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Sample records for leukaemia gene tel

  1. Aberrant Gene Expression in Acute Myeloid Leukaemia

    DEFF Research Database (Denmark)

    Bagger, Frederik Otzen

    model to investigate the role of telomerase in AML, we were able to translate the observed effect into human AML patients and identify specific genes involved, which also predict survival patterns in AML patients. During these studies we have applied methods for investigating differentially expressed......Summary Acute Myeloid Leukaemia (AML) is an aggressive cancer of the bone marrow, affecting formation of blood cells during haematopoiesis. This thesis presents investigation of AML using mRNA gene expression profiles (GEP) of samples extracted from the bone marrow of healthy and diseased subjects....... Here GEPs from purified healthy haematopoietic populations, with different levels of differentiation, form the basis for comparison with diseased samples. We present a mathematical transformation of mRNA microarray data to make it possible to compare AML samples, carrying expanded aberrant...

  2. Gene expression profiling in acute myeloid leukaemia

    NARCIS (Netherlands)

    de Jonge, H. J. M.; Huls, G.; de Bont, E. S. J. M.

    Acute myeloid leukaemia (AML) is a heterogeneous disease characterised by clonal malignant haematopoiesis with a differentiation arrest and excessive proliferation of leukaemic blasts. Over the past decades, the heterogeneity of AML has been illustrated by evolving classifications based on

  3. Identification of novel Notch target genes in T cell leukaemia

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    Warrander Fiona

    2009-06-01

    Full Text Available Abstract Background Dysregulated Notch signalling is believed to play an important role in the development and maintenance of T cell leukaemia. At a cellular level, Notch signalling promotes proliferation and inhibits apoptosis of T cell acute lymphoblastic leukaemia (T-ALL cells. In this study we aimed to identify novel transcriptional targets of Notch signalling in the T-ALL cell line, Jurkat. Results RNA was prepared from Jurkat cells retrovirally transduced with an empty vector (GFP-alone or vectors containing constitutively active forms of Notch (N1ΔE or N3ΔE, and used for Affymetrix microarray analysis. A subset of genes found to be regulated by Notch was chosen for real-time PCR validation and in some cases, validation at the protein level, using several Notch-transduced T-ALL and non-T-ALL leukaemic cell lines. As expected, several known transcriptional target of Notch, such as HES1 and Deltex, were found to be overexpressed in Notch-transduced cells, however, many novel transcriptional targets of Notch signalling were identified using this approach. These included the T cell costimulatory molecule CD28, the anti-apoptotic protein GIMAP5, and inhibitor of DNA binding 1 (1D1. Conclusion The identification of such downstream Notch target genes provides insights into the mechanisms of Notch function in T cell leukaemia, and may help identify novel therapeutic targets in this disease.

  4. KIT mutations confer a distinct gene expression signature in core binding factor leukaemia.

    Science.gov (United States)

    Lück, Sonja C; Russ, Annika C; Du, Juan; Gaidzik, Verena; Schlenk, Richard F; Pollack, Jonathan R; Döhner, Konstanze; Döhner, Hartmut; Bullinger, Lars

    2010-03-01

    Core binding factor (CBF) leukaemias, characterized by either inv(16)(p13.1q22) or t(8;21)(q22;q22), constitute acute myeloid leukaemia (AML) subgroups with favourable prognosis. However, 40-50% of patients relapse, emphasizing the need for risk-adapted treatment approaches. In this regard, studying secondary genetic aberrations, such as mutations of the KIT gene, is of great interest, particularly as they can be targeted by receptor tyrosine kinase inhibitors (TKI). However, so far little is known about the biology underlying KIT-mutated CBF leukaemias. We analysed gene expression profiles of 83 CBF AML cases with known KIT mutation status in order to gain novel insights in KIT-mutated CBF pathogenesis. KIT-mutated cases were characterized by deregulation of genes belonging to the NFkB signalling complex suggesting impaired control of apoptosis. Notably, a subgroup of KIT wildtype cases was also characterized by the KIT mutation signature due to yet unknown aberrations. Our data suggest that this CBF leukaemia subgroup might profit from TKI therapy, however, the relevance of the KIT mutation-associated signature remains to be validated prior to clinical implementation. Nevertheless, the existence of such a signature supports the notion of relevant biological differences in CBF leukaemia and might serve as diagnostic tool in the future.

  5. BMX tyrosine kinase gene is expressed in granulocytes and myeloid leukaemias.

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    Kaukonen, J; Lahtinen, I; Laine, S; Alitalo, K; Palotie, A

    1996-09-01

    The growth and maturation of haemopoietic cells is regulated by signal transduction through tyrosine protein kinases. Recently, a novel cytoplasmic tyrosine kinase gene in chromosome X, called Bmx, was identified in human bone marrow RNA. Bmx belongs to a subfamily of tyrosine kinases which are expressed in various haemopoietic cell lineages. We studied Bmx expression using RT-PCR of RNA from fractionated peripheral blood leucocytes, progenitor-enriched fractions of cord blood and from bone marrow or peripheral blood samples from leukaemia patients. Bmx was strongly expressed in haemopoietic tissues and enhanced in neutrophilic granulocytes. Bmx mRNA was also found in CD34-positive progenitor cells from cord blood. All samples (10/10) of patients with acute myeloid leukaemia and (4/4) with chronic myeloid leukaemia showed expression of Bmx. In contrast, none of the samples of acute lymphoid leukaemia (0/8) and only one out of six samples of chronic lymphoid leukaemia expressed Bmx. In conclusion, Bmx expression seems to be associated with myelopoiesis.

  6. A 17-gene stemness score for rapid determination of risk in acute leukaemia.

    Science.gov (United States)

    Ng, Stanley W K; Mitchell, Amanda; Kennedy, James A; Chen, Weihsu C; McLeod, Jessica; Ibrahimova, Narmin; Arruda, Andrea; Popescu, Andreea; Gupta, Vikas; Schimmer, Aaron D; Schuh, Andre C; Yee, Karen W; Bullinger, Lars; Herold, Tobias; Görlich, Dennis; Büchner, Thomas; Hiddemann, Wolfgang; Berdel, Wolfgang E; Wörmann, Bernhard; Cheok, Meyling; Preudhomme, Claude; Dombret, Herve; Metzeler, Klaus; Buske, Christian; Löwenberg, Bob; Valk, Peter J M; Zandstra, Peter W; Minden, Mark D; Dick, John E; Wang, Jean C Y

    2016-12-15

    Refractoriness to induction chemotherapy and relapse after achievement of remission are the main obstacles to cure in acute myeloid leukaemia (AML). After standard induction chemotherapy, patients are assigned to different post-remission strategies on the basis of cytogenetic and molecular abnormalities that broadly define adverse, intermediate and favourable risk categories. However, some patients do not respond to induction therapy and another subset will eventually relapse despite the lack of adverse risk factors. There is an urgent need for better biomarkers to identify these high-risk patients before starting induction chemotherapy, to enable testing of alternative induction strategies in clinical trials. The high rate of relapse in AML has been attributed to the persistence of leukaemia stem cells (LSCs), which possess a number of stem cell properties, including quiescence, that are linked to therapy resistance. Here, to develop predictive and/or prognostic biomarkers related to stemness, we generated a list of genes that are differentially expressed between 138 LSC(+) and 89 LSC(-) cell fractions from 78 AML patients validated by xenotransplantation. To extract the core transcriptional components of stemness relevant to clinical outcomes, we performed sparse regression analysis of LSC gene expression against survival in a large training cohort, generating a 17-gene LSC score (LSC17). The LSC17 score was highly prognostic in five independent cohorts comprising patients of diverse AML subtypes (n = 908) and contributed greatly to accurate prediction of initial therapy resistance. Patients with high LSC17 scores had poor outcomes with current treatments including allogeneic stem cell transplantation. The LSC17 score provides clinicians with a rapid and powerful tool to identify AML patients who do not benefit from standard therapy and who should be enrolled in trials evaluating novel upfront or post-remission strategies.

  7. Two novel imatinib-responsive PDGFRA fusion genes in chronic eosinophilic leukaemia.

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    Curtis, Claire E; Grand, Francis H; Musto, Pellegrino; Clark, Andrew; Murphy, John; Perla, Gianni; Minervini, Maria M; Stewart, Janet; Reiter, Andreas; Cross, Nicholas C P

    2007-07-01

    We identified two patients with a t(2;4)(p24;q12) and a t(4;12)(q2?3;p1?2), respectively, in association with BCR-ABL and FIP1L1-PDGFRA negative chronic eosinophilic leukaemia. Molecular analysis revealed a novel STRN-PDGFRA fusion for the t(2;4) and ETV6-PDGFRA for the t(4;12). The fusions were confirmed by specific amplification of the genomic breakpoints, reverse transcription polymerase chain reaction and fluorescence in situ hybridisation. Both patients were treated with imatinib and, following a rapid haematological response, achieved cytogenetic remission and a major molecular response. In conclusion, PDGFRA fuses to diverse partner genes in myeloid disorders. Identification of these fusions is important as they are particularly sensitive to imatinib.

  8. Selection of reference genes for quantitative PCR studies in purified B cells from B cell chronic lymphocytic leukaemia patients

    OpenAIRE

    Valceckiene, Vilma; Kontenyte, Rima; Jakubauskas, Arturas; Griskevicius, Laimonas

    2010-01-01

    Abstract Clinical heterogeneity of B-cell chronic lymphocytic leukaemia (B-CLL) makes it necessary to identify potent prognostic indicators to predict individual clinical course and select risk-adapted therapy. During the last years numerous gene expression models have been suggested as prognostic factors of B-CLL. Today quantitative polymerase chain reaction (qPCR) is a preferred method for rapid quantification of gene expression and validation of microarray data. Reliability of q...

  9. Analysis of rearranged immunoglobulin genes indicating a process of clonal evolution in chronic lymphocytic leukaemia.

    Science.gov (United States)

    Hakim, I; Rechavi, G; Brok-Simoni, F; Grossman, Z; Amariglio, N; Mandel, M; Ramot, B; Ben-Bassat, I; Katzir, N

    1993-07-01

    Chronic lymphocytic leukaemia (CLL) is known to be a stable monoclonal neoplasm. In contrast to early studies demonstrating no more than two hybridizing immunoglobulin heavy chain bands corresponding to the two expected alleles, we have demonstrated an unexpected multiband pattern when the HindIII-digested DNA samples from 38 CLL patients were analysed by Southern blot hybridization using JH and C mu gene probes. In order to characterize the genetic basis for the multiband pattern, we molecularly cloned the immunoglobulin heavy chain genes of one of the patients whose leukaemic DNA sample demonstrated three hybridizing JH bands and a loss of the germline band. The cloned rearranged immunoglobulin genes could be divided, based on the restriction mapping and the hybridization with the various probes, into two basic patterns representing two alleles. In one of the cloned rearranged immunoglobulin genes a secondary rearrangement occurred that resulted in the addition of 300 base-pair long sequence into the switch region, and the creation of a HindIII restriction site. The results of the study suggest that clonal evolution occurs in some CLL, and that many of these neoplasms are indeed oligoclonal due to the accumulation of secondary genetic changes.

  10. Immunoglobulin genes and T-cell receptors as molecular markers in children with acute lymphoblastic leukaemia

    Directory of Open Access Journals (Sweden)

    Lazić Jelena

    2009-01-01

    Full Text Available Introduction. Acute lymphoblastic leukaemia (ALL is a malignant clonal disease, one of the most common malignancies in childhood. Contemporary protocols ensure high remission rate and long term free survival. The ability of molecular genetic methods help to establish submicroscopic classification and minimal residual disease (MRD follow up, in major percent responsible for relapse. Objective. The aim of the study was to detect the frequency of IgH and TCR gene rearrangements and their correlation with clinical parameters. Methods. Forty-one children with ALL were enrolled in the study group, with initial diagnosis of IgH and TCR gene rearrangements by polimerase chain reaction ( PCR. MRD follow-up was performed in induction phase when morphological remission was expected, and after intensive chemiotherapy. Results. In the study group IgH rearrangement was detected in 82.9% of children at the diagnosis, while TCR rearrangement was seen in 56.1%. On induction day 33, clonal IgH rearrangements persisted in 39% and TCR rearrangements in 36.5% of children. Conclusion. Molecular analysis of genetic alterations and their correlation with standard prognostic parameters show the importance of risk stratification revision which leads to new therapy intensification approach. MRD stands out as a precise predictive factor for the relapse of disease.

  11. Induction of the pro-myelocytic leukaemia gene by type I and type II interferons

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    M. Heuser

    1998-01-01

    Full Text Available The physiological role of the pro-myelocytic leukaemia (PML gene product is poorly defined. Among other functions, PML is involved in haem atopoietic differentiation and in control of cell growth and tumorigenesis. We investigated the regulation of human PML expression by interferons (IFNs and IL-1 in various human haematopoietic lines (U937, THP1, HL60, NB4, in human diploid fibroblasts and in human peripheral blood leukocytes. Cytokineinduced modulation of PML expression was assessed by Northern blot analyses, flow cytometry studies and in situ immunolabelling. Our data show that IFNs and IL-1 upregulate PML transcript and protein expression in a time and dose-dependent manner. In situ immunolabelling revealed that upregulation of protein expression by IFN-α is a consequence of a marked increase in both the number and the intensity of the staining of so-called PML nuclear bodies. Our data suggest that stimulation of PML expression by interferons and IL-1 may account for upregulation of PMLproteins observed in inflammatory tissues and in proliferative states.

  12. A 4-gene expression score associated with high levels of Wilms Tumor-1 (WT1) expression is an adverse prognostic factor in acute myeloid leukaemia

    NARCIS (Netherlands)

    Niavarani, A. (Ahmadreza); Herold, T. (Tobias); Y. Reyal (Yasmin); M.C. Sauerland (Maria); T. Büchner (Thomas); W. Hiddemann (Wolfgang); S.K. Bohlander (Stefan); P.J.M. Valk (Peter); Bonnet, D. (Dominique)

    2016-01-01

    textabstractWilms Tumor-1 (WT1) expression level is implicated in the prognosis of acute myeloid leukaemia (AML). We hypothesized that a gene expression profile associated with WT1 expression levels might be a good surrogate marker. We identified high WT1 gene sets by comparing the gene expression p

  13. Protracted and variable latency of acute lymphoblastic leukemia after TEL-AML1 gene fusion in utero

    NARCIS (Netherlands)

    Wiemels, JL; Ford, AM; Van Wering, ER; Postma, A; Greaves, M

    1999-01-01

    We report a pair of identical twins with concordant acute lymphoblastic leukemia (ALL). Unusually, their diagnoses were spaced 9 years apart at ages 5 and 14, Leukemic cells in both twins had a TEL-AML1 rearrangement, which was characterized at the DNA level by an adaptation of a long distance polym

  14. Validation of a mouse xenograft model system for gene expression analysis of human acute lymphoblastic leukaemia

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    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.

  15. Transcriptional activation of immediate-early gene ETR101 by human T-cell leukaemia virus type I Tax

    DEFF Research Database (Denmark)

    Chen, Li; Ma, Shiliang; Li, Bo;

    2003-01-01

    Human T-cell leukaemia virus type I (HTLV-I) Tax regulates viral and cellular gene expression through interactions with multiple cellular transcription pathways. This study describes the finding of immediate-early gene ETR101 expression in HTLV-I-infected cells and its regulation by Tax. ETR101...... was persistently expressed in HTLV-I-infected cells but not in HTLV-I uninfected cells. Expression of ETR101 was dependent upon Tax expression in the inducible Tax-expressing cell line JPX-9 and also in Jurkat cells transiently transfected with Tax-expressing vectors. Tax transactivated the ETR101 gene promoter...... in a transient transfection assay. A series of deletion and mutation analyses of the ETR101 gene promoter indicated that a 35 bp region immediately upstream of the TATA-box sequence, which contains a consensus cAMP response element (CRE) and a G+C-rich sequence, is the critical responsive element for Tax...

  16. Transcriptional activation of immediate-early gene ETR101 by human T-cell leukaemia virus type I Tax

    DEFF Research Database (Denmark)

    Chen, Li; Ma, Shiliang; Li, Bo

    2003-01-01

    Human T-cell leukaemia virus type I (HTLV-I) Tax regulates viral and cellular gene expression through interactions with multiple cellular transcription pathways. This study describes the finding of immediate-early gene ETR101 expression in HTLV-I-infected cells and its regulation by Tax. ETR101...... was persistently expressed in HTLV-I-infected cells but not in HTLV-I uninfected cells. Expression of ETR101 was dependent upon Tax expression in the inducible Tax-expressing cell line JPX-9 and also in Jurkat cells transiently transfected with Tax-expressing vectors. Tax transactivated the ETR101 gene promoter......-DNA complex in HTLV-I-infected cell lines. EMSA with specific antibodies confirmed that the CREB transcription factor was responsible for formation of this specific protein-DNA complex. These results suggested that Tax directly transactivated ETR101 gene expression, mainly through a CRE sequence via the CREB...

  17. 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.

  18. Identification of a new site of sumoylation on Tel (ETV6) uncovers a PIAS-dependent mode of regulating Tel function.

    Science.gov (United States)

    Roukens, M Guy; Alloul-Ramdhani, Mariam; Vertegaal, Alfred C O; Anvarian, Zeinab; Balog, Crina I A; Deelder, André M; Hensbergen, Paul J; Baker, David A

    2008-04-01

    Cell proliferation and differentiation are governed by a finely controlled balance between repression and activation of gene expression. The vertebrate Ets transcriptional repressor Tel (ETV6) and its invertebrate orthologue Yan, play pivotal roles in cell fate determination although the precise mechanisms by which repression of gene expression by these factors is achieved are not clearly defined. Here, we report the identification and characterization of the primary site of sumoylation of Tel, lysine 11 (K11), which is highly conserved in vertebrates (except Danio rerio). We demonstrate that in cells PIAS3 binds to Tel and stimulates sumoylation of K11 in the nucleus. Both Tel monomers and oligomers are efficiently sumoylated on K11 in vitro; but in cells only Tel oligomers are found conjugated with SUMO, whereas sumoylation of Tel monomers is transitory and appears to sensitize them for proteasomal degradation. Mechanistically, sumoylation of K11 inhibits repression of gene expression by full-length Tel. In accordance with this observation, we found that sumoylation impedes Tel association with DNA. By contrast, a Tel isoform lacking K11 (TelM43) is strongly repressive. This isoform results from translation from an alternative initiation codon (M43) that is common to all Tel proteins that also contain the K11 sumoylation consensus site. We find that PIAS3 may have a dual, context-dependent influence on Tel; it mediates Tel sumoylation, but it also augments Tel's repressive function in a sumoylation-independent fashion. Our data support a model that suggests that PIAS-mediated sumoylation of K11 and the emergence of TelM43 in early vertebrates are linked and that this serves to refine spatiotemporal control of gene expression by Tel by establishing a pool of Tel molecules that are available either to be recycled to reinforce repression of gene expression or are degraded in a regulated fashion.

  19. Med-E-Tel

    Science.gov (United States)

    2006-04-01

    Y Sistemas De Información Geográfica: Nuevas Perspectivas Para El Manejo De Problemas En Salud Pública, Caso Particular La Malaria en el Estado...representatives, academia, researchers, local and international government representatives, health insurers, homecare services. The Med-e-Tel 2006...organizations, association executives, health insurers, military and government management (both at local /national and international level), academia

  20. Genome-wide association analysis implicates dysregulation of immunity genes in chronic lymphocytic leukaemia

    Science.gov (United States)

    Law, Philip J.; Berndt, Sonja I.; Speedy, Helen E.; Camp, Nicola J.; Sava, Georgina P.; Skibola, Christine F.; Holroyd, Amy; Joseph, Vijai; Sunter, Nicola J.; Nieters, Alexandra; Bea, Silvia; Monnereau, Alain; Martin-Garcia, David; Goldin, Lynn R.; Clot, Guillem; Teras, Lauren R.; Quintela, Inés; Birmann, Brenda M.; Jayne, Sandrine; Cozen, Wendy; Majid, Aneela; Smedby, Karin E.; Lan, Qing; Dearden, Claire; Brooks-Wilson, Angela R.; Hall, Andrew G.; Purdue, Mark P.; Mainou-Fowler, Tryfonia; Vajdic, Claire M.; Jackson, Graham H.; Cocco, Pierluigi; Marr, Helen; Zhang, Yawei; Zheng, Tongzhang; Giles, Graham G.; Lawrence, Charles; Call, Timothy G.; Liebow, Mark; Melbye, Mads; Glimelius, Bengt; Mansouri, Larry; Glenn, Martha; Curtin, Karen; Diver, W Ryan; Link, Brian K.; Conde, Lucia; Bracci, Paige M.; Holly, Elizabeth A.; Jackson, Rebecca D.; Tinker, Lesley F.; Benavente, Yolanda; Boffetta, Paolo; Brennan, Paul; Maynadie, Marc; McKay, James; Albanes, Demetrius; Weinstein, Stephanie; Wang, Zhaoming; Caporaso, Neil E.; Morton, Lindsay M.; Severson, Richard K.; Riboli, Elio; Vineis, Paolo; Vermeulen, Roel C. H.; Southey, Melissa C.; Milne, Roger L.; Clavel, Jacqueline; Topka, Sabine; Spinelli, John J.; Kraft, Peter; Ennas, Maria Grazia; Summerfield, Geoffrey; Ferri, Giovanni M.; Harris, Robert J.; Miligi, Lucia; Pettitt, Andrew R.; North, Kari E.; Allsup, David J.; Fraumeni, Joseph F.; Bailey, James R.; Offit, Kenneth; Pratt, Guy; Hjalgrim, Henrik; Pepper, Chris; Chanock, Stephen J.; Fegan, Chris; Rosenquist, Richard; de Sanjose, Silvia; Carracedo, Angel; Dyer, Martin J. S.; Catovsky, Daniel; Campo, Elias; Cerhan, James R.; Allan, James M.; Rothman, Nathanial; Houlston, Richard; Slager, Susan

    2017-01-01

    Several chronic lymphocytic leukaemia (CLL) susceptibility loci have been reported; however, much of the heritable risk remains unidentified. Here we perform a meta-analysis of six genome-wide association studies, imputed using a merged reference panel of 1,000 Genomes and UK10K data, totalling 6,200 cases and 17,598 controls after replication. We identify nine risk loci at 1p36.11 (rs34676223, P=5.04 × 10−13), 1q42.13 (rs41271473, P=1.06 × 10−10), 4q24 (rs71597109, P=1.37 × 10−10), 4q35.1 (rs57214277, P=3.69 × 10−8), 6p21.31 (rs3800461, P=1.97 × 10−8), 11q23.2 (rs61904987, P=2.64 × 10−11), 18q21.1 (rs1036935, P=3.27 × 10−8), 19p13.3 (rs7254272, P=4.67 × 10−8) and 22q13.33 (rs140522, P=2.70 × 10−9). These new and established risk loci map to areas of active chromatin and show an over-representation of transcription factor binding for the key determinants of B-cell development and immune response. PMID:28165464

  1. Incidence and clinical relevance of TEL/AML1 fusion genes in children with acute lymphoblastic leukemia enrolled in the German and Italian multicenter therapy trials. Associazione Italiana Ematologia Oncologia Pediatrica and the Berlin-Frankfurt-Münster Study Group.

    Science.gov (United States)

    Borkhardt, A; Cazzaniga, G; Viehmann, S; Valsecchi, M G; Ludwig, W D; Burci, L; Mangioni, S; Schrappe, M; Riehm, H; Lampert, F; Basso, G; Masera, G; Harbott, J; Biondi, A

    1997-07-15

    The molecular approach for the analysis of leukemia associated chromosomal translocations has led to the identification of prognostic relevant subgroups. In pediatric acute lymphoblastic leukemia (ALL), the most common translocations, t(9;22) and t(4;11), have been associated with a poorer clinical outcome. Recently the TEL gene at chromosome 12p13 and the AML1 gene at chromosome 21q22 were found to be involved in the translocation t(12;21)(p13;q22). By conventional cytogenetics, however, this chromosomal abnormality is barely detectable and occurs in less than 0.05% of childhood ALL. To investigate the frequency of the molecular equivalent of the t(12;21), the TEL/AML1 gene fusion, we have undertaken a prospective screening in the running German Berlin-Frankfurt-Münster (BFM) and Italian Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP) multicenter ALL therapy trials. We have analyzed 334 unselected cases of pediatric ALL patients consecutively referred over a period of 5 and 9 months, respectively. The overall incidence of the t(12;21) in pediatric ALL is 18.9%. The 63 cases positive for the TEL/AML1 chimeric products ranged in age between 1 and 12 years, and all but one showed CD10 and pre-B immunophenotype. Interestingly, one case displayed a pre-pre-B immunophenotype. Among the B-lineage subgroup, the t(12;21) occurs in 22.0% of the cases. Fifteen of 61 (24.6%) cases coexpressed at least two myeloid antigens (CD13, CD33, or CDw65) in more than 20% of the gated blast cells. DNA index was available for 59 of the 63 TEL/AML1 positive cases; a hyperdiploid DNA content (> or = 1.16) was detected in only four patients, being nonhyperdiploid in the remaining 55. Based on this prospective analysis, we retrospectively evaluated the impact of TEL/AML1 in prognosis by identifying the subset of B-lineage ALL children enrolled in the closed German ALL-BFM-90 and Italian ALL-AIEOP-91 protocols who had sufficient material for analysis. A total of 342 children

  2. Quantitative multiplex quantum dot in-situ hybridisation based gene expression profiling in tissue microarrays identifies prognostic genes in acute myeloid leukaemia

    Energy Technology Data Exchange (ETDEWEB)

    Tholouli, Eleni [Department of Haematology, Manchester Royal Infirmary, Oxford Road, Manchester, M13 9WL (United Kingdom); MacDermott, Sarah [The Medical School, The University of Manchester, Oxford Road, M13 9PT Manchester (United Kingdom); Hoyland, Judith [School of Biomedicine, Faculty of Medical and Human Sciences, The University of Manchester, Oxford Road, M13 9PT Manchester (United Kingdom); Yin, John Liu [Department of Haematology, Manchester Royal Infirmary, Oxford Road, Manchester, M13 9WL (United Kingdom); Byers, Richard, E-mail: richard.byers@cmft.nhs.uk [School of Cancer and Enabling Sciences, Faculty of Medical and Human Sciences, The University of Manchester, Stopford Building, Oxford Road, M13 9PT Manchester (United Kingdom)

    2012-08-24

    Highlights: Black-Right-Pointing-Pointer Development of a quantitative high throughput in situ expression profiling method. Black-Right-Pointing-Pointer Application to a tissue microarray of 242 AML bone marrow samples. Black-Right-Pointing-Pointer Identification of HOXA4, HOXA9, Meis1 and DNMT3A as prognostic markers in AML. -- Abstract: Measurement and validation of microarray gene signatures in routine clinical samples is problematic and a rate limiting step in translational research. In order to facilitate measurement of microarray identified gene signatures in routine clinical tissue a novel method combining quantum dot based oligonucleotide in situ hybridisation (QD-ISH) and post-hybridisation spectral image analysis was used for multiplex in-situ transcript detection in archival bone marrow trephine samples from patients with acute myeloid leukaemia (AML). Tissue-microarrays were prepared into which white cell pellets were spiked as a standard. Tissue microarrays were made using routinely processed bone marrow trephines from 242 patients with AML. QD-ISH was performed for six candidate prognostic genes using triplex QD-ISH for DNMT1, DNMT3A, DNMT3B, and for HOXA4, HOXA9, Meis1. Scrambled oligonucleotides were used to correct for background staining followed by normalisation of expression against the expression values for the white cell pellet standard. Survival analysis demonstrated that low expression of HOXA4 was associated with poorer overall survival (p = 0.009), whilst high expression of HOXA9 (p < 0.0001), Meis1 (p = 0.005) and DNMT3A (p = 0.04) were associated with early treatment failure. These results demonstrate application of a standardised, quantitative multiplex QD-ISH method for identification of prognostic markers in formalin-fixed paraffin-embedded clinical samples, facilitating measurement of gene expression signatures in routine clinical samples.

  3. 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.

  4. RT-PCR ANALYSIS OF E2A-PBX1, TEL-AML1, BCR-ABL AND MLL-AF4 FUSION GENE TRANSCRIPTS IN B-LINEAGE ACUTE LYMPHOBLASTIC LEUKEMIA

    Directory of Open Access Journals (Sweden)

    Iuliu-Cristian Ivanov

    2013-11-01

    Full Text Available Acute lymphoblastic leukemia represents a heterogeneous group of hematological malignancies, defined by clonal proliferation of lymphoid cells. Immunophenotyping by flow cytometry and molecular analysis for the detection of genetic anomalies are clinical standard procedures for diagnosis, sub-classification and post-therapeutic evaluation. Samples from 105 patients diagnosed with acute lymphoblastic leukemia were immunophenotyped at diagnosis and were investigated by molecular analysis in order to identify the occurrence of four fusion genes: MLL-AF4, TEL-AML-1, BCR-ABL-p190, E2A-PBX-1. There were no associations found between the immunophenotype and the presence of any fusion genes evaluated. Both methods in combination remain a prerequisite for an improved subclassification of hematological malignancies, therapeutic decision, and evaluation of treatment response.

  5. Chronic lymphocytic leukaemia

    Science.gov (United States)

    Kipps, Thomas J.; Stevenson, Freda K.; Wu, Catherine J.; Croce, Carlo M.; Packham, Graham; Wierda, William G.; O’Brien, Susan; Gribben, John; Rai, Kanti

    2017-01-01

    Chronic lymphocytic leukaemia (CLL) is a malignancy of CD5+ B cells that is characterized by the accumulation of small, mature-appearing lymphocytes in the blood, marrow and lymphoid tissues. Signalling via surface immunoglobulin, which constitutes the major part of the B cell receptor, and several genetic alterations play a part in CLL pathogenesis, in addition to interactions between CLL cells and other cell types, such as stromal cells, T cells and nurse-like cells in the lymph nodes. The clinical progression of CLL is heterogeneous and ranges from patients who require treatment soon after diagnosis to others who do not require therapy for many years, if at all. Several factors, including the immunoglobulin heavy-chain variable region gene (IGHV) mutational status, genomic changes, patient age and the presence of comorbidities, should be considered when defining the optimal management strategies, which include chemotherapy, chemoimmunotherapy and/or drugs targeting B cell receptor signalling or inhibitors of apoptosis, such as BCL-2. Research on the biology of CLL has profoundly enhanced our ability to identify patients who are at higher risk for disease progression and our capacity to treat patients with drugs that selectively target distinctive phenotypic or physiological features of CLL. How these and other advances have shaped our current understanding and treatment of patients with CLL is the subject of this Primer. PMID:28102226

  6. Immunoglobulin heavy variable (IGHV) genes and alleles: new entities, new names and implications for research and prognostication in chronic lymphocytic leukaemia.

    Science.gov (United States)

    Xochelli, Aliki; Agathangelidis, Andreas; Kavakiotis, Ioannis; Minga, Evangelia; Sutton, Lesley Ann; Baliakas, Panagiotis; Chouvarda, Ioanna; Giudicelli, Véronique; Vlahavas, Ioannis; Maglaveras, Nikos; Bonello, Lisa; Trentin, Livio; Tedeschi, Alessandra; Panagiotidis, Panagiotis; Geisler, Christian; Langerak, Anton W; Pospisilova, Sarka; Jelinek, Diane F; Oscier, David; Chiorazzi, Nicholas; Darzentas, Nikos; Davi, Fred; Ghia, Paolo; Rosenquist, Richard; Hadzidimitriou, Anastasia; Belessi, Chrysoula; Lefranc, Marie-Paule; Stamatopoulos, Kostas

    2015-01-01

    Νext generation sequencing studies in Homo sapiens have identified novel immunoglobulin heavy variable (IGHV) genes and alleles necessitating changes in the international ImMunoGeneTics information system (IMGT) GENE-DB and reference directories of IMGT/V-QUEST. In chronic lymphocytic leukaemia (CLL), the somatic hypermutation (SHM) status of the clonotypic rearranged IGHV gene is strongly associated with patient outcome. Correct determination of this parameter strictly depends on the comparison of the nucleotide sequence of the clonotypic rearranged IGHV gene with that of the closest germline counterpart. Consequently, changes in the reference directories could, in principle, affect the correct interpretation of the IGHV mutational status in CLL. To this end, we analyzed 8066 productive IG heavy chain (IGH) rearrangement sequences from our consortium both before and after the latest update of the IMGT/V-QUEST reference directory. Differences were identified in 405 cases (5 % of the cohort). In 291/405 sequences (71.9 %), changes concerned only the IGHV gene or allele name, whereas a change in the percent germline identity (%GI) was noted in 114/405 (28.1 %) sequences; in 50/114 (43.8 %) sequences, changes in the %GI led to a change in the mutational set. In conclusion, recent changes in the IMGT reference directories affected the interpretation of SHM in a sizeable number of IGH rearrangement sequences from CLL patients. This indicates that both physicians and researchers should consider a re-evaluation of IG sequence data, especially for those IGH rearrangement sequences that, up to date, have a GI close to 98 %, where caution is warranted.

  7. The outcome of Chronic lymphocytic leukaemia patients with 97% IGHV gene identity to germline is distinct from cases with identity and similar to those with 98% identity.

    Science.gov (United States)

    Davis, Zadie; Forconi, Francesco; Parker, Anton; Gardiner, Anne; Thomas, Peter; Catovsky, Daniel; Rose-Zerilli, Matthew; Strefford, Jonathan C; Oscier, David

    2016-04-01

    IGHV gene mutational status has prognostic significance in chronic lymphocytic leukaemia (CLL) but the percentage of mutations that correlates best with clinical outcome remains controversial. We initially studied 558 patients from diagnosis and found significant differences in median time to first treatment (TTFT) among Stage A patients and in overall survival (OS) for the whole cohort, between cases with identity and between cases with 97-98·99% and ≥99% identity, when cases from the IGHV3-21 Stereotype Subset #2 were excluded. A significant difference in progression-free survival (PFS) and OS between those with identity, but not between those with 97-98·99% and ≥99% identity was also observed in a validation cohort comprising 460 patients in the UK CLL4 trial. Cox Regression analyses in the Stage A cohort revealed that a model which incorporated identity as subgroups, was a better predictor of TTFT in CLL than using the 98% cut-off. Multivariate analysis selected the three mutational subgroups as independent predictors of TTFT in Stage A patients, and of OS in the diagnostic cohort. This study highlights that cases with 97% identity should not be considered to have the same prognosis as other cases with mutated IGHV genes defined as identity to germline.

