia chromosome creates a BCR–ABL1 fusion gene encoding for a chimeric BCR–ABL1 protein. It is present in 3–4% of pediatric acute lymphoblastic leukemia (Ph+ ALL), and about 25% of adult ALL cases. Prior to the advent of tyrosine kinase inhibitors (TKI), Ph+ ALL was associated with a very poor prognosis despite the use of intensive chemotherapy and frequently hematopoietic stem-cell transplantation (HSCT) in first remission. The development of TKIs revolutionized the therapy of Ph+ ALL. Addition of the first generation ABL1 class TKI imatinib to intensive chemotherapy dramatically increased the survival for children with Ph+ ALL and established that many patients can be cured without HSCT. In parallel, the mechanistic understanding of Ph+ ALL expanded exponentially through careful mapping of pathways downstream of BCR–ABL1, the discovery of mutations in master regulators of B-cell development such as IKZF1 (Ikaros), PAX5, and early B-cell factor (EBF), the recognition of the complex clonal architecture of Ph+ ALL, and the delineation of genomic, epigenetic, and signaling abnormalities contributing to relapse and resistance. Still, many important basic and clinical questions remain unanswered. Current clinical trials are testing second generation TKIs in patients with newly diagnosed Ph+ ALL. Neither the optimal duration of therapy nor the optimal chemotherapy backbone are currently defined. The role of HSCT in first remission and post-transplant TKI therapy also require further study. In addition, it will be crucial to continue to dig deeper into understanding Ph+ ALL at a mechanistic level, and translate findings into complementary targeted approaches. Expanding targeted therapies hold great promise to decrease toxicity and improve survival in this high-risk disease, which provides a paradigm for how targeted therapies can be incorporated into treatment of other high-risk leukemias. PMID:24724051

  8. Physical activity and late effects in childhood acute lymphoblastic leukemia long-term survivors.

    Science.gov (United States)

    Bertorello, N; Manicone, R; Galletto, C; Barisone, E; Fagioli, F

    2011-08-01

    In the present study the authors evaluated therapy-related long-term adverse effects and physical activity in a cohort of long-term survivors of childhood acute lymphoblastic leukemia (ALL), diagnosed in their center between March 1991 and August 2000, treated according to the AIEOP (Associazione Italiana di Ematologia e Oncologia Pediatrica) ALL 91 or 95 study protocol and regularly seen in the authors' long-term follow-up unit. The authors analyzed the long-term sequelae of major body systems in this cohort of subjects and administered an "ad hoc" questionnaire concerning sport. The authors found that 70 patients out of 102 (68.5%) showed no late effects, 10% presented only instrumental or neuropsychological test abnormalities, and 21.5% had 1 or more clinical late sequelae. None of the evidenced late effects represented a contraindication to do physical activity. Sixty-one percent of survivors do physical activity, most of them regularly. Sixty-one percent of males and 18.5% of females (P < .005) do competitive sport (sports rates are similar to those of the general age-matched population). Nearly all subjects spontaneously choose to do sport and think physical exercise is an important and useful resource for their health. The authors conclude that the more recent therapy regimens for leukemia treatment, excluding bone marrow transplantation, do not seem to cause such late effects as to prevent survivors from doing sport. Therefore, in the care of ALL survivors, physical activity is not only not contraindicated, but should also be promoted as much as possible. The development of specific educational programs is warranted as part of the care of cancer survivors.

  9. Hadamard Transforms

    CERN Document Server

    Agaian, Sos; Egiazarian, Karen; Astola, Jaakko

    2011-01-01

    The Hadamard matrix and Hadamard transform are fundamental problem-solving tools in a wide spectrum of scientific disciplines and technologies, such as communication systems, signal and image processing (signal representation, coding, filtering, recognition, and watermarking), digital logic (Boolean function analysis and synthesis), and fault-tolerant system design. Hadamard Transforms intends to bring together different topics concerning current developments in Hadamard matrices, transforms, and their applications. Each chapter begins with the basics of the theory, progresses to more advanced

  10. Demonstration of In situ Anaerobic Transformation of Toluene and Xylene Using Single-Well Push-Pull Tests and Deuterated BTEX Surrogates

    Science.gov (United States)

    Field, J. A.; Reusser, D. E.; Beller, H. R.; Istok, J. D.

    2001-12-01

    Obtaining unambiguous evidence of in-situ transformation of benzene, toluene, ethylbenzene and xylene (BTEX) in the subsurface is a difficult task. Recently, benzylsuccinic acid and its methyl analogues were shown to be unequivocal degradation products of anaerobic toluene and xylene biodegradation. Conducting tracer tests at BTEX-contaminated field sites is problematic because background contaminant concentrations potentially interfere with the interpretation of field test data. To avoid the time and cost associated with removing background contaminants, alternative approaches are needed. Deuterated analogs of toluene and xylene are well-suited for use in field tracer tests because they are inexpensive and can be distinguished analytically from background toluene and xylene. In this study, single-well push-pull tests, in which deuterated toluene and xylene were injected, were performed to assess the in-situ anaerobic biotransformation of toluene and xylene in BTEX-contaminated wells. A total of 4 single-well push-pull tests were conducted at BTEX-contaminated field sites near Portland, OR and Kansas City, KS. Test solutions consisting of 100 mg/L bromide, 250 mg/L nitrate, 0.4 to 2.5 mg/L toluene-d8, and 0.4 to 1.0 mg/L o-xylene-d10.were injected at a rate of 0.5 - 2 L/min. During the extraction phase, samples were taken daily to biweekly for up to 30 days. Samples for volatile organic analytes were collected in 40-mL volatile organic analysis (VOA) vials without headspace. Samples for BSA and methyl-BSA were collected in 1 L glass bottles and preserved with 5% (w/w) formalin. Samples were shipped on ice and stored at 4 C until analysis. Unambiguous evidence of toluene and xylene biotransformation was obtained with the in-situ formation of BSA and methyl-BSA. The concentrations of BSA ranged from below the detection limit (0.2 ug/L) to 1.5 ug/L. The concentrations of methyl-BSA ranged from below detection to the quantitation limit (0.7 ug/L). The highest BSA

  11. Outcomes after Induction Failure in Childhood Acute Lymphoblastic Leukemia

    Science.gov (United States)

    Schrappe, Martin; Hunger, Stephen P.; Pui, Ching-Hon; Saha, Vaskar; Gaynon, Paul S.; Baruchel, André; Conter, Valentino; Otten, Jacques; Ohara, Akira; Versluys, Anne Birgitta; Escherich, Gabriele; Heyman, Mats; Silverman, Lewis B.; Horibe, Keizo; Mann, Georg; Camitta, Bruce M.; Harbott, Jochen; Riehm, Hansjörg; Richards, Sue; Devidas, Meenakshi; Zimmermann, Martin

    2012-01-01

    BACKGROUND Failure of remission-induction therapy is a rare but highly adverse event in children and adolescents with acute lymphoblastic leukemia (ALL). METHODS We identified induction failure, defined by the persistence of leukemic blasts in blood, bone marrow, or any extramedullary site after 4 to 6 weeks of remission-induction therapy, in 1041 of 44,017 patients (2.4%) 0 to 18 years of age with newly diagnosed ALL who were treated by a total of 14 cooperative study groups between 1985 and 2000. We analyzed the relationships among disease characteristics, treatments administered, and outcomes in these patients. RESULTS Patients with induction failure frequently presented with high-risk features, including older age, high leukocyte count, leukemia with a T-cell phenotype, the Philadelphia chromosome, and 11q23 rearrangement. With a median follow-up period of 8.3 years (range, 1.5 to 22.1), the 10-year survival rate (±SE) was estimated at only 32±1%. An age of 10 years or older, T-cell leukemia, the presence of an 11q23 rearrangement, and 25% or more blasts in the bone marrow at the end of induction therapy were associated with a particularly poor outcome. High hyperdiploidy (a modal chromosome number >50) and an age of 1 to 5 years were associated with a favorable outcome in patients with precursor B-cell leukemia. Allogeneic stem-cell transplantation from matched, related donors was associated with improved outcomes in T-cell leukemia. Children younger than 6 years of age with precursor B-cell leukemia and no adverse genetic features had a 10-year survival rate of 72±5% when treated with chemotherapy only. CONCLUSIONS Pediatric ALL with induction failure is highly heterogeneous. Patients who have T-cell leukemia appear to have a better outcome with allogeneic stem-cell transplantation than with chemotherapy, whereas patients who have precursor B-cell leukemia without other adverse features appear to have a better outcome with chemotherapy. (Funded by Deutsche

  12. Second Malignant Neoplasms After Treatment of Childhood Acute Lymphoblastic Leukemia

    Science.gov (United States)

    Schmiegelow, Kjeld; Levinsen, Mette Frandsen; Attarbaschi, Andishe; Baruchel, Andre; Devidas, Meenakshi; Escherich, Gabriele; Gibson, Brenda; Heydrich, Christiane; Horibe, Keizo; Ishida, Yasushi; Liang, Der-Cherng; Locatelli, Franco; Michel, Gérard; Pieters, Rob; Piette, Caroline; Pui, Ching-Hon; Raimondi, Susana; Silverman, Lewis; Stanulla, Martin; Stark, Batia; Winick, Naomi; Valsecchi, Maria Grazia

    2013-01-01

    Purpose Second malignant neoplasms (SMNs) after diagnosis of childhood acute lymphoblastic leukemia (ALL) are rare events. Patients and Methods We analyzed data on risk factors and outcomes of 642 children with SMNs occurring after treatment for ALL from 18 collaborative study groups between 1980 and 2007. Results Acute myeloid leukemia (AML; n = 186), myelodysplastic syndrome (MDS; n = 69), and nonmeningioma brain tumor (n = 116) were the most common types of SMNs and had the poorest outcome (5-year survival rate, 18.1% ± 2.9%, 31.1% ± 6.2%, and 18.3% ± 3.8%, respectively). Five-year survival estimates for AML were 11.2% ± 2.9% for 125 patients diagnosed before 2000 and 34.1% ± 6.3% for 61 patients diagnosed after 2000 (P < .001); 5-year survival estimates for MDS were 17.1% ± 6.4% (n = 36) and 48.2% ± 10.6% (n = 33; P = .005). Allogeneic stem-cell transplantation failed to improve outcome of secondary myeloid malignancies after adjusting for waiting time to transplantation. Five-year survival rates were above 90% for patients with meningioma, Hodgkin lymphoma, thyroid carcinoma, basal cell carcinoma, and parotid gland tumor, and 68.5% ± 6.4% for those with non-Hodgkin lymphoma. Eighty-nine percent of patients with brain tumors had received cranial irradiation. Solid tumors were associated with cyclophosphamide exposure, and myeloid malignancy was associated with topoisomerase II inhibitors and starting doses of methotrexate of at least 25 mg/m2 per week and mercaptopurine of at least 75 mg/m2 per day. Myeloid malignancies with monosomy 7/5q− were associated with high hyperdiploid ALL karyotypes, whereas 11q23/MLL-rearranged AML or MDS was associated with ALL harboring translocations of t(9;22), t(4;11), t(1;19), and t(12;21) (P = .03). Conclusion SMNs, except for brain tumors, AML, and MDS, have outcomes similar to their primary counterparts. PMID:23690411

  13. RUNX1 is required for oncogenic Myb and Myc enhancer activity in T cell acute lymphoblastic leukemia.

    Science.gov (United States)

    Choi, AHyun; Illendula, Anuradha; Pulikkan, John A; Roderick, Justine E; Tesell, Jessica; Yu, Jun; Hermance, Nicole; Zhu, Lihua Julie; Castilla, Lucio H; Bushweller, John H; Kelliher, Michelle A

    2017-08-08

    The gene encoding the RUNX1 transcription factor is mutated in a subset of T cell acute lymphoblastic leukemia (T-ALL) patients and RUNX1 mutations are associated with a poor prognosis. These mutations cluster in the DNA binding Runt domain, are thought to represent loss-of-function mutations, indicating that RUNX1 suppresses T cell transformation. RUNX1 has been proposed to have tumor suppressor roles in TLX1/3 transformed human T-ALL cell lines and NOTCH1 T-ALL mouse models. Yet retroviral insertional mutagenesis screens identify RUNX genes as collaborating oncogenes in MYC-driven leukemia mouse models. To elucidate RUNX1 function(s) in leukemogenesis, we generated Tal1/Lmo2/Rosa26-CreER(T2)Runx1(f/f) mice and examined leukemia progression in the presence of vehicle or tamoxifen. We found that Runx1 deletion inhibits mouse leukemic growth in vivo and that RUNX silencing in human T-ALL cells triggers apoptosis. We demonstrate that a small molecule inhibitor, designed to interfere with CBFβ binding to RUNX proteins, impairs the growth of human T-ALL cell lines and primary patient samples. We demonstrate that a RUNX1 deficiency alters the expression of a crucial subset of TAL1- and NOTCH1-regulated genes including the MYB and MYC oncogenes, respectively. These studies provide genetic and pharmacologic evidence that RUNX1 has oncogenic roles and reveal RUNX1 as a novel therapeutic target in T-ALL. Copyright © 2017 American Society of Hematology.

  14. Novel cryptic chromosomal rearrangements detected in acute lymphoblastic leukemia detected by application of new multicolor fluorescent in situ hybridization approaches

    NARCIS (Netherlands)

    Karst, C; Gross, M; Haase, D; Wedding, U; Hoffken, K; Liehr, T; Mkrtchyan, H

    2006-01-01

    Routine cytogenetic analysis provides important information on diagnostic and prognostic relevance for hematological malignancies. However, it is often difficult to obtain good karyotypes, especially of cells from cases with acute lymphoblastic leukemia (ALL) because of poor morphology and spreading

  15. Unusual cytochemical reactivity for toluidine blue in granular acute lymphoblastic leukemia: a report of two rare cases

    Directory of Open Access Journals (Sweden)

    Rishu Agarwal

    2010-03-01

    Full Text Available Azurophilic granulation of blasts is a feature of acute myeloid leukemia (AML. Granular acute lymphoblastic leukemia (ALL may mimic AML due to the presence of cytoplasmic granules in lymphoblasts, but cytochemistry and immunophenotyping are helpful in making the correct diagnosis. Toluidine blue (TB is a metachromatic dye, which stains basophils and myeloid blasts that exhibit basophilic differentiation. Reactivity for TB has not been described in lymphoblasts. We herein report two cases of granular ALL with blasts exhibiting reactivity for TB that caused diagnostic dilemma. Immunophenotyping and cytogenetic studies were helpful in making a correct diagnosis. This report of two rare case highlight the reactivity of lymphoblasts with TB not hitherto described and the importance of a detailed diagnostic work-up in acute leukemia.

  16. Prospective study on incidence, risk factors, and long-term outcome of osteonecrosis in pediatric acute lymphoblastic leukemia.

    NARCIS (Netherlands)

    Winkel, M.L. te; Pieters, R.; Hop, W.C.J.; Groot-Kruseman, H.A. de; Lequin, M.H.; Sluis, I.M. van der; Bokkerink, J.P.M.; Leeuw, J.A. de; Bruin, M.C.; Egeler, R.M.; Veerman, A.J.P.; Heuvel-Eibrink, M.M. van den

    2011-01-01

    PURPOSE: We studied cumulative incidence, risk factors, therapeutic strategies, and outcome of symptomatic osteonecrosis in pediatric patients with acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS: Cumulative incidence of osteonecrosis was assessed prospectively in 694 patients treated with

  17. Prospective Study on Incidence, Risk Factors, and Long-Term Outcome of Osteonecrosis in Pediatric Acute Lymphoblastic Leukemia

    NARCIS (Netherlands)

    Winkel, Mariel L. Te; Pieters, Rob; Hop, Wim C. J.; de Groot-Kruseman, Hester A.; Lequin, Maarten H.; van der Sluis, Inge M.; Bokkerink, Jos P. M.; Leeuw, Jan A.; Bruin, Marrie C. A.; Egeler, R. Maarten; Veerman, Anjo J. P.; van den Heuvel-Eibrink, Marry M.

    2011-01-01

    Purpose We studied cumulative incidence, risk factors, therapeutic strategies, and outcome of symptomatic osteonecrosis in pediatric patients with acute lymphoblastic leukemia (ALL). Patients and Methods Cumulative incidence of osteonecrosis was assessed prospectively in 694 patients treated with th

  18. No major cognitive impairment in young children with acute lymphoblastic leukemia using chemotherapy only : A prospective longitudinal study

    NARCIS (Netherlands)

    Kingma, A; Van Dommelen, RI; Mooyaart, EL; Wilmink, JT; Deelman, BG; Kamps, WA

    2002-01-01

    Purpose: To study. using serial neuropsychological assessment and evaluation of school achievement, persistent neuropsychological late effects in children treated for acute lymphoblastic leukemia (ALL) at a young age with chemotherapy only. Patients and Methods: Twenty consecutive patients underwent

  19. Gene Dose Effects of GSTM1, GSTT1 and GSTP1 Polymorphisms on Outcome in Childhood Acute Lymphoblastic Leukemia

    DEFF Research Database (Denmark)

    Borst, Louise; Buchard, Anders; Rosthoj, Susanne

    2012-01-01

    Children with acute lymphoblastic leukemia (ALL) react very differently to chemotherapy. One explanation for this is inherited genetic variation. The glutathione S-transferase (GST) enzymes inactivate a number of chemotherapeutic drugs administered in childhood ALL therapy. Two multiplexing methods...

  20. Efficacy and Toxicity of Intrathecal Liposomal Cytarabine in First-line Therapy of Childhood Acute Lymphoblastic Leukemia

    DEFF Research Database (Denmark)

    Levinsen, Mette; Harila-Saari, Arja; Grell, Kathrine

    2016-01-01

    We investigated efficacy and toxicity of replacing conventional triple (cytarabine, methotrexate, and hydrocortisone) intrathecal therapy (TIT) with liposomal cytarabine during maintenance therapy among 40 acute lymphoblastic leukemia patients. Twenty-eight of 29 patients in the TIT arm received...

  1. DNA Methylation Adds Prognostic Value to Minimal Residual Disease Status in Pediatric T-Cell Acute Lymphoblastic Leukemia

    DEFF Research Database (Denmark)

    Borssén, Magnus; Haider, Zahra; Landfors, Mattias

    2016-01-01

    BACKGROUND: Despite increased knowledge about genetic aberrations in pediatric T-cell acute lymphoblastic leukemia (T-ALL), no clinically feasible treatment-stratifying marker exists at diagnosis. Instead patients are enrolled in intensive induction therapies with substantial side effects...

  2. Treosulfan, Fludarabine Phosphate, and Total-Body Irradiation Before Donor Stem Cell Transplant in Treating Patients With High-Risk Acute Myeloid Leukemia, Myelodysplastic Syndrome, Acute Lymphoblastic Leukemia

    Science.gov (United States)

    2013-10-29

    Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Blastic Phase Chronic Myelogenous Leukemia; Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Acute Myeloid Leukemia in Remission; Childhood Chronic Myelogenous Leukemia; Childhood Myelodysplastic Syndromes; Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Childhood Acute Lymphoblastic Leukemia

  3. Power transformers quality assurance

    CERN Document Server

    Dasgupta, Indrajit

    2009-01-01

    About the Book: With the view to attain higher reliability in power system operation, the quality assurance in the field of distribution and power transformers has claimed growing attention. Besides new developments in the material technology and manufacturing processes of transformers, regular diagnostic testing and maintenance of any engineering product may be ascertained by ensuring: right selection of materials and components and their quality checks. application of correct manufacturing processes any systems engineering. the user`s awareness towards preventive maintenance. The

  4. Transformer and Meter Tester

    Science.gov (United States)

    Stoms, R. M.

    1984-01-01

    Numerically-controlled 5-axis machine tool uses transformer and meter to determine and indicate whether tool is in home position, but lacks built-in test mode to check them. Tester makes possible test, and repair of components at machine rather then replace them when operation seems suspect.

  5. Evidence for deterministic chaos in aperiodic oscillations of acute lymphoblastic leukemia cells in long-term culture

    Science.gov (United States)

    Lambrou, George I.; Chatziioannou, Aristotelis; Vlahopoulos, Spiros; Moschovi, Maria; Chrousos, George P.

    Biological systems are dynamic and possess properties that depend on two key elements: initial conditions and the response of the system over time. Conceptualizing this on tumor models will influence conclusions drawn with regard to disease initiation and progression. Alterations in initial conditions dynamically reshape the properties of proliferating tumor cells. The present work aims to test the hypothesis of Wolfrom et al., that proliferation shows evidence for deterministic chaos in a manner such that subtle differences in the initial conditions give rise to non-linear response behavior of the system. Their hypothesis, tested on adherent Fao rat hepatoma cells, provides evidence that these cells manifest aperiodic oscillations in their proliferation rate. We have tested this hypothesis with some modifications to the proposed experimental setup. We have used the acute lymphoblastic leukemia cell line CCRF-CEM, as it provides an excellent substrate for modeling proliferation dynamics. Measurements were taken at time points varying from 24h to 48h, extending the assayed populations beyond that of previous published reports that dealt with the complex dynamic behavior of animal cell populations. We conducted flow cytometry studies to examine the apoptotic and necrotic rate of the system, as well as DNA content changes of the cells over time. The cells exhibited a proliferation rate of nonlinear nature, as this rate presented oscillatory behavior. The obtained data have been fit in known models of growth, such as logistic and Gompertzian growth.

  6. 电力变压器离线局部放电测量试验中的容升现象分析%Analysis of capacitive voltage rise during off-line partial discharge tests on power transformers

    Institute of Scientific and Technical Information of China (English)

    王烜; 曹晓珑; 李云阁; 刘英

    2007-01-01

    Partial discharge test on a transformer is carried out according to the items in IEC 60. During the test, unproved measuring system is calibrated by proved system at a voltage no less than 50% the rated testing voltage. The result is then extrapolated linearly, leading to an error related to the distribution of stray capacitance, which varies with the testing frequency, especially to large transformers. In this paper a factor, named the capacitive rise fact, is introduced to assess the rise. The factor can be adjusted to some extent by changing the reactance that is connected to the LV side of the testing circuit to lower the capacity of the power source. However, the factor changes when the voltage divider on the high voltage side is removed after the voltage ratio has been calculated, and a great error is resulted under unfavorable conditions.

  7. Diffusion tensor imaging and neurocognition in survivors of childhood acute lymphoblastic leukaemia.

    Science.gov (United States)

    Edelmann, Michelle N; Krull, Kevin R; Liu, Wei; Glass, John O; Ji, Qing; Ogg, Robert J; Sabin, Noah D; Srivastava, Deo Kumar; Robison, Leslie L; Hudson, Melissa M; Reddick, Wilburn E

    2014-11-01

    Survivors of childhood acute lymphoblastic leukaemia are at risk for neurocognitive impairment, though little information is available on its association with brain integrity, particularly for survivors treated without cranial radiation therapy. This study compares neurocognitive function and brain morphology in long-term adult survivors of childhood acute lymphoblastic leukaemia treated with chemotherapy alone (n = 36) to those treated with cranial radiation therapy (n = 39) and to healthy control subjects (n = 23). Mean (standard deviation) age at evaluation was 24.9 (3.6) years for the chemotherapy group and 26.7 (3.4) years for the cranial radiation therapy group, while time since diagnosis was 15.0 (1.7) and 23.9 (3.1) years, respectively. Brain grey and white matter volume and diffusion tensor imaging was compared between survivor groups and to 23 healthy controls with a mean (standard deviation) age of 23.1 (2.6) years. Survivors treated with chemotherapy alone had higher fractional anisotropy in fibre tracts within the left (P < 0.05), but not in the right, hemisphere when compared to controls. Survivors of acute lymphoblastic leukaemia, regardless of treatment, had a lower ratio of white matter to intracranial volume in frontal and temporal lobes (P < 0.05) compared with control subjects. Survivors of acute lymphoblastic leukaemia treated with chemotherapy alone performed worse in processing speed (P < 0.001), verbal selective reminding (P = 0.01), and academics (P < 0.05) compared to population norms and performed better than survivors treated with cranial radiation therapy on verbal selective reminding (P = 0.02), processing speed (P = 0.05) and memory span (P = 0.009). There were significant associations between neurocognitive performance and brain imaging, particularly for frontal and temporal white and grey matter volume. Survivors of acute lymphoblastic leukaemia treated with chemotherapy alone demonstrated significant long-term differences in

  8. Diphtheria Toxin/Human B-Cell Activating Factor Fusion Protein Kills Human Acute Lymphoblastic Leukemia BALL-1 Cells: An Experimental Study

    Institute of Scientific and Technical Information of China (English)

    Xin-pu Gao; Zheng-min Liu; Yu-lian Jiao; Bin Cui; Yue-ting Zhu; Jie Zhang; Lai-cheng Wang; Yue-ran Zhao

    2012-01-01

    Objective:This study aimed to express a fusion protein of diphtheria toxin and human B ceil-activating factor (DT388sBAFF) in Escherichia coli (E.coli) and investigate its activity in human B-lineage acute lymphoblastic leukemia 1 cells (BALL-1).Methods:A fragment of DT388sBAFF fusion gene was separated from plasmid pUC57-DT388sBAFF digested with Nde Ⅰ and Xho Ⅰ,and inserted into the expression vector pcold Ⅱ digested with the same enzymes.Recombinants were screened by the colony polymerase chain reaction (PCR) and restriction map.The recombinant expression vector was transformed into BL21 and its expression was induced by isopropyl β-D-1-thiogalactopyranoside (IPTG).The recombinant protein was identified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and Western blot,and then purified by Ni2+-NTA affinity chromatography.The expression level of B cell-activating factor receptor (BAFF-R) on BALL-1 cells was assessed by real-time PCR.The receptor binding capacity of recombinant protein was determined by cell fluorescent assay.The specific cytotoxicity of recombinant protein on BALL-1 cells was detected by 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT) assay.Results:The expression level of recombinant protein was 50% of total bacterial proteins in E.coli,and the recombinant protein could bind to BAFF-R-positive BALL-1 cells and thereby produce a cytotoxic effect on the cells.Conclusion:The fusion protein expression vector DT388sBAFF was successfully constructed and the recombinant protein with selective cytotoxicity against BALL-1 cells was obtained,providing foundation for further study of the therapy of human B-lineage acute lymphoblastic leukemia.

  9. Organelle transformation.

    Science.gov (United States)

    Bhattacharya, Anjanabha; Kumar, Anish; Desai, Nirali; Parikh, Seema

    2012-01-01

    The source of genetic information in a plant cell is contained in nucleus, plastids, and mitochondria. Organelle transformation is getting a lot of attention nowadays because of its superior performance over the conventional and most commonly used nuclear transformation for obtaining transgenic lines. Absence of gene silencing, strong predictable transgene expression, and its application in molecular pharming, both in pharmaceutical and nutraceuticals, are some of many advantages. Other important benefits of utilizing this technology include the absence of transgene flow, as organelles are maternally inherited. This may increase the acceptability of organelle transformation technology in the development of transgenic crops in a wider scale all over the globe. As the need for crop productivity and therapeutic compounds increases, organelle transformation may be able to bridge the gap, thereby having a definite promise for the future.

  10. Visualizing Transformation

    DEFF Research Database (Denmark)

    Pedersen, Pia

    2012-01-01

    Transformation, defined as the step of extracting, arranging and simplifying data into visual form (M. Neurath, 1974), was developed in connection with ISOTYPE (International System Of TYpographic Picture Education) and might well be the most important legacy of Isotype to the field of graphic...... design. Recently transformation has attracted renewed interest because of the book ‘The Transformer’ written by Robin Kinross and Marie Neurath. My on-going research project, summarized in this paper, identifies and depicts the essential principles of data visualization underlying the process...... of transformation with reference to Marie Neurath’s sketches on the Bilston Project. The material has been collected at the Otto and Marie Neurath Collection housed at the University of Reading, UK. By using data visualization as a research method to look directly into the process of transformation the project...

  11. Transformational leadership.

    Science.gov (United States)

    Luzinski, Craig

    2011-12-01

    This month, the director of the Magnet Recognition Program® takes an in-depth look at the Magnet® model component transformational leadership. The author examines the expectations for Magnet organizations around this component. What are the qualities that make a nursing leader truly transformational, and what is the best approach to successfully lead a healthcare organization through today's volatile healthcare environment?

  12. Landskabets transformation

    DEFF Research Database (Denmark)

    Munck Petersen, Rikke

    2005-01-01

    Seminaroplæg fra forskere. Faglige seminarer på KA, forår 2005. Belyser transformation af det danske landskab fysisk som holdningsmæssigt, samt hvordan phd-arbejdets egen proces håndterer den.......Seminaroplæg fra forskere. Faglige seminarer på KA, forår 2005. Belyser transformation af det danske landskab fysisk som holdningsmæssigt, samt hvordan phd-arbejdets egen proces håndterer den....

  13. Cerebral venous thrombosis in adult patients with acute lymphoblastic leukemia or lymphoblastic lymphoma during induction chemotherapy with l-asparaginase: The GRAALL experience.