  8. Environmental factors and leukaemia

    Energy Technology Data Exchange (ETDEWEB)

    Brandt, L.

    1985-01-01

    Investigations on the association between environmental hazards and the development of various types of leukaemia are reviewed. Regarding acute non-lymphocytic leukaemia (ANLL) exposure to ionizing radiation is a well-documented risk factor. According to several recent studies exposure to strong electromagnetic fields may be suspected to be of etiologic importance for ANLL. There is evidence that occupational handling of benzene is a risk factor and other organic solvents may also be leukaemogenic. Occupational exposure to petrol products has been proposed to be a risk factor although the hazardous substances have not yet been defined. Results of cytogenetic studies in ANLL suggest that exposure to certain environmental agents may be associated with relatively specific clonal chromosome aberrations. Exposure in utero to ionizing radiation has been proposed to be a risk factor for acute lymphocytic leukaemia (ALL) in children. Unlike ANLL there seems at present to be little evidence that ALL is related to exposure to some chemicals. Chronic myeloid leukaemia (CML) may follow exposure to high doses of ionizing radiation whereas such exposure seems to be of insignificant importance for the development of chronic lymphocytic leukaemia (CLL). According to some studies an abnormally high incidence of CLL may be found among farmers in the USA. These results have not been confirmed in Scandinavian studies. There seems to be little evidence that CML or CLL are related to occupational handling of some chemicals. 35 references.

  9. Acute promyelocytic leukaemia in patients originating in Latin America is associated with an increased frequency of the bcr1 subtype of the PML/RARalpha fusion gene.

    Science.gov (United States)

    Douer, Dan; Santillana, Sergio; Ramezani, Laleh; Samanez, Cesar; Slovak, Marilyn L; Lee, Ming S; Watkins, Kristy; Williams, Tony; Vallejos, Carlos

    2003-08-01

    The PML/RARalpha fusion gene in acute promyelocytic leukaemia (APL) has three subtypes based on the breakpoint site of the PML gene: long (bcr1), short (bcr3) and variable (bcr2) subtypes. The PML/RARalpha fusion protein is involved in the pathogenesis of APL and the breakpoint site of the PML gene might be associated with aetiological factor(s). Because APL is over-represented in patients that originate in Latin America (Latinos), we evaluated whether the distribution of the PML/RARalpha fusion mRNA in this population is different to that reported in non-Latinos. Among 52 APL patients (28 from Mexico and Central America diagnosed in Los Angeles and 24 from Peru, South America), bcr1, bcr2 and bcr3 expression was 75%, 10% and 15% respectively. However, bcr1 breakpoints were significantly higher compared with non-Latino patients (340/654, 52%) reported in four studies. Often bcr1 and bcr2 are reported together; 862 (60%) of 1429 non-Latino APL patients reported in nine studies were either bcr1 or bcr2, compared with 44 (85%) in our 52 Latino patients. This difference was also statistically significant when our patients were compared to each of the individual studies from USA and Europe, but not for a small series from China and Japan. These results suggest that the overrepresentation of APL among Latin American patients can be accounted for by an increase of a single subtype--bcr1, and the breakage sites in the PML gene may not be random but possibly influenced by genetic and/or environmental factor(s).

  10. Molecular expression of l-asparaginase gene from Nocardiopsis alba NIOT-VKMA08 in Escherichia coli: A prospective recombinant enzyme for leukaemia chemotherapy.

    Science.gov (United States)

    Meena, Balakrishnan; Anburajan, Lawrance; Vinithkumar, Nambali Valsalan; Shridhar, Divya; Raghavan, Rangamaran Vijaya; Dharani, Gopal; Kirubagaran, Ramalingam

    2016-09-30

    l-Asparaginase is an antineoplastic agent that selectively reduces the level of l-asparagine in blood and diminishes the proliferation of cancerous cells. Studies were carried out on the cloning and heterologous expression of l-asparaginase biosynthesis gene (ansA) from Nocardiopsis alba NIOT-VKMA08 to achieve the stable inducible system that overproduces the glutaminase-free recombinant l-asparaginase. Overexpression of recombinant l-asparaginase was achieved with an optimized final concentration of 1.5mM of isopropyl-β-d-thiogalactoside (IPTG) and the enzyme was expressed as a soluble protein. The recombinant enzyme was purified using nickel-nitrilotriacetic acid (Ni-NTA) chromatography and the purified enzyme disclosed an elevated level of asparaginase activity (158.1IU/mL). Optimum pH and temperature of the purified l-asparaginase for the hydrolysis of l-asparagine were 8.0 and 37°C and it was very specific for its natural substrate, l-asparagine. Detailed studies were carried out on the kinetics of enzyme reaction, catalytic activity, temperature and ionic strength and the thermostability of the l-asparaginase enzyme. The functional characterisation of the recombinant l-asparaginase was studied through Fourier transform infrared spectroscopy (FT-IR), nuclear magnetic resonance (NMR), in silico sequence analysis and protein structural modelling. Glutaminase activity was not detected in the recombinant l-asparaginase, which could reduce the probable side effects during leukaemia therapy.

  11. Value of Interphase Fluorescence in Situ Hybridization in Identification of TEL-AML1 Fusion Gene in Pediatric Cases with Acute Lymphoblastic Leukemia%FISH技术在儿童ALL TEL-AML1融合基因检测中的应用价值

    Institute of Scientific and Technical Information of China (English)

    王恺; 周永安; 苏丽萍; 解菊芬; 赵瑾; 马莉; 石磊

    2009-01-01

    目的 探讨双色间期荧光原位杂交(I-FISH)技术在儿童急件淋巴细胞白血病t(12;21)形成的TEL-AML1融合基因检测中的应用价值.方法 联合双色间期FISH和常规染色体核型分析技术(CCA)对31例儿童初治ALL的骨髓有核细胞进行t(12;21)TEL-AML1融合基因检测.结果 7例患儿经FISH检测发现TEL-AML1融合基因,占总病例的22.6%;而CCA检测均未发现有可疑的t(12;21).结论 FISH技术较常规染色体核型分析技术特异性强、敏感度高,可以有效检测出TEL-AML1融合基因,从而为儿童ALL的诊断确立、采用个体化治疗方案提供重要的依据.

  12. Regulation of the Ets transcription factor Tel

    NARCIS (Netherlands)

    Roukens, Mark Guido

    2010-01-01

    In this thesis we report novel studies on the molecular regulation of the transcriptional repressor Tel (Translocation Ets Leukemia). The work in this thesis is presented as follows: Chapter 1 is an introduction which summarizes the literature about Tel and its Drosophila orthologue Yan as it was k

  13. Edificio, en Tel-Aviv

    Directory of Open Access Journals (Sweden)

    Solotov, Nahum

    1964-03-01

    Full Text Available This building is a clear example of the efforts now being made by the new generations of Israel architects to develop a national architecture, based principally on prefabrication, and running contrary to the classic moulds so deeply rooted in the Middle East, and also to the strong wave of American style modernism. Up to now, this is the tallest building in Tel-Aviv. It consists of vertical pillars at ground level, which branch out into Y shaped supports at the second floor. A large block of apartments rises above these. The outer walls consist of prefabricated concrete parts; there is also a large trellice structure, made up of concrete units, which supports a number of projecting fittings; these provide shade and facilitate ventilation. This type of fittings has proved very useful throughout Israel as a means of solving the basic problem of shade against the sun and suitable ventilation.Constituye un claro exponente de la lucha que sostiene la. nueva generación de arquitectos, formados en Israel, por crear una arquitectura nacional propia—basada principalmente en la prefabricación—, contraria a los moldes clasicistas tan arraigados en el Oriente Medio y a la gran ola de arquitectura americanizante. El edificio, el más alto construido hasta la fecha, en la zona central de Tel-Aviv, arranca en planta baja de unos pilares verticales, que se abren en la planta primera en forma de Y, para sustentar el bloque de apartamentos. Los cerramientos de fachada están construidos con piezas prefabricadas de hormigón; y una gran celosía constituida por bloques de hormigón, a los cuales van adosadas unas piezas salientes que dan sombra y facilitan la ventilación, resolviendo acertadamente este problema fundamental en toda la arquitectura del país.

  14. Salmonella tel-el-kebir and terrapins.

    LENUS (Irish Health Repository)

    Lynch, M

    2012-02-03

    OBJECTIVES: An outbreak of Salmonella tel-el-kebir occurring over a 6-month period is described in this report. This is the first outbreak of S. tel-el-kebir in the reported literature. METHODS: S. tel-el-kebir was isolated from human faecal samples using conventional laboratory methods. RESULTS: Eight patients had S. tel-el-kebir isolated from faeces. All patients were owners of, or in close contact with, pet terrapins. The terrapins were purchased in the same pet shop, where they were imported from America. The epidemiological link with these pets was confirmed, as S. tel-el-kebir was isolated from cloacal swabs from the terrapins, and from terrapin water. Molecular biology studies using DNA amplification fingerprinting (DAF) gave identical fingerprint patterns for all human and terrapin isolates. CONCLUSIONS: Salmonellosis associated with exotic pets is a re-emerging disease in the 1990s, and measures to reduce this are discussed.

  15. CBL mutations do not frequently occur in paediatric acute myeloid leukaemia

    NARCIS (Netherlands)

    Coenen, Eva A.; Driessen, Emma M. C.; Zwaan, C. Michel; Stary, Jan; Baruchel, Andre; de Haas, Valerie; de Bont, Eveline S. J. M.; Reinhardt, Dirk; Kaspers, Gertjan J. L.; Arentsen-Peters, Susan T. C. J. M.; Meyer, Claus; Marschalek, Rolf; Pieters, Rob; Stam, Ronald W.; van den Heuvel-Eibrink, Marry M.

    2012-01-01

    RAS-pathway mutations, causing a proliferative advantage, occur in acute myeloid leukaemia (AML) and MLL-rearranged leukaemia. Recently, mutations in the Casitas B lineage lymphoma (CBL) gene were reported to be involved in RAS-pathway activation in various myeloid malignancies, but their role in pa

  16. President Rüütel kordab ennast

    Index Scriptorium Estoniae

    2002-01-01

    Kohtumisel Sloveenia suursaadikuga leidis president Arnold Rüütel, et Eestil ja Sloveenial on sarnasusi. Varem on president öelnud, et ühiseid jooni on Eestil ja Liibanonil ning Eestil ja El Salvadoril

  17. Comparison of loop-mediated isothermal amplification (LAMP) and nested-PCR assay targeting the RE and B1 gene for detection of Toxoplasma gondii in blood samples of children with leukaemia.

    Science.gov (United States)

    Fallahi, Shirzad; Seyyed Tabaei, Seyyed Javad; Pournia, Yadollah; Zebardast, Nozhat; Kazemi, Bahram

    2014-07-01

    Toxoplasmosis diagnosis constitutes an important measure for disease prevention and control. In this paper, a newly described DNA amplification technique, loop-mediated isothermal amplification (LAMP), and nested-PCR targeting the repeated element (RE) and B1 gene, were compared to each other for the detection of Toxoplasma gondii DNA in blood samples of children with leukaemia. One hundred ten blood samples from these patients were analyzed by LAMP and nested-PCR. Out of 50 seropositive samples (IgM+, IgG+), positive results were obtained with 92% and 86% on RE, B1-LAMP and 82% and 68% on RE, B1-nested PCR analyses, respectively. Of the 50 seronegative samples, three, two and one samples were detected positive by RE-LAMP, B1-LAMP and RE-nested PCR assays, respectively, while none were detected positive by B1-nested PCR. None of the 10 IgM-, IgG+ samples was detected positive after testing LAMP and nested-PCR assays in duplicate. This is the first report of a study in which the LAMP method was applied with high sensitivity and efficacy for the diagnosis of T. gonii in blood samples of children with leukaemia.

  18. Cancer progression by reprogrammed BCAA metabolism in myeloid leukaemia.

    Science.gov (United States)

    Hattori, Ayuna; Tsunoda, Makoto; Konuma, Takaaki; Kobayashi, Masayuki; Nagy, Tamas; Glushka, John; Tayyari, Fariba; McSkimming, Daniel; Kannan, Natarajan; Tojo, Arinobu; Edison, Arthur S; Ito, Takahiro

    2017-05-25

    Reprogrammed cellular metabolism is a common characteristic observed in various cancers. However, whether metabolic changes directly regulate cancer development and progression remains poorly understood. Here we show that BCAT1, a cytosolic aminotransferase for branched-chain amino acids (BCAAs), is aberrantly activated and functionally required for chronic myeloid leukaemia (CML) in humans and in mouse models of CML. BCAT1 is upregulated during progression of CML and promotes BCAA production in leukaemia cells by aminating the branched-chain keto acids. Blocking BCAT1 gene expression or enzymatic activity induces cellular differentiation and impairs the propagation of blast crisis CML both in vitro and in vivo. Stable-isotope tracer experiments combined with nuclear magnetic resonance-based metabolic analysis demonstrate the intracellular production of BCAAs by BCAT1. Direct supplementation with BCAAs ameliorates the defects caused by BCAT1 knockdown, indicating that BCAT1 exerts its oncogenic function through BCAA production in blast crisis CML cells. Importantly, BCAT1 expression not only is activated in human blast crisis CML and de novo acute myeloid leukaemia, but also predicts disease outcome in patients. As an upstream regulator of BCAT1 expression, we identified Musashi2 (MSI2), an oncogenic RNA binding protein that is required for blast crisis CML. MSI2 is physically associated with the BCAT1 transcript and positively regulates its protein expression in leukaemia. Taken together, this work reveals that altered BCAA metabolism activated through the MSI2-BCAT1 axis drives cancer progression in myeloid leukaemia.

  19. Detection of Translocation ETS Leukemia-Acute Myeloid Leukemia1 Fusion Gene in Acute Lymphoblastic Leukemia Children by Real-Time Fluorescent Quantitative Polymerase Chain Reaction and Its Clinical Significance%实时荧光定量反转录多聚酶链反应技术检测TEL-AML1融合基因阳性急性淋巴细胞白血病

    Institute of Scientific and Technical Information of China (English)

    张熔; 廖静; 李戈; 孙怀强; 石毓君; 杨季云

    2012-01-01

    Objective To establish a real - time fluorescent quantitative reverse transcription - polymerase chain reaction(qRT - PCR) for detection of TEL - AML1 fusion gene mRNA in acute lymphoblastic leukemia ( ALL) children and explore its clinical significance. Methods A qRT-PCR with a TaqMan fluorescence probe and 2-△△et relative quantitative method was used to dynamically detect the expression levels of TEL - AML1 fusion gene in 20 acute lymphoblastic leukemia children with TEL - AML1 fusion gene positive at the time of newly diagnosed (n =20) ,complete remission (n =20) ,recurrence period (n =2) ,and 15 children with normal bone marrow morphology and with non tumor and no blood disease as a control group. Results Median of the expression level of TEL - AML1 fusion gene at newly diagnosed, complete remission, relapse period were 0. 62,0. 31,0.76,0. 23,respectively,and there were significant differences (Pa 0. 05). The recurrence rate and event - free survival rate of patients with high level of TEL - AML1 expression ( > P75 of the control group) on day 33 were significantly higher and lower than those of low expression of children, respectively (P < 0. 05). Twenty patients on day 33 at the end of the first induction therapy achieved completely remission by bone marrow morphological examination. After intense and maintenance therapy, the high levels of the 8 children were declined. But the level of 1 case out of 8 cases abnormally increased and then the patient relapsed during maintenance therapy. After 2 months of ending chemotherapy, another 1 patient also relapsed with high TEL - AML1 level again. The levels of minimal residual disease were positive in 8 cases by qRT - PCR test, negative in 20 cases by bone marrow morphology and karyotype analysis tests, positive in 5 cases by real - time reaverse transcription - PCR test. Conclusions qRT - PCR is a rapid, efficient, sensitive and specific method. The expression level of TEL - AML1 gene on day 33 during induction

  20. Childhood leukemia genetic bottleneck phenomenon related to TEL-AML1: the postulation by a mathematical model

    Institute of Scientific and Technical Information of China (English)

    Petar Ivanovski; Ivan Ivanovski; Dimitrije Nikoli(c); Ivana Jovanovi(c)

    2012-01-01

    Childhood leukemia bottleneck phenomenon is the most mysterious corollary of the prenatal origin discovery of leukemogenic chromosome translocations.The bottleneck is evidence that leukemia initiation,by in utero acquired chromosome translocations that generate functional fusion genes,is far more common than the incidence rate of corresponding leukemia.For childhood TEL-AML1+ acute lymphoblastic leukemia (ALL) this equates to approximately 100 times.Practically this means that among a hundred children born with TEL-AML1 fusion gene,only one child will later in its life develop ALL.The key data necessary for unraveling of this mystery were discovered in 2002.It was the level of TEL-AML1 + cells' frequency.The bottleneck is caused by the very low body TEL-AML1 + cell count.Only one out of a thousand B cells carries TEL-AML1 fusion gene.TEL-AML1+ body cell count is low because TEL-AML1 fusion is generated at cell level of 10a to 10-4 just during the late fetal lymphopoiesis i.e.after the 36th gestational week.

  1. Childhood leukemia genetic bottleneck phenomenon related to TEL-AML1: the postulation by a mathematical model.

    Science.gov (United States)

    Ivanovski, Petar; Ivanovski, Ivan; Nikolić, Dimitrije; Jovanović, Ivana

    2012-03-01

    Childhood leukemia bottleneck phenomenon is the most mysterious corollary of the prenatal origin discovery of leukemogenic chromosome translocations. The bottleneck is evidence that leukemia initiation, by in utero acquired chromosome translocations that generate functional fusion genes, is far more common than the incidence rate of corresponding leukemia. For childhood TEL-AML1(+) acute lymphoblastic leukemia (ALL) this equates to approximately 100 times. Practically this means that among a hundred children born with TEL-AML1 fusion gene, only one child will later in its life develop ALL. The key data necessary for unraveling of this mystery were discovered in 2002. It was the level of TEL-AML1(+) cells’ frequency. The bottleneck is caused by the very low body TEL-AML1(+) cell count. Only one out of a thousand B cells carries TEL-AML1 fusion gene. TEL-AML1(+) body cell count is low because TEL-AML1 fusion is generated at cell level of 10(-3) to 10(-4) just during the late fetal lymphopoiesis i.e. after the 36th gestational week.

  2. Oral manifestations of acute leukaemia

    Directory of Open Access Journals (Sweden)

    Ivanović Mirjana

    2011-01-01

    Full Text Available Acute leukaemia is the most common form of chilhood cancer. The aim of this paper was to underline the importance of oral manifestations in children with acute leukaemia. The disease and its treatment can directly or indirectly affect oral health. Oral manifestations are gingival inflammation and enlargement. Leukaemic cells are capable of infiltrating the gingiva and the deeper periodontal tissues which leads to ulceration and infection of oral tissues. Gingival bleeding is a common sign in patients with leukaemia. Symptoms include local lymphadenopathy, mucous membrane Petechiae and ecchymoses. Cytotoxic drugs have direct effects like mucositis, involving atrophy, desquamation and ulceration of the mucosa, with increasing the risk for local and systemic infections. Leukaemia can directly influence dental care and dental treatment, while oral lesions may have life-threatening consequences. Knowledge and skills among dentists may also not be adequate to treat children with acute leukaemia. It is therefore imperative that all stomatologists be aware of dental problems that occur in leukaemia in order to be able to effectively carry out appropriate measures to mitigate these problems.

  3. Arnold Rüütel: Rossija - sosed i partnjor / Arnold Rüütel

    Index Scriptorium Estoniae

    Rüütel, Arnold, 1928-

    2001-01-01

    President Arnold Rüütel usub, et Venemaast saab EL-i astudes Eestile hea naaber ja äripartner. Vene Õigeusu Kirikust Eestis, kodakondsuse eksami keelenõuete lihtsustamisest, Eesti astumisest NATOsse ja Euroopa Liitu. Parlamendisaadik

  4. (TELS en la Zona Metropolitana de Guadalajara

    Directory of Open Access Journals (Sweden)

    Omar García Concepción

    2007-01-01

    Full Text Available La aparición de los fenómenos severos en el tiempo meteorológico (tornados, granizos y vientos lineales con rachas destructoras está relacionada con cambios importantes en la morfología de las tormentas eléctricas. Las tormentas que alcancen ese estadio son consideradas como un tipo especial de tormentas eléctricas llamadas tormentas eléctricas locales severas (TELS. El desarrollo de las TELS en la Zona Metropolitana de Guadalajara (ZMG es una realidad y se debe considerar en la protección de la sociedad, debido a las pérdidas de vidas, daños materiales y cuantiosas afectaciones que ocurren como consecuencia de éstas. Al no contar con una cronología de las TELS en la ZMG fue necesaria la compilación de las mismas como base para realizar su climatología. Entre los resultados obtenidos se destaca que las TELS ocurren desde mayo hasta noviembre, en particular, en los meses de junio, julio y agosto. La mayoría se presenta durante horas de la tarde o de la noche, pero un grupo nada despreciable también ocurre durante la madrugada. Queda establecido que las TELS constituyen un elemento importante del clima de la ZMG que no puede ser ignorado desde el punto de vista científico y mucho menos en la práctica, por los efectos que produce en muchas ocasiones.

  5. Introduction slides for RecSysTEL workshop

    NARCIS (Netherlands)

    Drachsler, Hendrik; Manouselis, Nikos; Santos, Olga; Verbert, Katrien

    2012-01-01

    Drachsler, H., Manouselis, N., Santos, O., & Verbert, K. (2012, 19 September). Introduction slides for RecSysTEL workshop. Presentation at the 2nd Workshop on Recommender Systems for Technolgy Enhancend Learning (RecSysTEL 2012) at EC-TEL 2012, Saarbrücken, Germany.

  6. Acute leukaemia following renal transplantation.

    Science.gov (United States)

    Subar, M; Gucalp, R; Benstein, J; Williams, G; Wiernik, P H

    1996-03-01

    Four renal transplant patients on immunosuppressive therapy who presented with acute myeloid leukaemia are described. In two cases, azathioprine may have played an important role as a cofactor in leukaemogenesis. In a third case, the alkylating agent cyclophosphamide may have contributed. All patients were treated for leukaemia with full doses of cytotoxic chemotherapy and, in each case, a functioning renal allograft was preserved throughout the treatment despite attenuation of immunosuppressive therapy. Three patients achieved complete remission. Of the three, one is surviving at 2 years and two expired during the pancytopenic phase of their treatment with no active leukaemia present, and with intact renal function. As increasing expertise in the field of organ transplantation allows patients to survive longer, such patients' exposure to immunosuppressive and potentially leukaemogenic drugs is prolonged. The risk of secondary neoplasia has been previously documented in this population. Two of the four cases reported here suffered from polycystic kidney disease as their underlying condition. While this report suggests that the leukaemias are related to renal transplantation, we cannot rule out an association with the underlying disease which led to the transplant. This report further suggests that the leukaemia that develops in such patients may respond to standard therapy, and that such treatment does not compromise the transplanted kidney.

  7. Associations of novel genetic variations in the folate-related and ARID5B genes with the pharmacokinetics and toxicity of high-dose methotrexate in paediatric acute lymphoblastic leukaemia.

    Science.gov (United States)

    Csordas, Katalin; Lautner-Csorba, Orsolya; Semsei, Agnes F; Harnos, Andrea; Hegyi, Marta; Erdelyi, Daniel J; Eipel, Oliver T; Szalai, Csaba; Kovacs, Gabor T

    2014-08-01

    High-dose methotrexate (HD-MTX) plays an important role in the consolidation therapy of acute lymphoblastic leukaemia (ALL) in many treatment regimens worldwide. However, there is a large interpatient variability in the pharmacokinetics and toxicity of the drug. We investigated the influence of single nucleotide polymorphisms (SNPs) in genes of the folate metabolic pathway, transporter molecules and transcription proteins on the pharmacokinetics and toxicity of MTX and 7-hydroxy-methotrexate (7-OH-MTX). 63 SNPs of 14 genes were genotyped and a total of 463 HD-MTX courses (administered according to the ALL-BFM 95 and ALL IC-BFM 2002 protocols) were analysed. Haematological, hepatic and renal toxicities, estimated by routine laboratory parameters were evaluated. Random forest and regression trees were used for variable selection and model building. Linear mixed models were established to prove the significance of the selected variables. SNPs (rs4948502, rs4948496, rs4948487) of the ARID5B gene were associated with the serum levels of MTX (P < 0·02), serum levels and area under the curve of 7-OH-MTX (P < 0·02) and with hypoproteinaemia (P = 0·004). SLCO1B1 rs4149056 also showed a significant association with serum MTX levels (P < 0·001). Our findings confirm the association of novel genetic variations in folate-related and ARID5B genes with the serum MTX levels and acute toxicity.

  8. Drosophila Tel2 is expressed as a translational fusion with EpsinR and is a regulator of wingless signaling.

    Directory of Open Access Journals (Sweden)

    Ji-Hoon Lee

    Full Text Available Tel2, a protein conserved from yeast to vertebrates, is an essential regulator of diverse cellular processes including telomere maintenance, DNA damage checkpoints, DNA repair, biological clocks, and cell signaling. The Drosophila Tel2 protein is produced as a translational fusion with EpsinR, a Clathrin adapter that facilitates vesicle trafficking between the Golgi and endosomes. EpsinR and Tel2 are encoded by a Drosophila gene called lqfR. lqfR is required for viability, and its specific roles include cell growth, proliferation, and planar cell polarity. We find that all of these functions of lqfR are attributed entirely to Tel2, not EpsinR. In addition, we find that Drosophila LqfR/Tel2 is a component of one or more protein complexes that contain E-cadherin and Armadillo. Moreover, Tel2 modulates E-cadherin and Armadillo cellular dynamics. We propose that at least one of the functions of Drosophila Tel2 is regulation of Wingless signaling.

  9. Tel, a Frequent Target of Leukemic Translocations, Induces Cellular Aggregation and Influences Expression of Extracellular Matrix Components

    Directory of Open Access Journals (Sweden)

    L. Van Rompaey

    1999-12-01

    Full Text Available Tel is an Ets transcription factor that is the target of chromosome translocations in lymphoid and myeloid leukemias and in solid tumors. It contains two functional domains, a pointed oligomerization domain and a DNAbinding domain. Retroviral transduction of a wild-type Tel cDNA into a clonal subline of NIH3T3 fibroblasts resulted in a striking morphologic change: at confluency, the cells reorganized into a specific “bridge-like” pattern over the entire surface of the culture dish, started migrating, thereby leaving circular holes in the monolayer. Thereafter, formation of cellular cords became apparent. This sequence of events was inhibited by coating the culture dishes with fibronectin and collagen IV. Retroviral transduction of Tel into MS1 endothelial cells reproduced the aggregation phenotype, but not the cellular cord formation. Tel -mutagenesis showed that both the pointed domain and the DNAbinding domain of Tel are required for the morphologic change. Other Ets family genes, Fli-1 and Ets-1 that are both endogenously expressed in endothelial cells, could not induce this morphologic change. Exogenous Tel expression is associated with transcriptional upregulation of entactin/nidogen, Smad5, Col3a1, CD44 and fibronectin, downregulation of Coliai and secretory leukocyte protease inhibitor. Interestingly, Tel, Smad5, fibronectin, Coliai and Col3a1 all have essential roles during vascular development.

  10. Eosinophilic leukaemia in a cat.

    Science.gov (United States)

    Sharifi, Hassan; Nassiri, Seyed Mahdi; Esmaelli, Hossein; Khoshnegah, Javad

    2007-12-01

    A 14-year-old female domestic shorthair cat was presented to Tehran University Veterinary Teaching Hospital for a persistent fever, anorexia, intermittent vomiting, weight loss and weakness. The main clinical signs were pale mucous membranes, dehydration and splenomegaly. The complete blood count and serum biochemistry tests revealed non-regenerative anaemia, thrombocytopenia and increased alkaline phosphatase (ALP) activity. An enzyme-linked immunosorbent assay (ELISA) test for feline leukaemia virus was negative. Blood film and bone marrow examination revealed a large number of immature eosinophils with variable sizes and numbers of faintly azurophilic granules. Cytochemical staining of blood film demonstrated 70% positive cells for ALP activity. Four percent CD34 positive cells were detected by flow cytometry. As eosinophilic leukaemia is difficult to identify by light microscopy, well-defined diagnostic criteria and the use of flow cytometry and cytochemical staining can improve the ability to correctly diagnose this type of leukaemia in cats.

  11. Arnold Rüütel ja Toomas Hendrik Ilves raamaturiiulil

    Index Scriptorium Estoniae

    2006-01-01

    Arnold Rüütel. Tuleviku taassünd. Tallinn : Ilo, 2001; Toomas Kall. Rüütel : rahva keeles ja meeles. Tallinn : Varrak, 2006; Eesti Vabariigi President Arnold Rüütel. [Tallinn] : Ilo, 2006; Arnold Rüütel. Agraar-tööstuskompleksi areng Eesti NSV-s. Tallinn : Valgus, 1982; Arnold Rüütel. President : [valik Vabariigi Presidendi Arnold Rüütli kõnedest]. Tallinn : Eesti Keele Sihtasutus, 2003; Toomas Hendrik Ilves. Eesti jõudmine. Tallinn : Varrak, 2006

  12. Arnold Rüütel ja Toomas Hendrik Ilves raamaturiiulil

    Index Scriptorium Estoniae

    2006-01-01

    Arnold Rüütel. Tuleviku taassünd. Tallinn : Ilo, 2001; Toomas Kall. Rüütel : rahva keeles ja meeles. Tallinn : Varrak, 2006; Eesti Vabariigi President Arnold Rüütel. [Tallinn] : Ilo, 2006; Arnold Rüütel. Agraar-tööstuskompleksi areng Eesti NSV-s. Tallinn : Valgus, 1982; Arnold Rüütel. President : [valik Vabariigi Presidendi Arnold Rüütli kõnedest]. Tallinn : Eesti Keele Sihtasutus, 2003; Toomas Hendrik Ilves. Eesti jõudmine. Tallinn : Varrak, 2006

  13. Sustainable Urban Renewal: The Tel Aviv Dilemma

    Directory of Open Access Journals (Sweden)

    Asaf Friedman Arch

    2014-04-01

    Full Text Available The city of Tel Aviv needs extensive urban renewal projects to answer the demand for housing. The area suitable for such a project is the older southern part of Tel Aviv, made up of small parcels of land with single units. This area has undergone an extreme gentrification process, which makes assembling small parcels into large ones a very difficult task. Owners holding out for higher prices may either prevent or significantly delay socially efficient redevelopment. The only current option for the Tel Aviv Municipality that will lead to efficient land assembly for private redevelopment currently is the option of private entrepreneurship. We wish to describe a mechanism that will solve the hold-out problem and lead to efficiency in land assembly without resorting to the intervention of the government to execute eminent domain. The mechanism requires the municipality to plan the development that will best suit the city, thus allowing the valuation of the parcel to reflect its true price for the owner. If the owners are still reluctant to sell, the municipality can then tax him according to the new value of the land.

  14. The function of the RNA-binding protein TEL1 in moss reveals ancient regulatory mechanisms of shoot development.

    Science.gov (United States)

    Vivancos, Julien; Spinner, Lara; Mazubert, Christelle; Charlot, Florence; Paquet, Nicolas; Thareau, Vincent; Dron, Michel; Nogué, Fabien; Charon, Céline

    2012-03-01

    The shoot represents the basic body plan in land plants. It consists of a repeated structure composed of stems and leaves. Whereas vascular plants generate a shoot in their diploid phase, non-vascular plants such as mosses form a shoot (called the gametophore) in their haploid generation. The evolution of regulatory mechanisms or genetic networks used in the development of these two kinds of shoots is unclear. TERMINAL EAR1-like genes have been involved in diploid shoot development in vascular plants. Here, we show that disruption of PpTEL1 from the moss Physcomitrella patens, causes reduced protonema growth and gametophore initiation, as well as defects in gametophore development. Leafy shoots formed on ΔTEL1 mutants exhibit shorter stems with more leaves per shoot, suggesting an accelerated leaf initiation (shortened plastochron), a phenotype shared with the Poaceae vascular plants TE1 and PLA2/LHD2 mutants. Moreover, the positive correlation between plastochron length and leaf size observed in ΔTEL1 mutants suggests a conserved compensatory mechanism correlating leaf growth and leaf initiation rate that would minimize overall changes in plant biomass. The RNA-binding protein encoded by PpTEL1 contains two N-terminus RNA-recognition motifs, and a third C-terminus non-canonical RRM, specific to TEL proteins. Removal of the PpTEL1 C-terminus (including this third RRM) or only 16-18 amino acids within it seriously impairs PpTEL1 function, suggesting a critical role for this third RRM. These results show a conserved function of the RNA-binding PpTEL1 protein in the regulation of shoot development, from early ancestors to vascular plants, that depends on the third TEL-specific RRM.

  15. Control of feline leukaemia virus.

    NARCIS (Netherlands)

    K. Weijer (Kees); F.G.C.M. Uytdehaag (Fons); A.D.M.E. Osterhaus (Albert)

    1989-01-01

    textabstractFeline leukaemia virus (FeLV) usually occurs in its natural species, the domestic cat. FeLV is also important to human individuals as a comparative model, as it may cause a variety of diseases, some malignant and some benign, such as immunosuppression, which bears a resemblance to AIDS (

  16. Reanalysis Of The PZ Tel System: Arguments For The Reality Of PZ Tel B To Be PZ Tel b

    Science.gov (United States)

    Jenkins, James

    2011-09-01

    I will present some new analysis of the PZ Tel system, which has recently been shown to host a young companion with a mass of around 30 Jupiter-masses, along with a debris disk of around 0.3 Lunar-masses. We have reanalyzed the iron abundance of the host star using our new spectral synthesis method, and contrary to previous results, we find the star to be super metal-rich, with a metallicity ([Fe/H]) of 0.2 dex. We also find the age of the system from chromospheric activities and pre-main sequence evolutionary models to be around 25Myrs. I will show some comparisons between the companion's bulk properties, such as broadband colours, and some of the latest evolutionary models as a function of metallicity. Finally, I will use these results to show how the companion to PZ Tel could be the first directly imaged extreme-Jovian extrasolar planet and not a low-mass brown dwarf. I acknowledge funding by Fondecyt through grant 3110004 and partial support from Centro de Astrofisica FONDAP 15010003, the GEMINI-CONICYT FUND and from the Comite Mixto ESO-GOBIERNO DE CHILE.