    Science.gov (United States)

    Couturier, Marie-Anne; Huguet, Françoise; Chevallier, Patrice; Suarez, Felipe; Thomas, Xavier; Escoffre-Barbe, Martine; Cacheux, Victoria; Pignon, Jean-Michel; Bonmati, Caroline; Sanhes, Laurence; Bories, Pierre; Daguindau, Etienne; Dorvaux, Véronique; Reman, Oumedaly; Frayfer, Jamile; Orvain, Corentin; Lhéritier, Véronique; Ifrah, Norbert; Dombret, Hervé; Hunault-Berger, Mathilde; Tanguy-Schmidt, Aline

    2015-11-01

    Central nervous system (CNS) thrombotic events are a well-known complication of acute lymphoblastic leukemia (ALL) induction therapy, especially with treatments including l-asparaginase (l-ASP). Data on risk factors and clinical evolution is still lacking in adult patients. We report on the clinical evolution of 22 CNS venous thrombosis cases occurring in 708 adults treated for ALL or lymphoblastic lymphoma (LL) with the Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL)-induction protocol, which included eight L-ASP (6,000 IU/m(2) ) infusions. The prevalence of CNS thrombosis was 3.1%. CNS thrombosis occurred after a median of 18 days (range: 11-31) when patients had received a median of three l-ASP injections (range: 2-7). Patients with CNS thrombosis exhibited a median antithrombin (AT) nadir of 47.5% (range: 36-67%) at Day 17 (range: D3-D28), and 95% of them exhibited AT levels lower than 60%. There were no evident increase in hereditary thrombotic risk factors prevalence, and thrombosis occurred despite heparin prophylaxis which was performed in 90% of patients. Acquired AT deficiency was frequently detected in patients with l-ASP-based therapy, and patients with CNS thrombosis received AT prophylaxis (45%) less frequently than patients without CNS thrombosis (83%), P = 0.0002). CNS thrombosis was lethal in 5% of patients, while 20% had persistent sequelae. One patient received all planned l-ASP infusions without recurrence of CNS thrombotic whereas l-ASP injections were discontinued in 20 patients during the management of thrombosis without a significant impact on overall survival (P = 0.4).

  14. Cable Type Installation of Main Transformer and Testing for Sensing Compression Resistance%电缆进线式主变压器安装及感应耐压试验研究

    Institute of Scientific and Technical Information of China (English)

    李彦

    2012-01-01

    基于某变电站主变压器的安装和试验经验,对电缆进线主变压器安装控制和感应耐压试验进行了研究,重点介绍了电缆进线式主变压器安装控制要点及感应耐压试验所遇到的困难、解决措施以及主变压器感应耐压试验方法和原理。%Based on the author's participation of a substation main transformer installation and test experience, this paper makes a study of the cable line installation of main transformer control induction voltage endurance test. It mainly introduces the cable type installation of main transformer and induction withstanding voltage test of control points and the difficulties encountered, solutions and the main transformer induction withstand voltage test method and principle.

  15. 变压器油老化对介损的影响及其绝缘寿命试验的研究%Influence of Aging Transformer Oil to Dielectric Loss Factor and Research on Insulation Life Test

    Institute of Scientific and Technical Information of China (English)

    王献敏; 马勇飞; 窦鹏

    2011-01-01

    The influence of aging transformer oil to dielectric loss factor is analyzed. The insulation life is tested.%对变压器油老化对介损的影响进行了分析,并对其绝缘寿命进行了试验.

  16. [Heterogeneity and clonal evolution in pediatric ETV6-RUNX1(+) acute lymphoblastic leukemia by quantitative multigene fluorescence in situ hybridization].

    Science.gov (United States)

    Zhang, L; Hu, L P; Liu, X M; Guo, Y; Yang, W Y; Zhang, J Y; Liu, F; Liu, T F; Wang, S C; Chen, X J; Ruan, M; Qi, B Q; Chang, L X; Chen, Y M; Zou, Y; Zhu, X F

    2017-07-14

    Objective: To evaluate heterogeneity and clonal evolution in pediatric ETV6-RUNX1(+) acute lymphoblastic leukemia (ALL) in China. Methods: Totally 48 children (<14 years) with newly diagnosed ETV6-RUNX1(+) ALL in Institute of Hematology and Blood Disease Hospital, CAMS and PUMC, from February 2006 to June 2011 were included. The copy number variations were analyzed by quantitative multigene fluorescence in situ hybridization (QM-FISH) in 48 patients. Non-normal distribution of measurement data were shown with Median (range) , count data were shown with percent (%) . Overall survival and event-free survival were estimated by the Kaplan-Meier method and compared with the log-rank test. Results: Forty-eight patients were tested by QM-FISH. Of 48 patients, 70.8% harbored one clone, 18.8% two subclones, and 10.4% three or more subclones. The clone heterogeneity was detected by two different models: the linear succession model and the branching evolution model. ETV6-RUNX1(+) ALL relapse evolved from an ancestral clone or a new clone. The patients relapsed from a new clone got the worse outcome. Conclusion: The clone evolution was detected in pediatric ETV6-RUNX1(+) ALL in China. QM-FISH might be helpful to evaluate the outcome of relapsed patients. A new clone was associated with a poorer outcome.

  17. Discovery and identification of potential biomarkers of pediatric Acute Lymphoblastic Leukemia

    Directory of Open Access Journals (Sweden)

    Cui Ziyou

    2009-03-01

    Full Text Available Abstract Background Acute lymphoblastic leukemia (ALL is a common form of cancer in children. Currently, bone marrow biopsy is used for diagnosis. Noninvasive biomarkers for the early diagnosis of pediatric ALL are urgently needed. The aim of this study was to discover potential protein biomarkers for pediatric ALL. Methods Ninety-four pediatric ALL patients and 84 controls were randomly divided into a "training" set (45 ALL patients, 34 healthy controls and a test set (49 ALL patients, 30 healthy controls and 30 pediatric acute myeloid leukemia (AML patients. Serum proteomic profiles were measured using surface-enhanced laser desorption/ionization-time-of-flight mass spectroscopy (SELDI-TOF-MS. A classification model was established by Biomarker Pattern Software (BPS. Candidate protein biomarkers were purified by HPLC, identified by LC-MS/MS and validated using ProteinChip immunoassays. Results A total of 7 protein peaks (9290 m/z, 7769 m/z, 15110 m/z, 7564 m/z, 4469 m/z, 8937 m/z, 8137 m/z were found with differential expression levels in the sera of pediatric ALL patients and controls using SELDI-TOF-MS and then analyzed by BPS to construct a classification model in the "training" set. The sensitivity and specificity of the model were found to be 91.8%, and 90.0%, respectively, in the test set. Two candidate protein peaks (7769 and 9290 m/z were found to be down-regulated in ALL patients, where these were identified as platelet factor 4 (PF4 and pro-platelet basic protein precursor (PBP. Two other candidate protein peaks (8137 and 8937 m/z were found up-regulated in the sera of ALL patients, and these were identified as fragments of the complement component 3a (C3a. Conclusion Platelet factor (PF4, connective tissue activating peptide III (CTAP-III and two fragments of C3a may be potential protein biomarkers of pediatric ALL and used to distinguish pediatric ALL patients from healthy controls and pediatric AML patients. Further studies with

  18. Acute Pancreatitis and Diabetic Ketoacidosis following L-Asparaginase/Prednisone Therapy in Acute Lymphoblastic Leukemia

    Directory of Open Access Journals (Sweden)

    Dania Lizet Quintanilla-Flores

    2014-01-01

    Full Text Available Acute pancreatitis and diabetic ketoacidosis are unusual adverse events following chemotherapy based on L-asparaginase and prednisone as support treatment for acute lymphoblastic leukemia. We present the case of a 16-year-old Hispanic male patient, in remission induction therapy for acute lymphoblastic leukemia on treatment with mitoxantrone, vincristine, prednisone, and L-asparaginase. He was hospitalized complaining of abdominal pain, nausea, and vomiting. Hyperglycemia, acidosis, ketonuria, low bicarbonate levels, hyperamylasemia, and hyperlipasemia were documented, and the diagnosis of diabetic ketoacidosis was made. Because of uncertainty of the additional diagnosis of acute pancreatitis as the cause of abdominal pain, a contrast-enhanced computed tomography was performed resulting in a Balthazar C pancreatitis classification.

  19. Molecular evidence for central nervous system involvement in children with newly diagnosed acute lymphoblastic leukemia.

    Science.gov (United States)

    Januszkiewicz, D A; Nowak, J S

    1995-01-01

    Central nervous system (CNS) involvement in children with newly diagnosed acute lymphoblastic leukemia (ALL) would have profound implication for the prognosis and accurate stratification of CNS prophylactic therapy. Using PCR technique with specific primers for V, D and J segments of TCRD gene, the pattern of TCRD gene rearrangements in bone marrow lymphoblasts and in cells from cerebrospinal fluid (CSF) have been investigated. The study involved 21 children at the time of diagnosis with B-lineage ALL. In nine of 21 patients incomplete TCRDVD gene rearrangement has been found in CSF cells, which was identical to that observed in bone marrow of the same children. It can be concluded that at least in 43 per cent of all analysed cases, there were signs of CNS involvement in newly diagnosed ALL patients.

  20. Purification and characterization of fetal hematopoietic cells that express the common acute lymphoblastic leukemia antigen (CALLA)

    DEFF Research Database (Denmark)

    Hokland, P; Rosenthal, P; Griffin, J D

    1983-01-01

    Fetal hematopoietic cells that express the common acute lymphoblastic leukemia antigen (CALLA) were purified from both fetal liver and fetal bone marrow by immune rosetting with sheep erythrocytes coated with rabbit anti-mouse immunoglobulin and by fluorescence-activated cell sorting. Dual...... lymphoblastic leukemia cell with respect to surface marker phenotype. A population of CALLA- cells devoid of mature erythroid and myeloid surface markers was found to contain higher numbers of TdT+ cells but lower numbers of cyto-mu, B1, and Ia+ cells than the CALLA+ subset. In vitro analysis of normal...... antigen. Furthermore, using methanol-fixed cells, it could be shown that approximately 20% contained intracytoplasmic mu chains (cyto-mu) and that approximately 15% were positive for the terminal transferase enzyme (TdT) marker. The CALLA+ fetal cells thus closely resemble the childhood acute...

  1. Treatment of refractory/relapsed adult acute lymphoblastic leukemia with bortezomib- based chemotherapy

    Directory of Open Access Journals (Sweden)

    Zhao J

    2015-06-01

    Full Text Available Junmei Zhao,* Chao Wang,* Yongping Song, Yuzhang Liu, Baijun FangHenan Key Lab of Experimental Haematology, Henan Institute of Haematology, Henan Tumor Hospital, Zhengzhou University, Zhengzhou, People’s Republic of China  *These authors contributed equally to this work Abstract: Nine pretreated patients aged >19 years with relapsed/refractory acute lymphoblastic leukemia (ALL were treated with a combination of bortezomib plus chemotherapy before allogeneic hematopoietic stem cell transplantation (allo-HSCT. Eight (88.9% patients, including two Philadelphia chromosome-positive ALL patients, achieved a complete remission. Furthermore, the evaluable patients have benefited from allo-HSCT after response to this reinduction treatment. We conclude that bortezomib-based chemotherapy was highly effective for adults with refractory/relapsed ALL before allo-HSCT. Therefore, this regimen deserves a larger series within prospective trials to confirm these results. Keywords: acute lymphoblastic leukemia, refractory, relapsed, bortezomib

  2. Non-infectious chemotherapy-associated acute toxicities during childhood acute lymphoblastic leukemia therapy

    Science.gov (United States)

    Schmiegelow, Kjeld; Müller, Klaus; Mogensen, Signe Sloth; Mogensen, Pernille Rudebeck; Wolthers, Benjamin Ole; Stoltze, Ulrik Kristoffer; Tuckuviene, Ruta; Frandsen, Thomas

    2017-01-01

    During chemotherapy for childhood acute lymphoblastic leukemia, all organs can be affected by severe acute side effects, the most common being opportunistic infections, mucositis, central or peripheral neuropathy (or both), bone toxicities (including osteonecrosis), thromboembolism, sinusoidal obstruction syndrome, endocrinopathies (especially steroid-induced adrenal insufficiency and hyperglycemia), high-dose methotrexate-induced nephrotoxicity, asparaginase-associated hypersensitivity, pancreatitis, and hyperlipidemia. Few of the non-infectious acute toxicities are associated with clinically useful risk factors, and across study groups there has been wide diversity in toxicity definitions, capture strategies, and reporting, thus hampering meaningful comparisons of toxicity incidences for different leukemia protocols. Since treatment of acute lymphoblastic leukemia now yields 5-year overall survival rates above 90%, there is a need for strategies for assessing the burden of toxicities in the overall evaluation of anti-leukemic therapy programs. PMID:28413626

  3. Mossbauer and XRD characterization of the phase transformations in a Fe-Mn-Al-C-Mo-Si-Cu as cast alloy during tribology test

    Energy Technology Data Exchange (ETDEWEB)

    Ramos, J. [Universidad Autónoma de Occidente (Colombia); Piamba, J. F. [Universidad del Valle, Departamento Física (Colombia); Sánchez, H. [Universidad del Valle, Escuela de Materiales (Colombia); Alcazar, G. A. Pérez, E-mail: gpgeperez@gmail.com [Universidad del Valle, Departamento Física (Colombia)

    2015-06-15

    In present study Fe-29.0Mn-6Al–0.9C-1.8Mo-1.6Si-0.4Cu (%w) alloy was obtained after melted in an induction furnace, and then molded as an ingot. From the as cast ingot it were cut samples for the different characterization measurements. The microstructure of the as-cast sample is of dendritic type and its XRD pattern was refined with the lines of the austenite, with a big volumetric fraction, and the lines of the martensite, with small volumetric fraction. The Mössbauer spectrum of the sample was fitted with a broad singlet which corresponds to disordered austenite. After the tribology test, its XRD pattern was refined with the lines of two austenite phases, one similar to the previous one and other with bigger lattice parameter. The total volumetric fraction of the austenite is smaller than that obtained for sample without wear. It was added the lines of the martensite phase with bigger volumetric fraction than that of the previous sample. The Mössbauer spectrum of the weared sample was fitted with two paramagnetic sites which correspond to the two Fe austenite phases and a hyperfine magnetic field distribution which is associated to the disordered original martensite and the new one which appears in the surface as a consequence of the wear process. These results show that during wear process the original austenite phase is transformed in martensite and in a new austenite phase. The increases of the martensitic phase improves mechanical properties and wear behavior.

  4. Test

    DEFF Research Database (Denmark)

    Bendixen, Carsten

    2014-01-01

    Bidrag med en kortfattet, introducerende, perspektiverende og begrebsafklarende fremstilling af begrebet test i det pædagogiske univers.......Bidrag med en kortfattet, introducerende, perspektiverende og begrebsafklarende fremstilling af begrebet test i det pædagogiske univers....

  5. Identification of Differentially Expressed Genes Associated with Prognosis of B Acute Lymphoblastic Leukemia

    OpenAIRE

    Idalia Garza-Veloz; Margarita L. Martinez-Fierro; Jose Carlos Jaime-Perez; Karol Carrillo-Sanchez; Maria Guadalupe Ramos-Del Hoyo; Angel Lugo-Trampe; Augusto Rojas-Martinez; Cesar Homero Gutierrez-Aguirre; Oscar Gonzalez-Llano; Rosario Salazar-Riojas; Alfredo Hidalgo-Miranda; David Gomez-Almaguer; Rocio Ortiz-Lopez

    2015-01-01

    Background. Acute lymphoblastic leukemia type B (B-ALL) is a neoplastic disorder with high mortality rates. The aim of this study was to validate the expression profile of 45 genes associated with signaling pathways involved in leukemia and to evaluate their association with the prognosis of B-ALL. Methods. 219 samples of peripheral blood mononuclear cells obtained from 73 B-ALL patients were studied at diagnosis, four, and eight weeks after starting treatment. Gene expression was analyzed by...

  6. Guillain-Barré syndrome in a child with acute lymphoblastic leukemia.

    Science.gov (United States)

    Aral, Y Z; Gursel, T; Ozturk, G; Serdaroglu, A

    2001-01-01

    A 4-year-old boy with acute lymphoblastic leukemia receiving maintenance treatment developed quadriparesis, facial palsy, difficulty in swallowing, and hypertension following a respiratory infection and candida septicemia. Examination of the cerebrospinal fluid was normal initially but later showed albuminocytologic dissociation, the characteristic finding of Guillain-Barré syndrome. Complete recovery occurred after treatment with intravenous immunoglobulin. Differential diagnosis of Guillain-Barré syndrome from vincristine toxicity in patients with leukemia and possible association with the infections are discussed.

  7. mRNA overexpression of BAALC: A novel prognostic factor for pediatric acute lymphoblastic leukemia

    OpenAIRE

    Azizi, Zahra; Rahgozar, Soheila; Moafi, Alireza; DABAGHI, MOHAMMAD; NADIMI, MOTAHAREH

    2015-01-01

    BAALC is a novel molecular marker in leukemia that is highly expressed in patients with acute leukemia. Increased expression levels of BAALC are known as poor prognostic factors in adult acute myeloid and lymphoid leukemia. The purpose of the present study was to evaluate the prognostic significance of the BAALC gene expression levels in pediatric acute lymphoblastic leukemia (ALL) and its association with MDR1. Using reverse transcription-quantitative polymerase chain reaction (RT-qPCR), the...

  8. 6-Thioguanine Induces Mitochondrial Dysfunction and Oxidative DNA Damage in Acute Lymphoblastic Leukemia Cells*

    OpenAIRE

    Zhang, Fan; Fu, Lijuan; Wang, Yinsheng

    2013-01-01

    Thiopurines are among the most successful chemotherapeutic agents used for treating various human diseases, including acute lymphoblastic leukemia and chronic inflammation. Although metabolic conversion and the subsequent incorporation of 6-thioguanine (SG) nucleotides into nucleic acids are considered important for allowing the thiopurine drugs to induce their cytotoxic effects, alternative mechanisms may also exist. We hypothesized that an unbiased analysis of SG-induced perturbation of the...

  9. The biogenesis of the MHC class II compartment in human I-cell disease B lymphoblasts

    OpenAIRE

    1996-01-01

    The localization and intracellular transport of major histocompatibility complex (MHC) class II molecules nd lysosomal hydrolases were studied in I-Cell Disease (ICD) B lymphoblasts, which possess a mannose 6-phosphate (Man-6-P)-independent targeting pathway for lysosomal enzymes. In the trans-Golgi network (TGN), MHC class II- invariant chain complexes colocalized with the lysosomal hydrolase cathepsin D in buds and vesicles that lacked markers of clathrin-coated vesicle-mediated transport. ...

  10. Fetal calf serum heat inactivation and lipopolysaccharide contamination influence the human T lymphoblast proteome and phosphoproteome

    Directory of Open Access Journals (Sweden)

    Rahman Hazir

    2011-11-01

    Full Text Available Abstract Background The effects of fetal calf serum (FCS heat inactivation and bacterial lipopolysaccharide (LPS contamination on cell physiology have been studied, but their effect on the proteome of cultured cells has yet to be described. This study was undertaken to investigate the effects of heat inactivation of FCS and LPS contamination on the human T lymphoblast proteome. Human T lymphoblastic leukaemia (CCRF-CEM cells were grown in FCS, either non-heated, or heat inactivated, having low ( Results A total of four proteins (EIF3M, PRS7, PSB4, and SNAPA were up-regulated when CCRF-CEM cells were grown in media supplemented with heat inactivated FCS (HE as compared to cells grown in media with non-heated FCS (NHE. Six proteins (TCPD, ACTA, NACA, TCTP, ACTB, and ICLN displayed a differential phosphorylation pattern between the NHE and HE groups. Compared to the low concentration LPS group, regular levels of LPS resulted in the up-regulation of three proteins (SYBF, QCR1, and SUCB1. Conclusion The present study provides new information regarding the effect of FCS heat inactivation and change in FCS-LPS concentration on cellular protein expression, and post-translational modification in human T lymphoblasts. Both heat inactivation and LPS contamination of FCS were shown to modulate the expression and phosphorylation of proteins involved in basic cellular functions, such as protein synthesis, cytoskeleton stability, oxidative stress regulation and apoptosis. Hence, the study emphasizes the need to consider both heat inactivation and LPS contamination of FCS as factors that can influence the T lymphoblast proteome.

  11. Mosaic Down syndrome and acute lymphoblastic B cell-leukemia. Case report

    Directory of Open Access Journals (Sweden)

    Parra-Baltazar, Isabel Mónica

    2016-10-01

    Full Text Available Down syndrome (DS or trisomy 21 is a constitutional chromosomal abnormality, which may be mosaic in 1 % to 4 % of cases. DS mosaic diagnosis is difficult because most patients have a normal phenotype and show no significant clinical abnormalities. Patients with DS have a higher risk of developing acute leukemia such as acute lymphoblastic leukemia (ALL. We report the case of a 19-year old woman with mosaic trisomy 21 and ALL.

  12. Identification of Interconnected Markers for T-Cell Acute Lymphoblastic Leukemia

    OpenAIRE

    Emine Guven Maiorov; Ozlem Keskin; Ozden Hatirnaz Ng; Ugur Ozbek; Attila Gursoy

    2013-01-01

    Hindawi Publishing Corporation BioMed Research International Volume 2013, Article ID 210253, 20 pages http://dx.doi.org/10.1155/2013/210253 Research Article Identification of Interconnected Markers for T-Cell Acute Lymphoblastic Leukemia Emine Guven Maiorov,1 Ozlem Keskin,1 Ozden Hatirnaz Ng,2 Ugur Ozbek,2 and Attila Gursoy1 1 Center for Computational Biology and Bioinformatics and College of Engineering, Koc¸ University, Rumelifeneri Yolu, Sariyer, 34450 Istanbu...

  13. Difficult diagnosis of invasive fungal infection predominantly involving the lower gastrointestinal tract in acute lymphoblastic leukaemia

    Directory of Open Access Journals (Sweden)

    Gulhadiye Avcu

    2016-03-01

    Full Text Available Invasive fungal infections are most commonly seen in immunocompromised patients and usually affect the respiratory system. Gastrointestinal system involvement of mucormycosis and invasive aspergillosis is rarely reported in childhood. Here we describe a 5 year old boy with acute lymphoblastic leukaemia who developed invasive fungal infection particularly affecting the lower gastrointestinal system to emphasise the difficulties in diagnosis and management of invasive fungal infections in immunocompromised patients.

  14. CYLD Regulates Noscapine Activity in Acute Lymphoblastic Leukemia via a Microtubule-Dependent Mechanism

    OpenAIRE

    Yang, Yunfan; Ran, Jie; Sun, Lei; Sun, Xiaodong; Luo, Youguang; Yan, Bing; Tala,; Liu, Min; Li, Dengwen; Zhang, Lei; Bao, Gang; Zhou, Jun

    2015-01-01

    Noscapine is an orally administrable drug used worldwide for cough suppression and has recently been demonstrated to disrupt microtubule dynamics and possess anticancer activity. However, the molecular mechanisms regulating noscapine activity remain poorly defined. Here we demonstrate that cylindromatosis (CYLD), a microtubule-associated tumor suppressor protein, modulates the activity of noscapine both in cell lines and in primary cells of acute lymphoblastic leukemia (ALL). Flow cytometry a...

  15. Aggravated bone density decline following symptomatic osteonecrosis in children with acute lymphoblastic leukemia.

    Science.gov (United States)

    den Hoed, Marissa A H; Pluijm, Saskia M F; te Winkel, Mariël L; de Groot-Kruseman, Hester A; Fiocco, Martha; Hoogerbrugge, Peter; Leeuw, Jan A; Bruin, Marrie C A; van der Sluis, Inge M; Bresters, Dorien; Lequin, Maarten H; Roos, Jan C; Veerman, Anjo J P; Pieters, Rob; van den Heuvel-Eibrink, Marry M

    2015-12-01

    Osteonecrosis and decline of bone density are serious side effects during and after treatment of childhood acute lymphoblastic leukemia. It is unknown whether osteonecrosis and low bone density occur together in the same patients, or whether these two osteogenic side-effects can mutually influence each other's development. Bone density and the incidence of symptomatic osteonecrosis were prospectively assessed in a national cohort of 466 patients with acute lymphoblastic leukemia (4-18 years of age) who were treated according to the dexamethasone-based Dutch Child Oncology Group-ALL9 protocol. Bone mineral density of the lumbar spine (BMDLS) (n=466) and of the total body (BMDTB) (n=106) was measured by dual X-ray absorptiometry. Bone density was expressed as age- and gender-matched standard deviation scores. Thirty patients (6.4%) suffered from symptomatic osteonecrosis. At baseline, BMDLS and BMDTB did not differ between patients who did or did not develop osteonecrosis. At cessation of treatment, patients with osteonecrosis had lower mean BMDLS and BMDTB than patients without osteonecrosis (respectively, with osteonecrosis: -2.16 versus without osteonecrosis: -1.21, Posteonecrosis: -1.73 versus without osteonecrosis: -0.57, Posteonecrosis had steeper BMDLS and BMDTB declines during follow-up than patients without osteonecrosis (interaction group time, Posteonecrosis. Bone density declines from the time that osteonecrosis is diagnosed; this suggests that the already existing decrease in bone density during acute lymphoblastic leukemia therapy is further aggravated by factors such as restriction of weight-bearing activities and destruction of bone architecture due to osteonecrosis. Osteonecrosis can, therefore, be considered a risk factor for low bone density in children with acute lymphoblastic leukemia.

  16. Duplication of the MYB oncogene in T cell acute lymphoblastic leukemia.

    Science.gov (United States)

    Lahortiga, Idoya; De Keersmaecker, Kim; Van Vlierberghe, Pieter; Graux, Carlos; Cauwelier, Barbara; Lambert, Frederic; Mentens, Nicole; Beverloo, H Berna; Pieters, Rob; Speleman, Frank; Odero, Maria D; Bauters, Marijke; Froyen, Guy; Marynen, Peter; Vandenberghe, Peter; Wlodarska, Iwona; Meijerink, Jules P P; Cools, Jan

    2007-05-01

    We identified a duplication of the MYB oncogene in 8.4% of individuals with T cell acute lymphoblastic leukemia (T-ALL) and in five T-ALL cell lines. The duplication is associated with a threefold increase in MYB expression, and knockdown of MYB expression initiates T cell differentiation. Our results identify duplication of MYB as an oncogenic event and suggest that MYB could be a therapeutic target in human T-ALL.

  17. Bone Marrow Cells in Acute Lymphoblastic Leukemia Create a Proinflammatory Microenvironment Influencing Normal Hematopoietic Differentiation Fates

    OpenAIRE

    2015-01-01

    B-cell acute lymphoblastic leukemia (B-ALL) is a serious public health problem in the pediatric population worldwide, contributing to 85% of deaths from childhood cancers. Understanding the biology of the disease is crucial for its clinical management and the development of therapeutic strategies. In line with that observed in other malignancies, chronic inflammation may contribute to a tumor microenvironment resulting in the damage of normal processes, concomitant to development and maintena...

  18. CD22: A Promising Target for Acute Lymphoblastic Leukemia Treatment | Center for Cancer Research

    Science.gov (United States)

    There are about 4,000 new cases of acute lymphoblastic leukemia (ALL) in the United States each year. Great improvements have been made in the treatment of ALL, but many patients suffer from side effects of standard therapy and continue to die of this disease. One of the most promising therapeutic strategies includes engineering T cells with a chimeric antigen receptor (CAR) that alters T cell specificity and function to recognize tumor antigens.

  19. Clinical features and early treatment response of central nervous system involvement in childhood acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Levinsen, Mette; Taskinen, Mervi; Abrahamsson, Jonas

    2014-01-01

    BACKGROUND: Central nervous system (CNS) involvement in childhood acute lymphoblastic leukemia (ALL) remains a therapeutic challenge. PROCEDURE: To explore leukemia characteristics of patients with CNS involvement at ALL diagnosis, we analyzed clinical features and early treatment response of 744...... leukemia and patients without such characteristics (0.50 vs. 0.61; P = 0.2). CONCLUSION: CNS involvement at diagnosis is associated with adverse prognostic features but does not indicate a less chemosensitive leukemia....

  20. Childhood Acute Lymphoblastic Leukemia Treatment (PDQ®)—Health Professional Version

    Science.gov (United States)

    For acute lymphoblastic leukemia (ALL), the 5-year survival rate rose from 60% to about 90% for children younger than 15 years and from 28% to about 75% for adolescents aged 15–19 years between 1975 and 2010. Get information about risk factors, signs, diagnosis, genomics, survival, risk-based treatment assignment, and induction and postinduction therapy for children and adolescents with newly diagnosed and recurrent ALL.

  1. Epigenetic inactivation of TWIST2 in acute lymphoblastic leukemia modulates proliferation, cell survival and chemosensitivity

    Science.gov (United States)

    Thathia, Shabnam H.; Ferguson, Stuart; Gautrey, Hannah E.; van Otterdijk, Sanne D.; Hili, Michela; Rand, Vikki; Moorman, Anthony V.; Meyer, Stefan; Brown, Robert; Strathdee, Gordon

    2012-01-01

    Background Altered regulation of many transcription factors has been shown to be important in the development of leukemia. TWIST2 modulates the activity of a number of important transcription factors and is known to be a regulator of hematopoietic differentiation. Here, we investigated the significance of epigenetic regulation of TWIST2 in the control of cell growth and survival and in response to cytotoxic agents in acute lymphoblastic leukemia. Design and Methods TWIST2 promoter methylation status was assessed quantitatively, by combined bisulfite and restriction analysis (COBRA) and pyrosequencing assays, in multiple types of leukemia and TWIST2 expression was determined by quantitative reverse transcriptase polymerase chain reaction analysis. The functional role of TWIST2 in cell proliferation, survival and response to chemotherapy was assessed in transient and stable expression systems. Results We found that TWIST2 was inactivated in more than 50% of cases of childhood and adult acute lymphoblastic leukemia through promoter hypermethylation and that this epigenetic regulation was especially prevalent in RUNX1-ETV6-driven cases. Re-expression of TWIST2 in cell lines resulted in a dramatic reduction in cell growth and induction of apoptosis in the Reh cell line. Furthermore, re-expression of TWIST2 resulted in increased sensitivity to the chemotherapeutic agents etoposide, daunorubicin and dexamethasone and TWIST2 hypermethylation was almost invariably found in relapsed adult acute lymphoblastic leukemia (91% of samples hypermethylated). Conclusions This study suggests a dual role for epigenetic inactivation of TWIST2 in acute lymphoblastic leukemia, initially through altering cell growth and survival properties and subsequently by increasing resistance to chemotherapy. PMID:22058208

  2. Drugs under preclinical and clinical study for treatment of acute and chronic lymphoblastic leukemia

    OpenAIRE

    Jacob JA; Salmani JMM; Chen B

    2016-01-01

    Joe Antony Jacob, Jumah Masoud Mohammad Salmani, Baoan Chen Department of Hematology and Oncology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, People’s Republic of China Abstract: Targeted therapy has modernized the treatment of both chronic and acute lymphoblastic leukemia. The introduction of monoclonal antibodies and combinational drugs has increased the survival rate of patients. Preclinical studies with various agents have resulted in positive outputs...