  17. Laktoosittoman jäätelön tuotekehitys

    OpenAIRE

    2016-01-01

    Insinöörityö tehtiin pienelle kotimaiselle jäätelötehtaalle, joka valmistaa lisäaineetonta ja kotimaisista raaka-aineista tehtyä jäätelöä. Työn tarkoituksena oli auttaa asiakasyritystä laktoosittoman jäätelön tuotekehityksessä. Yrityksellä on valikoimassaan vähälaktoosista jäätelöä, mutta laktoositonta jäätelöä ei ole vielä markkinoilla. Tuotekehityksessä olevan laktoosittoman jäätelön rakenteessa on esiintynyt niin kutsuttua hiekkaisuusvirhettä, joka johtuu tavallisesti laktoo...

  18. Atypical Chronic Myeloid Leukaemia with Trisomy 13: a Case Report

    Institute of Scientific and Technical Information of China (English)

    Guo-yu Hu; Chao-hui Yuan; Kui Tan; Zhen-zhen Chen

    2011-01-01

    ATYPICAL chronic myeloid leukaemia (aCML),which shows both myeloproliferative and myeIodysplastic features,is a type of myeloproliferative/myelodysplastic disease as defined by the World Health Organisation (WHO) classification of the myeloid neoplasms.1 Because of the presence of neutrophilic leukocytosis,aCML may resemble chronic myeIogenous leukemia (CML).However,in contrast with CML,aCML does not have the Philadelphia chromosome or the bcr/abl fusion gene.

  19. Arnold Rüütel hoidus kriisi sekkumast / Arnold Rüütel ; intervjueerinud Kai Kalamees

    Index Scriptorium Estoniae

    Rüütel, Arnold, 1928-

    2003-01-01

    President Arnold Rüütel vastab küsimustele, mida ta on teinud või kavatseb teha pingete leevendamiseks nii koalitsioonipartnerite vahel kui ka ühiskonnas ning kas ta plaanib kasutada oma mõjujõudu ühiskonna stabiilse arengu tagamiseks

  20. Arnold Rüütel hoidus kriisi sekkumast / Arnold Rüütel ; intervjueerinud Kai Kalamees

    Index Scriptorium Estoniae

    Rüütel, Arnold, 1928-

    2003-01-01

    President Arnold Rüütel vastab küsimustele, mida ta on teinud või kavatseb teha pingete leevendamiseks nii koalitsioonipartnerite vahel kui ka ühiskonnas ning kas ta plaanib kasutada oma mõjujõudu ühiskonna stabiilse arengu tagamiseks

  1. Arnold Rüütel: "Riik peaks rohkem hoolima inimesest" / Arnold Rüütel

    Index Scriptorium Estoniae

    Rüütel, Arnold, 1928-

    2009-01-01

    President Arnold Rüütel vastab küsimustele, mis puudutavad Eesti liitumist EL-i ja NATO-ga, eurot, põllumajandust, Nord Streami, Eesti Energia börsile viimist, tuumaelektrijaama rajamise plaani ning Eesti-Vene suhteid

  2. Cytokines and Epstein Barr virus (EBV) genes expression in blood chronic lymphocytic leukaemia (CLL) cells and their immortalised CLL cell lines.

    Science.gov (United States)

    Laytragoon-Lewin, Nongnit; Chen, Fu; Castro, Juan; Avila-Carino, Javier; Lewin, Freddi

    2003-01-01

    We have encountered two unique chronic lymphocytic leukaemia (CLL) patients, PG and NN. Some blood CLL cells of these patients have been infected and carry Epstein Barr virus (EBV) in vivo. In spite of their early-activated G0/G1 stage of post germinal center (GC) memory cells, ex vivo EBV-carrying blood CLL cells of PG clone expressed LMPs and used specific QUK splice for their EBNA1 expression, similar to the EBV-carrying cells of non-B origin. Interestingly, EBV-carrying CLL cells of NN clone expressed LMP2a and used UK-splice for their EBNA1 expression, similar to the in vivo EBV-carrying high density normal B cells in the blood of healthy individuals. The CLL-derived lines but not normal lymphoblastoid cell line (LCL) used QUK- and YUK-splice for their EBNA1 expression. As expected, LCL and their permanent CLL-derived lines used Cp promoter and up-regulated their EBNA2 expression. Blood CLL cells and the CLL-derived cell lines of these patients spontaneously produced cytokines as shown by microarray assay. The types and quantities of cytokines might relate to their CLL origin and viral strain in the given CLL cells. Neither blood CLL nor their CLL-derived cell lines express any detectable apoptosis-inducer ligands, CD95L or Apo 3L. As a consequence of cell cycle progression, CLL-derived cell lines up-regulated their co-stimulator molecules CD80 and apoptosis-related receptor CD95. Since only the rare EBV-carrying CLL cells grew in vitro, the combination of viral genome and cytokines seems to be critical for the outgrowth of EBV-carrying CLL cells over their EBV-negative counterpart in vitro but not in vivo.

  3. 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.

  4. Obmen ljubeznostjami / Arnold Rüütel, Peeter Kreitzberg

    Index Scriptorium Estoniae

    Rüütel, Arnold

    2001-01-01

    Presidendikandidaadid Rüütel ja Kreitzberg presidendivalimistega kaasnevatest pingetest. Refereeritud Arnold Rüütli intervjuud "Rüütel: Rahvaliit ei karda Kreitzbergi konkurentsi" ja Peeter Kreitzbergi intervjuud "Peeter Kreitzberg: Reeturlik Rahvaliit ootas kerget saaki", Eesti Päevaleht (2001/Aug/30)

  5. Analyzing 5 years of EC-TEL proceedings

    NARCIS (Netherlands)

    Reinhardt, Wolfgang; Meier, Christian; Drachsler, Hendrik; Sloep, Peter

    2011-01-01

    Reinhardt, W., Meier, C., Drachsler, H., & Sloep, P. B. (2011). Analyzing 5 years of EC-TEL proceedings. In C. D. Kloos, D. Gillet, R. M. Crespo García, F. Wild, & M. Wolpers (Eds.), Towards Ubiquitous Learning: 6th European Conference of Technology Enhanced Learning, EC-TEL 2011 (pp. 531-536). Sept

  6. Obmen ljubeznostjami / Arnold Rüütel, Peeter Kreitzberg

    Index Scriptorium Estoniae

    Rüütel, Arnold

    2001-01-01

    Presidendikandidaadid Rüütel ja Kreitzberg presidendivalimistega kaasnevatest pingetest. Refereeritud Arnold Rüütli intervjuud "Rüütel: Rahvaliit ei karda Kreitzbergi konkurentsi" ja Peeter Kreitzbergi intervjuud "Peeter Kreitzberg: Reeturlik Rahvaliit ootas kerget saaki", Eesti Päevaleht (2001/Aug/30)

  7. Rüütel kutsus Jaapani keisri Eestisse

    Index Scriptorium Estoniae

    2004-01-01

    Jaapanis ametlikul töövisiidil viibiv president Arnold Rüütel kohtus Tokyos Jaapani keisri Akihitoga. Kohtumisel olid kõne all eelkõige kultuuri- ja majandusküsimused. Kultuurikoostöö võimalustest vestlesid kohtumisel ka Ingrid Rüütel ja keisrinna Michiko. Ametlik visiit Jaapanisse 30.10-04.11.2004

  8. Mitotic crossover promotes leukemogenesis in children born with TEL-AML1 via the generation of loss of heterozygosity at 12p

    Directory of Open Access Journals (Sweden)

    Ivan Ivanovski

    2015-11-01

    Full Text Available TEL-AML1 (ETV6-RUNX1 fusion gene which is formed prenatally in 1% of the newborns, is a common genetic abnormality in childhood Bcell precursor acute lymphoblastic leukemia. But only one child out of a hundred children born with this fusion gene develops leukemia (bottleneck phenomenon later in its life, if contracts the second mutation. In other words, out of a hundred children born with TEL-AML1 only one child is at risk for leukemia development, which means that TEL-AML1 fusion gene is not sufficient for overt leukemia. There is a stringent requirement for a second genetic abnormality for leukemia development and this is the real or the ultimate cause of the leukemia bottleneck phenomenon. In most cases of TEL-AML1+ leukemia, the translocation t(12;21 is complemented with the loss of the normal TEL gene, not involved in the translocation, on the contralateral 12p. The loss of the normal TEL gene, i.e. loss of heterozygosity at 12p, occurs postnatally during the mitotic proliferation of TEL-AML1+ cell in the mitotic crossing over process. Mitotic crossing over is a very rare event with a frequency rate of 10–6 in a 10 kb region. The exploration and identification of the environmental exposure(s that cause(s proliferation of the TELAML1+ cell in which approximately 106 mitoses are generated to cause 12p loss of heterozygosity, i.e. TEL gene deletion, may contribute to the introduction of preventive measures for leukemia.

  9. Promoter hypermethylation of the retinoic acid receptor beta2 gene is frequent in acute myeloid leukaemia and associated with the presence of CBFβ-MYH11 fusion transcripts

    DEFF Research Database (Denmark)

    Rethmeier, Anita; Aggerholm, Anni; Olesen, Lene Hyldahl;

    2006-01-01

    was unmethylated in 10/10 bone marrow and 7/7 blood samples from healthy individuals, the gene was hypermethylated in 43% of the AML patients. The RARbeta2 degree of promoter methylation differed between and within individuals, and the mRNA transcription levels of the gene varied inter-individually by a factor...

  10. Induction of MTG8-specific cytotoxic T-cell lines: MTG8 is probably a tumour antigen that is recognized by cytotoxic T cells in AML1-MTG8-fused gene-positive acute myelogenous leukaemia.

    Science.gov (United States)

    Maeda, M; Otsuka, T; Kimura, N; Kozu, T; Fukuyama, T; Uchida, N; Sugio, Y; Itoh, Y; Iino, T; Inaba, S; Niho, Y

    2000-11-01

    Several reports have demonstrated the persistent detection of AML1-MTG8 fusion products, representing minimal residual disease (MRD), in patients with t(8;21) acute myelogenous leukaemia (AML) who are in long-term remission. It is probable that immune-mediated mechanisms that are able to suppress the expansion of MRD may result in the continuance of remission. It was previously shown that some t(8;21) AML patients had high anti-MTG8 antibody titres. MTG8 expression in normal adult tissues is limited to the brain or heart in which human leucocyte antigen (HLA) class I cell-surface antigens are either not or are only faintly detectable. We hypothesized that the overexpression of the MTG8 gene in t(8;21) AML cells could act as a possible tumour antigen, which might be able to induce the immune-mediated suppression of the expansion of MRD. We were able to induce HLA-A0201-restricted cytotoxic T-lymphocyte (CTL) lines against an MTG8 peptide (MTG8b amino acids 182-191) using monocyte-derived dendritic cells from a healthy donor. T-cell receptor (TCR)Valpha17, TCRVbeta14 and 15, and TCRJbeta2.1 and 2.3 are predominantly used in these CTL lines. Our data, which suggest that the MTG8 protein could be one of the tumour antigens recognized by CTLs, may be helpful in further investigations of TCR analysis in t(8;21) AML patients with HLA-A0201 who are in long-term remission.

  11. Expression of endometrial leukaemia inhibitory factor gene in patients with unexplained infertility%原因不明性原发不孕患者子宫内膜白血病抑制因子基因的表达

    Institute of Scientific and Technical Information of China (English)

    郭晓霞; 程绮馨; 王应雄

    2001-01-01

    Objective To investigate the expression of endometrial leukaemia inhibitory factor(LIF) gene in patients with unexplained infertility. Methods  By a quantitative reverse transcription-polymerase chain reaction (RT-PCR),the expression of LIF gene on endometrium during mid-luteal phase was detected in 35 unexplained infertility (infertility group) cases and 20 infertile cases due to tubal obstruction or male factor (control group). Results The level of LIF mRNA expression on endometrium during mid-luteal phase in infertility group was 0.448±0.239,significantly lower than those in the control group (1.093±0.761,P<0.01). Conclusions Our findings suggested LIF might play an important role in the process of implantation. The decreased expression of LIF gene might be one of the major causes of unexplained infertility.%目的探讨白血病抑制因子(LIF)基因在子宫内膜的表达与原因不明性原发不孕的关系。方法采用逆转录聚合酶链反应(RT-PCR)技术,对35例原因不明性原发不孕患者(病例组)和20例继发不孕患者(对组照)的黄体中期子宫内膜行LIF mRNA检测。结果对照组患者黄体中期LIF mRNA表达水平为1.093±0.761(±s,下同),病例组患者为0.448±0.239,两组相比,差异有极显著性(P<0.01)。结论 LIF可能参与了胚泡着床过程。LIF的基因表达缺陷或减弱,可能是导致原因不明性原发不孕的原因之一。

  12. TEL4Health research at University College Cork (UCC)

    NARCIS (Netherlands)

    Drachsler, Hendrik

    2013-01-01

    Drachsler, H. (2013, 12 May). TEL4Health research at University College Cork (UCC). Invited talk given at Application of Science to Simulation, Education and Research on Training for Health Professionals Centre (ASSERT for Health Care), Cork, Ireland.

  13. Technology Enhanced Learning: topics in tel & serious gaming

    NARCIS (Netherlands)

    Van Rosmalen, Peter

    2012-01-01

    Van Rosmalen, P. (2012, 30 November). Technology Enhanced Learning: topics in tel & serious gaming. Presentation at the course "Hightech Entrepreneurship and new Media (Serious Games)", RWTH Aachen Informatik 5 Information Systems, Aachen, Germany.

  14. Acceptance of TEL: Key Success Factors and Reasons of Failure

    NARCIS (Netherlands)

    Johnscher, Patrick; Kelle, Sebastian; Sigurðarson, Steinn

    2009-01-01

    Johnscher, P., Kelle, S., & Sigurðarson, S. (2008). Acceptance of TEL: Key Success Factors and Reasons of Failure. Presentation at the Prolearn Summer School on Technology Enhanced Learning & Knowledge Management 2008. March, 28, 2008, Ohrid, Fyr of Macedonia.

  15. 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 ...

  16. Unusual presentations of childhood acute lymphoblastic leukaemia

    African Journals Online (AJOL)

    PROF. EZECHUKWU

    2014-04-06

    Apr 6, 2014 ... leukaemia: A case report. Accepted: ... accumulation of lymphoid blasts in the bone marrow and some ... tion; typically its clinical presentation is related to bone marrow .... haematopoietic stem cell transplantation. Treatment.

  17. Prezident Estonii Arnold Rüütel : "Vremja sobirat kamni" / Arnold Rüütel ; interv. Valerija Bondarenko

    Index Scriptorium Estoniae

    Rüütel, Arnold, 1928-

    2002-01-01

    Presidendi elulugu, Eesti ja Tallinna lühitutvustus. President Arnold Rüütel Ukraina visiidist, varasemast tegevusest, Eesti iseseisvumisest, Euroopa Liitu ja NATOsse pürgimisest, kuritegevusest. Riigivisiit Ukraina Vabariiki 14.-18.10.2002

  18. Clinical relevance of molecular aberrations in paediatric acute myeloid leukaemia at first relapse

    NARCIS (Netherlands)

    Bachas, Costa; Schuurhuis, Gerrit Jan; Reinhardt, Dirk; Creutzig, Ursula; Kwidama, Zinia J.; Zwaan, C. Michel; van den Heuvel-Eibrink, Marry M.; De Bont, Evelina S. J. M.; Elitzur, Sarah; Rizzari, Carmelo; de Haas, Valerie; Zimmermann, Martin; Cloos, Jacqueline; Kaspers, Gertjan J. L.

    2014-01-01

    Outcome for relapsed paediatric acute myeloid leukaemia (AML) remains poor. Strong prognostic factors at first relapse are lacking, which hampers optimization of therapy. We assessed the frequency of molecular aberrations (FLT3, NRAS, KRAS, KIT, WT1 and NPM1 genes) at first relapse in a large set (n

  19. Clinical relevance of molecular aberrations in paediatric acute myeloid leukaemia at first relapse

    NARCIS (Netherlands)

    Bachas, Costa; Schuurhuis, Gerrit Jan; Reinhardt, Dirk; Creutzig, Ursula; Kwidama, Zinia J.; Zwaan, C. Michel; van den Heuvel-Eibrink, Marry M.; De Bont, Evelina S. J. M.; Elitzur, Sarah; Rizzari, Carmelo; de Haas, Valerie; Zimmermann, Martin; Cloos, Jacqueline; Kaspers, Gertjan J. L.

    2014-01-01

    Outcome for relapsed paediatric acute myeloid leukaemia (AML) remains poor. Strong prognostic factors at first relapse are lacking, which hampers optimization of therapy. We assessed the frequency of molecular aberrations (FLT3, NRAS, KRAS, KIT, WT1 and NPM1 genes) at first relapse in a large set (n

  20. DNA sequencing of a cytogenetically normal acute myeloid leukaemia genome.

    Science.gov (United States)

    Ley, Timothy J; Mardis, Elaine R; Ding, Li; Fulton, Bob; McLellan, Michael D; Chen, Ken; Dooling, David; Dunford-Shore, Brian H; McGrath, Sean; Hickenbotham, Matthew; Cook, Lisa; Abbott, Rachel; Larson, David E; Koboldt, Dan C; Pohl, Craig; Smith, Scott; Hawkins, Amy; Abbott, Scott; Locke, Devin; Hillier, Ladeana W; Miner, Tracie; Fulton, Lucinda; Magrini, Vincent; Wylie, Todd; Glasscock, Jarret; Conyers, Joshua; Sander, Nathan; Shi, Xiaoqi; Osborne, John R; Minx, Patrick; Gordon, David; Chinwalla, Asif; Zhao, Yu; Ries, Rhonda E; Payton, Jacqueline E; Westervelt, Peter; Tomasson, Michael H; Watson, Mark; Baty, Jack; Ivanovich, Jennifer; Heath, Sharon; Shannon, William D; Nagarajan, Rakesh; Walter, Matthew J; Link, Daniel C; Graubert, Timothy A; DiPersio, John F; Wilson, Richard K

    2008-11-06

    Acute myeloid leukaemia is a highly malignant haematopoietic tumour that affects about 13,000 adults in the United States each year. The treatment of this disease has changed little in the past two decades, because most of the genetic events that initiate the disease remain undiscovered. Whole-genome sequencing is now possible at a reasonable cost and timeframe to use this approach for the unbiased discovery of tumour-specific somatic mutations that alter the protein-coding genes. Here we present the results obtained from sequencing a typical acute myeloid leukaemia genome, and its matched normal counterpart obtained from the same patient's skin. We discovered ten genes with acquired mutations; two were previously described mutations that are thought to contribute to tumour progression, and eight were new mutations present in virtually all tumour cells at presentation and relapse, the function of which is not yet known. Our study establishes whole-genome sequencing as an unbiased method for discovering cancer-initiating mutations in previously unidentified genes that may respond to targeted therapies.

  1. Detailed molecular characterisation of acute myeloid leukaemia with a normal karyotype using targeted DNA capture.

    Science.gov (United States)

    Conte, N; Varela, I; Grove, C; Manes, N; Yusa, K; Moreno, T; Segonds-Pichon, A; Bench, A; Gudgin, E; Herman, B; Bolli, N; Ellis, P; Haddad, D; Costeas, P; Rad, R; Scott, M; Huntly, B; Bradley, A; Vassiliou, G S

    2013-09-01

    Advances in sequencing technologies are giving unprecedented insights into the spectrum of somatic mutations underlying acute myeloid leukaemia with a normal karyotype (AML-NK). It is clear that the prognosis of individual patients is strongly influenced by the combination of mutations in their leukaemia and that many leukaemias are composed of multiple subclones, with differential susceptibilities to treatment. Here, we describe a method, employing targeted capture coupled with next-generation sequencing and tailored bioinformatic analysis, for the simultaneous study of 24 genes recurrently mutated in AML-NK. Mutational analysis was performed using open source software and an in-house script (Mutation Identification and Analysis Software), which identified dominant clone mutations with 100% specificity. In each of seven cases of AML-NK studied, we identified and verified mutations in 2-4 genes in the main leukaemic clone. Additionally, high sequencing depth enabled us to identify putative subclonal mutations and detect leukaemia-specific mutations in DNA from remission marrow. Finally, we used normalised read depths to detect copy number changes and identified and subsequently verified a tandem duplication of exons 2-9 of MLL and at least one deletion involving PTEN. This methodology reliably detects sequence and copy number mutations, and can thus greatly facilitate the classification, clinical research, diagnosis and management of AML-NK.

  2. Hypoxia and hypoxia-inducible factors in leukaemias

    Directory of Open Access Journals (Sweden)

    Margaux eDeynoux

    2016-02-01

    Full Text Available Despite huge improvements in the treatment of leukaemia, the percentage of patients suffering relapse still remains significant. Relapse most often results from a small number of leukaemic stem cells (LSCs within the bone marrow, which are able to self-renew and therefore re-establish the full tumour. The marrow microenvironment contributes considerably in supporting the protection and development of leukaemic cells. LSCs share specific niches with normal haematopoietic stem cells with the niche itself being composed of a variety of cell types including mesenchymal stem/stromal cells, bone cells, immune cells, neuronal cells and vascular cells. A hallmark of the haematopoietic niche is low oxygen partial pressure, indeed this hypoxia is necessary for the long-term maintenance of HSCs. Hypoxia is a strong signal, principally maintained by members of the hypoxia-inducible factor family. In solid tumours, it has been well-established that hypoxia triggers intrinsic metabolic changes and microenvironmental modifications, such as the stimulation of angiogenesis, through activation of HIFs. As leukaemia is not considered a solid tumour, the role of oxygen in the disease was presumed to be inconsequential and remained long overlooked. This view has now been revised since hypoxia has been shown to influence leukaemic cell proliferation, differentiation and resistance to chemotherapy. However, the role of HIF proteins remains controversial with HIFs being considered as either oncogenes or tumour suppressor genes, depending on the study and model. The purpose of this review is to highlight our knowledge of hypoxia and HIFs in leukaemic development and therapeutic resistance, and to discuss the recent hypoxia-based strategies proposed to eradicate leukaemias.

  3. Native interface of the SAM domain polymer of TEL

    Directory of Open Access Journals (Sweden)

    Bowie James U

    2002-08-01

    Full Text Available Abstract Background TEL is a transcriptional repressor containing a SAM domain that forms a helical polymer. In a number of hematologic malignancies, chromosomal translocations lead to aberrant fusions of TEL-SAM to a variety of other proteins, including many tyrosine kinases. TEL-SAM polymerization results in constitutive activation of the tyrosine kinase domains to which it becomes fused, leading to cell transformation. Thus, inhibitors of TEL-SAM self-association could abrogate transformation in these cells. In previous work, we determined the structure of a mutant TEL-SAM polymer bearing a Val to Glu substitution in center of the subunit interface. It remained unclear how much the mutation affected the architecture of the polymer, however. Results Here we determine the structure of the native polymer interface. To accomplish this goal, we introduced mutations that block polymer extension, producing a heterodimer with a wild-type interface. We find that the structure of the wild-type polymer interface is quite similar to the mutant structure determined previously. With the structure of the native interface, it is possible to evaluate the potential for developing therapeutic inhibitors of the interaction. We find that the interacting surfaces of the protein are relatively flat, containing no obvious pockets for the design of small molecule inhibitors. Conclusion Our results confirm the architecture of the TEL-SAM polymer proposed previously based on a mutant structure. The fact that the interface contains no obvious potential binding pockets suggests that it may be difficult to find small molecule inhibitors to treat malignancies in this way.

  4. Acute leukaemia: making sense of a complex blood cancer.

    LENUS (Irish Health Repository)

    Meenaghan, Teresa

    2012-01-01

    Acute leukaemia represents a diverse group of blood cancers that affect both children and adults. Treatment schedules for these haematology cancers are often prolonged, with many associated side effects and complications. Nurses caring for patients with acute leukaemia require an anticipatory approach, where care is aimed at minimizing the side effects of treatment and being constantly vigilant for any impending adverse effects. Moreover, patients require support for the psychosocial issues that can arise for patients during their illness. This article provides an overview of acute lymphoblastic leukaemia and acute myeloid leukaemia. Nursing considerations in the care of patients being treated for acute leukaemia are also explored.

  5. Magnetic fields and leukaemia risks in UK electricity supply workers.

    Science.gov (United States)

    Sorahan, T

    2014-04-01

    To investigate whether leukaemia risks are related to occupational exposure to low-frequency magnetic fields. Leukaemia risks experienced by 73 051 employees of the former Central Electricity Generating Board of England and Wales were investigated for the period 1973-2010. All employees were hired in the period 1952-82 and were employed for at least 6 months with some employment in the period 1973-82. Detailed calculations had been performed by others to enable an assessment to be made of exposures to magnetic fields. Poisson regression was used to calculate relative risks (rate ratios) of developing leukaemia or leukaemia subtypes for categories of lifetime, distant (lagged) and recent (lugged) exposure. Findings for all leukaemias combined were unexceptional; risks were close to unity for all exposure categories and there was no suggestion of risks increasing with cumulative (or recent or distant) magnetic field exposures. There were no statistically significant dose-response effects shown for acute myeloid leukaemia, chronic myeloid leukaemia or chronic lymphocytic leukaemia. There was a significant positive trend for acute lymphocytic leukaemia (ALL), but this was based, in the main, on unusually low risks in the lowest exposure category. This study found no convincing evidence to support the hypothesis that exposure to magnetic fields is a risk factor for leukaemia, and the findings are consistent with the hypotheses that both distant and recent magnetic field exposures are not causally related to the generality of leukaemia. The limited positive findings for ALL may well be chance findings.

  6. Klinefelter syndrome and acute basophilic leukaemia--case report.

    Science.gov (United States)

    Ljubić, Nives; Lang, Nada; Skelin, Ika Kardum; Lasan, Ruzica; Dominis, Mara; Perković, Leila; Zupanić-Krmek, Dubraka; Grgurević-Batinica, Anita

    2010-06-01

    Patients with 47, XXY karyotype (Klinefelter syndrome) appear to have increased risk of developing cancer, especially male breast cancer, germ cell tumours and non Hodgkin lymphomas, but rarely acute myeloid leukaemia. We report a patient with acute basophilic leukaemia with 47, XXY karyotype in both the tumour and constitutional cells. Acute basophilic leukaemia is very rare disease comprising less than 1% of all acute myeloid leukaemias. Morphological characteristic of leukaemic blast cells is moderately basophilic cytoplasm containing a variable number of coarse basophilic granules. The most characteristic cytochemical reaction is metachromatic positivity with toluidine blue. Blast are myeloperoxidase negative. Also leukemic blasts express myeloid and monocyte markers. There is no consistent chromosomal abnormality identified in this leukaemia. This is the first reported case of acute basophilic leukaemia in patient with Klinefelter syndrome. In this article the medical history of the patient is given and the possible connection between Klinefelter syndrome and acute myeloid leukaemia is discussed.

  7. Arnold Rüütel külastas Shanghaid

    Index Scriptorium Estoniae

    2005-01-01

    President Arnold Rüütel külastas Hiina riigivisiidil olles Shanghaid, käis Aasia kõrgeimas Shanghai Oriental Pearli teletornis, avas Eesti-Hiina ärifoorumi. Riigivisiit Hiina Rahvavabariiki 23.-30.08.2005

  8. Rüütel responds to Russian criticism

    Index Scriptorium Estoniae

    2004-01-01

    President Arnold Rüütel kinnitas intervjuus ajalehele Molodjozh Estonii, et Eesti täidab inimõiguste küsimuse kõiki rahvusvahelisi nõudmisi. Presidendi sõnul on eestlased Kirde-Eestis ise muutunud vähemuseks

  9. President Rüütel plaanib traktoriostu / Tiit Reinberg

    Index Scriptorium Estoniae

    Reinberg, Tiit, 1975-

    2005-01-01

    Ilmunud ka: Järva Teataja 11. juuni, lk. 1. Säreveres põllumajandusmessi "Agri 2005" külastades teatas president Arnold Rüütel, et tal on plaanis endale traktor soetada. Presidendile andis nõu samuti messi külastanud parlamendiliige Tiit Tammsaar. Vabariigi President Türil 10.06.2005

  10. Arnold Rüütel gotov osudit kommunizm

    Index Scriptorium Estoniae

    2001-01-01

    President Arnold Rüütli hinnangul sooritasid kuriteo Eesti rahva vastu mitte kommunistliku partei üksikliikmed, vaid NKVD ja KGB. Pealk. ajalehes Sillamjaeskii Vestnik (2001) 29. sept., lk. 2: "Arnold Rüütel zaveril Estoniju v svojei gotovnosti osudit kommunizm"

  11. Rüütel nimetas ametisse neli suursaadikut

    Index Scriptorium Estoniae

    2006-01-01

    President Arnold Rüütel nimetas Jaak Jõerüüdi suursaadikuks Lätis, Mart Tarmaku suursaadikuks Portugalis, Aino Leppik von Wireni suursaadikuks Iisraelis ja Sander Soone suursaadikuks Lääne-Euroopa Liidu ning Euroopa Liidu poliitika- ja julgeolekukomitee juures Brüsselis. Allk.: BNS

  12. Teaching Gender in Israel: Experiences at the Tel Aviv University

    Science.gov (United States)

    Fenster, Tovi

    2011-01-01

    This paper examines the ways in which neoliberal economic policies are affecting academic work in Israeli universities, prioritizing programs that can generate their own funding, External philanthropic support from North America has enabled creation of an interdisciplinary Women and Gender Studies Program at Tel Aviv University that draws…

  13. A Survey on Linked Data and the Social Web as facilitators for TEL recommender systems

    NARCIS (Netherlands)

    Dietze, Stefan; Drachsler, Hendrik; Daniela, Giordano

    2014-01-01

    Personalisation, adaptation and recommendation are central features of TEL environments. In this context, information retrieval techniques are applied as part of TEL recommender systems to filter and recommend learning resources or peer learners according to user preferences and requirements.

  14. Cross Federal Workgroup on Telehealth (FedTel) Inventory of Activities

    Data.gov (United States)

    U.S. Department of Health & Human Services — This dataset is a collection of the submitted activities and projects from member of the Cross Federal Workgroup on Telehealth (FedTel). The FedTel's membership...

  15. 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 ...

  16. 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...

  17. Arnold Rüütel ei armasta Kadrioru lossi / Arnold Rüütel ; intervjueerinud Sulev Valner

    Index Scriptorium Estoniae

    Rüütel, Arnold, 1928-

    2001-01-01

    Arnold Rüütel oma kandideerimisest presidendi ametikohale, parteilise kuuluvuse peatamise sisulisest tähendusest, poliitilise konsensuse saavutamise vajalikkusest maaelu osas, presidendi sekkumisest päevapoliitikasse, koostööst valitsusega, kavatsetavast kommunismi hukkamõistust Riigikogus, presidendi meeskonnast jm. Ilmunud ka lüh. Meie Maa (2001) 29. sept., lk. 4. Parlamendisaadik

  18. NA62 Level 0 trigger: TELDES and InterTEL boards testing and integration scenario

    CERN Document Server

    Lupi, Matteo

    2015-01-01

    TELDES is a TEL62 daughter-board used in the generation of the Liquid Krypton Calorimeter primitive for the Level 0 Trigger of the NA62 Experiment. InterTEL is a daughter-board used to interconnect the TEL62s used in the CEDAR, LAV and RICH detectors.

  19. Introducing GaLA: Serious Game potentials, challenges and TEL-related issues

    NARCIS (Netherlands)

    Earp, Jeffrey; Klemke, Roland

    2011-01-01

    Earp, J., & Klemke, R. (2011, 21 September). Introducing GaLA: Serious Game potentials, challenges and TEL-related issues. Presented at TEL-Think-Tank Workshop at the 6th European conference on Technology enhanced learning: towards ubiquitous learning (EC-TEL 2011), Palermo, Italy.

  20. Arnold Rüütel: Eesti riigipead peaks valima rahvas või valijamehed / Arnold Rüütel ; intervjueerinud Tuuli Koch, Ingvar Bärenklau

    Index Scriptorium Estoniae

    Rüütel, Arnold, 1928-

    2006-01-01

    Ilmunud ka: Postimees : na russkom jazõke (2006) 14. sept., lk. 4-5; Virumaa Teataja (2006) 20. sept., lk. 6, pealk.: Arnold Rüütel presidendivalimisi Riigikogule ei usaldaks, lüh. President Arnold Rüütel pooldab presidendi otsevalimist või ilma Riigikogu vooruta kohe valimiskogus, tutvustab oma valimisplatvormi, räägib oma tervisest ja presidendiametist. Vt. samas: Rüütel: üks aasta selles neetud keskkomitee sekretäri ametis

  1. Arnold Rüütel: Eesti riigipead peaks valima rahvas või valijamehed / Arnold Rüütel ; intervjueerinud Tuuli Koch, Ingvar Bärenklau

    Index Scriptorium Estoniae

    Rüütel, Arnold, 1928-

    2006-01-01

    Ilmunud ka: Postimees : na russkom jazõke (2006) 14. sept., lk. 4-5; Virumaa Teataja (2006) 20. sept., lk. 6, pealk.: Arnold Rüütel presidendivalimisi Riigikogule ei usaldaks, lüh. President Arnold Rüütel pooldab presidendi otsevalimist või ilma Riigikogu vooruta kohe valimiskogus, tutvustab oma valimisplatvormi, räägib oma tervisest ja presidendiametist. Vt. samas: Rüütel: üks aasta selles neetud keskkomitee sekretäri ametis

  2. SWI/SNF Subunits SMARCA4, SMARCD2 and DPF2 Collaborate in MLL-Rearranged Leukaemia Maintenance.

    Directory of Open Access Journals (Sweden)

    V Adam Cruickshank

    Full Text Available Alterations in chromatin structure caused by deregulated epigenetic mechanisms collaborate with underlying genetic lesions to promote cancer. SMARCA4/BRG1, a core component of the SWI/SNF ATP-dependent chromatin-remodelling complex, has been implicated by its mutational spectrum as exerting a tumour-suppressor function in many solid tumours; recently however, it has been reported to sustain leukaemogenic transformation in MLL-rearranged leukaemia in mice. Here we further explore the role of SMARCA4 and the two SWI/SNF subunits SMARCD2/BAF60B and DPF2/BAF45D in leukaemia. We observed the selective requirement for these proteins for leukaemic cell expansion and self-renewal in-vitro as well as in leukaemia. Gene expression profiling in human cells of each of these three factors suggests that they have overlapping functions in leukaemia. The gene expression changes induced by loss of the three proteins demonstrate that they are required for the expression of haematopoietic stem cell associated genes but in contrast to previous results obtained in mouse cells, the three proteins are not required for the expression of c-MYC regulated genes.