  3. Multipath Transformational Development of User Interfaces with Graph Transformations

    Science.gov (United States)

    Limbourg, Quentin; Vanderdonckt, Jean

    In software engineering, transformational development is aimed at developing computer systems by transforming a coarse-grained specification of a system to its final code through a series of transformation steps. Transformational development is known to bring benefits such as: correctness by construction, explicit mappings between development steps, and reversibility of transformations. No comparable piece exists in the literature that provides a formal system applying transformational development in the area of user interface engineering. This chapter defines such a system. For this purpose, a mathematical system for expressing specifications and transformation rules is introduced. This system is based on graph transformations. The problem of managing the transformation rules is detailed, e.g., how to enable a developer to access, define, extend, restrict or relax, test, verify, and apply appropriate transformations. A tool supporting this development paradigm is also described and exemplified. Transformational development, applied to the development of user interfaces of interactive systems, allows reusability of design knowledge used to develop user interfaces and fosters incremental development of user interfaces by applying alternative transformations.

  4. Myeloid Sarcoma Presenting with Leukemoid Reaction in a Child Treated for Acute Lymphoblastic Leukemia

    Directory of Open Access Journals (Sweden)

    Aylin Canbolat Ayhan

    2014-01-01

    Full Text Available Background. Myeloid sarcoma is an extramedullary neoplasm of immature myeloid cells. Our study reports a presentation of myeloid sarcoma which presented with severe leukemoid reaction as a secondary malignancy in a patient who was treated for acute lymphoblastic leukemia previously. The case emphasizes the difficulties in diagnosis of patients who do not have concomitant leukemia. Case Presentation. A 6-year-old girl who was treated for acute lymphoblastic leukemia previously presented with fatigue, paleness, and hepatosplenomegaly. Peripheral blood smear and bone marrow aspirate examination did not demonstrate any blasts in spite of severe leukemoid reaction with a white cell count 158000/mm3. FDG/PET CT revealed slight uptake in cervical and supraclavicular lymph nodes. Excisional lymph node biopsy was performed from these lymph nodes and it showed myeloid sarcoma. Conclusion. Myeloid sarcoma can develop as a secondary malignancy in children who are treated for acute lymphoblastic leukemia. It can be associated with severe leukemoid reaction and diagnosis may be difficult if there is not concomitant leukemia. PET/CT is helpful in such cases.

  5. Frequency of chromosomally-integrated human herpesvirus 6 in children with acute lymphoblastic leukemia.

    Directory of Open Access Journals (Sweden)

    Annie Gravel

    Full Text Available INTRODUCTION: Human herpesvirus 6 (HHV-6 is a ubiquitous pathogen infecting nearly 100% of the human population. Of these individuals, between 0.2% and 1% of them carry chromosomally-integrated HHV-6 (ciHHV-6. The biological consequences of chromosomal integration by HHV-6 remain unknown. OBJECTIVE: To determine and compare the frequency of ciHHV-6 in children with acute lymphoblastic leukemia to healthy blood donors. METHODOLOGY: A total of 293 DNA samples from children with pre-B (n=255, pre-pre-B (n=4, pre-T (n=26 and undetermined (n=8 leukemia were analyzed for ciHHV-6 by quantitative TaqMan PCR (QPCR using HHV-6 specific primers and probe. As control, DNA samples from 288 healthy individuals were used. Primers and probe specific to the cellular GAPDH gene were used to estimate integrity and DNA content. RESULTS: Out of 293 DNA samples from the leukemic cohort, 287 contained amplifiable DNA. Of these, only 1 (0.35% contained ciHHV-6. Variant typing indicates that the ci-HHV-6 corresponds to variant A. None of the 288 DNA samples from healthy individuals contained ciHHV-6. CONCLUSION: The frequency of ciHHV-6 in children with acute lymphoblastic leukemia is similar (p=0.5 to that of healthy individuals. These results suggest that acute lymphoblastic leukemia does not originate as a consequence to integration of HHV-6 within the chromosomes.

  6. Activation of IGF-1 and insulin signaling pathways ameliorate mitochondrial function and energy metabolism in Huntington's Disease human lymphoblasts.

    Science.gov (United States)

    Naia, Luana; Ferreira, I Luísa; Cunha-Oliveira, Teresa; Duarte, Ana I; Ribeiro, Márcio; Rosenstock, Tatiana R; Laço, Mário N; Ribeiro, Maria J; Oliveira, Catarina R; Saudou, Frédéric; Humbert, Sandrine; Rego, A Cristina

    2015-02-01

    Huntington's disease (HD) is an inherited neurodegenerative disease caused by a polyglutamine repeat expansion in the huntingtin protein. Mitochondrial dysfunction associated with energy failure plays an important role in this untreated pathology. In the present work, we used lymphoblasts obtained from HD patients or unaffected parentally related individuals to study the protective role of insulin-like growth factor 1 (IGF-1) versus insulin (at low nM) on signaling and metabolic and mitochondrial functions. Deregulation of intracellular signaling pathways linked to activation of insulin and IGF-1 receptors (IR,IGF-1R), Akt, and ERK was largely restored by IGF-1 and, at a less extent, by insulin in HD human lymphoblasts. Importantly, both neurotrophic factors stimulated huntingtin phosphorylation at Ser421 in HD cells. IGF-1 and insulin also rescued energy levels in HD peripheral cells, as evaluated by increased ATP and phosphocreatine, and decreased lactate levels. Moreover, IGF-1 effectively ameliorated O2 consumption and mitochondrial membrane potential (Δψm) in HD lymphoblasts, which occurred concomitantly with increased levels of cytochrome c. Indeed, constitutive phosphorylation of huntingtin was able to restore the Δψm in lymphoblasts expressing an abnormal expansion of polyglutamines. HD lymphoblasts further exhibited increased intracellular Ca(2+) levels before and after exposure to hydrogen peroxide (H2O2), and decreased mitochondrial Ca(2+) accumulation, being the later recovered by IGF-1 and insulin in HD lymphoblasts pre-exposed to H2O2. In summary, the data support an important role for IR/IGF-1R mediated activation of signaling pathways and improved mitochondrial and metabolic function in HD human lymphoblasts.

  7. Treatment of childhood T-cell lymphoblastic lymphoma according to the strategy for acute lymphoblastic leukaemia, without radiotherapy: long term results of the EORTC CLG 58881 trial.

    Science.gov (United States)

    Uyttebroeck, Anne; Suciu, Stefan; Laureys, Geneviève; Robert, Alain; Pacquement, Hélène; Ferster, Alina; Marguerite, Geneviève; Mazingue, Françoise; Renard, Marleen; Lutz, Patrick; Rialland, Xavier; Mechinaud, Françoise; Cavé, Hélène; Baila, Liliana; Bertrand, Yves

    2008-04-01

    From June 1989 through to November 1998, 121 children with newly diagnosed T-cell lymphoblastic lymphoma (T-LBL) were included in the EORTC 58881 trial conducted by the Children's Leukaemia Group. The therapy regimen was based on a Berlin-Frankfurt-Munster protocol, for a total duration of 24 months. Cranial irradiation, prophylactic cranial and local, was omitted, even for patients with central nervous involvement at diagnosis. In total, 119 patients were evaluable. The median follow-up was 6.7 years. The overall event-free survival (EFS) rate at 6 years was 77.5% (standard error (SE)=4%). Median time of relapse was 1 year after complete remission (range 0.2-5.9 years). Only two (1.8%) patients had an isolated central nervous system relapse. For patients with complete response (n=16) to the 7-day prephase, the EFS rate at 6 years was 100% versus 14% (P<0.001) for patients with no response (n=7). Overall survival rate at 6 years was 86% (SE=3%). An intensive acute lymphoblastic leukaemia type chemotherapy regimen without irradiation leads to a high cure and survival rate in childhood T-LBL without an increased CNS recurrence. This suggests that prophylactic cranial irradiation can safely be omitted. Response to the prephase appeared to be a strong prognostic factor for EFS.

  8. Clonal diversity of Ig and T-cell receptor gene rearrangements in childhood B-precursor acute lymphoblastic leukaemia.

    Science.gov (United States)

    Stankovic, T; Weston, V; McConville, C M; Green, E; Powell, J E; Mann, J R; Darbyshire, P J; Taylor, A M

    2000-01-01

    The majority of paediatric B precursor acute lymphoblastic leukaemias in children are derived from a single transformed haematopoietic cell with complete or partial VDJ recombination within the immunoglobulin heavy chain gene. A high frequency of patients also show rearrangements within TCRdelta and TCRgamma loci and in up to 40% of children there is an excess of immune system gene rearrangements compared with the number of identified alleles of immune system genes, suggesting the presence of multiple leukaemic subclones -clonal diversity. It has been observed by us and other investigators that in individual patients the pattern of immune system gene rearrangements often changes between presentation and relapse. In order to explore the possibility that clonal diversity plays a biological role during disease progression we optimised methods for subclone detection and analysed the prognostic significance of clonal diversity among 75 children with B precursor-ALL. Our results suggest that clonal diversity plays a role in disease progression as patients with oligoclonal disease showed a significantly shorter disease free survival than patients with monoclonal disease. This trend was of particular importance in the 'standard risk' group of ALL where aggressive disease could not be recognised by other means. In addition, generation of independent subclones from an early, non-rearranged tumour progenitor appears to be a common feature among leukaemias with aggressive clinical behaviour. We speculate on the type of genetic factors which may participate both in the generation of subclones and also in wider genomic instability and which are likely to be required for the aggressive clinical phenotype in children with ALL.

  9. The need for a life-cycle based aging paradigm for nanomaterials: importance of real-world test systems to identify realistic particle transformations

    Science.gov (United States)

    Mitrano, Denise M.; Nowack, Bernd

    2017-02-01

    Assessing the risks of manufactured nanomaterials (MNM) has been almost exclusively focused on the pristine, as-produced materials with far fewer studies delving into more complex, real world scenarios. However, when considering a life-cycle perspective, it is clear that MNM released from commercial products during manufacturing, use and disposal are far more relevant both in terms of more realistic environmental fate and transport as well as environmental risk. The quantity in which the particles are released and their (altered) physical and chemical form should be identified and it is these metrics that should be used to assess the exposure and hazard the materials pose. The goal of this review is to (1) provide a rationale for using a life-cycle based approach when dealing with MNM transformations, (2) to elucidate the different chemical and physical forces which age and transform MNM and (3) assess the pros and cons of current analytical techniques as they pertain to the measurement of aged and transformed MNM in these complex release scenarios. Specifically, we will describe the possible transformations common MNM may undergo during the use or disposal of nano-products based on how these products will be used by the consumer by taking stock of the current nano-enabled products on the market. Understanding the impact of these transformations may help forecast the benefits and/or risks associated with the use of products containing MNM.

  10. Vitamin and mineral supplements in pregnancy and the risk of childhood acute lymphoblastic leukaemia: a case-control study

    Directory of Open Access Journals (Sweden)

    Skegg David CG

    2007-07-01

    Full Text Available Abstract Background An earlier case-control study from Western Australia reported a protective effect of maternal folic acid supplementation during pregnancy on the risk of childhood acute lymphoblastic leukaemia (ALL. The present study tested that association. Methods A national case-control study was conducted in New Zealand. The mothers of 97 children with ALL and of 303 controls were asked about vitamin and mineral supplements taken during pregnancy. Results There was no association between reported folate intake during pregnancy and childhood ALL (adjusted odds ratio (OR 1.1, 95% confidence interval (CI 0.5–2.7. Combining our results with the study from Western Australia and another study from Québec in a meta-analysis gave a summary OR of 0.9 (95% CI 0.8–1.1. Conclusion Our own study, of similar size to the Australian study, does not support the hypothesis of a protective effect of folate on childhood ALL. Neither do the findings of the meta-analysis.

  11. Vitamin and mineral supplements in pregnancy and the risk of childhood acute lymphoblastic leukaemia: a case-control study.

    Science.gov (United States)

    Dockerty, John D; Herbison, Peter; Skegg, David C G; Elwood, Mark

    2007-07-03

    An earlier case-control study from Western Australia reported a protective effect of maternal folic acid supplementation during pregnancy on the risk of childhood acute lymphoblastic leukaemia (ALL). The present study tested that association. A national case-control study was conducted in New Zealand. The mothers of 97 children with ALL and of 303 controls were asked about vitamin and mineral supplements taken during pregnancy. There was no association between reported folate intake during pregnancy and childhood ALL (adjusted odds ratio (OR) 1.1, 95% confidence interval (CI) 0.5-2.7). Combining our results with the study from Western Australia and another study from Québec in a meta-analysis gave a summary OR of 0.9 (95% CI 0.8-1.1). Our own study, of similar size to the Australian study, does not support the hypothesis of a protective effect of folate on childhood ALL. Neither do the findings of the meta-analysis.

  12. A meta-analysis of the neuropsychological sequelae of chemotherapy-only treatment for pediatric acute lymphoblastic leukemia.

    Science.gov (United States)

    Peterson, Catherine C; Johnson, Courtney E; Ramirez, Lisa Y; Huestis, Samantha; Pai, Ahna L H; Demaree, Heath A; Drotar, Dennis

    2008-07-01

    Mixed findings on the neuropsychological sequelae of chemotherapy-only treatment for pediatric acute lymphoblastic leukemia (ALL), without radiation, indicate the need for a comprehensive meta-analytic review. The purpose of the current study was to conduct a meta-analysis assessing neuropsychological and academic functioning differences between children with ALL treated solely with chemotherapy and comparison groups. Thirteen articles met inclusion criteria for the meta-analysis and were analyzed using a random effects model, weighted least squares methods. Mean effect sizes were significantly different from zero for multiple domains of intelligence and academic achievement; processing speed; verbal memory; and some aspects of executive functioning and fine motor skills, indicating worse functioning in ALL survivors. Effect sizes for visual-motor skills and visual memory were not significantly different from zero. Results support the presence of neuropsychological and academic sequelae for ALL survivors treated solely with chemotherapy and highlight the need for ongoing follow-up of children with ALL using a standardized neuropsychological test battery and research methodology. (c) 2008 Wiley-Liss, Inc.

  13. CD90 and CD110 correlate with cancer stem cell potentials in human T-acute lymphoblastic leukemia cells

    Energy Technology Data Exchange (ETDEWEB)

    Yamazaki, Hiroto; Nishida, Hiroko; Iwata, Satoshi [Division of Clinical Immunology, Advanced Clinical Research Center, Institute of Medical Science, University of Tokyo, Tokyo 108-8639 (Japan); Dang, Nam H. [Department of Hematologic Malignancies, Nevada Cancer Institute, Las Vegas, NV (United States); Morimoto, Chikao, E-mail: morimoto@ims.u-tokyo.ac.jp [Division of Clinical Immunology, Advanced Clinical Research Center, Institute of Medical Science, University of Tokyo, Tokyo 108-8639 (Japan)

    2009-05-29

    Although cancer stem cells (CSCs) have been recently identified in myeloid leukemia, published data on lymphoid malignancy have been sparse. T-acute lymphoblastic leukemia (T-ALL) is characterized by the abnormal proliferation of T-cell precursors and is generally aggressive. As CD34 is the only positive-selection marker for CSCs in T-ALL, we performed extensive analysis of CD markers in T-ALL cell lines. We found that some of the tested lines consisted of heterogeneous populations of cells with various levels of surface marker expression. In particular, a small subpopulation of CD90 (Thy-1) and CD110 (c-Mpl) were shown to correlate with stem cell properties both in vitro and in transplantation experiments. As these markers are expressed on hematopoietic stem cells, our results suggest that stem cell-like population are enriched in CD90+/CD110+ fraction and they are useful positive-selection markers for the isolation of CSCs in some cases of T-ALL.

  14. Identity transformation

    DEFF Research Database (Denmark)

    Neergaard, Helle; Robinson, Sarah; Jones, Sally

    This paper develops the concept of ‘pedagogical nudging’ and examines four interventions in an entrepreneurship classroom and the potential it has for student identity transformation. Pedagogical nudging is positioned as a tool, which in the hands of a reflective, professional, with an understand......This paper develops the concept of ‘pedagogical nudging’ and examines four interventions in an entrepreneurship classroom and the potential it has for student identity transformation. Pedagogical nudging is positioned as a tool, which in the hands of a reflective, professional......, as well as the resources they have when they come to the classroom. It also incorporates perspectives from (ii) transformational learning and explores the concept of (iii) nudging from a pedagogical viewpoint, proposing it as an important tool in entrepreneurship education. The study incorporates......) assists students in straddling the divide between identities, the emotions and tensions this elicits, and (iv) transform student understanding. We extend nudging theory into a new territory. Pedagogical nudging techniques may be able to unlock doors and bring our students beyond the unacknowledged...

  15. Sustainable transformation

    DEFF Research Database (Denmark)

    Andersen, Nicolai Bo

    , that it can be adapted to changing functional needs, and that it has an architectural and cultural value. A specific proposal for a transformation that enhances the architectural qualities and building heritage values of an existing building forms the empirical material, which is discussed using different...

  16. ADE Transform

    CERN Document Server

    Donagi, Ron

    2015-01-01

    There is a beautiful correspondence between configurations of lines on a rational surface and tautological bundles over that surface. We extend this correspondence to families, by means of a generalized Fourier-Mukai transform that relates spectral data to bundles over a rational surface fibration.

  17. Transformer core

    NARCIS (Netherlands)

    Mehendale, A.; Hagedoorn, Wouter; Lötters, Joost Conrad

    2010-01-01

    A transformer core includes a stack of a plurality of planar core plates of a magnetically permeable material, which plates each consist of a first and a second sub-part that together enclose at least one opening. The sub-parts can be fitted together via contact faces that are located on either side

  18. Transformer core

    NARCIS (Netherlands)

    Mehendale, A.; Hagedoorn, Wouter; Lötters, Joost Conrad

    2008-01-01

    A transformer core includes a stack of a plurality of planar core plates of a magnetically permeable material, which plates each consist of a first and a second sub-part that together enclose at least one opening. The sub-parts can be fitted together via contact faces that are located on either side

  19. Transformational change

    NARCIS (Netherlands)

    Termeer, Katrien; Dewulf, Art; Biesbroek, Robbert

    2016-01-01

    Although transformational change is a rather new topic in climate change adaptation literature, it has been studied in organisational theory for over 30 years. This paper argues that governance scholars can learn much from organisation theory, more specifically regarding the conceptualisation of

  20. Floral Transformation of Wheat

    Science.gov (United States)

    Agarwal, Sujata; Loar, Star; Steber, Camille; Zale, Janice

    A method is described for the floral transformation of wheat using a protocol similar to the floral dip of Arabidopsis. This method does not employ tissue culture of dissected embryos, but instead pre-anthesis spikes with clipped florets at the early, mid to late uninucleate microspore stage are dipped in Agrobacterium infiltration media harboring a vector carrying anthocyanin reporters and the NPTII selectable marker. T1 seeds are examined for color changes induced in the embryo by the anthocyanin reporters. Putatively transformed seeds are germinated and the seedlings are screened for the presence of the NPTII gene based on resistance to paromomycin spray and assayed with NPTII ELISAs. Genomic DNA of putative transformants is digested and analyzed on Southern blots for copy number to determine whether the T-DNA has integrated into the nucleus and to show the number of insertions. The non-optimized transformation efficiencies range from 0.3 to 0.6% (number of transformants/number of florets dipped) but the efficiencies are higher in terms of the number of transformants produced/number of seeds set ranging from 0.9 to 10%. Research is underway to maximize seed set and optimize the protocol by testing different Agrobacterium strains, visual reporters, vectors, and surfactants.

  1. Chemo-sensitivity in a panel of B-cell precursor acute lymphoblastic leukemia cell lines, YCUB series, derived from children.

    Science.gov (United States)

    Goto, Hiroaki; Naruto, Takuya; Tanoshima, Reo; Kato, Hiromi; Yokosuka, Tomoko; Yanagimachi, Masakatsu; Fujii, Hisaki; Yokota, Shumpei; Komine, Hiromi

    2009-10-01

    Sensitivity to 10 anticancer drugs was evaluated in 6 childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL) cell lines. Authenticity of newly established cell lines was confirmed by genomic fingerprinting. The line YCUB-5R established at relapse was more resistant to 4-hydroperoxy-cyclophosphamide, cytarabine, L-asparaginase, topotecan, fludarabine, and etoposide than YCUB-5 from the same patient at diagnosis. Of the drugs tested, etoposide and SN-38 (irinotecan) showed highest efficacy in the panel, with 50% growth inhibition at 0.22-1.8 microg/ml and 0.57-3.6 ng/ml, respectively. This cell line panel offers an in vitro model for the development of new therapies for childhood BCP-ALL.

  2. Testing of SIR (a transformable robotic submarine) in Lake Tahoe for future deployment at West Antarctic Ice Sheet grounding lines of Siple Coast

    Science.gov (United States)

    Powell, R. D.; Scherer, R. P.; Griffiths, I.; Taylor, L.; Winans, J.; Mankoff, K. D.

    2011-12-01

    A remotely operated vehicle (ROV) has been custom-designed and built by DOER Marine to meet scientific requirements for exploring subglacial water cavities. This sub-ice rover (SIR) will explore and quantitatively document the grounding zone areas of the Ross Ice Shelf cavity using a 3km-long umbilical tether by deployment through an 800m-long ice borehole in a torpedo shape, which is also its default mode if operational failure occurs. Once in the ocean cavity it transforms via a diamond-shaped geometry into a rectangular form when all of its instruments come alive in its flight mode. Instrumentation includes 4 cameras (one forward-looking HD), a vertical scanning sonar (long-range imaging for spatial orientation and navigation), Doppler current meter (determine water current velocities), multi-beam sonar (image and swath map bottom topography), sub-bottom profiler (profile sub-sea-floor sediment for geological history), CTD (determine salinity, temperature and depth), DO meter (determine dissolved oxygen content in water), transmissometer (determine suspended particulate concentrations in water), laser particle-size analyzer (determine sizes of particles in water), triple laser-beams (determine size and volume of objects), thermistor probe (measure in situ temperatures of ice and sediment), shear vane probe (determine in situ strength of sediment), manipulator arm (deploy instrumentation packages, collect samples), shallow ice corer (collect ice samples and glacial debris), water sampler (determine sea water/freshwater composition, calibrate real-time sensors, sample microbes), shallow sediment corer (sample sea floor, in-ice and subglacial sediment for stratigraphy, facies, particle size, composition, structure, fabric, microbes). A sophisticated array of data handling, storing and displaying will allow real-time observations and environmental assessments to be made. This robotic submarine and other instruments will be tested in Lake Tahoe in September, 2011 and

  3. Risk group assignment differs for children and adults 1-45 yr with acute lymphoblastic leukemia treated by the NOPHO ALL-2008 protocol

    DEFF Research Database (Denmark)

    Toft, Nina; Birgens, Henrik; Abrahamsson, Jonas;

    2013-01-01

    The prognosis of acute lymphoblastic leukemia is poorer in adults than in children. Studies have indicated that young adults benefit from pediatric treatment, although no upper age limit has been defined.......The prognosis of acute lymphoblastic leukemia is poorer in adults than in children. Studies have indicated that young adults benefit from pediatric treatment, although no upper age limit has been defined....

  4. CREBBP knockdown enhances RAS/RAF/MEK/ERK signaling in Ras pathway mutated acute lymphoblastic leukemia but does not modulate chemotherapeutic response.

    Science.gov (United States)

    Dixon, Zach A; Nicholson, Lindsay; Zeppetzauer, Martin; Matheson, Elizabeth; Sinclair, Paul; Harrison, Christine J; Irving, Julie A E

    2017-04-01

    Relapsed acute lymphoblastic leukemia is the most common cause of cancer-related mortality in young people and new therapeutic strategies are needed to improve outcome. Recent studies have shown that heterozygous inactivating mutations in the histone acetyl transferase, CREBBP, are particularly frequent in relapsed childhood acute lymphoblastic leukemia and associated with a hyperdiploid karyotype and KRAS mutations. To study the functional impact of CREBBP haploinsufficiency in acute lymphoblastic leukemia, RNA interference was used to knock down expression of CREBBP in acute lymphoblastic leukemia cell lines and various primagraft acute lymphoblastic leukemia cells. We demonstrate that attenuation of CREBBP results in reduced acetylation of histone 3 lysine 18, but has no significant impact on cAMP-dependent target gene expression. Impaired induction of glucocorticoid receptor targets was only seen in 1 of 4 CREBBP knockdown models, and there was no significant difference in glucocorticoid-induced apoptosis, sensitivity to other acute lymphoblastic leukemia chemotherapeutics or histone deacetylase inhibitors. Importantly, we show that CREBBP directly acetylates KRAS and that CREBBP knockdown enhances signaling of the RAS/RAF/MEK/ERK pathway in Ras pathway mutated acute lymphoblastic leukemia cells, which are still sensitive to MEK inhibitors. Thus, CREBBP mutations might assist in enhancing oncogenic RAS signaling in acute lymphoblastic leukemia but do not alter response to MEK inhibitors. Copyright© Ferrata Storti Foundation.

  5. Incidence and risk factors for central nervous system relapse in children and adolescents with acute lymphoblastic leukemia

    Science.gov (United States)

    Cancela, Camila Silva Peres; Murao, Mitiko; Viana, Marcos Borato; de Oliveira, Benigna Maria

    2012-01-01

    Background Despite all the advances in the treatment of childhood acute lymphoblastic leukemia, central nervous system relapse remains an important obstacle to curing these patients. This study analyzed the incidence of central nervous system relapse and the risk factors for its occurrence in children and adolescents with acute lymphoblastic leukemia. Methods This study has a retrospective cohort design. The studied population comprised 199 children and adolescents with a diagnosis of acute lymphoblastic leukemia followed up at Hospital das Clinicas, Universidade Federal de Minas Gerais (HC-UFMG) between March 2001 and August 2009 and submitted to the Grupo Brasileiro de Tratamento de Leucemia da Infância - acute lymphoblastic leukemia (GBTLI-LLA-99) treatment protocol. Results The estimated probabilities of overall survival and event free survival at 5 years were 69.5% (± 3.6%) and 58.8% (± 4.0%), respectively. The cumulative incidence of central nervous system (isolated or combined) relapse was 11.0% at 8 years. The estimated rate of isolated central nervous system relapse at 8 years was 6.8%. In patients with a blood leukocyte count at diagnosis ≥ 50 x 109/L, the estimated rate of isolated or combined central nervous system relapse was higher than in the group with a count 50 x 109/L at diagnosis seems to be a significant prognostic factor for a higher incidence of central nervous system relapse in childhood acute lymphoblastic leukemia. PMID:23323068

  6. Incidence and risk factors for central nervous system relapse in children and adolescents with acute lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    Camila Silva Peres Cancela

    2012-01-01

    Full Text Available BACKGROUND: Despite all the advances in the treatment of childhood acute lymphoblastic leukemia, central nervous system relapse remains an important obstacle to curing these patients. This study analyzed the incidence of central nervous system relapse and the risk factors for its occurrence in children and adolescents with acute lymphoblastic leukemia. METHODS: This study has a retrospective cohort design. The studied population comprised 199 children and adolescents with a diagnosis of acute lymphoblastic leukemia followed up at Hospital das Clinicas, Universidade Federal de Minas Gerais (HC-UFMG between March 2001 and August 2009 and submitted to the Grupo Brasileiro de Tratamento de Leucemia da Infância - acute lymphoblastic leukemia (GBTLI-LLA-99 treatment protocol. RESULTS: The estimated probabilities of overall survival and event free survival at 5 years were 69.5% ( 3.6% and 58.8% ( 4.0%, respectively. The cumulative incidence of central nervous system (isolated or combined relapse was 11.0% at 8 years. The estimated rate of isolated central nervous system relapse at 8 years was 6.8%. In patients with a blood leukocyte count at diagnosis > 50 x 10(9/L, the estimated rate of isolated or combined central nervous system relapse was higher than in the group with a count 50 x 10(9/L at diagnosis seems to be a significant prognostic factor for a higher incidence of central nervous system relapse in childhood acute lymphoblastic leukemia.

  7. Universal Residuals: A Multivariate Transformation *

    Science.gov (United States)

    Brockwell, A.E.

    2007-01-01

    Rosenblatt's transformation has been used extensively for evaluation of model goodness-of-fit, but it only applies to models whose joint distribution is continuous. In this paper we generalize the transformation so that it applies to arbitrary probability models. The transformation is simple, but has a wide range of possible applications, providing a tool for exploratory data analysis and formal goodness-of-fit testing for a very general class of probability models. The method is demonstrated with specific examples. PMID:18670587

  8. Universal Residuals: A Multivariate Transformation.

    Science.gov (United States)

    Brockwell, A E

    2007-08-01

    Rosenblatt's transformation has been used extensively for evaluation of model goodness-of-fit, but it only applies to models whose joint distribution is continuous. In this paper we generalize the transformation so that it applies to arbitrary probability models. The transformation is simple, but has a wide range of possible applications, providing a tool for exploratory data analysis and formal goodness-of-fit testing for a very general class of probability models. The method is demonstrated with specific examples.