  3. Central line-related bacteraemia due to Roseomonas mucosa in a neutropenic patient with acute myeloid leukaemia in Piraeus, Greece.

    Science.gov (United States)

    Christakis, G B; Perlorentzou, S; Alexaki, P; Megalakaki, A; Zarkadis, I K

    2006-08-01

    A case of central venous catheter-related bacteraemia due to Roseomonas mucosa in a neutropenic patient with acute myelogenous leukaemia is reported. The patient was successfully treated with amikacin and piperacillin-tazobactam. The clinical isolate was identified as R. mucosa by 16S rRNA gene sequencing.

  4. [History of the Hôtel-Dieu of Bourges].

    Science.gov (United States)

    Albou, P

    1996-01-01

    Bourges hospital (Hôtel-Dieu de Bourges, 1527) is one of the last to be built in France modeled in the Beaune style (1443) with chapel and wards linked in one line. The former gothic part, built between 1510 and 1527, was later completed by two Renaissance doors (1511 and 1533) and by two classical style wings built after the 1628 plague. Following the Revolution, the gothic part was divided by a floor which somewhat alters the interior appearance of the whole construction. The closing of the general care unit in November 1994 (and transfer of the Bourges General Hospital to new premises) now renders feasible the restoration of the former hospital (Hôtel-Dieu) almost unknown until now, thereby giving it the place it might fully desserve in the architectural and tourist heritage of Bourges.

  5. Nucleophosmin mutation analysis in acute myeloid leukaemia: Immunohistochemistry as a surrogate for molecular techniques

    OpenAIRE

    Anita Chopra; Sushant Soni; Haraprasad Pati; Dev Kumar; Rahul Diwedi; Deepak Verma; Garima Vishwakama; Sameer Bakhshi; Suman Kumar; Ajay Gogia; Rajive Kumar

    2016-01-01

    Background & objectives: Mutation of nucleophosmin (NPM1) gene in the absence of FLT3-ITD (FMS related tyrosine kinase 3 - internal tandem duplications) mutation carries a good prognosis in cytogenetically normal acute myeloid leukaemia (AML). NPM1, a multifunctional nucleolar phosphoprotein that shuttles between nucleus and cytoplasm, gets trapped in the cytoplasm when mutated. Immunohistochemical (IHC) demonstration of its aberrant cytoplasmic location (NPMc+) has been suggested as a simple...

  6. Fusion of NUP98 and the SET binding protein 1 (SETBP1) gene in a paediatric acute T cell lymphoblastic leukaemia with t(11;18)(p15;q12)

    DEFF Research Database (Denmark)

    Panagopoulos, Ioannis; Kerndrup, Gitte; Carlsen, Niels

    2007-01-01

    Three NUP98 chimaeras have previously been reported in T cell acute lymphoblastic leukaemia (T-ALL): NUP98/ADD3, NUP98/CCDC28A, and NUP98/RAP1GDS1. We report a T-ALL with t(11;18)(p15;q12) resulting in a novel NUP98 fusion. Fluorescent in situ hybridisation showed NUP98 and SET binding protein 1......(SETBP1) fusion signals; other analyses showed that exon 12 of NUP98 was fused in-frame with exon 5 of SETBP1. Nested polymerase chain reaction did not amplify the reciprocal SETBP1/NUP98, suggesting that NUP98/SETBP1 transcript is pathogenetically important. SETBP1 has previously not been implicated...

  7. Acute Myeloid Leukaemia of Donor Cell Origin Developing 17 Years after Allogenic Hematopoietic Cell Transplantation for Acute Promyelocytic Leukaemia

    Science.gov (United States)

    Jiménez, Pilar; Alvarez, J. Carlos; Garrido, Pilar; Lorente, J. Antonio; Palacios, Jorge; Ruiz-Cabello, Francisco

    2012-01-01

    Donor cell leukaemia (DCL) is a rare complication of allogenic hematopoietic cell transplantation (HCT). We report the case of a female patient with acute promyelocytic leukaemia (APL), FAB type M3, who developed acute myeloid leukaemia (AML) type M5 of donor origin 17 years after allogenic bone marrow transplantation (BMT) from her HLA-matched sister. Morphology and immunophenotyping showed differences with the initial leukaemia, and short tandem repeat (STR) analysis confirmed donor-type haematopoiesis. Interphase fluorescence in situ hybridisation (FISH) showed an 11q23 deletion. Given that the latency period between transplant and development of leukaemia was the longest reported to date, we discuss the mechanisms underlying delayed leukaemia onset. PMID:23675279

  8. Structure of the intact ATM/Tel1 kinase.

    Science.gov (United States)

    Wang, Xuejuan; Chu, Huanyu; Lv, Mengjuan; Zhang, Zhihui; Qiu, Shuwan; Liu, Haiyan; Shen, Xuetong; Wang, Weiwu; Cai, Gang

    2016-05-27

    The ataxia-telangiectasia mutated (ATM) protein is an apical kinase that orchestrates the multifaceted DNA-damage response. Normally, ATM kinase is in an inactive, homodimer form and is transformed into monomers upon activation. Besides a conserved kinase domain at the C terminus, ATM contains three other structural modules, referred to as FAT, FATC and N-terminal helical solenoid. Here we report the first cryo-EM structure of ATM kinase, which is an intact homodimeric ATM/Tel1 from Schizosaccharomyces pombe. We show that two monomers directly contact head-to-head through the FAT and kinase domains. The tandem N-terminal helical solenoid tightly packs against the FAT and kinase domains. The structure suggests that ATM/Tel1 dimer interface and the consecutive HEAT repeats inhibit the binding of kinase substrates and regulators by steric hindrance. Our study provides a structural framework for understanding the mechanisms of ATM/Tel1 regulation as well as the development of new therapeutic agents.

  9. O uso de leitores de tela no TelEduc

    Directory of Open Access Journals (Sweden)

    Roberto Sussumu Wataya

    2006-06-01

    Full Text Available Investigou-se, no Ambiente Telemático TelEduc, a acessibilidade de Pessoas com Necessidades Especiais Visuais (PNEV's, utilizando os softwares Leitores de Tela - LT DosVox e Jaws, tendo como ponto de partida uma revisão de literatura relacionada ao uso de tecnologias de informação e comunicação (TIC e à Educação a Distância (EAD. Primeiramente investigou-se como os softwares LT, as ferramentas e os conteúdos do curso do programa do Proinesp-II auxiliaram a capacitação à distância de professores no uso de informática na Educação Especial. Em uma segunda etapa, analisou-se o uso dos referidos softwares LT e das ferramentas da plataforma TelEduc com duas PNEV's, em vinte sessões, gravadas e transcritas em forma de tabelas. Resultados indicam, entre outros aspectos, que ambos os softwares LT - DosVox e Jaws -, com pequenas diferenças entre si, permitem o acesso das PNEV's no TelEduc.

  10. Feverfew: weeding out the root of leukaemia.

    Science.gov (United States)

    Guzman, Monica L; Jordan, Craig T

    2005-09-01

    Malignant stem cells are central to the pathogenesis and perpetuation of acute myelogenous leukaemia (AML). Despite their crucial role, standard chemotherapy often does not target these critical cells and, thus, the 'root' of leukaemic disease is not eradicated. To derive better therapies, unique molecular features of malignant stem cells have been characterised for AML and evaluated with regard to ablation of disease. In the course of such studies, the compound parthenolide, which is derived from the medicinal plant feverfew, has recently been shown to preferentially induce AML stem cells to undergo apoptosis. Importantly, parthenolide had no discernable effect on normal blood cells. Thus, this naturally occurring agent may provide new avenues of investigation for the treatment of leukaemia. In this article, characteristics of parthenolide are reviewed.

  11. Prolonged remission maintenance in acute myeloid leukaemia.

    Science.gov (United States)

    Spiers, A S; Goldman, J M; Catovsky, D; Costello, C; Galton, D A; Pitcher, C S

    1977-08-27

    Twenty-five patients with acute myeloid leukaemia were treated with three quadruple drug combinations in predetermined rotation: TRAP (thioguanine, daunorubicin, cytarabine, prednisolone); COAP (cyclophosphamide, vincristine, cytarabine, prednisolone); and POMP (prednisolone, vincristine, methotrexate, mercaptopurine). Fifteen patients (60%) achieved complete remission and five (20%) partial remission. For maintenance, five-day courses of drugs were administered every 14 to 21 days and doses were increased to tolerance. The median length of complete remission was 66 weeks. In eight patients remission maintenance treatment was discontinued and some remained in complete remission for over two years. In this series the remission induction rate was comparable with that reported for other regimens and complete remission lasted longer with this intensive maintenance regimen than with others. Nevertheless, the TRAP programme must still be regarded as only palliative treatment for acute myeloid leukaemia.

  12. Large geomagnetic field anomalies revealed in Bronze to Iron Age archeomagnetic data from Tel Megiddo and Tel Hazor, Israel

    Science.gov (United States)

    Shaar, Ron; Tauxe, Lisa; Ron, Hagai; Ebert, Yael; Zuckerman, Sharon; Finkelstein, Israel; Agnon, Amotz

    2016-05-01

    Geomagnetic field measurements from the past few centuries show heightened secular variation activity in the southern hemisphere associated with the south Atlantic anomaly (SAA). It is uncertain whether geomagnetic anomalies at a similar scale have existed in the past owing to limited coverage and uncertainties in the paleomagnetic database. Here we provide new evidence from archaeological sources in the Levant suggesting a large positive northern hemisphere anomaly, similar in magnitude to the SAA during the 9th-8th centuries BCE, called ;Levantine Iron Age anomaly;. We also report an additional geomagnetic spike in the 8th century. The new dataset comprises 73 high precision paleointensity estimates from ca. 3000 BCE to 732 BCE, and five directional measurements between the 14th and the 9th centuries BCE. Well-dated pottery and cooking ovens were collected from twenty archaeological strata in two large contemporaneous stratigraphical mounds (tells) in Israel: Tel Megiddo and Tel Hazor. The new data are combined with previously published data and interpreted automatically using the PmagPy Thellier GUI program. The Tel Megiddo and Tel Hazor data sets demonstrate excellent internal consistency and remarkable agreement with published data from Mesopotamia (Syria). The data illustrate the evolution of an extreme geomagnetic high that culminated in at least two spikes between the 11th and the 8th centuries BCE (Iron Age in the Levant). The paleomagnetic directional data of the 9th century BCE show positive inclination anomalies, and deviations of up to 22° from the averaged geocentric axial dipole (GAD) direction. From comparison of the Levantine archaeomagnetic data with IGRF model for 2015 we infer the ;Levantine Iron Age anomaly; between the 10th and the 8th centuries BCE is a local positive anomaly. The eastward extent of the anomaly is currently unknown.

  13. 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.

  14. 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.

  15. Chronic lymphocytic leukaemia: contemporary conceptions of etiology, pathogenesis and peculiarities of clinical manifestations (review

    Directory of Open Access Journals (Sweden)

    Chesnokova N.P.

    2011-06-01

    Full Text Available The research work presents an analysis of literature review and results of investigations on the problems of etiology, pathogenesis, classification and peculiarities of clinical manifestations of chronic lymphocytic leukaemia. Special attention is paid to both contemporary conceptions of carcinogenesis, reflecting the role of proto-oncogenes activation, an-tioncogenes and apoptosis genes suppression in mechanisms of neoplasia development and «specific mechanisms» of oncogenic transformation induction of B-lymphocytes and the subsequent development of the stages of promotion, progression and marked clinical manifestations of formation. Possibility of further improvement of use of immune phe-notype character and oncomarkers in diagnostics of chronic lymphocytic leukaemia clinical variants and in evaluation of effectiveness of its therapy has been indicated in the article

  16. The genetic basis of early T-cell precursor acute lymphoblastic leukaemia.

    Science.gov (United States)

    Zhang, Jinghui; Ding, Li; Holmfeldt, Linda; Wu, Gang; Heatley, Sue L; Payne-Turner, Debbie; Easton, John; Chen, Xiang; Wang, Jianmin; Rusch, Michael; Lu, Charles; Chen, Shann-Ching; Wei, Lei; Collins-Underwood, J Racquel; Ma, Jing; Roberts, Kathryn G; Pounds, Stanley B; Ulyanov, Anatoly; Becksfort, Jared; Gupta, Pankaj; Huether, Robert; Kriwacki, Richard W; Parker, Matthew; McGoldrick, Daniel J; Zhao, David; Alford, Daniel; Espy, Stephen; Bobba, Kiran Chand; Song, Guangchun; Pei, Deqing; Cheng, Cheng; Roberts, Stefan; Barbato, Michael I; Campana, Dario; Coustan-Smith, Elaine; Shurtleff, Sheila A; Raimondi, Susana C; Kleppe, Maria; Cools, Jan; Shimano, Kristin A; Hermiston, Michelle L; Doulatov, Sergei; Eppert, Kolja; Laurenti, Elisa; Notta, Faiyaz; Dick, John E; Basso, Giuseppe; Hunger, Stephen P; Loh, Mignon L; Devidas, Meenakshi; Wood, Brent; Winter, Stuart; Dunsmore, Kimberley P; Fulton, Robert S; Fulton, Lucinda L; Hong, Xin; Harris, Christopher C; Dooling, David J; Ochoa, Kerri; Johnson, Kimberly J; Obenauer, John C; Evans, William E; Pui, Ching-Hon; Naeve, Clayton W; Ley, Timothy J; Mardis, Elaine R; Wilson, Richard K; Downing, James R; Mullighan, Charles G

    2012-01-11

    Early T-cell precursor acute lymphoblastic leukaemia (ETP ALL) is an aggressive malignancy of unknown genetic basis. We performed whole-genome sequencing of 12 ETP ALL cases and assessed the frequency of the identified somatic mutations in 94 T-cell acute lymphoblastic leukaemia cases. ETP ALL was characterized by activating mutations in genes regulating cytokine receptor and RAS signalling (67% of cases; NRAS, KRAS, FLT3, IL7R, JAK3, JAK1, SH2B3 and BRAF), inactivating lesions disrupting haematopoietic development (58%; GATA3, ETV6, RUNX1, IKZF1 and EP300) and histone-modifying genes (48%; EZH2, EED, SUZ12, SETD2 and EP300). We also identified new targets of recurrent mutation including DNM2, ECT2L and RELN. The mutational spectrum is similar to myeloid tumours, and moreover, the global transcriptional profile of ETP ALL was similar to that of normal and myeloid leukaemia haematopoietic stem cells. These findings suggest that addition of myeloid-directed therapies might improve the poor outcome of ETP ALL.

  17. Acute leukaemia following malignant ependymoma: a case report

    Energy Technology Data Exchange (ETDEWEB)

    Pai, M.R.; Advani, S.H.; Gopal, R.; Nair, C.N.; Saikia, T.; Kamat, D.M.

    1985-05-01

    Though an increasing number of chemotherapy- and radiotherapy-related leukaemias are being reported, acute promyelocytic leukaemia developing as a therapy-related second malignancy is still uncommon. Here the authors report a case of acute promyelocytic leukemia, microgranular variant, developing in a case of intracranial malignant ependymoma, 1.5 years following treatment with craniospinal radiotherapy.

  18. A solid state Marx generator for TEL2

    Energy Technology Data Exchange (ETDEWEB)

    Kamerdzhiev, V.; Pfeffer, H.; Saewert, G.; Shiltsev, V.; /Fermilab

    2007-06-01

    The solid-state Marx generator modulates the anode of the electron gun to produce the electron beam pulses in the second Tevatron Electron Lens (TEL2). It is capable of driving the 60 pF terminal with 600 ns pulses of up to 6 kV with a p.r.r. of 50 kHz. The rise and fall times are 150 ns. Stangenes Industries developed the unit and is working on a second version which will go to higher voltage and have the ability to vary its output in 396 ns intervals over a 5 {micro}s pulse.

  19. Secondary pure erythroid leukaemia in relapsed acute lymphoblastic leukaemia: lineage switch or chemotherapy effect?

    Science.gov (United States)

    Gupta, Sanjeev Kumar; Kumar, Rajive; Chharchhodawala, Taher; Kumar, Lalit

    2014-05-19

    Pure erythroid leukaemia is a rare subtype of acute myeloid leukaemia (AML) and its occurrence at acute lymphoblastic leukaemia (ALL) relapse has not been reported earlier. A 39-year-old man received chemotherapy for Philadelphia-negative B cell ALL. Subsequently, he developed pure erythroid leukaemia with >80% immature erythroid precursors in bone marrow showing block positivity on periodic acid-Schiff stain, expressing CD71, CD34 but lacking CD235a. The interval between exposure to multidrug chemotherapy including cyclophosphamide and AML diagnosis was 2 years and 9 months. No cytogenetic abnormality was detected at the time of relapse. The patient died 2 weeks after starting AML chemotherapy. The relatively narrow time interval (usually 5-10 years) between chemotherapy and AML development and normal karyotype at relapse raises a possibility of lineage switch besides therapy-related AML as the likely pathogenesis. Further exploration of such cases may unravel the pathways responsible for lineage assignment in pluripotent stem cells. 2014 BMJ Publishing Group Ltd.

  20. Molecular analysis of a 444 bp fragment of the bovine leukaemia virus gp51 env gene reveals a high frequency of non-silent point mutations and suggests the presence of two subgroups of BLV in Chile.

    Science.gov (United States)

    Felmer, R; Muñoz, G; Zúñiga, J; Recabal, M

    2005-06-15

    With the aim of achieve a better understanding of the epidemiology and distribution of bovine leukaemia virus (BLV) infection in Chile, we assessed the suitability of using DNA isolated from the leukocyte fraction of bulk milk samples to carry out PCR-RFLP and DNA sequence analysis. The env fragment of BLV was successfully amplified from 33 serologically positive bulk milk samples collected from different geographical areas in the south of Chile. Restriction analysis allowed to classify 17 isolates within the Australian subgroup and 16 within the Belgium subgroup. DNA sequence and multiple alignment analysis of eight Chilean isolates showed a significantly higher frequency of single and double nucleotide substitutions. Most of these mutations were non-silent, resulting in changes at the protein level in several important epitopes of gp51. The Chilean sequences and 59 BLV env sequences available at GenBank, were subjected to a phylogenetic analysis, resulting in four different clusters. The groups identified were not related to those previously defined by restriction analysis. Chilean isolates were included in two different clusters and were genetically not related to isolates collected from neighbouring countries. Considering our results we can conclude: (i) bulk milk samples are suitable to identify the presence of BLV allowing epidemiological and genetic studies to be conducted on large geographical areas; (ii) at least four different genetic groups of BLV were identified by phylogenetic analysis, with Chilean isolates included in two different sub clusters.

  1. Estimation of current cumulative incidence of leukaemia-free patients and current leukaemia-free survival in chronic myeloid leukaemia in the era of modern pharmacotherapy

    Directory of Open Access Journals (Sweden)

    Trněný Marek

    2011-10-01

    Full Text Available Abstract Background The current situation in the treatment of chronic myeloid leukaemia (CML presents a new challenge for attempts to measure the therapeutic results, as the CML patients can experience multiple leukaemia-free periods during the course of their treatment. Traditional measures of treatment efficacy such as leukaemia-free survival and cumulative incidence are unable to cope with multiple events in time, e.g. disease remissions or progressions, and as such are inappropriate for the efficacy assessment of the recent CML treatment. Methods Standard nonparametric statistical methods are used for estimating two principal characteristics of the current CML treatment: the probability of being alive and leukaemia-free in time after CML therapy initiation, denoted as the current cumulative incidence of leukaemia-free patients; and the probability that a patient is alive and in any leukaemia-free period in time after achieving the first leukaemia-free period on the CML treatment, denoted as the current leukaemia-free survival. The validity of the proposed methods is further documented in the data of the Czech CML patients consecutively recorded between July 2003 and July 2009 as well as in simulated data. Results The results have shown a difference between the estimates of the current cumulative incidence function and the common cumulative incidence of leukaemia-free patients, as well as between the estimates of the current leukaemia-free survival and the common leukaemia-free survival. Regarding the currently available follow-up period, both differences have reached the maximum (12.8% and 20.8%, respectively at 3 years after the start of follow-up, i.e. after the CML therapy initiation in the former case and after the first achievement of the disease remission in the latter. Conclusions Two quantities for the evaluation of the efficacy of current CML therapy that may be estimated with standard nonparametric methods have been proposed in

  2. Yeast pol4 promotes tel1-regulated chromosomal translocations.

    Directory of Open Access Journals (Sweden)

    Jose F Ruiz

    Full Text Available DNA double-strand breaks (DSBs are one of the most dangerous DNA lesions, since their erroneous repair by nonhomologous end-joining (NHEJ can generate harmful chromosomal rearrangements. PolX DNA polymerases are well suited to extend DSB ends that cannot be directly ligated due to their particular ability to bind to and insert nucleotides at the imperfect template-primer structures formed during NHEJ. Herein, we have devised genetic assays in yeast to induce simultaneous DSBs in different chromosomes in vivo. The repair of these breaks in trans could result in reciprocal chromosomal translocations that were dependent on classical Ku-dependent NHEJ. End-joining events leading to translocations were mainly based on the formation of short base pairing between 3'-overhanging DNA ends coupled to gap-filling DNA synthesis. A major proportion of these events were specifically dependent on yeast DNA polymerase Pol4 activity. In addition, we have discovered that Pol4-Thr(540 amino acid residue can be phosphorylated by Tel1/ATM kinase, which could modulate Pol4 activity during NHEJ. Our data suggest that the role of Tel1 in preventing break-induced chromosomal translocations can, to some extent, be due to its stimulating effect on gap-filling activity of Pol4 to repair DSBs in cis. Overall, this work provides further insight to the molecular mechanisms of DSB repair by NHEJ and presents a new perspective to the understanding of how chromosomal translocations are formed in eukaryotic cells.

  3. Exploring the acute myeloid leukaemias

    Directory of Open Access Journals (Sweden)

    TB Thapa

    2013-10-01

    Full Text Available The acute myeloid leukemias are genetically a diverse group of neoplasm with varied clinical behavior and response to treatment. Advances in immunophenotyping, cytogenetics and molecular genetics have resulted in better understanding of their genesis. Risk stratification of different variants is now emerging. Therapy strategies are now increasingly being developed considering the inherent biological behavior of the different subtypes. It is anticipated that in the future, deeper secrets of these once fatal diseases will be unraveled by advances in newer genomic techniques. It is hoped that future use of gene specific tailored therapy and strategies will result in longer survival in cases showing poorer prognosis at present. DOI: http://dx.doi.org/10.3126/jpn.v3i6.9001 Journal of Pathology of Nepal (2013 Vol. 3, 497-501

  4. President Arnold Rüütel : kui ma poleks president, siis oleksin talupidaja / Arnold Rüütel ; intervjueerinud Toivo Tänavsuu

    Index Scriptorium Estoniae

    Rüütel, Arnold, 1928-

    2005-01-01

    President Arnold Rüütel vastab küsimustele, mis puudutavad Ettevõtluse Auhinna konkurssi, EL-iga liitumisega kaasnenud eeliseid Eesti majandusele, lähiaastatel lahendamist vajavaid probleeme Eesti majanduses

  5. President Arnold Rüütel : kui ma poleks president, siis oleksin talupidaja / Arnold Rüütel ; intervjueerinud Toivo Tänavsuu

    Index Scriptorium Estoniae

    Rüütel, Arnold, 1928-

    2005-01-01

    President Arnold Rüütel vastab küsimustele, mis puudutavad Ettevõtluse Auhinna konkurssi, EL-iga liitumisega kaasnenud eeliseid Eesti majandusele, lähiaastatel lahendamist vajavaid probleeme Eesti majanduses

  6. Juubilar Arnold Rüütel soovib Eestisse vähem vaesust ja kiuslikkust / Arnold Rüütel ; interv. Agnes Kuus

    Index Scriptorium Estoniae

    Rüütel, Arnold, 1928-

    2008-01-01

    Ilmunud ka: Postimees : na russkom jazõke 12. mai lk. 5. Intervjuu president Arnold Rüütliga tema 80. sünnipäeva puhul, milles juubilar meenutab pingelisi aegu seoses Eesti iseseisvumisega. Vt. samas: Arnold Rüütel 80; President Toomas Hendrik Ilves hindab Rüütli tasakaalukust. President T. H. Ilvese sõnul aitas president Rüütel tuua Euroopat Eestimaale lähemale

  7. Juubilar Arnold Rüütel soovib Eestisse vähem vaesust ja kiuslikkust / Arnold Rüütel ; interv. Agnes Kuus

    Index Scriptorium Estoniae

    Rüütel, Arnold, 1928-

    2008-01-01

    Ilmunud ka: Postimees : na russkom jazõke 12. mai lk. 5. Intervjuu president Arnold Rüütliga tema 80. sünnipäeva puhul, milles juubilar meenutab pingelisi aegu seoses Eesti iseseisvumisega. Vt. samas: Arnold Rüütel 80; President Toomas Hendrik Ilves hindab Rüütli tasakaalukust. President T. H. Ilvese sõnul aitas president Rüütel tuua Euroopat Eestimaale lähemale

  8. Asparagine synthetase expression is linked with L-asparaginase resistance in TEL-AML1-negative but not TEL-AML1-positive pediatric acute lymphoblastic leukemia.

    Science.gov (United States)

    Stams, Wendy A G; den Boer, Monique L; Holleman, Amy; Appel, Inge M; Beverloo, H Berna; van Wering, Elisabeth R; Janka-Schaub, Gritta E; Evans, William E; Pieters, Rob

    2005-06-01

    Resistance to L-asparaginase in leukemic cells may be caused by an elevated cellular expression of asparagine synthetase (AS). Previously, we reported that high AS expression did not correlate to L-asparaginase resistance in TEL-AML1-positive B-lineage acute lymphoblastic leukemia (ALL). In the present study we confirmed this finding in TEL-AML1-positive patients (n = 28) using microarrays. In contrast, 35 L-asparaginase-resistant TEL-AML1-negative B-lineage ALL patients had a significant 3.5-fold higher AS expression than 43 sensitive patients (P < .001). Using real-time quantitative polymerase chain reaction (RTQ-PCR), this finding was confirmed in an independent group of 39 TEL-AML1-negative B-lineage ALL patients (P = .03). High expression of AS was associated with poor prognosis (4-year probability of disease-free survival [pDFS] 58% +/- 11%) compared with low expression (4-year pDFS 83% +/- 7%; P = .009). We conclude that resistance to l-asparaginase and relapse risk are associated with high expression of AS in TEL-AML1-negative but not TEL-AML1-positive B-lineage ALL.

  9. Framework of Quality Assurance of TEL Integration into an Educational Organization

    Science.gov (United States)

    Volungeviciene, Airina; Tereseviciene, Margarita; Tait, Alan

    2014-01-01

    This research paper addresses the issues of integration of technology enhanced learning (TEL) into an educational organization. Good practice experience cannot be directly transferred to new organisations due to different contextual conditions. The TEL integration depends significantly upon a very rapid development of services and information…

  10. President Arnold Rüütel siirdas Kalevipojale südame / Meelis Lainvoo

    Index Scriptorium Estoniae

    Lainvoo, Meelis

    2003-01-01

    Rakvere Teatri suvelavastuse "Kalevipoeg" viimasel etendusel osalesid Arnold ja Ingrid Rüütel ning poliitikud Tõnis Palts, Tõnis Lukas, Arvo Haug ja Tõnu Kõiv. President Arnold Rüütel pani Neerutis Sadulamäel Kalevipoja kujule viimase kivi. Skulptuuri autori Seaküla Simsoni kommentaar

  11. Whole-genome sequencing identifies recurrent mutations in chronic lymphocytic leukaemia

    Science.gov (United States)

    Puente, Xose S.; Pinyol, Magda; Quesada, Víctor; Conde, Laura; Ordóñez, Gonzalo R.; Villamor, Neus; Escaramis, Georgia; Jares, Pedro; Beà, Sílvia; González-Díaz, Marcos; Bassaganyas, Laia; Baumann, Tycho; Juan, Manel; López-Guerra, Mónica; Colomer, Dolors; Tubío, José M. C.; López, Cristina; Navarro, Alba; Tornador, Cristian; Aymerich, Marta; Rozman, María; Hernández, Jesús M.; Puente, Diana A.; Freije, José M. P.; Velasco, Gloria; Gutiérrez-Fernández, Ana; Costa, Dolors; Carrió, Anna; Guijarro, Sara; Enjuanes, Anna; Hernández, Lluís; Yagüe, Jordi; Nicolás, Pilar; Romeo-Casabona, Carlos M.; Himmelbauer, Heinz; Castillo, Ester; Dohm, Juliane C.; de Sanjosé, Silvia; Piris, Miguel A.; de Alava, Enrique; Miguel, Jesús San; Royo, Romina; Gelpí, Josep L.; Torrents, David; Orozco, Modesto; Pisano, David G.; Valencia, Alfonso; Guigó, Roderic; Bayés, Mónica; Heath, Simon; Gut, Marta; Klatt, Peter; Marshall, John; Raine, Keiran; Stebbings, Lucy A.; Futreal, P. Andrew; Stratton, Michael R.; Campbell, Peter J.; Gut, Ivo; López-Guillermo, Armando; Estivill, Xavier; Montserrat, Emili; López-Otín, Carlos; Campo, Elías

    2012-01-01

    Chronic lymphocytic leukaemia (CLL), the most frequent leukaemia in adults in Western countries, is a heterogeneous disease with variable clinical presentation and evolution1,2. Two major molecular subtypes can be distinguished, characterized respectively by a high or low number of somatic hypermutations in the variable region of immunoglobulin genes3,4. The molecular changes leading to the pathogenesis of the disease are still poorly understood. Here we performed whole-genome sequencing of four cases of CLL and identified 46 somatic mutations that potentially affect gene function. Further analysis of these mutations in 363 patients with CLL identified four genes that are recurrently mutated: notch 1 (NOTCH1), exportin 1 (XPO1), myeloid differentiation primary response gene 88 (MYD88) and kelch-like 6 (KLHL6). Mutations in MYD88 and KLHL6 are predominant in cases of CLL with mutated immunoglobulin genes, whereas NOTCH1 and XPO1 mutations are mainly detected in patients with unmutated immunoglobulins. The patterns of somatic mutation, supported by functional and clinical analyses, strongly indicate that the recurrent NOTCH1, MYD88 and XPO1 mutations are oncogenic changes that contribute to the clinical evolution of the disease. To our knowledge, this is the first comprehensive analysis of CLL combining whole-genome sequencing with clinical characteristics and clinical outcomes. It highlights the usefulness of this approach for the identification of clinically relevant mutations in cancer. PMID:21642962

  12. Emulgointi- ja stabilointiaineiden vaikutus jäätelön aistinvaraiseen laatuun ja sulamisominaisuuksiin

    OpenAIRE

    2014-01-01

    Insinöörityön tarkoituksena oli tutkia, voidaanko asiakasyrityksen kaupallisen jäätelön sisältämien lisäaineiden (emulgointi- ja stabilointiaineet) määrää vähentää jäätelön makua, rakennetta ja sulamisominaisuuksia muuttamatta. Tavoitteena oli, että kehitelty jäätelö sisältäisi lukumäärällisesti vähemmän lisäaineita, mutta olisi muuten (maku, haju, ulkonäkö, rakenne, sulamisominaisuudet) edelleen samanlaista kuin asiakasyrityksen kaupallinen jäätelö. Työssä valmistettiin kolme koejäätelöe...

  13. RAG-dependent recombination at cryptic RSSs within TEL-AML1 t(12;21)(p13;q22) chromosomal translocation region.

    Science.gov (United States)

    Numata, Masashi; Saito, Shoko; Nagata, Kyosuke

    2010-11-26

    The recombination activating gene (RAG) is a lymphoid-specific endonuclease involved in the V(D)J recombination. It has long been proposed that mis-targeting of RAG proteins is one of the factors contributing to lymphoid chromosomal translocation bearing authentic recombination signal sequences (RSSs) in immunoglobulin (Ig) and T cell receptor (TCR) gene loci or cryptic RSSs (cRSSs). However, it is unclear whether primary sequence-dependent targeting mistake involved in the chromosomal translocation bearing no Ig/TCR gene loci is mediated by RAG proteins. Using an extrachromosomal recombination assay, we found RAG-dependent recombination in the regions dense in breakpoints within TEL and AML1 gene loci related to acute lymphoid leukemia-associated t(12;21)(p13;q22) chromosomal translocation. Sequence analyses revealed several heptamer-like sequences located in the vicinity of RAG-dependent recombination sites. By chromatin immunoprecipitation (ChIP) and ligation-mediated PCR (LM-PCR) assays, we have shown that RAG proteins bind to and cleave the TEL translocation region dense in breakpoints. These results suggest that mis-targeting of RAG proteins to cRSSs within TEL and AML1 translocation regions might be responsible for the t(12;21)(p13;q22) chromosomal translocation not bearing Ig/TCR regions. Copyright © 2010 Elsevier Inc. All rights reserved.

  14. Serum & cerebrospinal fluid ferritin levels in children with acute leukaemia.

    Science.gov (United States)

    Srinivasan, A; Rusia, U; Anand, N K; Sood, S K

    1989-06-01

    Serum and CSF ferritin were estimated in 35 consecutive patients of acute leukaemia at the time of admission and on induction of remission. Serum ferritin levels were significantly raised in 94 per cent patients of acute leukaemia. The mean (+/- SD) serum ferritin (314.36 +/- 158.4 micrograms/1) was significantly higher when compared with control values (P less than 0.001). Remission induction resulted in significant fall in serum ferritin values to a mean of 149 (+/- 98.7) micrograms/l (P less than 0.05). Serum ferritin is thus of value in assessing the state of remission and is a sensitive indicator of the leukaemic cell mass and the state of activity of the disease. CSF ferritin levels in acute leukaemia were comparable to normal control values. CSF ferritin did not reflect CNS involvement in acute leukaemia and therefore its value as a tumour marker of CNS infiltration is doubtful.

  15. [Biphenotypic acute leukaemia with Burkitt-like cytology].

    Science.gov (United States)

    Coche, D; Bergues, B; Harrivel, V; Guillaume, N

    2009-01-01

    Biphenotypic acute leukaemia (BAL) represents about 5% of adult acute leukaemia. Based on a previously described scoring system, the European Group for Immunologic Classification of Leukaemia (EGIL) proposed a set of diagnostic criteria for BAL. This scoring system is based on the number and degree of the specificity of several markers for myeloid or T/B lymphoid blasts. Here, we report the case of a BAL with Burkitt-like cytology, corresponding to "the acute lymphoblastic leukaemia, Burkitt type" L3 for the FAB classification. By flow cytometry, the blasts showed a positivity for B lymphoid cytoplasmic (CD79a and mu) and membrane (CD19, CD22, CD24, IgM) markers AND a positivity for the myeloid (CD13, CD33, CD65, CD15) markers.

  16. Chronic lymphocytic leukaemia: case control epidemiological study in Yorkshire.

    OpenAIRE

    Cartwright, R. A.; Bernard, S.M.; Bird, C. C.; Darwin, C. M.; O'Brien, C; Richards, I D; Roberts, B; McKinney, P A

    1987-01-01

    This is the second report of a large case control study of lymphoma/leukaemia occurring in Yorkshire during 1979-84, and deals with chronic lymphocytic leukaemia presenting either in its haematological (CLL) or more solid lymphomatous (malignant lymphoma-lymphocytic or MLL) forms. In all, 330 cases and 561 controls were interviewed. The results support the concept that CLL/MLL is a condition of multiple aetiologies with evidence for genetic predisposition through an excess of family cases, im...

  17. Trace elements in scalp hair of leukaemia patients

    Directory of Open Access Journals (Sweden)

    Khuder Ali

    2014-08-01

    Full Text Available The aim of this study was to determine the concentration of Fe, Ni, Cu, Zn and Pb in scalp hair of leukaemia patients and healthy volunteers, using the optimised XRF method. Leukaemia hair samples were classifi ed corresponding to type, growth and age of the participants. The results showed that the studied trace elements (TEs in both of leukaemia and control groups were positively skewed. In comparison with the control group, lower Fe, Cu, Zn and Pb and higher of Ni medians were found in all studied leukaemia patients. The median rank obtained by Mann-Whitney U-test revealed insignifi cant differences between the leukaemia patients subgroups and the controls. An exact probability (α 0.70 in the scalp hair of control group were observed between Ni/Fe-Ni, Cu/Fe-Cu, Zn/Fe-Zn, Pb/Fe-Pb, Cu/Ni-Zn/Ni, Cu/Ni-Pb/Ni, Zn/Ni-Pb/Ni, Zn/Fe-Zn/Cu, Pb/Ni-Ni and Ni/Fe-Pb/Ni, whereas only very strong positive ratios in the scalp hair of leukaemia patients group were observed between Ni/Fe-Ni, Cu/Fe-Cu, Zn/Fe-Zn and Pb/Fe-Pb, all correlations were signifi cant at p < 0.05. Other strong and signifi cant correlations were also observed in scalp hair of both groups. Signifi cant differences between grouping of studied TEs in all classifi ed leukaemia groups and controls were found using principal component analysis (PCA. The results of PCA confi rmed that the type and the growth of leukaemia factors were more important in element loading than the age factor.

  18. Active acute leukaemia: should transplant be offered to all patients?

    Science.gov (United States)

    Avni, Batia; Shapira, Michael Y; Resnick, Igor B; Stepensky, Polina; Or, Reuven; Grisariu, Sigal

    2016-06-24

    The probability of achieving long term remission for patients with refractory acute leukaemia is very low. Allogeneic stem cell transplantation (SCT) is offered to these patients in order to improve their dismal outcome. We retrospectively analyzed 361 acute leukaemia patients, who underwent allogeneic SCT in the Hadassah's bone marrow transplantation department between the years 2005 and 2012 and identified 84 patients with active leukaemia at transplantation. Median age was 34 years. Sixty four patients were diagnosed with acute myeloid leukaemia (AML), 18 patients with acute lymphoblastic leukaemia and two with biphenotypic leukaemia. The majority of patients were diagnosed with de-novo AML and transplanted at relapse. In the surviving patients, median follow up was 15 months. One year OS was 20%. At time of last follow up, 13 patients were alive (15.5%): ten patients with AML and two patients with acute lymphoblastic leukaemia. In the univariate analysis, factors associated with significantly better overall survival were as follows: matched unrelated donor (p = 0.006), matched donor (p = 0.014) and occurrence of acute graft-versus-host disease (aGVHD) (p = 0.019). Karnofsky performance score at SCT and occurrence of cGVHD were found to be borderline significant. Only matched unrelated donor and aGVHD were found to affect overall survival significantly in the multivariate analysis. Other than performance score at SCT, none of the pretransplant patients' characteristics were found to influence survival. In conclusion, as none of the pretransplant characteristics were found to influence the ability to select the patients that will benefit from HSC transplantation, this work supports offering HSCT to all active leukaemia eligible patients with reasonable performance status. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  19. Adrenal crisis in a patient with acute myeloid leukaemia

    OpenAIRE

    Li, Wang; Okwuwa, Ikemefuna; Toledo-Frazzini, Karla; Alhomosh, Alaaedin

    2013-01-01

    Adrenal crisis is a group of clinical manifestation predominantly with hypotensive shock, electrolyte imbalance in a patient with adrenal insufficiency or in a patient who was abruptly withdrawn from glucocorticoid treatment acute myeloid leukaemia (AML) is one of the most common acute leukaemia in adults. Though the above diseases are commonly seen in individual patients, the coexistence of both conditions in the same patient is rare. We reported a 64-year-old African-American man with a his...

  20. PCR-based clonality assessment in patients with lymphocytic leukaemias: a single-institution experience

    Indian Academy of Sciences (India)

    Bojana M. Cikota; Ljiljana J. Tukić; Olivera T. Tarabar; Dragana T. Stamatović; Marija N. Elez; Zvonko M. Magić

    2009-12-01

    PCR-based clonality testing can be performed in all lymphoproliferations by analysing gene rearrangements of antigen receptors, rearrangements that are unique for each kind of lymphocyte. Reactive lymphoproliferations have polyclonally rearranged Ig/TCR genes, whereas malignant proliferations (leukaemias and lymphomas) show clonal rearrangements. The aim of this study was to assess the clinical benefits of clonality testing with previously evaluated consensus primers in leukaemia patients. The study included peripheral blood and bone marrow samples of 67 leukaemia patients (32 B-CLL, 24 B-ALL and 11 T-ALL). Clonality testing was based on PCR amplification of rearranged I$_{\\text{gH}}$ and TCR genes. During diagnosis, monoclonal pattern was found in all analysed B-CLL and T-ALL samples. Testing in B-ALL patients showed positive results in all bone marrow and one peripheral blood samples. Results of clonality testing in B-CLL patients during follow-up were concordant between peripheral blood and bone marrow. Obtained results corresponded to clinical course in all but one patient. In B-ALL group, results of molecular testing in peripheral blood and bone marrow confirmed remission estimated according to clinical criteria in all except one patient. Before any clinical sign of relapse, monoclonal pattern was found in six/seven patients by bone marrow and in three/seven patients by peripheral blood analysis, respectively. Results of molecular monitoring in T-ALL patients did not confirme clinical evaluation in two patients. Obtained results indicate high accuracy of re-evaluated primers for clonality assessment in ALL and CLL patients at the time of diagnosis. Results of clonality testing in B-ALL patients indicate that bone marrow analysis has higher sensitivity compared to analysis of peripheral blood.

  1. Somatic mutations of isocitrate dehydrogenases 1 and 2 are prognostic and follow-up markers in patients with acute myeloid leukaemia with normal karyotype

    Directory of Open Access Journals (Sweden)

    Virijevic Marijana

    2016-12-01

    Full Text Available Mutations in the isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2 genes are frequent molecular lesions in acute myeloid leukaemia with normal karyotype (AML-NK. The effects of IDH mutations on clinical features and treatment outcome in AML-NK have been widely investigated, but only a few studies monitored these mutations during follow-up.

  2. In vitro drug resistance and prognostic impact of p16(INK4A)/p15(INK4B) deletions in childhood T-cell acute lymphoblastic leukaemia

    NARCIS (Netherlands)

    Ramakers-van Woerden, NL; Pieters, R; Slater, RM; Loonen, A.H.; Beverloo, HB; van Drunen, E; Heyman, M; Moreno, TC; Rots, MG; van Wering, ER; Kamps, WA; Janka-Schaub, GE; Veerman, AJP

    2001-01-01

    p16 gene deletions are present in about 70% of primary paediatric T-cell acute lymphoblastic leukaemia (T-ALL) and 20% of common/precursor B-cell ALL cases. It is not clear what the impact of the frequent p16 deletions is within the subgroup of T-lineage ALL. We studied the relationship between p16/

  3. Effect of the histone deacetylase inhibitor depsipeptide on B-cell differentiation in both TEL-AML1-positive and negative childhood acute lymphoblastic leukemia.

    Science.gov (United States)

    Stams, Wendy A G; den Boer, Monique L; Beverloo, H Berna; Kazemier, Karin M; van Wering, Elisabeth R; Janka-Schaub, Gritta E; Pieters, Rob

    2005-12-01

    The fusion protein TEL-AML1 in t(12;21)+ acute lymphoblastic leukemia (ALL) recruits co-repressors and histone deacetylases (HDAC), which transrepress AML1 target genes. Normal bone marrow cells were more resistant to HDAC inhibitor FK228 induced cell killing than were cells from ALL patients with or without t(12;21). FK228 induced differentiation in ALL, irrespective of the presence of t(12;21).

  4. Tel2 structure and function in the Hsp90-dependent maturation of mTOR and ATR complexes

    Energy Technology Data Exchange (ETDEWEB)

    Takai, Hiroyuki; Xie, Yihu; de Lange, Titia; Pavletich, Nikola P. (Rockefeller); (SKI)

    2010-09-20

    We reported previously that the stability of all mammalian phosphatidylinositol 3-kinase-related protein kinases (PIKKs) depends on their interaction with Tel2, the ortholog of yeast Tel2 and Caenorhabditis elegans Clk-2. Here we provide evidence that Tel2 acts with Hsp90 in the maturation of PIKK complexes. Quantitative immunoblotting showed that the abundance of Tel2 is low compared with the PIKKs, and Tel2 preferentially bound newly synthesized ATM, ATR, mTOR, and DNA-PKcs. Tel2 complexes contained, in addition to Tti1-Tti2, the Hsp90 chaperone, and inhibition of Hsp90 interfered with the interaction of Tel2 with the PIKKs. Analysis of in vivo labeled nascent protein complexes showed that Tel2 and Hsp90 mediate the formation of the mTOR TORC1 and TORC2 complexes and the association of ATR with ATRIP. The structure of yeast Tel2, reported here, shows that Tel2 consists of HEAT-like helical repeats that assemble into two separate {alpha}-solenoids. Through mutagenesis, we identify a surface patch of conserved residues involved in binding to the Tti1-Tti2 complex in vitro. In vivo, mutation of this conserved patch affects cell growth, levels of PIKKs, and ATM/ATR-mediated checkpoint signaling, highlighting the importance of Tti1-Tti2 binding to the function of Tel2. Taken together, our data suggest that the Tel2-Tti1-Tti2 complex is a PIKK-specific cochaperone for Hsp90.

  5. Somatic PTPN11 mutations in childhood acute myeloid leukaemia.

    Science.gov (United States)

    Tartaglia, Marco; Martinelli, Simone; Iavarone, Ivano; Cazzaniga, Giovanni; Spinelli, Monica; Giarin, Emanuela; Petrangeli, Valentina; Carta, Claudio; Masetti, Riccardo; Aricò, Maurizio; Locatelli, Franco; Basso, Giuseppe; Sorcini, Mariella; Pession, Andrea; Biondi, Andrea

    2005-05-01

    Somatic mutations in PTPN11, the gene encoding the transducer SHP-2, have emerged as a novel class of lesions that upregulate RAS signalling and contribute to leukaemogenesis. In a recent study of 69 children and adolescents with de novo acute myeloid leukaemia (AML), we documented a non-random distribution of PTPN11 mutations among French-American-British (FAB) subtypes. Lesions were restricted to FAB-M5 cases, where they were relatively common (four of 12 cases). Here, we report on the results of a molecular screening performed on 181 additional unselected patients, enrolled in participating institutions of the Associazione Italiana Ematologia Oncologia Pediatrica-AML Study Group, to provide a more accurate picture of the prevalence, spectrum and distribution of PTPN11 mutations in childhood AML and to investigate their clinical relevance. We concluded that PTPN11 defects do not represent a frequent event in this heterogeneous group of malignancies (4.4%), although they recur in a considerable percentage of patients with FAB-M5 (18%). PTPN11 lesions rarely occur in other subtypes. Within the FAB-M5 group no clear association of PTPN11 mutations with any clinical variable was evident. Nearly two third of the patients with this subtype were found to harbour an activating mutation in PTPN11, NRAS, KRAS2 or FLT3.

  6. Reduced activity of TAFI (thrombin-activatable fibrinolysis inhibitor) in acute promyelocytic leukaemia

    NARCIS (Netherlands)

    Meijers, JCM; Oudijk, EJD; Mosnier, LO; Nieuwenhuis, HK; Fijnheer, R; Bouma, Bonno N.; Bos, R

    Acute promyelocytic leukaemia (APL) is a disease that is distinguished from other leukaemias by the high potential for early haemorrhagic death. Several processes are involved, such as disseminated intravascular coagulation and hyperfibrinolysis. Recently, TAFI (thrombin-activatable fibrinolysis

  7. The acute promyelocytic leukaemia success story: curing leukaemia through targeted therapies.

    Science.gov (United States)

    Rice, K L; de Thé, H

    2014-07-01

    The recent finding that almost all patients with acute promyelocytic leukaemia (APL) may be cured using a combination of retinoic acid (RA) and arsenic trioxide (As(2)O(3)) (N Engl J Med, 369, 2013 and 111) highlights the progress made in our understanding of APL pathogenesis and therapeutic approaches over the past 25 years. The study of APL has revealed many important lessons related to transcriptional control, nuclear organization, epigenetics and the role of proteolysis in biological control. Even more important has been the clinical demonstration that molecularly targeted therapy can eradicate disease. © 2014 The Association for the Publication of the Journal of Internal Medicine.

  8. Rossija tozhe nas poimjot / Arnold Rüütel ; interv. Garanzha, Jevgenija

    Index Scriptorium Estoniae

    Rüütel, Arnold, 1928-

    2004-01-01

    President Arnold Rüütel Eestist Euroopa Liidu liikmena, presidendi rollist, omandireformi tagajärgedest, suhtumisest fašismiilmingutesse, Teise maailmasõja sündmustele hinnangu andmisest, Eesti-Vene suhete tulevikust

  9. Rüütel kutsus Juštšenko Eestisse

    Index Scriptorium Estoniae

    2005-01-01

    President Arnold Rüütel saatis Viktor Juštšenkole õnnitluse presidendivalimistel saavutatud edu puhul, kutsudes teda Eestisse visiidile. Ilmunud ka Vaba Eesti Sõna = Free Estonian Word (2005) 18. jaan., lk. 2

  10. 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

  11. Leukaemia relapse after allogeneic transplants for acute myeloid leukaemia: predictive role of WT1 expression.

    Science.gov (United States)

    Pozzi, Sarah; Geroldi, Simona; Tedone, Elisabetta; Luchetti, Silvia; Grasso, Raffaella; Colombo, Nicoletta; Di Grazia, Carmen; Lamparelli, Teresa; Gualandi, Francesca; Ibatici, Adalberto; Bregante, Stefania; Van Lint, Maria Teresa; Raiola, Anna Maria; Dominietto, Alida; Varaldo, Riccardo; Signori, Alessio; Bacigalupo, Andrea

    2013-02-01

    We assessed WT1 expression (expressed as messenger copies/10(4) ABL1) from marrow cells of 122 patients with acute myeloid leukaemia (AML), before and after an unmanipulated allogeneic haemopoietic stem cell transplant (HSCT). The median age was 44 years (15-69), 59% were in first remission, 74% received a myeloablative conditioning regimen and the median follow up was 865 d (34-2833). Relapse was higher in 67 patients with WT1 expression, at any time post-HSCT, exceeding 100 copies (54%), as compared to 16%, for 55 patients with post-HSCT WT1 expression <100 copies (P < 0·0001). Similarly, actuarial 5-year survival (OS) was 40% vs. 63%, respectively (P = 0·03). In multivariate Cox analysis, WT1 expression post-HSCT was the strongest predictor of relapse (Hazard Ratio [HR] 4·5, P = 0·0001), independent of disease phase (HR 2·3, P = 0·002). Donor lymphocyte infusions (DLI) were given to 17 patients because of increasing WT1 levels: their OS was 44%, vs. 14% for 21 patients with increasing WT1 expression who did not receive DLI (P = 0·004). In conclusion, WT1 expression post-HSCT is a strong predictor of leukaemia relapse and survival in AML; WT1 may be used as a marker for early interventional therapy.

  12. Structural studies on leukaemia inhibitory factor

    Energy Technology Data Exchange (ETDEWEB)

    Norton, R.S.; Maurer, T.; Smith, D.K. [Biomolecular Research Institute, Parville (Australia); Nicola, N.A. [Institute of Medical Research, Melbourne (Australia)

    1994-12-01

    Leukaemia Inhibitory Factor (LIF) is a pleiotropic cytokine that acts on a wide range of target cells, including mega-karyocytes, osteoblasts, hepatocytes, adipocytes, neurons, embryonic stem cells, and primordial germ cells. Many of its activities are shared with other cytokines, particularly interleukin-6, oncostatin-M, ciliary neurotrophic factor, and granulocyte colony-stimulating factor (G-CSF). Although secreted in vivo as a glycoprotein, nonglycosylated recombinant protein expressed in E. coli is fully active and has been used in our nuclear magnetic resonance (NMR) studies of the three-dimensional structure and structure-function relationships of LIF. With 180 amino acids and a molecular mass of about 20 kDa, OF is too large for direct structure determination by two-dimensional and three-dimensional {sup 1}HNMR. It is necessary to label the protein with the stable isotopes {sup 15}N and {sup 13}C and employ heteronuclear three-dimensional NMR in order to resolve and interpret the spectral information required for three-dimensional structure determination. This work has been undertaken with both human LIF and a mouse-human chimaera that binds to the human LIF receptor with the same affinity as the human protein and yet expresses in E. coli at much higher levels. Sequence-specific resonance assignments and secondary structure elements for these proteins will be presented and progress towards determination of their three-dimensional structures described.

  13. 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.

  14. Chronic myeloid leukaemia with extreme thrombocytosis.

    Science.gov (United States)

    Verma, Shailendra Prasad; Subbiah, Arunkumar; Jacob, Sajini Elizabeth; Basu, Debdatta

    2015-08-19

    We report two cases of chronic myeloid leukaemia (CML) with extreme thrombocytosis. The first patient was a 65-year-old man who presented with prolonged history of upper abdominal discomfort, anorexia and two episodes of recent gum bleeds without fever or other bleeding manifestations. He was a chronic smoker with no other comorbidities. Examination revealed moderate hepatosplenomegaly. On investigation, he was found to have extreme thrombocytosis (3,500,000/mm(3)) and leucocytosis with moderate anaemia. In view of the leucocytosis, he was investigated for CML and found to be positive for BCR-ABL by reverse transcription PCR (RT-PCR). He received imatinib 400 mg/day and achieved complete haematological response at the end of 3 months. The second patient was a 7-year-old boy who presented with fever, cough and cold of 2-week duration. Examination revealed mild hepatomegaly with palpable spleen tip. Haemogram and peripheral smear revealed moderate leucocytosis with extreme thrombocytosis (2,800,000/mm(3)). On evaluation, he was found to be BCR-ABL positive and responded well to imatinib treatment. In both these cases, massive thrombocytosis was an unusual presentation of a well-known entity, namely, CML. This degree of thrombocytosis is usually seen only in essential thrombocytosis. 2015 BMJ Publishing Group Ltd.

  15. President Rüütel : lähedastele on raskem kingitust valida / Arnold Rüütel ; intervjueerinud Tiina Ansip

    Index Scriptorium Estoniae

    Rüütel, Arnold, 1928-

    2005-01-01

    Ilmunud ka: Linnaleht : Tartu (2005) 23. dets., lk. B2 ; Linnaleht : Pärnu (2005) 23. dets, lk. B2. President Arnold Rüütel vastab küsimustele jõulupühade ja aastavahetuse tähistamise ning kingituste tegemise kohta

  16. Anu Samarüütel-Long: sama kleiti võiks toota mitukümmend aastat / Anu Samarüütel-Long ; intervjueerinud Tanel Veenre

    Index Scriptorium Estoniae

    Samarüütel-Long, Anu, 1966-

    2010-01-01

    Anu Samarüütel-Long oma mais 2010 ilmunud reisikirjast "Minu London", Londonisse elama asumisest, õpingutest seal, Londonist kui loovlinnast, eesti disainist, soovist teha moedisaini, koostööst Montoniga, lihtsuse saavutamisest, eetilisest tootmisest, kunsti ja kaubanduse dialoogist jm.

  17. Arnold Rüütel ei tea veel järgmise presidendi nime / Arnold Rüütel ; intervjueerinud Toomas Sildam

    Index Scriptorium Estoniae

    Rüütel, Arnold, 1928-

    2005-01-01

    Ilmunud ka: Postimees : na russkom jazõke (2005) 30. dets., lk 2-3. President Arnold Rüütel vastab aastalõpuintervjuus küsimustele, mis puudutavad tema hinnangut sisepoliitilisele olukorrale Eestis ja valitsuse tegevusele, Eesti-Vene suhteid, eelseisvaid presidendivalimisi ning tema võimalikku taaskandideerimist presidendiks. Lisad: 3 mõtet; 3 mõtet

  18. Arnold Rüütel: "Kohati jääb meie erakondadel puudu sisemisest demokraatiast." / Arnold Rüütel ; intervjueerinud Urmo Soonvald

    Index Scriptorium Estoniae

    Rüütel, Arnold, 1928-

    2004-01-01

    President Arnold Rüütel vastab küsimustele, mis puudutavad vedurijuhtide streiki, noorte arstide lahkumist välismaale, Rahvaliidu saadikurühma tekkimist Tallinna volikogus, Res Publica ja Reformierakonna võimalikku liitumist, Leedu-visiiti

  19. Arnold Rüütel: e-hääletamine tuleb niikuinii / Arnold Rüütel ; intervjueerinud Kai Kalamees

    Index Scriptorium Estoniae

    Rüütel, Arnold, 1928-

    2005-01-01

    President Arnold Rüütel vastab küsimustele, mis on seotud tema otsusega mitte kuulutada välja e-hääletamist lubavat seadust. Presidendi sõnul ei mõjuta tema otsus kuidagi e-hääletuse tänavust toimumist

  20. Anu Samarüütel-Long: sama kleiti võiks toota mitukümmend aastat / Anu Samarüütel-Long ; intervjueerinud Tanel Veenre

    Index Scriptorium Estoniae

    Samarüütel-Long, Anu, 1966-

    2010-01-01

    Anu Samarüütel-Long oma mais 2010 ilmunud reisikirjast "Minu London", Londonisse elama asumisest, õpingutest seal, Londonist kui loovlinnast, eesti disainist, soovist teha moedisaini, koostööst Montoniga, lihtsuse saavutamisest, eetilisest tootmisest, kunsti ja kaubanduse dialoogist jm.

  1. Arnold Rüütel: "Kohati jääb meie erakondadel puudu sisemisest demokraatiast." / Arnold Rüütel ; intervjueerinud Urmo Soonvald

    Index Scriptorium Estoniae

    Rüütel, Arnold, 1928-

    2004-01-01

    President Arnold Rüütel vastab küsimustele, mis puudutavad vedurijuhtide streiki, noorte arstide lahkumist välismaale, Rahvaliidu saadikurühma tekkimist Tallinna volikogus, Res Publica ja Reformierakonna võimalikku liitumist, Leedu-visiiti

  2. Arnold Rüütel ei tea veel järgmise presidendi nime / Arnold Rüütel ; intervjueerinud Toomas Sildam

    Index Scriptorium Estoniae

    Rüütel, Arnold, 1928-

    2005-01-01

    Ilmunud ka: Postimees : na russkom jazõke (2005) 30. dets., lk 2-3. President Arnold Rüütel vastab aastalõpuintervjuus küsimustele, mis puudutavad tema hinnangut sisepoliitilisele olukorrale Eestis ja valitsuse tegevusele, Eesti-Vene suhteid, eelseisvaid presidendivalimisi ning tema võimalikku taaskandideerimist presidendiks. Lisad: 3 mõtet; 3 mõtet

  3. Arnold Rüütel: e-hääletamine tuleb niikuinii / Arnold Rüütel ; intervjueerinud Kai Kalamees

    Index Scriptorium Estoniae

    Rüütel, Arnold, 1928-

    2005-01-01

    President Arnold Rüütel vastab küsimustele, mis on seotud tema otsusega mitte kuulutada välja e-hääletamist lubavat seadust. Presidendi sõnul ei mõjuta tema otsus kuidagi e-hääletuse tänavust toimumist

  4. Measurable residual disease testing in acute myeloid leukaemia.

    Science.gov (United States)

    Hourigan, C S; Gale, R P; Gormley, N J; Ossenkoppele, G J; Walter, R B

    2017-07-01

    There is considerable interest in developing techniques to detect and/or quantify remaining leukaemia cells termed measurable or, less precisely, minimal residual disease (MRD) in persons with acute myeloid leukaemia (AML) in complete remission defined by cytomorphological criteria. An important reason for AML MRD-testing is the possibility of estimating the likelihood (and timing) of leukaemia relapse. A perfect MRD-test would precisely quantify leukaemia cells biologically able and likely to cause leukaemia relapse within a defined interval. AML is genetically diverse and there is currently no uniform approach to detecting such cells. Several technologies focused on immune phenotype or cytogenetic and/or molecular abnormalities have been developed, each with advantages and disadvantages. Many studies report a positive MRD-test at diverse time points during AML therapy identifies persons with a higher risk of leukaemia relapse compared with those with a negative MRD-test even after adjusting for other prognostic and predictive variables. No MRD-test in AML has perfect sensitivity and specificity for relapse prediction at the cohort- or subject levels and there are substantial rates of false-positive and -negative tests. Despite these limitations, correlations between MRD-test results and relapse risk have generated interest in MRD-test result-directed therapy interventions. However, convincing proof that a specific intervention will reduce relapse risk in persons with a positive MRD-test is lacking and needs testing in randomized trials. Routine clinical use of MRD-testing requires further refinements and standardization/harmonization of assay platforms and results reporting. Such data are needed to determine whether results of MRD-testing can be used as a surrogate end point in AML therapy trials. This could make drug-testing more efficient and accelerate regulatory approvals. Although MRD-testing in AML has advanced substantially, much remains to be done.

  5. Chronic lymphocytic leukaemia: case control epidemiological study in Yorkshire.

    Science.gov (United States)

    Cartwright, R A; Bernard, S M; Bird, C C; Darwin, C M; O'Brien, C; Richards, I D; Roberts, B; McKinney, P A

    1987-07-01

    This is the second report of a large case control study of lymphoma/leukaemia occurring in Yorkshire during 1979-84, and deals with chronic lymphocytic leukaemia presenting either in its haematological (CLL) or more solid lymphomatous (malignant lymphoma-lymphocytic or MLL) forms. In all, 330 cases and 561 controls were interviewed. The results support the concept that CLL/MLL is a condition of multiple aetiologies with evidence for genetic predisposition through an excess of family cases, immune perturbation demonstrated by excessive previous skin diseases and phenylbutazone use, and viral involvement shown by links with infectious diseases and multiple sclerosis.

  6. Risk of acute myelogenous leukaemia and myelodysplasia following cancer treatment.

    Science.gov (United States)

    van Leeuwen, F E

    1996-03-01

    Now that a substantial group of cancer patients has such a favourable prognosis, it has become increasingly important to evaluate the long-term complications of treatment. Of all late effects of treatment, secondary leukaemia is one of the most serious. Increased risk of AML has been observed both after RT and after CT; however, several types of CT have much stronger leukaemogenic properties than RT. Limited field radiation in the therapeutic dose range is associated with very little or no increased risk of leukaemia, which has been attributed to cell killing at the higher radiation doses. With respect to CT, two different syndromes of treatment-related AML have been recognized. Risk of alkylating agent-related AML is highest in the 5-10 year follow-up period and seems to decrease afterwards. This type of leukaemia is often preceded by MDS, and is characterized by deletions of chromosomes 5 and 7. Leukaemias related to treatment with the topoisomerase II inhibitors are characterized by a short induction period, presentation as myelomonocytic or monocytic leukaemia (rather than MDS) and balanced chromosomal translocations involving bands 11q23 and 21q22. This review addresses the risk of secondary AML and MDS following treatment of HD, NHL, testicular cancer, ovarian cancer, breast cancer and paediatric malignancies. In patients with HD, the risk of AML is higher with an increasing number of mechlorethamine-procarbazine-containing cycles, a greater number of CT episodes, and after splenectomy. The majority of data shows that RT does not add to the leukaemia risk from CT, but this issue is still surrounded by some controversy. ABV(D)-treated patients have a very low risk of AML. Generally, patients with NHL, testicular cancer and breast cancer experience much lower risk of AML than patients with HD. NHL and breast cancer treatment regimens with cumulative cyclophosphamide doses of 20 g or less do not confer an appreciable increase of AML. Recently, strongly increased

  7. Exit of pediatric pre-B acute lymphoblastic leukaemia cells from the bone marrow to the peripheral blood is not associated with cell maturation or alterations in gene expression

    Directory of Open Access Journals (Sweden)

    Wiebe Thomas

    2008-08-01

    Full Text Available Abstract Background Childhood pre-B acute lymphoblastic leukemia (ALL is a bone marrow (BM derived disease, which often disseminates out of the BM cavity, where malignant cells to a variable degree can be found circulating in the peripheral blood (PB. Normal pre-B cells are absolutely dependent on BM stroma for survival and differentiation. It is not known whether transformed pre-B ALL cells retain any of this dependence, which possibly could impact on drug sensitivity or MRD measurements. Results Pre-B ALL cells, highly purified by a novel method using surface expression of CD19 and immunoglobulin light chains, from BM and PB show a very high degree of similarity in gene expression patterns, with differential expression of vascular endothelial growth factor (VEGF as a notable exception. In addition, the cell sorting procedure revealed that in 2 out of five investigated patients, a significant fraction of the malignant cells had matured beyond the pre-B cell stage. Conclusion The transition of ALL cells from the BM into the circulation does not demand, or result in, major changes of gene expression pattern. This might indicate an independence of BM stroma on the part of transformed pre-B cells, which contrasts with that of their normal counterparts.

  8. 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.

  9. Chronic lymphocytic leukaemia: clinical-aetiological findings in 66 patients and their families

    Directory of Open Access Journals (Sweden)

    Weber Walter

    2007-12-01

    Full Text Available Abstract Background Little is known about the aetiology of chronic lymphocytic leukaemia (CLL. The family medical history is a "genomic tool" capturing interactions of genetic susceptibility, shared environment and common behaviours. Methods A cohort of 66 consecutives patients with CLL (probands was studied in a medical oncology practice (W.W. from 1981 until 2005. A German version of the NCI medical history questionnaire for cancer aetiology was used. Familial clustering analysis was done by comparing the proportion of specific tumours in the first degree relatives of the CLL practice cohort with corresponding proportions of population-based cancer registry data. Results 18 (41% male and 5 (23% female CLL probands had multiple malignancies, e.g. 2 meningiomas, 7 and 19 years after diagnosis of CLL. 46 (12% first degree relatives had malignancies with an excess of CLL. Other conspicuous familial associations are CLL with malignancies of the upper GI tract (oesophagus, stomach and of the nervous system. Conclusion 1. Chronic lymphocytic leukaemia clusters in some families like any other disease. Predisposition genes should be searched. 2. Cancer prevention and early detection should be continued in CLL patients because of their longevity and high risk for multiple malignancies. 3. The overrepresentation of upper GI malignancies in first degree relatives of CLL patients calls for targeted oesophago-gastroscopy screening studies.

  10. [Detection of bovine leukaemia virus (BLV) in tissue samples of naturally and experimentally infected cattle].

    Science.gov (United States)

    Teifke, Jens P; Vahlenkamp, Thomas W

    2008-01-01

    Enzootic bovine leukaemia (EBL) which is caused by the bovine leukaemia virus (BLV) still plays a remarkable role despite a significant success in sanitation programmes. In the Federal Republic of Germany it was not possible to eradicate the disease until today. Sporadically during slaughter or necropsy of cattle neoplastic lesions of the lymphatic tissues are observed that need to be clarified with regard to BLV as etiological agent. Due to the fact that in most instances no serological data are available from the respective animals and blood drawings from the original holdings are not easy to obtain the polymerase chain reaction (PCR) opens new avenues as supplementary diagnostic tool to test unfixed lymphatic tissues for the presence of BLV proviral DNA. Lymph node tissues from 10 naturally or experimentally BLV-infected cattle, which have been monitored virologically and serologically, and tissues from 4 negative animals were processed, DNA was extracted and subjected to PCR to amplify BLV env gene specific sequences. The results show that in cattle with BLV-induced leukosis as well as in cattle, which were clinically healthy and unsuspicious at slaughter or at post-mortem, either with persistent lymphocytosis (PL) or without, BLV proviral DNA could be detected easily in samples of lymphatic tissues and in high concordance with serological data. In this article data from the National and OIE reference laboratory for EBL at the Friedrich-Loeffler-Institut (FLI, Germany) are presented. Elaborated laboratory protocols for processing of tissue samples and performing of BLV-PCR are recommended.

  11. Childhood leukaemia in the Netherlands : a register based epidemiologic study

    NARCIS (Netherlands)

    H.A. Moll (Henriëtte)

    1983-01-01

    textabstractLeukaemia, literally "white blood", is the most common type of malignancy in childhood (Birch et al., 1980). The clinical features are caused by abnormal proliferation of one or more of the blood-forming cellular elements. The immature malignant cells usually disturb normal haematopoiesi

  12. Tuberculosis complicating imatinib treatment for chronic myeloid leukaemia

    NARCIS (Netherlands)

    Daniels, J. M. A.; Vonk-Noordegraaf, A.; Janssen, J. J. W. M.; Postmus, P. E.; van Altena, R.