  9. Discrete transforms

    CERN Document Server

    Firth, Jean M

    1992-01-01

    The analysis of signals and systems using transform methods is a very important aspect of the examination of processes and problems in an increasingly wide range of applications. Whereas the initial impetus in the development of methods appropriate for handling discrete sets of data occurred mainly in an electrical engineering context (for example in the design of digital filters), the same techniques are in use in such disciplines as cardiology, optics, speech analysis and management, as well as in other branches of science and engineering. This text is aimed at a readership whose mathematical background includes some acquaintance with complex numbers, linear differen­ tial equations, matrix algebra, and series. Specifically, a familiarity with Fourier series (in trigonometric and exponential forms) is assumed, and an exposure to the concept of a continuous integral transform is desirable. Such a background can be expected, for example, on completion of the first year of a science or engineering degree cour...

  10. XML Transformations

    Directory of Open Access Journals (Sweden)

    Felician ALECU

    2012-04-01

    Full Text Available XSLT style sheets are designed to transform the XML documents into something else. The two most popular parsers of the moment are the Document Object Model (DOM and the Simple API for XML (SAX. DOM is an official recommendation of the W3C (available at http://www.w3.org/TR/REC-DOM-Level-1, while SAX is a de facto standard. A good parser should be fast, space efficient, rich in functionality and easy to use.

  11. Transformative Agency

    DEFF Research Database (Denmark)

    Majgaard, Klaus

    The purpose of this paper is to enhance the conceptual understanding of the mediatory relationship between paradoxes on an organizational and an individual level. It presents a concept of agency that comprises and mediates between a structural and individual pole. The constitution of this agency ...... is achieved through narrative activity that oscillates between the poles and transforms paradoxes through the configuration of plots and metaphors. Empirical cases are introduced in order to illustrate the implications of this understanding....

  12. RF transformer

    Science.gov (United States)

    Smith, James L.; Helenberg, Harold W.; Kilsdonk, Dennis J.

    1979-01-01

    There is provided an improved RF transformer having a single-turn secondary of cylindrical shape and a coiled encapsulated primary contained within the secondary. The coil is tapered so that the narrowest separation between the primary and the secondary is at one end of the coil. The encapsulated primary is removable from the secondary so that a variety of different capacity primaries can be utilized with one secondary.

  13. Subspaces of FMmlet transform

    Institute of Scientific and Technical Information of China (English)

    邹红星; 戴琼海; 赵克; 陈桂明; 李衍达

    2002-01-01

    The subspaces of FMmlet transform are investigated.It is shown that some of the existing transforms like the Fourier transform,short-time Fourier transform,Gabor transform,wavelet transform,chirplet transform,the mean of signal,and the FM-1let transform,and the butterfly subspace are all special cases of FMmlet transform.Therefore the FMmlet transform is more flexible for delineating both the linear and nonlinear time-varying structures of a signal.

  14. Power transformers - Part 1: General

    CERN Document Server

    International Electrotechnical Commission. Geneva

    2000-01-01

    Applies to three-phase and single-phase transformers including autotransformers. Defines the rating and connection symbols. Gives certain specifications for transformers having a tapped winding. Defines information which shall be marked on the rating plate and the tests to be conducted. Supersedes IEC 60076-1(1976) and IEC 60076-4 (1976).

  15. Acute T-cell lymphoblastic leukaemia presenting with cutaneous involvement in a child: a rare case report

    Directory of Open Access Journals (Sweden)

    Lohit Kumar Kalita

    2015-05-01

    Full Text Available Primary cutaneous involvement in T-cell lymphoblastic leukemia is rare in childhood. We present a case of 6-year-old girl admitted to our hospital because of multiple skin lesions. She was looked pale and weak. Generalized lymphadenopathy was present. Complete blood count revealed 216,000/mm3 white blood cell count. Peripheral blood smear showed 80% lymphoblasts. Bone marrow aspiration revealed 96% blastic cells with immunophenotype and morphological characteristics of acute lymphoblastic leukemia (T-ALL which was confirmed by flowcytometry. ALL BFM -95 remission induction treatment protocol was started. Skin lesion remained same after two month of the cytotoxic therapy. The symptoms became more aggressive and she died after 4 months of treatment. [Int J Res Med Sci 2015; 3(5.000: 1285-1287

  16. Relationship between the general condition of acute lymphoblastic leukemia patients with remission rate and convulsion as an adverse effect chemotherapy

    Directory of Open Access Journals (Sweden)

    Rusdi Andid

    2017-02-01

    Full Text Available A retrospective study on the relationship between the general condition of acute lymphoblastic leukemia patients with remission rale and convulsion as an adverse effect of chemotherapy was conducted in leukemia patients of the hematology-oncology subdivision, Departmenl of Child Health, Medical School, University of North Sumatra, Medan. Of 114 children with acute lymphoblastic leukemia, 81 (71.05% received chemotherapy, 31 patients among them was in good general condition. Remission rate of the 31 patients was 80.6% (25 children. Whereas in the remaining 50 patients, the remission rate among them was 84% (42 patients. There was no significant relationship between their general condition to the recurrence rate of acute lymphoblastic leukemia patients who had been administered chemotherapy during induction phase. Convulsion was found In 2 cases, due to CNS leukemia.

  17. Disseminated fusariosis and endogenous fungal endophthalmitis in acute lymphoblastic leukemia following platelet transfusion possibly due to transfusion-related immunomodulation

    Directory of Open Access Journals (Sweden)

    Yong Ku

    2011-11-01

    Full Text Available Abstract Background To report a case of disseminated fusariosis with endogenous endophthalmitis in a patient with acute lymphoblastic leukemia. Transfusion-associated immune modulation secondary to platelet transfusion could play an important role in the pathophysiology of this case. Case Presentation A 9 year-old male with acute lymphoblastic leukemia complicated by pancytopenia and disseminated Intravascular coagulation was given platelet transfusion. He developed disseminated fusariosis and was referred to the ophthalmology team for right endogenous endophthalmitis. The infection was controlled with aggressive systemic and intravitreal antifungals. Conclusion Patients with acute lymphoblastic leukemia are predisposed to endogenous fungal endophthalmitis. Transfusion-associated immune modulation may further increase host susceptibility to such opportunistic infections.

  18. Relations of FMmlet Transform to Some Integral Transforms

    Institute of Scientific and Technical Information of China (English)

    ZOUHongxing; DAIQionghai; WANGDianjun; LIYanda

    2004-01-01

    In this paper, we explore the relationships between FMmlet transform and some of the existing integral transforms, namely, the chirplet transform, dispersion transform, wavelet transform, chirp-Fourier transform, Short-time fourier transform (STFT), Gabor transform, Fourier transform, cosine transform, sine transform,Hartley transform, Laplace transform, z-transform, Mellintransform, Hilbert transform, autocorrelation function,cross-correlation function, energy, and the mean value.It is shown that all of these transforms are subspaces of FMmlet transform with specific parameters.

  19. Higher frequencies of chromosomal aberrations in lymphocytes of children with acute lymphoblastic leukemia after in vitro gamma irradiation

    Directory of Open Access Journals (Sweden)

    A Ramyar

    2012-12-01

    Full Text Available Background: Acute lymphoblastic leukemia (ALL is the most common malignancy in childhood, characterized by excess lymphoblasts, and immature white blood cells that are continuously multiplying and overproducing in the bone marrow. The aim of this investigation was to measure the sensitivity of lymphocytes against gamma irradiation in patients with acute lymphoblastic leukemia, and also find out the effect of such irradiations in causing chromosomal abnormalities.Methods: In this investigation performed between April 2010 and July 2011, at the Department of Genetics, Cancer Institute of Iran, we studied the effects of gamma irradiation on the lymphocytes of 20 children with acute lymphoblastic leukemia. The lymphocytes of 30 healthy donors were used to establish as a normal response to gamma irradiation and seven age-matched ataxia telangiectasia patients were recruited as positive control. The chromosomal radiosensitivity was assessed with the G2- and the G0-assay. We compared the mean number of chromosomal abnormalities such as chromosome and chromatid breakages, chromosome and chromatid gaps, and chromatid exchanges in one-hundred metaphases of patients and control groups.Results: The frequency of chromosomal aberrations was statistically higher among patients with acute lymphoblastic leukemia than the normal controls (P<0.01. In total, 65% of the patients were sensitive to gamma irradiation, but the remaining 35% were similar to the normal controls. Patients with ataxia telangiectasia showed the highest sensitivity to gamma irradiation (P=0.001.Conclusion: Our results showed that a high percentage of patients with acute lymphoblastic leukemia were sensitive to irradiation, meaning that maximum care should be taken during their treatment to avoid unnecessary X-rays or radiotherapies.

  20. Deletions of the long arm of chromosome 5 define subgroups of T-cell acute lymphoblastic leukemia.

    Science.gov (United States)

    La Starza, Roberta; Barba, Gianluca; Demeyer, Sofie; Pierini, Valentina; Di Giacomo, Danika; Gianfelici, Valentina; Schwab, Claire; Matteucci, Caterina; Vicente, Carmen; Cools, Jan; Messina, Monica; Crescenzi, Barbara; Chiaretti, Sabina; Foà, Robin; Basso, Giuseppe; Harrison, Christine J; Mecucci, Cristina

    2016-08-01

    Recurrent deletions of the long arm of chromosome 5 were detected in 23/200 cases of T-cell acute lymphoblastic leukemia. Genomic studies identified two types of deletions: interstitial and terminal. Interstitial 5q deletions, found in five cases, were present in both adults and children with a female predominance (chi-square, P=0.012). Interestingly, these cases resembled immature/early T-cell precursor acute lymphoblastic leukemia showing significant down-regulation of five out of the ten top differentially expressed genes in this leukemia group, including TCF7 which maps within the 5q31 common deleted region. Mutations of genes known to be associated with immature/early T-cell precursor acute lymphoblastic leukemia, i.e. WT1, ETV6, JAK1, JAK3, and RUNX1, were present, while CDKN2A/B deletions/mutations were never detected. All patients had relapsed/resistant disease and blasts showed an early differentiation arrest with expression of myeloid markers. Terminal 5q deletions, found in 18 of patients, were more prevalent in adults (chi-square, P=0.010) and defined a subgroup of HOXA-positive T-cell acute lymphoblastic leukemia characterized by 130 up- and 197 down-regulated genes. Down-regulated genes included TRIM41, ZFP62, MAPK9, MGAT1, and CNOT6, all mapping within the 1.4 Mb common deleted region at 5q35.3. Of interest, besides CNOT6 down-regulation, these cases also showed low BTG1 expression and a high incidence of CNOT3 mutations, suggesting that the CCR4-NOT complex plays a crucial role in the pathogenesis of HOXA-positive T-cell acute lymphoblastic leukemia with terminal 5q deletions. In conclusion, interstitial and terminal 5q deletions are recurrent genomic losses identifying distinct subtypes of T-cell acute lymphoblastic leukemia. Copyright© Ferrata Storti Foundation.

  1. Rapid progression of mediastinal tumor within a few days: A case report of T cell lymphoblastic lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Ahn, Tae Ran; Lee, Young Kyung; Jun, Hyun Jung; Jung, Eun Ah; Son, Jin Sung [Seoul Medical Center, Seoul (Korea, Republic of)

    2016-05-15

    T-cell lymphoblastic lymphoma is a highly aggressive tumor derived from lymphocyte of the thymus, which accounts for 2% of non-Hodgkin's lymphoma. The disease occurs most commonly in adolescent and young adult males. It often results in respiratory emergency because of high proliferation rate. In this case, we confirmed the rapid progression of T-cell lymphoblastic lymphoma through the chest CT scan with one week interval. Three days of empirical chemotherapy resulted in substantial reduction of mediastinal mass, pleural thickening and pleural effusion.

  2. Randomized double blind trial of ciprofloxacin prophylaxis during induction treatment in childhood acute lymphoblastic leukemia in the WK-ALL protocol in Indonesia

    Directory of Open Access Journals (Sweden)

    Widjajanto PH

    2013-02-01

    Full Text Available Pudjo H Widjajanto,1 Sumadiono Sumadiono,1 Jacqueline Cloos,2,3 Ignatius Purwanto,1 Sutaryo Sutaryo,1 Anjo JP Veerman1,21Pediatric Hematology and Oncology Division, Department of Pediatrics, Dr Sardjito Hospital, Medical Faculty, Universitas Gadjah Mada, Yogyakarta, Indonesia; 2Pediatric Oncology/Hematology Division, Department of Pediatrics, 3Department of Hematology, VU University Medical Center, Amsterdam, The NetherlandsObjectives: Toxic death is a big problem in the treatment of childhood acute lymphoblastic leukemia (ALL, especially in low-income countries. Studies of ciprofloxacin as single agent prophylaxis vary widely in success rate. We conducted a double-blind, randomized study to test the effects of ciprofloxacin monotherapy as prophylaxis for sepsis and death in induction treatment of the Indonesian childhood ALL protocol.Methods: Patients were randomized to the ciprofloxacin arm (n = 58 and to the placebo arm (n = 52. Oral ciprofloxacin monotherapy or oral placebo was administered twice a day. All events during induction were recorded: toxic death, abandonment, resistant disease, and complete remission rate.Results: Of 110 patients enrolled in this study, 79 (71.8% achieved CR. In comparison to the placebo arm, the ciprofloxacin arm had lower nadir of absolute neutrophil count during induction with median of 62 (range: 5–884 versus 270 (range: 14–25,480 × 109 cells/L (P > 0.01, greater risks for experiencing fever (50.0% versus 32.7%, P = 0.07, clinical sepsis (50.0% versus 38.5%, P = 0.22, and death (18.9% versus 5.8%, P = 0.05.Conclusion: In our setting, a reduced intensity protocol in a low-income situation, the data warn against using ciprofloxacin prophylaxis during induction treatment. A lower nadir of neutrophil count and higher mortality were found in the ciprofloxacin group.Keywords: ciprofloxacin, prophylaxis, childhood acute lymphoblastic leukemia, randomized trial, low-income country

  3. Hamlet's Transformation.

    Science.gov (United States)

    Usher, P. D.