    Although imatinib is not considered a predisposing factor for tuberculosis (TB), the present case report describes three patients in whom imatinib treatment for chronic myeloid leukaemia was complicated by TB. This raises the question of whether imatinib increases susceptibility to TB. There are

  13. Maternal diet quality before pregnancy and risk of childhood leukaemia.

    Science.gov (United States)

    Singer, Amanda W; Carmichael, Suzan L; Selvin, Steve; Fu, Cecilia; Block, Gladys; Metayer, Catherine

    2016-10-01

    Previous studies on maternal nutrition and childhood leukaemia risk have focused on the role of specific nutrients such as folate and have not considered broader measures of diet quality, which may better capture intake of diverse nutrients known to impact fetal development. We examined the relationship between maternal diet quality before pregnancy, as summarised by a diet quality index, and risk of childhood acute lymphoblastic leukaemia (ALL) and acute myeloid leukaemia (AML) in a case-control study in California. Dietary intake in the year before pregnancy was assessed using FFQ in 681 ALL cases, 103 AML cases and 1076 matched controls. Conditional logistic regression was used to estimate OR and 95 % CI for diet quality continuous score and quartiles (Q1-Q4). Higher maternal diet quality score was associated with reduced risk of ALL (OR 0·66; 95 % CI 0·47, 0·93 for Q4 v. Q1) and possibly AML (OR 0·42; 95 % CI 0·15, 1·15 for Q4 v. Q1). No single index component appeared to account for the association. The association of maternal diet quality with risk of ALL was stronger in children diagnosed under the age of 5 years and in children of women who did not report using vitamin supplements before pregnancy. These findings suggest that the joint effects of many dietary components may be important in influencing childhood leukaemia risk.

  14. 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

  15. 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...

  16. Arnold Rüütel: riigikogu peab hoiduma Iraagi küsimuses populismist / Arnold Rüütel ; intervjueerinud Urmet Kook

    Index Scriptorium Estoniae

    Rüütel, Arnold, 1928-

    2006-01-01

    President Arnold Rüütel vastab küsimustele, mis puudutavad tema tervist, presidendiks kandideerimist, tema maailmavaadet ja minevikku ning suhet religiooniga, Keskerakonna ja Rahvaliidu koostöölepingut, 1991. aasta putšistide nimetatud Eesti asevalitsejat, Venemaa hiljutist nooti seoses piirilepinguga, presidendi edasisi plaane, samuti tema suhtumist kohustuslikku religiooniõpetusse, Iraagi-missiooni pikendamisse, võõrtööjõu sissetoomisse

  17. Arnold Rüütel: riigikogu peab hoiduma Iraagi küsimuses populismist / Arnold Rüütel ; intervjueerinud Urmet Kook

    Index Scriptorium Estoniae

    Rüütel, Arnold, 1928-

    2006-01-01

    President Arnold Rüütel vastab küsimustele, mis puudutavad tema tervist, presidendiks kandideerimist, tema maailmavaadet ja minevikku ning suhet religiooniga, Keskerakonna ja Rahvaliidu koostöölepingut, 1991. aasta putšistide nimetatud Eesti asevalitsejat, Venemaa hiljutist nooti seoses piirilepinguga, presidendi edasisi plaane, samuti tema suhtumist kohustuslikku religiooniõpetusse, Iraagi-missiooni pikendamisse, võõrtööjõu sissetoomisse

  18. Whole-Exome Sequencing of ETV6/RUNX1 in Four Childhood Acute Lymphoblastic Leukaemia Cases

    Science.gov (United States)

    Zakaria, Zubaidah; Othman, Norodiyah; Ismail, Azli; Kamaluddin, Nor Rizan; Esa, Ezalia; Abdul Rahman, Eni Juraida; Mat Yusoff, Yuslina; Mohd Fauzi, Fazlin; Sew Keoh, Ten

    2017-04-01

    Background: ETV6/RUNX1 gene fusion is the most frequently seen chromosomal abnormality in childhood acute lymphobastic leukamia (ALL). However, additional genetic changes are known to be required for the development of this type of leukaemia. Therefore, we here aimed to assess the somatic mutational profile of four ALL cases carrying the ETV6/RUNX1 fusion gene using whole-exome sequencing. Methods: DNA was isolated from bone marrow samples using a QIAmp DNA Blood Mini kit and subsequently sequenced using the Illumina MiSeq system. Results: We identified 12,960 to17,601 mutations in each sample, with a total of 16,466 somatic mutations in total. Some 15,533 variants were single nucleotide polymorphisms (SNPs), 129 were substitutions, 415 were insertions and 389 were deletions. When taking into account the coding region and protein impact, 1,875 variants were synonymous and 1,956 were non-synonymous SNPs. Among non-synonymous SNPs, 1,862 were missense, 13 nonsense, 35 frameshifts, 11 nonstop, 3 misstart, 15 splices disrupt and 17 in-frame indels. A total of 86 variants were located in leukaemia-related genes of which 32 variants were located in the coding regions of GLI2, SP140, GATA2, SMAD5, KMT2C, CDH17, CDX2, FLT3, PML and MOV10L1. Conclusions: Detection and identification of secondary genetic alterations are important in identifying new therapeutic targets and developing rationally designed treatment regimens with less toxicity in ALL patients. Creative Commons Attribution License

  19. Tel Aviver Jahrbuch für deutsche Geschichte, XXVII-1998

    Directory of Open Access Journals (Sweden)

    Dominique Trimbur

    2008-06-01

    Full Text Available Although Israel has only one German department, in Jerusalem, German studies are flourishing in this country. Not only has the Israeli University system just been enhanced by a new center devoted to this field (in Beer Sheva, under Professor Frank Stern, the Institute of German  History of Tel Aviv University has confirmed its dynamism and capabilities for in-depth work with the publication of the new Tel Aviver Jahrbuch für deutsche Geschichte. Complementing the broad range of works publish...

  20. El teléfono celular y las aproximaciones para su estudio

    OpenAIRE

    Ana Luz Ruelas

    2010-01-01

    En este artículo se abordan los principales antecedentes del estudio del teléfono fijo, que nos dan un marco apropiado para introducirnos al estudio del teléfono celular, comparando los inicios de la adopción de ambas tecnologías, así como sus efectos sociales. Se discuten también algunos enfoques sugeridos por estudiosos de las comunicaciones pues son un marco para analizar este dispositivo de la comunicación. Otorgamos especial atención a las iniciales visiones distópicas que provocó su pro...

  1. Childhood leukaemia incidence below the age of 5 years near French nuclear power plants

    Energy Technology Data Exchange (ETDEWEB)

    Laurier, D [Institute for Radiation Protection and Nuclear Safety, IRSN/DRPH/SRBE, BP 17, 92262 Fontenay aux Roses cedex (France); Hemon, D; Clavel, J [INSERM Unit 754, Villejuif (France)], E-mail: Dominique.laurier@irsn.fr

    2008-09-01

    A recent study indicated an excess risk of leukaemia among children under the age of 5 years living in the vicinity of nuclear power plants in Germany. We present results relating to the incidence of childhood leukaemia in the vicinity of nuclear power plants in France for the same age range. These results do not indicate an excess risk of leukaemia in young children living near French nuclear power plants. (note)

  2. Childhood leukaemia incidence below the age of 5 years near French nuclear power plants.

    Science.gov (United States)

    Laurier, D; Hémon, D; Clavel, J

    2008-09-01

    A recent study indicated an excess risk of leukaemia among children under the age of 5 years living in the vicinity of nuclear power plants in Germany. We present results relating to the incidence of childhood leukaemia in the vicinity of nuclear power plants in France for the same age range. These results do not indicate an excess risk of leukaemia in young children living near French nuclear power plants.

  3. Persistence of DNMT3A R882 mutations during remission does not adversely affect outcomes of patients with acute myeloid leukaemia

    Science.gov (United States)

    Bhatnagar, Bhavana; Eisfeld, Ann-Kathrin; Nicolet, Deedra; Mrózek, Krzysztof; Blachly, James S.; Orwick, Shelley; Lucas, David M.; Kohlschmidt, Jessica; Blum, William; Kolitz, Jonathan E.; Stone, Richard M.; Bloomfield, Clara D.; Byrd, John C.

    2016-01-01

    Summary Somatic mutation of the DNMT3A gene at the arginine R882 site is common in acute myeloid leukaemia (AML). The prognostic significance of DNMT3A R882 mutation clearance, using traditional diagnostic next generation sequencing (NGS) methods, during complete remission (CR) in AML patients is controversial. We examined the impact of clearing DNMT3A R882 mutations at diagnosis to the detectable threshold of NGS methods, persist in the majority of AML patients in CR. PMID:27476855

  4. Kas Arnold Rüütel valetas süümevannet andes? / Anneli Ammas, Garel Püüa

    Index Scriptorium Estoniae

    Ammas, Anneli, 1962-

    2006-01-01

    Autorite hinnangul tekib 31. augustil Eesti Ekspressis ilmunud artikli põhjal, milles käsitleti Johannes Hindi represseerimist, küsimus, kas Arnold Rüütel on valetanud Eesti Vabariigile korduvalt süümevannet andes. TÜ professori Kalle Meruski seisukoht. Lisa: Rüütel käskis kontrolli tugevdada

  5. Tel1 and Rif2 Regulate MRX Functions in End-Tethering and Repair of DNA Double-Strand Breaks.

    Directory of Open Access Journals (Sweden)

    Corinne Cassani

    2016-02-01

    Full Text Available The cellular response to DNA double-strand breaks (DSBs is initiated by the MRX/MRN complex (Mre11-Rad50-Xrs2 in yeast; Mre11-Rad50-Nbs1 in mammals, which recruits the checkpoint kinase Tel1/ATM to DSBs. In Saccharomyces cerevisiae, the role of Tel1 at DSBs remains enigmatic, as tel1Δ cells do not show obvious hypersensitivity to DSB-inducing agents. By performing a synthetic phenotype screen, we isolated a rad50-V1269M allele that sensitizes tel1Δ cells to genotoxic agents. The MRV1269MX complex associates poorly to DNA ends, and its retention at DSBs is further reduced by the lack of Tel1. As a consequence, tel1Δ rad50-V1269M cells are severely defective both in keeping the DSB ends tethered to each other and in repairing a DSB by either homologous recombination (HR or nonhomologous end joining (NHEJ. These data indicate that Tel1 promotes MRX retention to DSBs and this function is important to allow proper MRX-DNA binding that is needed for end-tethering and DSB repair. The role of Tel1 in promoting MRX accumulation to DSBs is counteracted by Rif2, which is recruited to DSBs. We also found that Rif2 enhances ATP hydrolysis by MRX and attenuates MRX function in end-tethering, suggesting that Rif2 can regulate MRX activity at DSBs by modulating ATP-dependent conformational changes of Rad50.

  6. Genome‐wide analysis of cytogenetic aberrations in ETV6/RUNX1‐positive childhood acute lymphoblastic leukaemia

    DEFF Research Database (Denmark)

    Borst, Louise; Wesolowska, Agata; Joshi, Tejal

    2012-01-01

    The chromosomal translocation t(12;21) resulting in the ETV6/RUNX1 fusion gene is the most frequent structural cytogenetic abnormality among patients with childhood acute lymphoblastic leukaemia (ALL). We investigated 62 ETV6/RUNX1‐positive childhood ALL patients by single nucleotide polymorphism......, and gains of 10 and 21) seemed independent of each other. Finally, we identified the most common regions with recurrent gains and losses, which comprise microRNA clusters with known oncogenic or tumour‐suppressive roles. The present study sheds further light on the genetic diversity of ETV6/RUNX1‐positive...

  7. Adenovirus protein IX sequesters host-cell promyelocytic leukaemia protein and contributes to efficient viral proliferation.

    Science.gov (United States)

    Rosa-Calatrava, Manuel; Puvion-Dutilleul, Francine; Lutz, Pierre; Dreyer, Dominique; de Thé, Hugues; Chatton, Bruno; Kedinger, Claude

    2003-10-01

    The product of adenovirus type 5 (Ad5) gene IX, protein IX (pIX), is a multifunctional protein that stabilizes the viral capsid and has transcriptional activity. We show that pIX also contributes to the Ad5-induced reorganization of the host-cell nuclear ultrastructure: pIX induces the formation of specific and dynamic nuclear inclusions, and the host promyelocytic leukaemia (PML) protein, which is the main structural organizer of PML bodies, is stably relocated and confined within the pIX-induced inclusions late in infection. Our results suggest that Ad5 has evolved a unique strategy that leads to the sustained neutralization of PML bodies throughout infection, thereby ensuring optimal viral proliferation.

  8. 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...... to parts of the highly specific rearranged T-cell receptor delta (TCR-delta), T-cell receptor gamma (TCR-gamma), or immunoglobulin heavy chain (IgH) genes of the malignant clone. Using primers located externally to the restriction site the competitor and the DNA from the malignant clone will be amplified...... 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...

  9. Intelligent Techniques Using Molecular Data Analysis in Leukaemia: An Opportunity for Personalized Medicine Support System.

    Science.gov (United States)

    Banjar, Haneen; Adelson, David; Brown, Fred; Chaudhri, Naeem

    2017-01-01

    The use of intelligent techniques in medicine has brought a ray of hope in terms of treating leukaemia patients. Personalized treatment uses patient's genetic profile to select a mode of treatment. This process makes use of molecular technology and machine learning, to determine the most suitable approach to treating a leukaemia patient. Until now, no reviews have been published from a computational perspective concerning the development of personalized medicine intelligent techniques for leukaemia patients using molecular data analysis. This review studies the published empirical research on personalized medicine in leukaemia and synthesizes findings across studies related to intelligence techniques in leukaemia, with specific attention to particular categories of these studies to help identify opportunities for further research into personalized medicine support systems in chronic myeloid leukaemia. A systematic search was carried out to identify studies using intelligence techniques in leukaemia and to categorize these studies based on leukaemia type and also the task, data source, and purpose of the studies. Most studies used molecular data analysis for personalized medicine, but future advancement for leukaemia patients requires molecular models that use advanced machine-learning methods to automate decision-making in treatment management to deliver supportive medical information to the patient in clinical practice.

  10. Acute myeloid dendritic cell leukaemia with specific cutaneous involvement: a diagnostic challenge.

    Science.gov (United States)

    Ferran, M; Gallardo, F; Ferrer, A M; Salar, A; Pérez-Vila, E; Juanpere, N; Salgado, R; Espinet, B; Orfao, A; Florensa, L; Pujol, R M

    2008-05-01

    Myeloid or type 1 dendritic cell leukaemia is an exceedingly rare haematopoietic neoplasm characterized by a specific immunophenotypic profile close to plasmacytoid dendritic cell and acute myelogenous leukaemia. A 77-year-old man presenting specific cutaneous infiltration by myeloid dendritic cell leukaemia is reported. The clinical features as well as the cutaneous histopathological and immunohistochemical features led to the initial diagnosis of CD4+/CD56+ haematodermic neoplasm. However, extensive immunophenotypic studies performed from peripheral blood blasts disclosed that leukaemic cells expressed myeloid dendritic cell markers, confirming the diagnosis. The diagnostic difficulties of specific cutaneous involvement by myeloid dendritic cell leukaemia on the basis of routine histopathological and immunohistochemical features are highlighted.

  11. Rüütel pakub külalistele elegantset kamamaiust / Kaarel Kaas

    Index Scriptorium Estoniae

    Kaas, Kaarel, 1978-

    2003-01-01

    Ilmunud ka: Infopress (2003) 21. veebr., nr. 8 lk. 139. President Arnold Rüütel koos proua Ingrid Rüütliga pakub Eesti riigi 85. sünnipäeval eestimaiseid roogasid. OÜ Catering Service tegevjuhi Marko Meigase, Scandic Hotel Palace'i toitlustusjuhi Svea Juurikase ja presidendi pressiesindaja Ester Šanki kommentaarid

  12. Rüütel pakub külalistele elegantset kamamaiust / Kaarel Kaas

    Index Scriptorium Estoniae

    Kaas, Kaarel, 1978-

    2003-01-01

    Ilmunud ka: Infopress (2003) 21. veebr., nr. 8 lk. 139. President Arnold Rüütel koos proua Ingrid Rüütliga pakub Eesti riigi 85. sünnipäeval eestimaiseid roogasid. OÜ Catering Service tegevjuhi Marko Meigase, Scandic Hotel Palace'i toitlustusjuhi Svea Juurikase ja presidendi pressiesindaja Ester Šanki kommentaarid

  13. A Delphi Study on Technology Enhanced Learning (TEL) Applied on Computer Science (CS) Skills

    Science.gov (United States)

    Porta, Marcela; Mas-Machuca, Marta; Martinez-Costa, Carme; Maillet, Katherine

    2012-01-01

    Technology Enhanced Learning (TEL) is a new pedagogical domain aiming to study the usage of information and communication technologies to support teaching and learning. The following study investigated how this domain is used to increase technical skills in Computer Science (CS). A Delphi method was applied, using three-rounds of online survey…

  14. Rüütel nimetas NATO, OSCE ja Euroopa Nõukogu suursaadikud

    Index Scriptorium Estoniae

    2003-01-01

    President Arnold Rüütel nimetas Harri Tiido Eesti suursaadikuks NATO juures, Alar Streimanni suursaadikuks Euroopa Nõukogu juures ja Gea Renneli alaliseks esindajaks OSCE juures. Ühtlasi kutsus president tagasi senise suursaadiku NATO juures Sulev Kannikese ja suursaadiku Euroopa Nõukogu juures Ants Froschi

  15. Informing TEL Strategy through Formal and Informal Channels: A Case Study

    Science.gov (United States)

    Walker, David; Sloan, David; Boyle, Lynn; Walsh, Lorraine

    2011-01-01

    Purpose: The purpose of this paper is to outline and discuss a multifaceted approach to embedding change in academic practice, resulting in the integration of technology-enhanced learning (TEL) within the wider institutional strategic approach to learning and teaching. Design/methodology/approach: This approach is evidenced through a discussion of…

  16. Rüütel : "Russkije ne ponimajut smõsla okkupatsii" / Konstantin Morenko

    Index Scriptorium Estoniae

    Morenko, Konstantin

    2005-01-01

    President Arnold Rüütel teatas 7. märtsil Kadriorus ametlikult, et ei kavatse osaleda Moskvas toimuvatel 9. mai üritustel. Ajakirjanike küsimustele president pärast avalduse esitamist ei vastanud. Vt. samas Venemaa riigiduuma väliskomisjoni esimehe Konstantin Kossatšovi kommentaare

  17. Implementation of Tel Aviv University MOOCs in Academic Curriculum: A Pilot Study

    Science.gov (United States)

    Soffer, Tal; Cohen, Anat

    2015-01-01

    The study presented in this paper examines the feasibility of using MOOCs [Massive open online courses] as a learning environment in academic courses. This paper focuses on the students who participated in two MOOCs offered by Tel Aviv University (TAU) during the year 2013. The preliminary findings of this pilot study illustrate the scope of…

  18. Benchmark cool companions: New ages and abundances for the PZ Tel system

    CERN Document Server

    Jenkins, James S; Ivanyuk, Oleksiy; Gallardo, Jose; Jones, Matias I; Day-Jones, Avril C; Jones, Hugh R A; Ruiz, Maria-Teresa; Pinfield, David J; Yakovina, Larissa

    2011-01-01

    We present new ages and abundance measurements for the pre-main sequence star PZ Tel. PZ Tel was recently found to host a young and low-mass companion. Using FEROS spectra we have measured atomic abundances (e.g. Fe and Li) and chromospheric activity for PZ Tel and used these to obtain metallicity and age estimates for the companion. We find PZ Tel to be a rapidly rotating (vsini=73\\pm5km/s), ~solar metallicity star (logN(Fe)=-4.37\\pm0.06dex or [Fe/H]=0.05\\pm0.20dex) with a measured mean logR'HK of -4.12. We measure a NLTE lithium abundance of logN(Li)=3.1\\pm0.1dex, which from depletion models gives rise to an age of 7+4-2 Myrs for the system. The measured chromospheric activity returns an age of 26\\pm2Myrs, as does fitting pre-main sequence evolutionary tracks (Tau_evol=22\\pm3Myrs), both of which are in disagreement with the lithium age. We speculate on reasons for this difference and introduce new models for lithium depletion that incorporates both rotation and magnetic field affects. We also synthesize sol...

  19. A case of Mac Tel 2 with an unusual sub macular vitelliform lesion.

    Science.gov (United States)

    Lekha, T; Sarwate, Nikit; Sarwate, Renuka

    2015-01-01

    Observational case report describing the clinical, FFA, OCT and mfERG findings in an elderly female patient with atypical features of macular telangiectasia (Mac Tel 2) RESULTS: A 71-year-old lady was detected to have characteristic features of Mac Tel 2 in the left eye (LE) and a yellowish sub macular vitelliform like lesion in the right eye (RE). FFA showed ill defined hyper fluorescence in the RE and telangiectasia and parafoveal leakage typical of Mac Tel 2 in the LE. On OCT RE had hyper reflective clump of echoes subfoveally with an intact RPE and LE had foveal thinning with hypo reflective intraretinal cavities. mfERG responses were normal in the RE and reduced in the LE. During the course of 3 years LE showed natural progression while RE remained unchanged. Structural and functional evaluation of an unusual sub macular vitelliform lesion seen in association with Mac Tel 2 and its course over a period of 3 years is described. The differentiating features of this lesion from adult onset foveomacular vitelliform dystrophy (AFMD) are discussed.

  20. President Rüütel kohtus kohalike eestlastega / Peeter Grüner

    Index Scriptorium Estoniae

    Grüner, Peeter

    2006-01-01

    President Arnold Rüütel kohtus töövisiidil San Fransiscosse kohalike eestlastega ning tänas oma ettekandes pagulaseestlasi Eesti taasiseseisvumuseks antud panuse eest. Töövisiit Ameerika Ühendriikidesse 17.-21.01.2006

  1. Rüütel sõidab Auschwitzi mälestustseremooniale

    Index Scriptorium Estoniae

    2005-01-01

    President Arnold Rüütel osaleb Poola presidendi Aleksander Kwasniewski kutsel Auschwitz-Birkenau muuseumis koonduslaagri vabastamise 60. aastapäevale pühendatud mälestustseremoonial. Töövisiit Poola 26.-28.01.2005

  2. [History of the renovation of the hôtel-Dieu of Bourges].

    Science.gov (United States)

    Gitton, Philippe

    2006-01-01

    From the 16th to the 20th century "hôtel-Dieu" was the main hospital in the Berry capital. In the 30's the mayor decided to renovate the building but in 1994 the construction of a new hospital--"Centre Hospitalier Jacques-Coeur"--freed the ancient building which became a historical centre for culture et tourism in the region.

  3. Absolute parameters of eclipsing binaries in Southern Hemisphere sky - II: QY Tel

    Science.gov (United States)

    Erdem, A.; Sürgit, D.; Engelbrecht, C. A.; van Heerden, H. P.; Manick, R.

    2016-11-01

    This paper presents the first analysis of spectroscopic and photometric observations of the neglected southern eclipsing binary star, QY Tel. Spectroscopic observations were carried out at the South African Astronomical Observatory in 2013. New radial velocity curves from this study and V light curves from the All Sky Automated Survey were solved simultaneously using modern light and radial velocity curve synthesis methods. The final model describes QY Tel as a detached binary star where both component stars fill at least half of their Roche limiting lobes. The masses and radii were found to be 1.32 (± 0.06) M⊙, 1.74 (± 0.15) R⊙ and 1.44 (± 0.09) M⊙, 2.70 (± 0.16) R⊙ for the primary and secondary components of the system, respectively. The distance to QY Tel was calculated as 365 (± 40) pc, taking into account interstellar extinction. The evolution case of QY Tel is also examined. Both components of the system are evolved main-sequence stars with an age of approximately 3.2 Gy, when compared to Geneva theoretical evolution models.

  4. Üksik Rüütel mõisaaidas / Helju Koger

    Index Scriptorium Estoniae

    Koger, Helju, 1943-

    2008-01-01

    Kurna mõisa aidast ümberehitatud restoran Üksik Rüütel. Omanikud Anatoli Rabitski ja Aleksei Turtshak. Koridori seinamaalid tegi Aleksei Dorotshevski. Restoranis on Kalapalee, Rüütlisaal, Rüütlikoobas ja Kohviorg. 10 värv. vaadet

  5. Vocational Education Approach: New TEL Settings--New Prospects for Teachers' Instructional Activities?

    Science.gov (United States)

    Hämäläinen, Raija; De Wever, Bram

    2013-01-01

    This study focuses on vocational education teachers' instructional activities in a new technology-enhanced learning (TEL) setting. A content analysis is applied to investigate teachers' and students' interactions in a 3D game context. The findings illustrate that when teachers' and students' interactions are mediated by a…

  6. Extramedullary Myeloid Cell Tumour Presenting As Leukaemia Cutis

    Directory of Open Access Journals (Sweden)

    Thappa Devinder Mohan

    2002-01-01

    Full Text Available We herewith report a case of extramedullary myeloid cell tumour presenting as leukaemia cutis for its rarity. It occurred in a 50 year old male patient who presented to us with a 40 days history of painless raised solid skin swellings over the trunk. Histopathological examination of the skin biopsy and bone marrow biopsy showed features suggestive of non-Hodgkin’s lymphoma. Immunophenotyping on skin biopsy specimens and bone marrow biopsy found tumour cells expressing CD43 and Tdt but were negative for CD3 and CD20. These features were consistent with extramedullary myeloid cell tumour involving skin and subcutis (cutaneous manifestation of acute myeloid leukaemia.

  7. High-flow priapism in acute lymphatic leukaemia

    Energy Technology Data Exchange (ETDEWEB)

    Mentzel, Hans-Joachim; Vogt, Susanna; Kaiser, Werner A. [Institute of Diagnostic and Interventional Radiology, Department of Pediatric Radiology, Friedrich-Schiller-Universitaet Jena, Bachstrasse 18, 07740, Jena (Germany); Kentouche, Karim; Doerfel, Claus; Zintl, Felix [Department of Paediatrics, University of Jena (Germany)

    2004-07-01

    Priapism is defined as prolonged and persistent erection of the penis without sexual stimulation. It is associated with excessive hyperleukocytosis (e.g. in acute or chronic leukaemia); however, this complication is rarely seen in the pediatric population. We report a 12-year-old boy suffering from acute leukaemia presenting with, at first intermittent, but increasingly persistent erection. Doppler US revealed signs of high-flow priapism. MRI excluded intrapelvic tumour masses, and three-dimensional contrast-enhanced MR angiography could not demonstrate an arteriovenous fistula or thrombosis. Cavernosal blood-gas measurement was in agreement with high-flow priapism. On the basis of the imaging findings, invasive therapeutic management was avoided in our patient with a successful outcome. (orig.)

  8. Genome-scale definition of the transcriptional programme associated with compromised PU.1 activity in acute myeloid leukaemia.

    Science.gov (United States)

    Sive, J I; Basilico, S; Hannah, R; Kinston, S J; Calero-Nieto, F J; Göttgens, B

    2016-01-01

    Transcriptional dysregulation is associated with haematological malignancy. Although mutations of the key haematopoietic transcription factor PU.1 are rare in human acute myeloid leukaemia (AML), they are common in murine models of radiation-induced AML, and PU.1 downregulation and/or dysfunction has been described in human AML patients carrying the fusion oncogenes RUNX1-ETO and PML-RARA. To study the transcriptional programmes associated with compromised PU.1 activity, we adapted a Pu.1-mutated murine AML cell line with an inducible wild-type PU.1. PU.1 induction caused transition from leukaemia phenotype to monocytic differentiation. Global binding maps for PU.1, CEBPA and the histone mark H3K27Ac with and without PU.1 induction showed that mutant PU.1 retains DNA-binding ability, but the induction of wild-type protein dramatically increases both the number and the height of PU.1-binding peaks. Correlating chromatin immunoprecipitation (ChIP) Seq with gene expression data, we found that PU.1 recruitment coupled with increased histone acetylation induces gene expression and activates a monocyte/macrophage transcriptional programme. PU.1 induction also caused the reorganisation of a subgroup of CEBPA binding peaks. Finally, we show that the PU.1 target gene set defined in our model allows the stratification of primary human AML samples, shedding light on both known and novel AML subtypes that may be driven by PU.1 dysfunction.

  9. 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.

  10. Leukaemia and low dose radiation. Is there an association between leukaemia and cumulative external dose amongst the British Nuclear Fuel plc. (BNFL) workers?

    Energy Technology Data Exchange (ETDEWEB)

    McGeoghegan, D.; Binks, K. [Westlakes Scientific Consulting, Cumbria (United Kingdom)

    2000-05-01

    A detailed examination of the BNFL leukaemia data is presented, for the period 1941-1995, using the recently assembled company wide BNFL epidemiological database and the BNFL leukaemia case-control data set. The association of this occupationally exposed cohort is examined with respect to both leukaemia mortality and leukaemia morbidity. The excess relative risk for total leukaemia excluding chronic lymphatic leukaemia amongst the BNFL radiation workers was found to be 3.64 Sv{sup -1} (90% CI -0.13-11.22); for Sellafield and Springfields this figure was 7.99 Sv{sup -1} (90% CI 1.50-29.5) and -1.97 Sv{sup -1} (90% CI<-2.23-6.11) respectively. A 14-20% increase in risk is noted when dosimetry adjusted for measurement error, is used to determine the excess relative risk. The association between leukaemia and cumulative external radiation is found to be particularly associated with the Sellafield plant; the Springfields plant gave consistently negative risk estimates. (author)

  11. President Arnold Rüütel: Eestis on alanud valimiste eelne sisepoliitiline võitlus / Arnold Rüütel ; intervjueerinud Urmo Soonvald

    Index Scriptorium Estoniae

    Rüütel, Arnold, 1928-

    2005-01-01

    President Arnold Rüütel vastab küsimustele, mis puudutavad tema kohtumist Venemaa presidendi Vladimir Putiniga, Eesti-Vene piirilepingule allakirjutamist, Läti presidendi Vaira Vike-Freiberga otsust sõita 9. maiks Moskvasse, välisministeeriumiga seotud skandaali, poliitikute selgitusi riigisaladuse ümber tekkinud skandaali kohta, erakorralisi valimisi kui võimalikku lahendust praegusele sisepoliitilisele olukorrale, Eesti välisministri puudumist Brüsselis toimuval kohtumisel USA presidendiga, kohtumist välisministrikandidaat Rein Langiga

  12. President Arnold Rüütel: Eestis on alanud valimiste eelne sisepoliitiline võitlus / Arnold Rüütel ; intervjueerinud Urmo Soonvald

    Index Scriptorium Estoniae

    Rüütel, Arnold, 1928-

    2005-01-01

    President Arnold Rüütel vastab küsimustele, mis puudutavad tema kohtumist Venemaa presidendi Vladimir Putiniga, Eesti-Vene piirilepingule allakirjutamist, Läti presidendi Vaira Vike-Freiberga otsust sõita 9. maiks Moskvasse, välisministeeriumiga seotud skandaali, poliitikute selgitusi riigisaladuse ümber tekkinud skandaali kohta, erakorralisi valimisi kui võimalikku lahendust praegusele sisepoliitilisele olukorrale, Eesti välisministri puudumist Brüsselis toimuval kohtumisel USA presidendiga, kohtumist välisministrikandidaat Rein Langiga

  13. True histiocytic lymphoma following B-acute lymphoblastic leukaemia: case report with evidence for a common clonal origin in both neoplasms.

    Science.gov (United States)

    Bouabdallah, R; Abéna, P; Chetaille, B; Aurran-Schleinitz, T; Sainty, D; Dubus, P; Arnoulet, C; Coso, D; Xerri, L; Gastaut, J A

    2001-06-01

    True histiocytic lymphoma (THL) is a very rare type of non-Hodgkin's lymphoma (NHL) in which neoplastic cells exhibit markers of histiocytic differentiation. Some cases of THL have been reported in patients with previous acute lymphoblastic leukaemia (ALL), especially in children and young adults, in whom the acute leukaemia was of T-cell origin. The relationship between the initial lymphoid tumour and the secondary THL remains unclear, as a common monoclonal origin shared by both neoplasms has never been definitively demonstrated. We report a patient with B-ALL who developed a nodal and extranodal tumour with histological and immunohistochemical features of THL 4 years after the initial diagnosis. Genotypic study showed that both neoplasms contained the same immunoglobulin heavy gene rearrangement, which has not been reported previously.

  14. Live cell detection of chromosome 2 deletion and Sfpi1/PU1 loss in radiation-induced mouse acute myeloid leukaemia.

    Science.gov (United States)

    Olme, C-H; Finnon, R; Brown, N; Kabacik, S; Bouffler, S D; Badie, C

    2013-10-01

    The CBA/H mouse model of radiation-induced acute myeloid leukaemia (rAML) has been studied for decades to bring to light the molecular mechanisms associated with multistage carcinogenesis. A specific interstitial deletion of chromosome 2 found in a high proportion of rAML is recognised as the initiating event. The deletion leads to the loss of Sfpi, a gene essential for haematopoietic development. Its product, the transcription factor PU.1 acts as a tumour suppressor in this model. Although the deletion can be detected early following ionising radiation exposure by cytogenetic techniques, precise characterisation of the haematopoietic cells carrying the deletion and the study of their fate in vivo cannot be achieved. Here, using a genetically engineered C57BL/6 mouse model expressing the GFP fluorescent molecule under the control of the Sfpi1 promoter, which we have bred onto the rAML-susceptible CBA/H strain, we demonstrate that GFP expression did not interfere with X-ray induced leukaemia incidence and that GFP fluorescence in live leukaemic cells is a surrogate marker of radiation-induced chromosome 2 deletions with or without point mutations on the remaining allele of the Sfpi1 gene. This study presents the first experimental evidence for the detection of this leukaemia initiating event in live leukemic cells.

  15. 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.

  16. Birth weight in offspring and leukaemia risk in parents-A nation-wide register-based cohort study from Denmark

    DEFF Research Database (Denmark)

    Marklund, Maria; Rostgaard, Klaus; Hjalgrim, Lisa

    2013-01-01

    with parental risk of leukaemia overall or of leukaemia subtypes except for a twofold increased acute lymphatic leukaemia risk in fathers of high birth weight offspring and an increasing paternal risk of chronic myeloid leukaemia with increasing offspring birth weight. These may both be chance findings. Our...

  17. Arnold Rüütel: meie küla käis käest kätte / Arnold Rüütel ; intervjueerinud Enno Tammer

    Index Scriptorium Estoniae

    Rüütel, Arnold, 1928-

    2005-01-01

    President Arnold Rüütel Teise maailmasõjaga seotud mälestustest, Molotov-Ribbentropi paktist, Moskvas võidupüha tähistamisel mitteosalemise põhjustest ja 2006. a. presidendivalimistel osalemisest

  18. THE NEIGHBORHOOD OF FLORENTIN: A WINDOW TO THE GLOBALIZATION OF TEL AVIV

    Directory of Open Access Journals (Sweden)

    Caroline ROZENHOLC

    2010-12-01

    Full Text Available Aside from open conflicts within Israel-Palestine, the neighborhood of Florentin is a key-space where to observe and decipher how globalization impacts on the daily-life scale and banal forms of identification and territorial appropriation. Situated south of the Tel Aviv Jaffa agglomeration, and standing in between the two historical entities, the neighborhood of Florentin also offers a fertile analytic ground for a better understanding and different narrative of Tel Aviv itself as well as the contemporary Israeli society in some of its complexity and diversity. Here, graffiti and other traces left in the streets and on the walls of Florentin by successive waves of population constitute the thread to follow for deep-reading the place.

  19. President Arnold Rüütel tahab anda noortele peredele maad / Mati Määrits

    Index Scriptorium Estoniae

    Määrits, Mati, 1958-

    2005-01-01

    Põlvamaa omavalitsusjuhid avaldasid toetust president Arnold Rüütli ettepanekule anda maad eelkõige noortele peredele. Presidendi juuresolekul ei leitud aga üksmeelt haridusinvesteeringute jaotamises laste arvust lähtudes. President Arnold Rüütel vastab küsimusele, kas kaks päeva Põlvamaal suutsid teda millegagi üllatada. Maakonnavisiit Põlvamaale 08.-09.06.2005

  20. President Arnold Rüütel tahab anda noortele peredele maad / Mati Määrits

    Index Scriptorium Estoniae

    Määrits, Mati, 1958-

    2005-01-01

    Põlvamaa omavalitsusjuhid avaldasid toetust president Arnold Rüütli ettepanekule anda maad eelkõige noortele peredele. Presidendi juuresolekul ei leitud aga üksmeelt haridusinvesteeringute jaotamises laste arvust lähtudes. President Arnold Rüütel vastab küsimusele, kas kaks päeva Põlvamaal suutsid teda millegagi üllatada. Maakonnavisiit Põlvamaale 08.-09.06.2005

  1. Resolved debris disk emission around eta Tel: a young Solar System or ongoing planet formation?

    CERN Document Server

    Smith, R; Wyatt, M C; Moerchen, M M; Telesco, C M

    2008-01-01

    60% of the A star members of the 12 Myr old beta Pictoris moving group (BPMG) show significant excess emission in the mid-infrared, several million years after the proto-planetary disk is thought to disperse. Theoretical models suggest this peak may coincide with the formation of Pluto-sized planetesimals in the disk, stirring smaller bodies into collisional destruction. Here we present resolved mid-infrared imaging of the disk of eta Tel (A0V in the BPMG) and consider its implications for the state of planet formation in this system. eta Tel was observed at 11.7 and 18.3um using T-ReCS on Gemini South. The resulting images were compared to simple disk models to constrain the radial distribution of the emitting material. The emission observed at 18.3um is shown to be significantly extended beyond the PSF along a position angle 8 degrees. This is the first time dust emission has been resolved around eta Tel. Modelling indicates that the extension arises from an edge-on disk of radius 0.5 arcsec (~24 AU). Combi...

  2. Recifest Tel Avivi : moodne arhitektuur ja kliimaga kohandumine / Guilah Naslavsky, Izabel Amaral ; tõlk. Tiina Randus

    Index Scriptorium Estoniae

    Naslavsky, Guilah

    2006-01-01

    Näidatakse kahe erineva kultuuri modernismiadaptsioonide sarnasusi Tel Avivis ja Recifes. Artikkel on valminud 2006. a. toimunud XI rahvusvahelisel DOCOMOMO konverentsil "Other" Modernisms peetud ettekande põhjal

  3. Recifest Tel Avivi : moodne arhitektuur ja kliimaga kohandumine / Guilah Naslavsky, Izabel Amaral ; tõlk. Tiina Randus

    Index Scriptorium Estoniae

    Naslavsky, Guilah

    2006-01-01

    Näidatakse kahe erineva kultuuri modernismiadaptsioonide sarnasusi Tel Avivis ja Recifes. Artikkel on valminud 2006. a. toimunud XI rahvusvahelisel DOCOMOMO konverentsil "Other" Modernisms peetud ettekande põhjal

  4. Rüütel handed over the Order of the Gross of Terra Mariana to George H. W. Bush

    Index Scriptorium Estoniae

    2005-01-01

    President Arnold Rüütel andis New Yorgis USA endisele presidendile Georg Herbert Walker Bushile Eesti iseseisvuspüüdluste toetamise eest Maarjamaa Risti I klassi ordeni. Töövisiit New Yorki 13.-17.09.2005

  5. Rüütel handed over the Order of the Gross of Terra Mariana to George H. W. Bush

    Index Scriptorium Estoniae

    2005-01-01

    President Arnold Rüütel andis New Yorgis USA endisele presidendile Georg Herbert Walker Bushile Eesti iseseisvuspüüdluste toetamise eest Maarjamaa Risti I klassi ordeni. Töövisiit New Yorki 13.-17.09.2005

  6. [Characteristic of the yeast isolated from patients with leukaemia].

    Science.gov (United States)

    Fedorovskaia, E A; Rybal'skaia, A P; Skachkova, N K; Mel'nik, E A; Nemirovskaia, L N; Nagornaia, S S; Babich, T V; Polishchuk, L V

    2008-01-01

    It has been shown that biotopes of upper respiratory system and intestine were contaminated with yeast in 44.6% of patients with leukaemia (of 112 examined ones). Their quantity exceeds the boundary value for practically healthy people and is > or = 10(2) KOE/ml in the nasal activity and fauces and leucemia the mycotic complications are mainly caused by anamorphous yeast of ascomycetic affinity. Candida albicans, as well as C. glabrata, C. rugosa and Candida sp. play the leading role. The Candida genus species are mainly sensitive to amphotericine B, clotrisamol and nistatin.

  7. The Effects of Herbs and Fruits on Leukaemia

    Directory of Open Access Journals (Sweden)

    Tayebeh Azam Saedi

    2014-01-01

    Full Text Available In developing countries, herbal therapy is the first and basis form of treatment for most types of diseases. About 75–80% of the world’s population prefers herbal therapy as a major treatment due to its better adequacy and satisfactoriness, which enhance human body’s symmetry with minimal side effects. Fruits and plants have been presented from the past as promising tools in becoming a natural anticancer agents. Many of these plant extracts are currently used in cancer therapy and prevention. This review paper will particularly explore and emphasize on herbs and fruits used in the treatment of the leukaemia.

  8. [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...

  9. The MRX Complex Ensures NHEJ Fidelity through Multiple Pathways Including Xrs2-FHA-Dependent Tel1 Activation.

    Directory of Open Access Journals (Sweden)

    Daichi Iwasaki

    2016-03-01

    Full Text Available Because DNA double-strand breaks (DSBs are one of the most cytotoxic DNA lesions and often cause genomic instability, precise repair of DSBs is vital for the maintenance of genomic stability. Xrs2/Nbs1 is a multi-functional regulatory subunit of the Mre11-Rad50-Xrs2/Nbs1 (MRX/N complex, and its function is critical for the primary step of DSB repair, whether by homologous recombination (HR or non-homologous end joining. In human NBS1, mutations result truncation of the N-terminus region, which contains a forkhead-associated (FHA domain, cause Nijmegen breakage syndrome. Here we show that the Xrs2 FHA domain of budding yeast is required both to suppress the imprecise repair of DSBs and to promote the robust activation of Tel1 in the DNA damage response pathway. The role of the Xrs2 FHA domain in Tel1 activation was independent of the Tel1-binding activity of the Xrs2 C terminus, which mediates Tel1 recruitment to DSB ends. Both the Xrs2 FHA domain and Tel1 were required for the timely removal of the Ku complex from DSB ends, which correlates with a reduced frequency of imprecise end-joining. Thus, the Xrs2 FHA domain and Tel1 kinase work in a coordinated manner to maintain DSB repair fidelity.

  10. Traffic-related air pollution and risk for leukaemia of an adult population.

    Science.gov (United States)

    Raaschou-Nielsen, Ole; Ketzel, Matthias; Harbo Poulsen, Aslak; Sørensen, Mette

    2016-03-01

    Air pollution causes lung cancer, but associations with other cancers have not been established. We investigated whether long-term exposure to traffic-related air pollution is associated with the risk of the general population for leukaemia. We identified 1,967 people in whom leukaemia was diagnosed in 1992-2010 from a nation-wide cancer registry and selected 3,381 control people at random, matched on sex and year of birth, from the entire Danish population. Residential addresses since 1971 were traced in a population registry, and outdoor concentrations of NOx and NO2 , as indicators of traffic-related air pollution, were calculated at each address in a dispersion model. We used conditional logistic regression to estimate the risk for leukaemia after adjustment for income, educational level, cohabitation status and co-morbidity. In linear analyses, we found odds ratios for acute myeloid leukaemia of 1.20 (95% confidence interval: 1.04-1.38) per 20 µg/m(3) increase in NOx and 1.31 (1.02-1.68) per 10 µg/m(3) increase in NO2 , calculated as time-weighted average exposure at all addresses since 1971. We found no association with chronic myeloid or lymphocytic leukaemia. This study indicates an association between long-term exposure to traffic-related air pollution and acute myeloid leukaemia in the general population, but not for other subtypes of leukaemia.

  11. President Rüütel : raha eest saab osta poliitikat ja valimiskampaaniat / Arnold Rüütel ; intervjueerinud Margus Mets, Toomas Sildam

    Index Scriptorium Estoniae

    Rüütel, Arnold, 1928-

    2002-01-01

    Ilmunud ka: Põhjarannik (2002) 21. dets., lk. 2-3: "Meie ühiskonna huvid pole enam ühtsed" ; Järva Teataja (2002) 21. dets., lk. 4 ; Valgamaalane (2002) 21. dets., lk. 2 ; Sakala (2002) 21. dets., lk. 6-7 ; Virumaa Teataja (2002) 21. dets., lk. 6-7 ; Pärnu Postimees (2002) 21.dets., lk. 8-9 ; Severnoje Poberezhje (2002) 21. dets., lk. 2-3: "Interessõ nashego obshtshestva boleje ne jedinõ" ; Estonija (2002) 21. dets., lk. 2 ; Narvskaja Gazeta (2002) 24. dets., lk. 1: "Prezident Estonii otvetil na voprossõ tshitatelei gazet", lüh. President Arnold Rüütel vastab aastalõpuintervjuus lugejate küsimustele, mis puudutavad riigi maamajandust, välispoliitikat ning sisepoliitilisi probleeme: isikukultuslikke ilminguid poliitikute seas, Riigikogu suurust, riigikeele seisundit, Petserimaad, NSVL-lt repressioonihüvitiste väljanõudmist

  12. President Rüütel : raha eest saab osta poliitikat ja valimiskampaaniat / Arnold Rüütel ; intervjueerinud Margus Mets, Toomas Sildam

    Index Scriptorium Estoniae

    Rüütel, Arnold, 1928-

    2002-01-01

    Ilmunud ka: Põhjarannik (2002) 21. dets., lk. 2-3: "Meie ühiskonna huvid pole enam ühtsed" ; Järva Teataja (2002) 21. dets., lk. 4 ; Valgamaalane (2002) 21. dets., lk. 2 ; Sakala (2002) 21. dets., lk. 6-7 ; Virumaa Teataja (2002) 21. dets., lk. 6-7 ; Pärnu Postimees (2002) 21.dets., lk. 8-9 ; Severnoje Poberezhje (2002) 21. dets., lk. 2-3: "Interessõ nashego obshtshestva boleje ne jedinõ" ; Estonija (2002) 21. dets., lk. 2 ; Narvskaja Gazeta (2002) 24. dets., lk. 1: "Prezident Estonii otvetil na voprossõ tshitatelei gazet", lüh. President Arnold Rüütel vastab aastalõpuintervjuus lugejate küsimustele, mis puudutavad riigi maamajandust, välispoliitikat ning sisepoliitilisi probleeme: isikukultuslikke ilminguid poliitikute seas, Riigikogu suurust, riigikeele seisundit, Petserimaad, NSVL-lt repressioonihüvitiste väljanõudmist

  13. Childhood leukaemia and lymphoma: African experience supports a role for environmental factors in leukaemogenesis

    OpenAIRE

    Williams, Christopher KO; Foroni, Letizia; Luzzatto,Lucio; Saliu, Idris; Levine, Arthur; Greaves, Mel F.

    2014-01-01

    Major differences exist in the nature of leukaemia and lymphoma in low-income African children compared to those in the high-income countries. These include the absence of the peak incidence of acute lymphoblastic leukaemia (ALL) in under-five-year olds that characterizes the disease in high-income countries. Conversely, chloroma association with acute myelogenous leukaemia (CA-AML/AMML) and Burkitt’s lymphoma (BL) are rare in the high-income countries. This report describes clinical and labo...

  14. MicroRNAs as Potential Biomarkers in Acute Promyelocytic Leukaemia

    Directory of Open Access Journals (Sweden)

    Imilia Ismail

    2014-01-01

    Full Text Available Acute promyelocytic leukaemia (APL is an M3 subtype of acute myeloid leukaemia (AML. This classification is based on the morphology of promyelocytic cell. The clinical characteristics of APL can be recognized by haemorrhagic episodes, a differentiation block at the promyelocytic stage, and sensitivity to the differentiation response to all-trans-retinoic acid (ATRA. Cytogenetically, APL is characterized by a balanced reciprocal translocation between chromosomes 15 and 17, which results in the production of PML/RARα fusion protein. Recent studies reported that microRNAs (miRNAs have also been proposed to contribute to the pathogenesis of APL. miRNAs have been associated with the pathogenesis of cancer and their involvement as oncogenic and tumour suppressor activities have been identified. They are involved in various biological processes including the cell proliferation, differentiation, growth and development, metabolism, apoptosis, and haematopoiesis. The new discovery of miRNAs as possible therapeutic markers will provide new insight for the diagnosis and therapeutic entries for the treatment of APL. This review highlights the potential of miRNAs as biomarkers in APL.

  15. Impact of NOD2 polymorphisms on infectious complications following chemotherapy in patients with acute myeloid leukaemia.

    Science.gov (United States)

    Yomade, Olaposi; Spies-Weisshart, Bärbel; Glaser, Anita; Schnetzke, Ulf; Hochhaus, Andreas; Scholl, Sebastian

    2013-08-01

    We sought to investigate the relationship between polymorphisms of the NOD2 gene and infectious complications following intensive induction chemotherapy in patients with acute myeloid leukaemia (AML). We hypothesised that single nucleotide polymorphisms (SNPs) of the NOD2 gene are associated with a higher rate of infections during the phase of severe neutropenia. In 131 AML patients receiving induction therapy, the presence of the three most frequent polymorphisms of NOD2 (Arg702Trp, Gly908Arg, Leu1007fsinsC) was analysed. SNP analyses by means of genomic PCR incorporating fluorescence-labelled probes with characteristic melting curves were performed using the LightCycler platform. Our data suggest a significantly lower probability of mucositis or enteritis in AML patients lacking any of the three evaluated NOD2 polymorphisms. Furthermore, bloodstream cultures of AML patients carrying either a missense or a frameshift mutation of NOD2 were significantly more frequently tested positive concerning Streptococcus spp. In contrast, the presence of NOD2 polymorphisms had no impact on such important infectious complications as systemic inflammatory response syndrome or sepsis, the rate of central venous catheter infections or the incidence of pneumonia including fungal infections. Our data represent one of the first reports investigating the impact of polymorphisms of the innate immune system on infectious complications in patients with neutropenia following chemotherapy. A correlation between NOD2 polymorphisms and infectious events in AML patients is demonstrated.

  16. Mitochondrial cytochrome c oxidase subunit II variations predict adverse prognosis in cytogenetically normal acute myeloid leukaemia.

    Science.gov (United States)

    Silkjaer, Trine; Nyvold, Charlotte Guldborg; Juhl-Christensen, Caroline; Hokland, Peter; Nørgaard, Jan Maxwell

    2013-10-01

    Alterations in the two catalytic genes cytochrome c oxidase subunits I and II (COI and COII) have recently been suggested to have an adverse impact on prognosis in patients with acute myeloid leukaemia (AML). In order to explore this in further detail, we sequenced these two mitochondrial genes in diagnostic bone marrow or blood samples in 235 patients with AML. In 37 (16%) patients, a non-synonymous variation in either COI or COII could be demonstrated. No patients harboured both COI and COII non-synonymous variations. Twenty-four (10%) patients had non-synonymous variations in COI, whereas 13 (6%) patients had non-synonymous variations in COII. The COI and COII are essential subunits of cytochrome c oxidase that is the terminal enzyme in the oxidative phosphorylation complexes. In terms of disease course, we observed that in patients with a normal cytogenetic analysis at disease presentation (CN-AML) treated with curative intent, the presence of a non-synonymous variation in the COII was an adverse prognostic marker for both overall survival and disease-free survival (DFS) in both univariate (DFS; hazard ratio (HR) 4.4, P = 0.006) and multivariate analyses (DFS; HR 7.2, P = 0.001). This is the first demonstration of a mitochondrial aberration playing an adverse prognostic role in adult AML, and we argue that its role as a potentially novel adverse prognostic marker in the subset of CN-AML should be explored further.

  17. Constitutional and somatic rearrangement of chromosome 21 in acute lymphoblastic leukaemia.

    Science.gov (United States)

    Li, Yilong; Schwab, Claire; Ryan, Sarra L; Papaemmanuil, Elli; Robinson, Hazel M; Jacobs, Patricia; Moorman, Anthony V; Dyer, Sara; Borrow, Julian; Griffiths, Mike; Heerema, Nyla A; Carroll, Andrew J; Talley, Polly; Bown, Nick; Telford, Nick; Ross, Fiona M; Gaunt, Lorraine; McNally, Richard J Q; Young, Bryan D; Sinclair, Paul; Rand, Vikki; Teixeira, Manuel R; Joseph, Olivia; Robinson, Ben; Maddison, Mark; Dastugue, Nicole; Vandenberghe, Peter; Haferlach, Claudia; Stephens, Philip J; Cheng, Jiqiu; Van Loo, Peter; Stratton, Michael R; Campbell, Peter J; Harrison, Christine J

    2014-04-03

    Changes in gene dosage are a major driver of cancer, known to be caused by a finite, but increasingly well annotated, repertoire of mutational mechanisms. This can potentially generate correlated copy-number alterations across hundreds of linked genes, as exemplified by the 2% of childhood acute lymphoblastic leukaemia (ALL) with recurrent amplification of megabase regions of chromosome 21 (iAMP21). We used genomic, cytogenetic and transcriptional analysis, coupled with novel bioinformatic approaches, to reconstruct the evolution of iAMP21 ALL. Here we show that individuals born with the rare constitutional Robertsonian translocation between chromosomes 15 and 21, rob(15;21)(q10;q10)c, have approximately 2,700-fold increased risk of developing iAMP21 ALL compared to the general population. In such cases, amplification is initiated by a chromothripsis event involving both sister chromatids of the Robertsonian chromosome, a novel mechanism for cancer predisposition. In sporadic iAMP21, breakage-fusion-bridge cycles are typically the initiating event, often followed by chromothripsis. In both sporadic and rob(15;21)c-associated iAMP21, the final stages frequently involve duplications of the entire abnormal chromosome. The end-product is a derivative of chromosome 21 or the rob(15;21)c chromosome with gene dosage optimized for leukaemic potential, showing constrained copy-number levels over multiple linked genes. Thus, dicentric chromosomes may be an important precipitant of chromothripsis, as we show rob(15;21)c to be constitutionally dicentric and breakage-fusion-bridge cycles generate dicentric chromosomes somatically. Furthermore, our data illustrate that several cancer-specific mutational processes, applied sequentially, can coordinate to fashion copy-number profiles over large genomic scales, incrementally refining the fitness benefits of aggregated gene dosage changes.

  18. El Palacio de Correos y Telégrafos de Valencia: Procesos y Sistemas Constructivos

    OpenAIRE

    Gamero Bernal, Víctor

    2016-01-01

    El edificio de Correos y Telégrafos de Valencia se construye en el período 1915-1923 y formó parte de las infraestructuras subvencionadas por el gobierno de Maura para la modernización de los servicios postales en España. El jurado del concurso para el proyecto la Casa de Correos de Valencia falló a favor de la propuesta del arquitecto D. Miguel Ángel Navarro, natural de Zaragoza. El palacio, de estilo ecléctico, ocupa un lugar preferente dentro de la plaza del Ayuntam...

  19. President Arnold Rüütli avaldus / Arnold Rüütel

    Index Scriptorium Estoniae

    Rüütel, Arnold, 1928-

    2006-01-01

    Ilmunud ka: Eesti Päevaleht : Eriväljaanne Lennart Meri 29.III 1929 - 14.III 2006. Eesti Vabariigi president 1992-2001, 14. märts, lk. 2 ; Virumaa Teataja, 15. märts, lk. 11, pealk.: Presidendi avaldus 14. märtsil 2006 ; Videvik, 16. märts, lk. 1. President Arnold Rüütel teatab president Lennart Meri surmast ning avaldab kaastunnet president Lennart Meri perekonnale ja kõigile lähedastele. Samas ka: Ametlik teade

  20. Rüütel jagas esimesed 500 teenetemärki / Toomas Sildam

    Index Scriptorium Estoniae

    Sildam, Toomas, 1961-

    2006-01-01

    President Arnold Rüütel autasustab seoses vabariigi 88. aastapäeva ja iseseisvuse taastamise 15. aastapäevaga 834 inimest, 22. veebruaril andis president teenetemärgi üle enam kui 500 inimesele. President allkirjastas ka otsuse, millega autasustatakse Torino taliolümpial kuldmedali võitnud Kristina Šmiguni, Andrus Veerpalu ning nende treenereid Mati Alaveri ja Anatoli Šmiguni. Arvamust avaldab Eesti Evangeelse Luterliku Kiriku peapiiskop Andres Põder. Lisa: President Rüütli kolm mõtet. Fotol presidendipaar koos Valgetähe V klassi teenetemärgi saanud Reet Linna ja Anne Veskiga

  1. Plataforma para robótica cooperativa soportada por teléfonos inteligentes android

    OpenAIRE

    2015-01-01

    Un teléfono inteligente ofrece muchas funcionalidades útiles dentro de un proyecto de robótica, especialmente robótica móvil. En este contexto, en este trabajo se presenta el diseño y desarrollo de un conjunto de herramientas para desarrollar proyectos de robótica, específicamente robótica cooperativa, que utilicen dispositivos con sistema operativo Android. La primera herramienta es una biblioteca desarrollada para Android que encapsula tareas comunes en robótica cooperativa como requerimien...

  2. President Arnold Rüütli avaldus / Arnold Rüütel

    Index Scriptorium Estoniae

    Rüütel, Arnold, 1928-

    2006-01-01

    Ilmunud ka: Eesti Päevaleht : Eriväljaanne Lennart Meri 29.III 1929 - 14.III 2006. Eesti Vabariigi president 1992-2001, 14. märts, lk. 2 ; Virumaa Teataja, 15. märts, lk. 11, pealk.: Presidendi avaldus 14. märtsil 2006 ; Videvik, 16. märts, lk. 1. President Arnold Rüütel teatab president Lennart Meri surmast ning avaldab kaastunnet president Lennart Meri perekonnale ja kõigile lähedastele. Samas ka: Ametlik teade

  3. Louis I. Kahn, el paisaje telúrico y las maquetas de arcilla

    OpenAIRE

    Jové Sandoval, José María

    2016-01-01

    Kahn siempre mantuvo una especial conexión con el paisaje reconociéndose desde muy temprano en sus dibujos y pinturas, especialmente en sus bocetos de viaje. Él forjó una idea de un paisaje telúrico, formado por el moldeado del suelo en conjunción con la arquitectura; para trabajarlo y transmitirlo encontraría un instrumento muy eficaz: las maquetas de arcilla. Estos peculiares modelos surgieron a partir del año 1961, cuando se produjo la colaboración con el escultor Isamu Noguchi en...

  4. El teléfono inteligente (smartphone) como herramienta pedagógica

    OpenAIRE

    Javier Organista-Sandoval; Lewis McAnally Salas; Gilles Lavigne

    2013-01-01

    Se presenta un estudio sobre cobertura y usos educativos del celular con estudiantes y docentes de dos campi de la Universidad Autónoma de Baja California. Se seleccionó una muestra al azar con 12% de estudiantes y 24% de docentes, a quienes se les aplicó una encuesta para precisar la posesión de celular, sus características técnicas, los usos educativos realizados y las ventajas y desventajas de su uso en cursos universitarios. La posesión de teléfono celular se acerca a 97% tanto para estud...

  5. Perfiles mentalistas en el TEL pragmático. Aplicaciones para la intervención

    OpenAIRE

    2007-01-01

    A partir de las referencias que describen problemas en la pragmática de la lengua y en la comprensión de tareas de teoría de la mente en niños con un subtipo de trastornos Específico del Lenguaje (TEL), existe un grupo de niños diagnosticado como con Trastorno Pragmático del Lenguaje (TPL). Este trabajo intenta describir algunos parámetros de intervención educativa sobre este tipo de trastorno que, al no presentar problemas fonéticos, suele ser poco atendido por especialistas en interve...

  6. Ofatumumab in previously untreated chronic lymphocytic leukaemia. No clear advantages when added to chlorambucil.

    Science.gov (United States)

    2015-11-01

    In a trial including 447 leukaemia patients in whom fludarabine was unsuitable, adding ofatumumabto chlorambucil prolonged time to disease progression or death but did not reduce overall mortality. Adverse effects were more numerous.

  7. Role of mesenchymal stem cells in leukaemia: Dr. Jekyll or Mr. Hyde?

    Science.gov (United States)

    Wong, Rebecca S Y; Cheong, Soon-Keng

    2014-08-01

    Mesenchymal stem cells (MSCs) have captured the attention of researchers today due to their multipotent differentiation capacity. Also, they have been successfully applied clinically, in the treatment of various diseases of the heart and musculoskeletal systems, with encouraging results. Their supportive role in haematopoiesis and their anti-inflammatory and immunomodulatory properties have enhanced their contribution towards the improvement of engraftment and the treatment of graft-versus-host disease in patients receiving haematopoietic stem cell transplantation. However, there is a growing body of research that supports the involvement of MSCs in leukaemogenesis with several genetic and functional abnormalities having been detected in the MSCs of leukaemia patients. MSCs also exert leukaemia-enhancing effects and induce chemotherapy resistance in leukaemia cells. This paper addresses the key issues in the therapeutic value as well as the harmful effects of the MSCs in leukaemia with a sharp focus on the recent updates in the published literature.

  8. Birth weight in offspring and leukaemia risk in parents--a nation-wide register-based cohort study from Denmark.

    Science.gov (United States)

    Marklund, Maria; Rostgaard, Klaus; Hjalgrim, Lisa; Schmiegelow, Kjeld; Hjalgrim, Henrik

    2013-02-01

    Spurred by previous observations we assessed the relationship between offspring birth weight and parental leukaemia risk in a register-based investigation including 2.4 million parents of 2 million Danish children. Regardless of analytical approach, offspring birth weight was not associated with parental risk of leukaemia overall or of leukaemia subtypes except for a twofold increased acute lymphatic leukaemia risk in fathers of high birth weight offspring and an increasing paternal risk of chronic myeloid leukaemia with increasing offspring birth weight. These may both be chance findings. Our investigation indicates that offspring birth weight is not strongly associated with parental leukaemia risk. Copyright © 2012 Elsevier Ltd. All rights reserved.

  9. [Necrotizing tonsillitis and renal vein thrombosis due to acute myeloid leukaemia].

    Science.gov (United States)

    Akram, Javed; Josefsson, Pernilla; Rømeling, Frans

    2012-09-03

    A 37-year-old woman was admitted to hospital with severe tonsillitis with unilateral necrotizing tonsillitis. She suddenly got fever, malaise, difficulties swallowing, pain in the throat and deterioration despite four days of penicillin treatment. During hospitalisation, she experienced abdominal pain, and blood tests showed pancytopenia. She was transferred to a haematological department, where a bone marrow biopsy showed acute myeloid leukaemia. Subsequently, an abdominal computed tomography with intravenous contrast revealed bilateral renal vein thrombosis, probably because of coagulopathy due to leukaemia.

  10. SIRT2 activates G6PD to enhance NADPH production and promote leukaemia cell proliferation

    Science.gov (United States)

    Xu, Shuang-Nian; Wang, Tian-Shi; Li, Xi; Wang, Yi-Ping

    2016-01-01

    Like most other types of cancer cells, leukaemia cells undergo metabolic reprogramming to support rapid proliferation through enhancing biosynthetic processes. Pentose phosphate pathway (PPP) plays a pivotal role in meeting the anabolic demands for cancer cells. However, the molecular mechanism by which PPP contributes to leukaemia remains elusive. Here, we report that leukaemia cell proliferation is dependent on the oxidative branch of PPP, in particular the first and rate-limiting enzyme glucose-6-phosphate dehydrogenase (G6PD). Knockdown of G6PD reduces NADPH level in acute myeloid leukaemia (AML) cell lines. Exogenous lipid supplements partially restore the proliferation of G6PD-depleted cells. Deacetylase SIRT2 promotes NADPH production through deacetylating G6PD at lysine 403 (K403). Activation of G6PD by SIRT2 supports the proliferation and clonogenic activity of leukaemia cells. Chemical inhibitors against SIRT2 suppress G6PD activity, leading to reduced cell proliferation of leukaemia cells, but not normal hematopoietic stem and progenitor cells. Importantly, SIRT2 is overexpressed in clinical AML samples, while K403 acetylation is downregulated and G6PD catalytic activity is increased comparing to that of normal control. Together, our study reveals that acetylation regulation of G6PD is involved in the metabolic reprogramming of AML, and SIRT2 serves as a promising target for further therapeutic investigations. PMID:27586085

  11. Nuclear power plants and childhood leukaemia: lessons from the past and future directions.

    Science.gov (United States)

    Kuehni, C; Spycher, B D

    2014-01-01

    In the 1980s, leukaemia clusters were discovered around nuclear fuel reprocessing plants in Sellafield and Dounreay in the United Kingdom. This raised public concern about the risk of childhood leukaemia near nuclear power plants (NPPs). Since then, the topic has been well-studied, but methodological limitations make results difficult to interpret. Our review aims to: (1.) summarise current evidence on the relationship between NPPs and risk of childhood leukaemia, with a focus on the Swiss CANUPIS (Childhood cancer and nuclear power plants in Switzerland) study; (2.) discuss the limitations of previous research; and (3.) suggest directions for future research. There are various reasons that previous studies produced inconclusive results. These include: inadequate study designs and limited statistical power due to the low prevalence of exposure (living near a NPP) and outcome (leukaemia); lack of accurate exposure estimates; limited knowledge of the aetiology of childhood leukaemia, particularly of vulnerable time windows and latent periods; use of residential location at time of diagnosis only and lack of data on address histories; and inability to adjust for potential confounders. We conclude that risk of childhood leukaemia around NPPs should continue to be monitored and that study designs should be improved and standardised. Data should be pooled internationally to increase the statistical power. More research needs to be done on other putative risk factors for childhood cancer such as low-dose ionizing radiation, exposure to certain chemicals and exposure to infections. Studies should be designed to allow examining multiple exposures.

  12. Leukaemia inhibitory factor--an exercise-induced myokine

    DEFF Research Database (Denmark)

    Broholm, Christa; Pedersen, Bente Klarlund

    2010-01-01

    During and following exercise skeletal muscle synthesises and releases a number of myokines that exert their effects either systemically or locally within the muscle. Several of these myokines influence metabolism, regeneration and/or hypertrophy and are therefore considered to be important...... to oscillations in intracellular Ca2+ concentrations. However, circulating levels of LIF are not increased with exercise suggesting that LIF exerts its effect locally. LIF stimulates muscle satellite cell proliferation and is involved in muscle hypertrophy and regeneration. Thus, LIF may be produced by skeletal...... contributing factors in muscle homeostasis and muscle adaptation to exercise training. Leukaemia inhibitory factor (LIF) is produced and released from muscle cells in vitro and from intact skeletal muscle in vivo. During exercise, skeletal muscle potently up-regulates LIF mRNA expression, likely due...

  13. Thermoelectric-Driven Liquid-Metal Plasma-Facing Structures (TELS) Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Ruzic, David [Univ. of Illinois, Urbana-Champaign, IL (United States)

    2016-12-17

    The Thermoelectric-Driven Liquid-Metal Plasma-Facing Structures (TELS) project was able to establish the experimental conditions necessary for flowing liquid metal surfaces in order to be utilized as surfaces facing fusion relevant energetic plasma flux. The work has also addressed additional developments along with progressing along the timeline detailed in the proposal. A no-cost extension was requested to conduct other relevant experiment- specifically regarding the characterization droplet ejection during energetic plasma flux impact. A specially designed trench module, which could accommodate trenches with different aspect ratios was fabricated and installed in the TELS setup and plasma gun experiments were performed. Droplet ejection was characterized using high speed image acquisition and also surface mounted probes were used to characterize the plasma. The Gantt chart below had been provided with the original proposal, indicating the tasks to be performed in the third year of funding. These tasks are listed above in the progress report outline, and their progress status is detailed below.

  14. Les Hôtels de patrimoine de Bucarest: entre conservation, transformation et démolation

    Directory of Open Access Journals (Sweden)

    ANDREEA-LORETA CERCLEUX

    2014-10-01

    Full Text Available Le patrimoine construit représente une ressource qu i joue un rôle important dans la régénération et la promotion des villes. L’article analyse les immeubles des hôtels de patrimoine de Bucarest, anciens et encore en fonction, prenant en considération leur état de préservation et leur trajet comme destination économique. L’étude d es trois catégories des hôtels identifiés (préservés, transformés et démolis facilite la com préhension de l’histoire hôtelière au niveau de la capitale pendant les dernières deux siècles et d e l’approche concernant les projets urbains mis en œuvre pour différents enjeux économiques, n’oubli ant pas le coté culturel.