    1997-12-01

    William Shakespeare's Hamlet has much evidence to suggest that the Bard was aware of the cosmological models of his time, specifically the geocentric bounded Ptolemaic and Tychonic models, and the infinite Diggesian. Moreover, Shakespeare describes how the Ptolemaic model is to be transformed to the Diggesian. Hamlet's "transformation" is the reason that Claudius, who personifies the Ptolemaic model, summons Rosencrantz and Guildenstern, who personify the Tychonic. Pantometria, written by Leonard Digges and his son Thomas in 1571, contains the first technical use of the word "transformation." At age thirty, Thomas Digges went on to propose his Perfit Description, as alluded to in Act Five where Hamlet's age is given as thirty. In Act Five as well, the words "bore" and "arms" refer to Thomas' vocation as muster-master and his scientific interest in ballistics. England's leading astronomer was also the father of the poet whose encomium introduced the First Folio of 1623. His oldest child Dudley became a member of the Virginia Company and facilitated the writing of The Tempest. Taken as a whole, such manifold connections to Thomas Digges support Hotson's contention that Shakespeare knew the Digges family. Rosencrantz and Guildenstern in Hamlet bear Danish names because they personify the Danish model, while the king's name is latinized like that of Claudius Ptolemaeus. The reason Shakespeare anglicized "Amleth" to "Hamlet" was because he saw a parallel between Book Three of Saxo Grammaticus and the eventual triumph of the Diggesian model. But Shakespeare eschewed Book Four, creating this particular ending from an infinity of other possibilities because it "suited his purpose," viz. to celebrate the concept of a boundless universe of stars like the Sun.

  4. Rotary Transformer

    Science.gov (United States)

    McLyman, Colonel Wm. T.

    1996-01-01

    None given. From first Par: Many spacecraft (S/C) and surface rovers require the transfer of signals and power across rotating interfaces. Science instruments, antennas and solar arrays are elements needing rotary power transfer for certain (S/C) configurations. Delivery of signal and power has mainly been done by using the simplest means, the slip ring approach. This approach, although simple, leaves debris generating noise over a period of time...The rotary transformer is a good alternative to slip rings for signal and power transfer.

  5. TRANSFORMER APPARATUS

    Science.gov (United States)

    Wolfgang, F.; Nicol, J.

    1962-11-01

    Transformer apparatus is designed for measuring the amount of a paramagnetic substance dissolved or suspended in a diamagnetic liquid. The apparatus consists of a cluster of tubes, some of which are closed and have sealed within the diamagnetic substance without any of the paramagnetic material. The remaining tubes are open to flow of the mix- ture. Primary and secondary conductors are wrapped around the tubes in such a way as to cancel noise components and also to produce a differential signal on the secondaries based upon variations of the content of the paramagnetic material. (AEC)

  6. Clinical use of blinatumomab for B-cell acute lymphoblastic leukemia in adults

    Directory of Open Access Journals (Sweden)

    Lee KJ

    2016-08-01

    Full Text Available Kum Ja Lee,1 Vivian Chow,1 Ashley Weissman,2 Sunil Tulpule,3 Ibrahim Aldoss,4 Mojtaba Akhtari5 1Department of Clinical Pharmacy and Pharmaceutical Economics and Policy, University of Southern California, 2Department of Pharmacy, University of Southern California Norris Cancer Hospital, Los Angeles, CA, 3Department of Medicine, Raritan Bay Medical Center, Perth Amboy, NJ, 4Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, CA, 5Jane Anne Nohl Division of Hematology and Center for the Study of Blood Diseases, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA, USA Abstract: Adults with relapsed or refractory B-cell acute lymphoblastic leukemia have a dismal prognosis with a short median overall survival that can be measured in months. Because most patients will have chemotherapy-resistant disease, allogeneic hematopoietic stem cell transplantation remains the only potentially curative treatment. Despite advances in current management, patients continue to have poor outcomes and lack of durable responses. Thus, new therapies with alternative modes of actions are currently being investigated. Blinatumomab is a novel bispecific T-cell engager that simultaneously binds CD3-positive cytotoxic T-cells and CD19-positive B-cells, resulting in selective lysis of tumor cells. It has shown promising results in patients with relapsed or refractory acute lymphoblastic leukemia or those achieving hematologic response with persistent minimum residual disease. Future clinical trials will answer questions regarding its optimal place in the treatment paradigm. Dose-limiting toxicities include immunological toxicities and cytokine release syndrome. However, most patients tolerate the therapy relatively well. This review will focus on the pharmacology, clinical efficacy, and safety of blinatumomab in the treatment of adult B-cell acute lymphoblastic leukemia while highlighting its unique drug

  7. Testicular involvement in acute lymphoblastic leukemia. Consequences of radiotherapy and chemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Brauner, R.; Czernichow, P.; Rappaport, R.; Schaison, G.

    1986-06-05

    Acute lymphoblastic leukemia has a higher mortality rate in boys as a result of possible testicular involvement; indeed, the testicle is the site of initial relapse in 6% of cases and is involved in 15% of all cases. Clinical diagnosis of testicular involvement is usually readily established. Treatment is delivery of 24 grays to both testicles and intensification of chemotherapy. In children who recover from their leukemia, this irradiation produces not only destruction of germ cells but also endocrine impairment which should be looked for and treated; replacement therapy with slow-action testosterone will be combined with the other hormonal treatments which pituitary deficiencies secondary to cranial irradiation may require.

  8. [ICO-35 monoclonal antibodies to the antigen of acute lymphoblastic leukemia].

    Science.gov (United States)

    Baryshnikov, A Iu; Tupitsyn, N N; Korotkova, O V; Kadagidze, Z G; Dostot, E; Shmidt, M; Boumsell, L

    1989-01-01

    ICO-35 monoclonal antibodies (Mabs) were produced following BALB/c mouse immunization with peripheral blood cells from a patient with lymphoid type of chronic myeloid leukemia in blast crisis (SML BC) ICO-35. Mabs detect antigen on CD10-positive cells from patients with acute lymphoblastic leukemia, CML BC, CD10-positive cells of Reh line and are not bound to other cells. Comparative studies of reactivity of ICO-35 and K 503 Mabs to CD10 antigen revealed their similarity. However, in contrast to K503 ICO-35 Mabs do not react with granulocytes.

  9. Competitive PCR for quantification of minimal residual disease in acute lymphoblastic leukaemia

    DEFF Research Database (Denmark)

    Nyvold, C; Madsen, H O; Ryder, L P;

    2000-01-01

    A very precise and reproducible polymerase chain reaction (PCR) method was developed in order to quantify minimal residual disease (MRD) in children with acute lymphoblastic leukaemia (ALL). A clone-specific competitor was constructed by introducing a restriction site in a PCR product identical...... under identical conditions. After restriction enzyme cleavage, the PCR products originating from the competitor and the malignant clone can be distinguished by size in a gel electrophoresis step and the amount of residual disease can be determined. The method is very sensitive with a detection limit...

  10. Suppressed spontaneous secretion of growth hormone in girls after treatment for acute lymphoblastic leukaemia.

    OpenAIRE

    Moëll, C; Garwicz, S; Westgren, U; Wiebe, T; Albertsson-Wikland, K.

    1989-01-01

    The spontaneous secretion of growth hormone during a 24 hour period and the response of growth hormone to growth hormone releasing hormone was studied in 13 girls who had received treatment for acute lymphoblastic leukemia that included cranial irradiation with 20-24 Gy in 12-14 fractions. At the time of investigation the girls were at varying stages of puberty and had normal concentrations of thyroid hormones. The mean interval between the end of treatment and investigation was 4.6 years. Th...

  11. Acute myeloid leukaemia after treatment for acute lymphoblastic leukaemia in girl with Bloom syndrome.

    Science.gov (United States)

    Adams, Madeleine; Jenney, Meriel; Lazarou, Laz; White, Rhian; Birdsall, Sanda; Staab, Timo; Schindler, Detlev; Meyer, Stefan

    2013-09-18

    Bloom syndrome (BS) is an inherited genomic instability disorder caused by disruption of the BLM helicase and confers an extreme cancer predisposition. Here we report on a girl with BS who developed acute lymphoblastic leukaemia (ALL) at age nine, and treatment-related acute myeloid leukaemia (t-AML) aged 12. She was compound heterozygous for the novel BLM frameshift deletion c.1624delG and the previously described c.3415C>T nonsense mutation. Two haematological malignancies in a child with BS imply a fundamental role for BLM for normal haematopoiesis, in particular in the presence of genotoxic stress.

  12. Successful Treatment of Fanconi Anemia and T-Cell Acute Lymphoblastic Leukemia

    Directory of Open Access Journals (Sweden)

    Terrie Flatt

    2012-01-01

    Full Text Available Fanconi anemia is associated with an increased risk of malignancy. Patients are sensitive to the toxic effects of chemotherapy. We report the case of a patient with Fanconi anemia who developed T-cell acute lymphoblastic leukemia. He experienced chemotherapy-related complications including prolonged neutropenia, grade IV vincristine neuropathy, and disseminated aspergillosis. He was successfully treated with modified dosing of cytarabine and intrathecal methotrexate followed by allogeneic bone marrow transplant. The aspergillosis was treated with systemic antifungal treatment and surgical resection. Now 30 months after bone marrow transplant the patient is without evidence of aspergillosis or leukemia.

  13. PEG-asparaginase allergy in children with acute lymphoblastic leukemia in the NOPHO ALL2008 protocol

    DEFF Research Database (Denmark)

    Henriksen, Louise Tram; Harila-Saari, Arja; Ruud, Ellen;

    2015-01-01

    BACKGROUND: L-Asparaginase is an effective drug in the treatment of childhood acute lymphoblastic leukemia (ALL). The use of L-asparaginase may be limited by serious adverse events of which allergy is the most frequent. The objective of this study was to describe the clinical aspects of PEG......-asparaginase allergy in children treated according to the Nordic Society of Paediatric Haematology and Oncology (NOPHO) ALL2008 protocol. PROCEDURE: Children (1-17 years) enrolled in the NOPHO ALL2008 protocol between July 2008 and August 2011, who developed PEG-asparaginase allergy were identified through the NOPHO...

  14. Treatment of Childhood Acute Lymphoblastic Leukemia: Prognostic Factors and Clinical Advances.

    Science.gov (United States)

    Vrooman, Lynda M; Silverman, Lewis B

    2016-10-01

    While the majority of children and adolescents with newly diagnosed childhood acute lymphoblastic leukemia (ALL) will be cured, as many as 20 % of patients will experience relapse. On current treatment regimens, the intensity of upfront treatment is stratified based upon prognostic factors with the aim of improving cure rates (for those at the highest risk of relapse) and minimizing treatment-related morbidity (for lower-risk patients). Here we review advances in the understanding of prognostic factors and their application. We also highlight novel treatment approaches aimed at improving outcomes in childhood ALL.

  15. Meralgia Paresthetica as a Presentation of Acute Appendicitis in a Girl With Acute Lymphoblastic Leukemia.

    Science.gov (United States)

    Nishimura, Miho; Kodama, Yuichi; Fukano, Reiji; Okamura, Jun; Ogaki, Kippei; Sakaguchi, Yoshihisa; Migita, Masahiro; Inagaki, Jiro

    2015-04-01

    A 7-year-old girl with Philadelphia chromosome-positive acute lymphoblastic leukemia developed recurrent fever and meralgia paresthetica (MP) during chemotherapy, which resolved after administration of antibiotics. Five months after the onset of these symptoms, enhanced computed tomography showed a periappendiceal abscess extending into the psoas muscle. The cause of her fever and MP was thought to be appendicitis, which probably developed during induction chemotherapy but did not result in typical abdominal pain. Patients with recurrent fever and MP should be evaluated by imaging examinations including computed tomography to search for appendicitis.

  16. FACIAL PALSY AS FIRST PRESENTATION OF ACUTE LYMPHOBLASTIC LEUKEMIA: A CASE REPORT

    Directory of Open Access Journals (Sweden)

    S. Inaloo

    2008-11-01

    Full Text Available ObjectiveFacial paralysis in children is very often idiopathic and isolated facial nerve palsy, resulting from leukemic infiltration is a rare occurrence. Here we present the case of a 14 year-old boy with acute lymphobastic leukemia, who first presented with isolated right side peripheral facial nerve paralysis and was initially diagnosed with Bell's palsy.ConclusionThe presence of Bell's palsy in young children requires a complete evaluation, keeping in mind the possibility of leptomeningeal disease.Key words: Lymphoblastic Leukemia, Facial nerve palsy, Children.

  17. Bacillus cereus catheter related bloodstream infection in a patient with acute lymphoblastic leukemia.

    Science.gov (United States)

    Gurler, N; Oksuz, L; Muftuoglu, M; Sargin, Fd; Besisik, Sk

    2012-01-01

    Bacillus cereus infection is rarely associated with actual infection and for this reason single positive blood culture is usually regarded as contamination . However it may cause a number of infections, such catheter-related bloodstream infections. Significant catheter-related bloodstream infections (CRBSI) caused by Bacillus spp. are mainly due to B. cereus and have been predominantly reported in immunocompromised hosts. Catheter removal is generally advised for management of infection. In this report, catheter-related bacteremia caused by B. cereus in a patient with acute lymphoblast c leukemia (ALL) in Istanbul Medical Faculty was presented.

  18. Vincristine-induced peripheral neuropathy in a neonate with congenital acute lymphoblastic leukemia.

    Science.gov (United States)

    Baker, Steven K; Lipson, David M

    2010-04-01

    We report the case of a 46-day-old boy with a fulminant vincristine-induced peripheral neuropathy after treatment for congenital acute lymphoblastic leukemia. Flaccid paralysis developed at the end of the first phase of induction, requiring intubation and ventilation for 51 days. Treatment was initiated with levocarnitine, N-acetylcysteine, and pyridoxine and progressive reversal of the neuropathy occurred over the next 4 months. Potential differences in pathogenesis and presentation of vincristine neurotoxicity and Guillian-Barre syndrome in the neonate are discussed.

  19. Methotrexate resistance in relation to treatment outcome in childhood acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Wojtuszkiewicz, Anna; Peters, Godefridus J; van Woerden, Nicole L

    2015-01-01

    BACKGROUND: Methotrexate (MTX) eradicates leukemic cells by disrupting de novo nucleotide biosynthesis and DNA replication, resulting in cell death. Since its introduction in 1947, MTX-containing chemotherapeutic regimens have proven instrumental in achieving curative effects in acute lymphoblastic...... leukemia (ALL). However, drug resistance phenomena pose major obstacles to efficacious ALL chemotherapy. Moreover, clinically relevant molecular mechanisms underlying chemoresistance remain largely obscure. Several alterations in MTX metabolism, leading to impaired accumulation of this cytotoxic agent...... resistant to MTX at diagnosis may allow for tailoring novel treatment strategies to individual leukemia patients....

  20. Targetable kinase-activating lesions in Ph-like acute lymphoblastic leukemia | Office of Cancer Genomics

    Science.gov (United States)

    Publication Abstract:  Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) is characterized by a gene-expression profile similar to that of BCR-ABL1-positive ALL, alterations of lymphoid transcription factor genes, and a poor outcome. The frequency and spectrum of genetic alterations in Ph-like ALL and its responsiveness to tyrosine kinase inhibition are undefined, especially in adolescents and adults. We performed genomic profiling of 1725 patients with precursor B-cell ALL and detailed genomic analysis of 154 patients with Ph-like ALL.