  15. The Cosmic Ray Hodoscopes for Testing Thin Gap Chambers at the Technion and Tel Aviv University

    CERN Document Server

    Etzion, E; Amram, N; Benhammou, Ya; Ben-Moshe, M; Bella, G; Ginzburg, J; Gernitzky, Y; Harel, A; Landsman, Hagar Yaël; Panikashvili, N; Rozen, Y; Tarem, S; Warszawski, E; Wasilewski, J; Levinson, L

    2004-01-01

    Thin gap chambers (TGCs) are built for the muon trigger chambers in the endcap region of the LHC experiment ATLAS. More than 2500 ATLAS TGCs are being produced at the Weizmann institute in Israel, and in Shandong University in China. Detailed testing of these chambers is performed at the Technion and at the Tel-Aviv University. Two cosmic ray hodoscopes for testing the operation of these detectors were built in Israel. In these hodoscopes the response of the chambers to energetic cosmic ray muons is recorded and analyzed. The hodoscopes measure the exact time and space location of the cosmic ray hit and read out the chambers which are being tested to verify that they produce a corresponding signal within the required time interval. The cosmic ray hodoscopes built at the Technion and at the Tel Aviv University for the test of ATLAS TGCs are described. The mechanical structure, readout electronics, data acquisition and operating scheme are presented. Typical TGC test results are presented and discussed.

  16. Impact of the Functional CD5 Polymorphism A471V on the Response of Chronic Lymphocytic Leukaemia to Conventional Chemotherapy Regimens

    Science.gov (United States)

    Delgado, Julio; Bielig, Torsten; Bonet, Lizette; Carnero-Montoro, Elena; Puente, Xose S.; Colomer, Dolors; Bosch, Elena; Campo, Elias; Lozano, Francisco

    2016-01-01

    Summary The CD5 lymphocyte receptor -a bona fide immunohistochemical marker of chronic lymphocytic leukaemia (CLL) cells- is a negative regulator of activation signals from the antigen-specific B-cell receptor (BCR). Given that signalling components of the BCR are important contributors to the variable clinical behaviour of CLL, the relevance of functional variants of CD5 on CLL prognosis was explored. The results show that germline-encoded CD5 variants influence the survival to conventional chemotherapies from CLL patients with unmutated IGVH genes. This result supports the notion that CD5 is not only a phenotypic marker but a relevant player in CLL cell biology. PMID:26991857

  17. Rapid detection of t(15;17)(q24;q21) in acute promyelocytic leukaemia by microwave-assisted fluorescence in situ hybridization.

    Science.gov (United States)

    Soriani, Silvia; Mura, Cinzia; Panico, Anna Rita; Scarpa, Anna Maria; Recchimuzzo, Patrizia; Dadati, Raffaella; Farioli, Renata; De Canal, Gabriella; Mura, Maria Angela; Cesana, Clara

    2017-03-01

    Acute promyelocytic leukaemia (APL) is a hematologic malignancy characterized by the rearrangement of the PML and RARα genes, mostly due to a reciprocal chromosomal translocation t(15;17)(q24;q21). A quick APL diagnosis is essential for starting a prompt suitable therapy. We describe a new rapid diagnostic laboratory approach to detect the PML-RARα rearrangement, which gives clear genetic results within 30 min of hybridization. It combines quick cell harvesting, fluorescence in situ hybridization performed with commercial DNA probe and microwave beams supplied by a domestic microwave oven. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

  18. Modelling the mechanism of GR/c-Jun/Erg crosstalk in apoptosis of acute lymphoblastic leukaemia

    Directory of Open Access Journals (Sweden)

    Daphne eChen

    2012-11-01

    Full Text Available Acute lymphoblastic leukaemia (ALL is one of the most common forms of malignancy that occurs in lymphoid progenitor cells, particularly in children. Synthetic steroid hormones glucocorticoids (GCs are widely used as part of the ALL treatment regimens due to their apoptotic function, but their use also brings about various side effects and drug resistance. The identification of the molecular differences between the GCs responsive and resistant cells therefore are essential to decipher such complexity and can be used to improve therapy. However, the emerging picture is complicated as the activities of genes and proteins involved are controlled by multiple factors. By adapting the systems biology framework to address this issue, we here integrated the available knowledge together with experimental data via the building of a series of mathematical models. This rationale enabled us to unravel molecular interactions involving c-Jun in GC induced apoptosis and identify Erg as determinant for GC resistance. The results revealed an alternative potential mechanism where c-Jun may be an indirect GR target that is controlled via an upstream repressor protein. The models also highlight the importance of Erg for GR function, particularly in GC sensitive C7 cells where Erg directly regulates GR in agreement with our previous experimental results. Our models describe potential GR-controlled molecular mechanisms of c-Jun/Bim and Erg regulation. We also demonstrate the importance of using a systematic approach to translate human disease processes into computational models in order to derive information-driven new hypotheses.

  19. New Quantitative Method to Identify NPM1 Mutations in Acute Myeloid Leukaemia

    Directory of Open Access Journals (Sweden)

    Sarah Huet

    2013-01-01

    Full Text Available Somatic mutations in the NPM1 gene, which encodes for nucleophosmin, have been reported to be the most frequent genetic abnormalities found in acute myeloid leukaemia (AML. Their identification and quantification remain crucial for the patients’ residual disease monitoring. We investigated a new method that could represent a novel reliable alternative to sequencing for its identification. This method was based on high-resolution melting analysis in order to detect mutated patients and on an allele-specific oligonucleotide real-time quantitative polymerase chain reaction (ASO-RQ-PCR for the identification and quantification of the transcripts carrying NPM1 mutations (NPM1m. Few patients carrying known NPM1m enabled us to set up a table with the different primers’ ΔCT values, identifying a profile for each mutation type. We then analysed a series of 337 AML patients' samples for NPM1 mutational status characterization and confirmed the ASO-RQ-PCR results by direct sequencing. We identified some mutations in 86 samples, and the results were fully correlated in 100% of the 36 sequenced samples. We also detected other rare NPM1m in two samples, that we confirmed by direct sequencing. This highly specific method provides a novel quick, useful, and costless tool, easy to use in routine practice.

  20. Eflúvio telógeno pós quadro de dengue - relatos de casos

    OpenAIRE

    2015-01-01

    Introdução: Eflúvio telógeno (ET) é uma forma de alopecia difusa caracterizada pelo aumento do número de fios na fase telógena, como resultado de uma mudança anormal no ciclo folicular, podendo ser crônica ou transitória. ET pode ser desencadeado por: febre, cirurgia, drogas, doenças sistêmicas, estresse, entre outros. Não existe explicação definitiva para o fenômeno, mas sabe-se que as alterações aceleram a entrada dos fios da fase anágena para a fase telógena. Geralmente o ET ocorre cerca d...

  1. Utilización de Internet y dependencia a teléfonos móviles en adolescentes

    Directory of Open Access Journals (Sweden)

    Julio Ruiz-Palmero

    2016-01-01

    Full Text Available El objetivo principal del presente trabajo ha sido analizar el uso que los adolescentes realizan de Internet y los teléfonos móviles. Se utilizó un diseño descriptivo, para la muestra se seleccionaron aleatoriamente 10 centros educativos, registrando 874 encuestas. Los adolescentes utilizan masivamente la Red, accediendo a la misma cada vez más a través del teléfono móvil, no aparecen casos llamativos de dependencia en el empleo del teléfono móvil. Otro de los problemas detectados ha sido el del tiempo de conexión a Internet, que aumenta de manera significativa al igual que destacan otros estudios similares. Es fundamental potenciar el papel de familias y centros educativos para dotar a los jóvenes de estrategias que les permitan realizar unos usos adecuados.

  2. The clinical importance of myeloid antigen coexpression and TEL-AML1 mutation in patients with childhood acute lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    Ayşen Türedi Yıldırım

    2013-03-01

    Full Text Available Objective: In this study, we aim to investigate the relationship,if any, between clinical features, prognosis, and thecoexpressions and TEL-AML1 mutation in patients withacute lymphoblastic leukemia (ALL.Methods: Eigthy-three patients with acute lymphoblasticleukemia were retrospectively examined. Age, gender,White blood cell count, hemoglobin level, platelet count,ALL subtypei (B or T ALL, risk groups, surface antigensdeteceted by flow cytometry, existence of TEL-AML1 mutations,response, remission and relapse status at 8., 15.ve 33. Days of treatment were recorded and analyzed.Results: 15 (18% out of 83 were identified with aberrantantigen expression. Of these patients, twelve (14.4%had myeloid antigen coexpression (CD13 and/or CD33,two with B cell ALL had CD2 and CD7 coexpressions respectively,one with T cell ALL had CD19 coexpression.No significant differences were found between patientswith and without myeloid antigen coexpression in terms ofhemoglobin levels, white blood cells and platelet counts,responses given on the 8th, 15th, and 30th days on the treatment,risk groups, and relapse (p>0.05. Myeloid antigencoexpression was found in 4 of 13 patients who were identifiedwith TEL-AML1 mutation. No significant relationshipwas found between this mutation and coexpressions. Norelapse and exitus were observed in four patients with coexpressionand TEL-AML1.Conclusion: The prognosis and clinical features showsno statistically significant relationship with the presence ofneither Myeloid antigen expression nor TEL-AML1 mutation.We believe, however, the future studies involving biggersample sizes will prove to be useful in terms of moreconvincing results. J Clin Exp Invest 2013; 4(1: 90-94Key words: Acute lenfoblastic leukemia, coexpression,TEL-AML1 mutation, prognosis

  3. Rüütel jääb meelde peamiselt välise muljega / Jaanus Piirsalu

    Index Scriptorium Estoniae

    Piirsalu, Jaanus, 1973-

    2006-01-01

    Eesti Päevalehe tellitud ja uuringufirma Faktum-Ariko läbiviidud küsitlusest teemal, mis märksõnad meenutavad inimestele Rüütli ametiaega presidendina. Graafik: Presidendi institutsiooni usaldus. Kaart: Reisumehed Meri ja Rüütel. Vt. samas: Merist eristab Rüütlit venelaste poolehoid. Lisad: President Arnold Rüütli patronaazhi all on olnud ja on järgmised ettevõtmised; Kurjategijad, kellele Arnold Rüütel armu andis

  4. Temporal trends in childhood leukaemia incidence following exposure to radioactive fallout from atmospheric nuclear weapons testing.

    Science.gov (United States)

    Wakeford, Richard; Darby, Sarah C; Murphy, Michael F G

    2010-05-01

    Notably raised rates of childhood leukaemia incidence have been found near some nuclear installations, in particular Sellafield and Dounreay in the United Kingdom, but risk assessments have concluded that the radiation doses estimated to have been received by children or in utero as a result of operations at these installations are much too small to account for the reported increases in incidence. This has led to speculation that the risk of childhood leukaemia arising from internal exposure to radiation following the intake of radioactive material released from nuclear facilities has been substantially underestimated. The radionuclides discharged from many nuclear installations are similar to those released into the global environment by atmospheric nuclear weapons testing, which was at its height in the late-1950s and early-1960s. Measurements of anthropogenic radionuclides in members of the general public resident in the vicinity of Sellafield and Dounreay have found levels that do not differ greatly from those in persons living remote from nuclear installations that are due to ubiquitous exposure to the radioactive debris of nuclear weapons testing. Therefore, if the leukaemia risk to children resulting from deposition within the body of radioactive material discharged from nuclear facilities has been grossly underestimated, then a pronounced excess of childhood leukaemia would have been expected as a consequence of the short period of intense atmospheric weapons testing. We have examined childhood leukaemia incidence in 11 large-scale cancer registries in three continents for which data were available at least as early as 1962. We found no evidence of a wave of excess cases corresponding to the peak of radioactive fallout from atmospheric weapons testing. The absence of a discernible increase in the incidence of childhood leukaemia following the period of maximum exposure to the radioactive debris of this testing weighs heavily against the suggestion that

  5. Occupation and risk of lymphoid and myeloid leukaemia in the European Prospective Investigation into Cancer and Nutrition (EPIC).

    Science.gov (United States)

    Saberi Hosnijeh, Fatemeh; Christopher, Yvette; Peeters, Petra; Romieu, Isabelle; Xun, Wei; Riboli, Elio; Raaschou-Nielsen, Ole; Tjønneland, Anne; Becker, Nikolaus; Nieters, Alexandra; Trichopoulou, Antonia; Bamia, Christina; Orfanos, Philip; Oddone, Enrico; Luján-Barroso, Leila; Dorronsoro, Miren; Navarro, Carmen; Barricarte, Aurelio; Molina-Montes, Esther; Wareham, Nick; Vineis, Paolo; Vermeulen, Roel

    2013-07-01

    Established risk factors for leukaemia do not explain the majority of leukaemia cases. Previous studies have suggested the importance of occupation and related exposures in leukaemogenesis. We evaluated possible associations between job title and selected hazardous agents and leukaemia in the European Prospective Investigation into Cancer and Nutrition. The mean follow-up time for 241 465 subjects was 11.20 years (SD 2.42 years). During the follow-up period, 477 incident cases of myeloid and lymphoid leukaemia occurred. Data on 52 occupations considered a priori to be at high risk of developing cancer were collected through standardised questionnaires. Occupational exposures were estimated by linking the reported occupations to a job exposure matrix. Cox proportional hazard models were used to explore the association between occupation and related exposures and risk of leukaemia. The risk of lymphoid leukaemia significantly increased for working in chemical laboratories (HR 8.35, 95% CI 1.58 to 44.24), while the risk of myeloid leukaemia increased for working in the shoe or other leather goods industry (HR 2.54, 95% CI 1.28 to 5.06). Exposure-specific analyses showed a non-significant increased risk of myeloid leukaemias for exposure to benzene (HR 1.15, 95% CI 0.75 to 1.40; HR=1.60, 95% CI 0.95 to 2.69 for the low and high exposure categories, respectively). This association was present both for acute and chronic myeloid leukaemia at high exposure levels. However, numbers were too small to reach statistical significance. Our findings suggest a possible role of occupational exposures in the development of both lymphoid and myeloid leukaemia. Exposure to benzene seemed to be associated with both acute and chronic myeloid leukaemia.

  6. Arnold Rüütel : kui lapsi ei sünni, kes siis Eesti ühiskonnas väärtusi loob? / Arnold Rüütel ; intervjueerinud Kärt Karpa

    Index Scriptorium Estoniae

    Rüütel, Arnold, 1928-

    2007-01-01

    President Arnold Rüütel vastab küsimustele, mis puudutavad tema praegust tegevust, Eestis taasiseseisvumise järel tehtud vigu, maapiirkondade kõrvalejäämist, Eesti poliitika ideoloogia muutumist taasiseseisvumisest alates, suhtumist ülemnõukogu saadikuisse, pronksööd, Rahvaliitu, suhtumist Rahvaliidu ja SDE võimalikku ühinemisse

  7. Arnold Rüütel : kui lapsi ei sünni, kes siis Eesti ühiskonnas väärtusi loob? / Arnold Rüütel ; intervjueerinud Kärt Karpa

    Index Scriptorium Estoniae

    Rüütel, Arnold, 1928-

    2007-01-01

    President Arnold Rüütel vastab küsimustele, mis puudutavad tema praegust tegevust, Eestis taasiseseisvumise järel tehtud vigu, maapiirkondade kõrvalejäämist, Eesti poliitika ideoloogia muutumist taasiseseisvumisest alates, suhtumist ülemnõukogu saadikuisse, pronksööd, Rahvaliitu, suhtumist Rahvaliidu ja SDE võimalikku ühinemisse

  8. Two separate pathways regulate protein stability of ATM/ATR-related protein kinases Mec1 and Tel1 in budding yeast.

    Science.gov (United States)

    Goto, Greicy H; Ogi, Hiroo; Biswas, Himadri; Ghosh, Avik; Tanaka, Seiji; Sugimoto, Katsunori

    2017-08-01

    Checkpoint signaling requires two conserved phosphatidylinositol 3-kinase-related protein kinases (PIKKs): ATM and ATR. In budding yeast, Tel1 and Mec1 correspond to ATM and ATR, respectively. The Tel2-Tti1-Tti2 (TTT) complex connects to the Rvb1-Rvb2-Tah1-Pih1 (R2TP) complex for the protein stability of PIKKs; however, TTT-R2TP interaction only partially mediates ATM and ATR protein stabilization. How TTT controls protein stability of ATM and ATR remains to be precisely determined. Here we show that Asa1, like Tel2, plays a major role in stabilization of newly synthesized Mec1 and Tel1 proteins whereas Pih1 contributes to Mec1 and Tel1 stability at high temperatures. Although Asa1 and Pih1 both interact with Tel2, no Asa1-Pih1 interaction is detected. Pih1 is distributed in both the cytoplasm and nucleus wheres Asa1 localizes largely in the cytoplasm. Asa1 and Pih1 are required for proper DNA damage checkpoint signaling. Our findings provide a model in which two different Tel2 pathways promote protein stabilization of Mec1 and Tel1 in budding yeast.

  9. Platelet doubling after the first azacitidine cycle is a promising predictor for response in myelodysplastic syndromes (MDS), chronic myelomonocytic leukaemia (CMML) and acute myeloid leukaemia (AML) patients in the Dutch azacitidine compassionate named patient programme

    NARCIS (Netherlands)

    van der Helm, Lieke H.; Alhan, Canan; Wijermans, Pierre W.; Kooy, Marinus van Marwijk; Schaafsma, Ron; Biemond, Bart J.; Beeker, Aart; Hoogendoorn, Mels; van Rees, Bastiaan P.; de Weerdt, Okke; Wegman, Jurgen; Libourel, Ward J.; Luykx-de Bakker, Sylvia A.; Minnema, Monique C.; Brouwer, Rolf E.; Boer, Fransien Croon-de; Eefting, Matthijs; Jie, Kon-Siong G.; de Loosdrecht, Arjan A. van; Koedam, Jan; Veeger, Nic J. G. M.; Vellenga, Edo; Huls, Gerwin

    2011-01-01

    The efficacy of azacitidine in the treatment of high-risk myelodysplastic syndromes (MDS), chronic myelomonocytic leukaemia (CMML) and acute myeloid leukaemia (AML) (20-30% blasts) has been demonstrated. To investigate the efficacy of azacitidine in daily clinical practice and to identify predictors

  10. Implementation of Tel Aviv University MOOCs in Academic Curriculum: A Pilot Study

    Directory of Open Access Journals (Sweden)

    Tal Soffer

    2015-02-01

    Full Text Available The study presented in this paper examines the feasibility of using MOOCs as a learning environment in academic courses. This paper focuses on the students who participated in two MOOCs offered by Tel Aviv University (TAU during the year 2013. The preliminary findings of this pilot study illustrate the scope of student activity, the learning intensity, and learner path. In addition, attitudes of TAU students who participated in these courses as part of their curriculum are presented. From TAU’s perspective, the presented MOOCs are considered to be a successful experience for all those involved: the students, who were very satisfied with their learning and high achievements; the lecturer team, who were very enthusiastic and satisfied with the learning process as well as the new experience; and the University policy makers, who took the challenge and integrated this new model of learning into the academic environment.

  11. Seroepidemiology of Leishmania spp. in dogs residing in Telêmaco Borba, Paraná, Brazil

    Directory of Open Access Journals (Sweden)

    Caroline Constantino

    2014-12-01

    Full Text Available Leishmaniasis is an important metazoonosis caused by protozoa of the genus Leishmania and has a heteroxenic life cycle involving invertebrate and vertebrate hosts. Transmission occurs during the blood meal of infected phlebotomine sand flies in wild species, domestic animals, and humans. The dog is a reservoir for the parasite causing visceral leishmaniasis (VL, whereas in American tegumentary leishmaniasis (ATL, dogs are erratic hosts that are accidentally infected, as in humans. Dogs are considered an important indicator of the parasite and its vectors in the environment, thus highlighting the importance of diagnosis in these animals. This study aimed to assess the seroepidemiology of Leishmania spp. in dogs in the municipality of Telêmaco Borba that were part of a castration campaign. Blood samples from 191 dogs were collected, and their owners were surveyed on various epidemiological variables. Serological analysis was performed using indirect immunofluorescence (IIF and rapid immunochromatography (DPP®. Screening by IIF identified 13 (6.81% positive animals, none of which were positive for the DPP® test, which is specific for VL. Statistical analysis of the questionnaire responses indicated a significant association between seropositivity and the presence of stacked or composting leaves in the backyard (p = 0.0498, forest areas (squares, woods, parks near the residence (p = 0.0015, and poorly healing ulcerated or nodular epidermal lesions in the dog (p = 0.0138. This study revealed the presence of anti-Leishmania spp. IgG antibodies in dogs residing in Telêmaco Borba, suggesting the presence of the parasite and vector in the environment. In addition, the existence of stacked or composting leaves in the backyard, forest areas near the residence, and epidermal lesions in dogs are factors associated with Leishmania spp. infection in pet dogs.

  12. Tom Rüütel: Tööandjal on igal juhul kasud sees / intervjueerinud Helen Kask

    Index Scriptorium Estoniae

    Rüütel, Tom

    2013-01-01

    Kui oluliseks peab Tom töötamist ning millisena näeb ta tööandjate suhtumst erivajadusega töötajasse? Millised on Tomi mõtted seoses töövõimetoetuse (TVK) reformiga? Tom Rüütel õpib Tallinna Ülikoolis magistrantuuri teisel kursusel rakenduslikku sotsiaaltööd

  13. Mre11 ATLD17/18 mutation retains Tel1/ATM activity but blocks DNA double-strand break repair

    NARCIS (Netherlands)

    O. Limbo (Oliver); D. Moiani (Davide); A. Kertokalio (Aryandi); C. Wyman (Claire); J.A. Tainer (John); P. Russell (Paul)

    2012-01-01

    textabstractThe Mre11 complex (Mre11-Rad50-Nbs1 or MRN) binds double-strand breaks where it interacts with CtIP/Ctp1/Sae2 and ATM/Tel1 to preserve genome stability through its functions in homology-directed repair, checkpoint signaling and telomere maintenance. Here, we combine biochemical, structur

  14. Organizing the Library to Suit the Undergraduates' Information Gathering Behavior at the Tel-Hai Academic College in Israel

    Science.gov (United States)

    Chai, Iris

    2007-01-01

    The study examined the factors influencing information gathering behavior of undergraduates at Tel-Hai Academic College, so that library services can cope effectively with this behavior. Related to the findings, we changed our circulation desk to become a "one stop shop" for directions to all library information.

  15. Telomerasa y telómero: su estructura y dinámica en salud y enfermedad

    Directory of Open Access Journals (Sweden)

    Diego L. Mengual Gómez

    2014-02-01

    Full Text Available La telomerasa es la enzima responsable del mantenimiento de la longitud de los telómeros mediante la adición de secuencias repetitivas ricas en guanina, y su actividad se observa principalmente en gametos, células madre y células tumorales. En las células somáticas humanas el potencial de proliferación es limitado, alcanzando la senescencia luego de 50-70 divisiones celulares, debido a que la ADN polimerasa no es capaz de copiar el ADN en los extremos de los cromosomas. Por el contrario, en la mayoría de las células tumorales el potencial de replicación es ilimitado debido al mantenimiento de la longitud telomérica dado por la telomerasa. Los telómeros tienen proteínas adicionales que regulan la unión de la telomerasa. De la misma manera la telomerasa también se asocia con un complejo de proteínas que regulan su actividad. Este trabajo se centra en la estructura y función del complejo telómero/telomerasa y a cómo las alteraciones en su comportamiento conducen al desarrollo de diversas enfermedades, principalmente cáncer. El desarrollo de inhibidores del sistema telómero / telomerasa podría ser un blanco con posibilidades prometedoras.

  16. Tom Rüütel: Tööandjal on igal juhul kasud sees / intervjueerinud Helen Kask

    Index Scriptorium Estoniae

    Rüütel, Tom

    2013-01-01

    Kui oluliseks peab Tom töötamist ning millisena näeb ta tööandjate suhtumst erivajadusega töötajasse? Millised on Tomi mõtted seoses töövõimetoetuse (TVK) reformiga? Tom Rüütel õpib Tallinna Ülikoolis magistrantuuri teisel kursusel rakenduslikku sotsiaaltööd

  17. Adult T-cell leukaemia and lymphoma: report of two cases and a brief review of the literature

    NARCIS (Netherlands)

    H.C. van Zaanen; J.G. Pegels

    2002-01-01

    textabstractHuman T-cell lymphotropic virus type 1 (HTLV-1) can cause adult T-cell leukaemia/lymphoma (ATLL). Two patients originating from the Caribbean area with ATLL are described. The first patient developed respiratory insufficiency due to acute T-cell leukaemia. The diagnosis

  18. Has fallout from the Chernobyl accident caused childhood leukaemia in Europe? An update on epidemiologic evidence

    Energy Technology Data Exchange (ETDEWEB)

    Hoffmann, W. [Bremen Inst. for Prevention Research and Social Medicine (BIPS), Bremen (Germany)

    2001-07-01

    Background: According to radiation risk estimates uniformly adopted by various official organizations, exposure to Chernobyl fallout is unlikely to have caused any measurable health risk in central Europe. Methods and Results: A reevaluation of ECLIS (European Childhood Leukaemia and Lymphoma Incidence Study), a large IARC-coordinated project revealed a slightly higher leukaemia incidence in the most contaminated European regions, and an increasing trend with estimated cumulative excess radiation dose. The excess corresponds to 20 cases of childhood leukaemia in the study area until 1991. Recent evidence from Greece and Germany indicate significantly higher risks in the cohort of children in utero at the time of the initial fallout. In Greece, a positive trend was observed over three regions of increasing average fallout contamination (p=0.005). Conclusion: Chernobyl fallout could well have caused a small, but significant excess of childhood leukaemia cases in Europe. The etiologic mechanism might include an induction of chromosome aberrations in early pregnancy. Increased risks in the birth cohort exposed in utero correspond to 11 excess cases in Greece and another 11.4 excess cases in Germany alone. Exposure misclassification and underascertainment of incident cases render post-Chernobyl risk estimates probably too low. If indeed Chernobyl fallout has caused childhood leukaemia cases in Europe, we would also expect an increased incidence for other childhood cancers and excess malignancies in adults as well as non-malignant diseases of all ages. Neither of these endpoints have as yet been systematically studied. (orig.)

  19. Child and adolescent Down syndrome-associated leukaemia: the Irish experience.

    Science.gov (United States)

    O'Rafferty, C; Kelly, J; Storey, L; Ryan, C; O'Marcaigh, A; Smith, O

    2015-12-01

    Down syndrome (DS), the most common syndromic chromosomal abnormality is associated with a unique susceptibility to develop both acute myeloid (ML) and lymphoblastic leukaemia (ALL). These leukaemias differ from the non-DS-related types of leukaemia and are thought to be distinct biological entities. To perform a retrospective review of our experience of treating DS-related leukaemia at Our Lady's Children's Hospital. Data were extracted from a database established in 2000 to prospectively gather data on DS-associated leukaemias and their outcomes following polychemotherapy. Kaplan-Meier survival curves were constructed. Nineteen patients with DS-ML were treated and 19 with DS-ALL. Sixteen (84%) patients with DS-ML are alive and in complete remission with a median follow-up of 7 years. All deaths in this cohort were due to treatment-related mortality (TRM). Of the DS-ALL patients, 12 (63%) remain alive with a median follow-up of 3.6 years. TRM accounted for five of the six deaths. One death was due to leukaemic relapse. High cure rates are seen in DS-ML using contemporary polychemotherapy protocols, however, there is significant TRM in this cohort. DS-ALL does not have the same high cure rate as non-DS-ALL (>90%) and again this is mainly due to an excess of TRM.

  20. Granulocytic sarcoma of the femur in a patient with acute megakaryoblastic leukaemia

    Directory of Open Access Journals (Sweden)

    Čolović Milica

    2011-01-01

    Full Text Available Introduction. Granulocytic sarcoma, chloroma or myeloblastoma are observed in 3% to7% of acute myeloid leukaemia and represents localized tumour composed of collection of immature leukaemic cells. It appears most frequently in patients with M2, M4 and M5 subtypes of acute myeloid leukaemia Case Outline. A 58-year-old female presented with pain and oedema of the right upper limb in November 2009. After two months the patinet had fracture dislocation and numerous osteolytic lesions of the right femur. Immunohistochemistry of tumour biopsy showed megakaryoblastic granulocytic sarcoma which was CD31++, F-XIII++, CD34-, FVIII+++, S100-, aktin-, EMA++, Bcl2++, CD43++, with positive proliferative marker measured with Ki-67 positivity in more of 50% of cells. Aspirate of bone marrow and immunophenotyping with flowcytometry revealed diagnosis of acute megakaryoblastic leukaemia. The course of the disease was rapid and the patient died before commencing chemotherapy, five months after first complaints. Conclusion. Granulocytic sarcoma is extramedullary localization of collection of leukaemia cells which can proceed, to arise concomitantly with leukaemia, or may be the only manifestation of the disease. The diagnosis can be established only with immunohystochemistry.

  1. Epidural spinal cord compression as initial clinical presentation of an acute myeloid leukaemia: case report and literature review

    Institute of Scientific and Technical Information of China (English)

    Dominique N'Dri Oka; Alpha Boubacar Bah; André Valentin Tokpa; Louis Derou

    2016-01-01

    Epidural localization of myeloid leukaemia is rarely reported.Spinal cord compression as an initial presentation of acute myeloid leukaemia is extremely rare.This is a report of a 17-year-old black boy who presented to emergency department with neurological symptoms of spinal cord compression.Imaging modalities showed multiple soft tissue masses in the epidural space.After surgical treatment,histopathological examination of the epidural mass showed myeloid leukaemia cells infiltration.Literature review on Medline and "scholar Google" database was done.The characteristics and management of extra-medullary leukaemia are discussed.Granulocytic sarcoma,myeloid sarcoma or chloroma with acute myeloid leukaemia should be considered as part of epidural spinal cord compression.Therefore surgery is indicated on an emergent basis.

  2. Functional dissection of Caenorhabditis elegans CLK-2/TEL2 cell cycle defects during embryogenesis and germline development.

    Directory of Open Access Journals (Sweden)

    Sandra C Moser

    2009-04-01

    Full Text Available CLK-2/TEL2 is essential for viability from yeasts to vertebrates, but its essential functions remain ill defined. CLK-2/TEL2 was initially implicated in telomere length regulation in budding yeast, but work in Caenorhabditis elegans has uncovered a function in DNA damage response signalling. Subsequently, DNA damage signalling defects associated with CLK-2/TEL2 have been confirmed in yeast and human cells. The CLK-2/TEL2 interaction with the ATM and ATR DNA damage sensor kinases and its requirement for their stability led to the proposal that CLK-2/TEL2 mutants might phenocopy ATM and/or ATR depletion. We use C. elegans to dissect developmental and cell cycle related roles of CLK-2. Temperature sensitive (ts clk-2 mutants accumulate genomic instability and show a delay of embryonic cell cycle timing. This delay partially depends on the worm p53 homolog CEP-1 and is rescued by co-depletion of the DNA replication checkpoint proteins ATL-1 (C. elegans ATR and CHK-1. In addition, clk-2 ts mutants show a spindle orientation defect in the eight cell stages that lead to major cell fate transitions. clk-2 deletion worms progress through embryogenesis and larval development by maternal rescue but become sterile and halt germ cell cycle progression. Unlike ATL-1 depleted germ cells, clk-2-null germ cells do not accumulate DNA double-strand breaks. Rather, clk-2 mutant germ cells arrest with duplicated centrosomes but without mitotic spindles in an early prophase like stage. This germ cell cycle arrest does not depend on cep-1, the DNA replication, or the spindle checkpoint. Our analysis shows that CLK-2 depletion does not phenocopy PIKK kinase depletion. Rather, we implicate CLK-2 in multiple developmental and cell cycle related processes and show that CLK-2 and ATR have antagonising functions during early C. elegans embryonic development.

  3. Climatología de las tormentas eléctricas locales severas (TELS en la Zona Metropolitana de Guadalajara

    Directory of Open Access Journals (Sweden)

    Omar García Concepción

    2012-02-01

    Full Text Available La aparición de los fenómenos severos en el tiempo meteorológico (tornados, granizos y vientos lineales con rachas destructoras está relacionada con cambios importantes en la morfología de las tormentas eléctricas. Las tormentas que alcancen ese estadio son consideradas como un tipo especial de tormentas eléctricas llamadas tormentas eléctricas locales severas (TELS. El desarrollo de las TELS en la Zona Metropolitana de Guadalajara (ZMG es una realidad y se debe considerar en la protección de la sociedad, debido a las pérdidas de vidas, daños materiales y cuantiosas afectaciones que ocurren como consecuencia de éstas. Al no contar con una cronología de las TELS en la ZMG fue necesaria la compilación de las mismas como base para realizar su climatología. Entre los resultados obtenidos se destaca que las TELS ocurren desde mayo hasta noviembre, en particular, en los meses de junio, julio y agosto. La mayoría se presenta durante horas de la tarde o de la noche, pero un grupo nada despreciable también ocurre durante la madrugada. Queda establecido que las TELS constituyen un elemento importante del clima de la ZMG que no puede ser ignorado desde el punto de vista científico y mucho menos en la práctica, por los efectos que produce en muchas ocasiones.

  4. Clofarabine in the treatment of poor risk acute myeloid leukaemia.

    LENUS (Irish Health Repository)

    Krawczyk, Janusz

    2010-09-01

    Clofarabine is a second generation nucleoside analogue. It inhibits DNA repair and activates the mitochondrial apoptotic pathway leading to cell death. In vitro clofarabine has demonstrated synergy with daunorubicin and Ara-C and in phase II clinical trials has shown promising activity in poor risk Acute myeloid leukaemia (AML) patients. In our institution over a 24 month period 22 AML patients (11 M, 11 F) with poor risk features, deemed unsuitable for standard therapy, were treated with clofarabine, alone (eight patients) or in combination (14 patients) for up to three cycles of treatment. The median age was 67.5 years (24-76) with 16 patients > 60 years. At the time of treatment 18 patients had active AML. Four patients intolerant of standard induction received clofarabine as consolidation. The overall response rate (ORR) for the 18 patients with active AML was 61%, nine patients (50%) achieving a complete response (CR). Induction and consolidation were well tolerated with no unexpected toxicities. Predictably, all patients developed grade 4 neutropenia but the median duration was only 20 days (17-120). Induction mortality was acceptable at 17%. In conclusion, clofarabine (alone or in combination) is active in poor risk AML with an acceptable safety profile and should be considered a potential option in poor risk AML patients.

  5. 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.

  6. Scrapie strain-specific interactions with endogenous murine leukaemia virus.

    Science.gov (United States)

    Carp, R I; Meeker, H C; Caruso, V; Sersen, E

    1999-01-01

    The finding that a senescence-accelerated mouse (SAMP8) shows early brain ageing, with histopathological changes resembling those seen in scrapie, combined with the discovery of high levels of endogenous murine leukaemia virus (MuLV) in brains of SAMP8 mice prompted us to examine the effect of scrapie infection on MuLV titres in this strain and in one of its progenitors, the AKR strain. Three scrapie strains (ME7, 22L and 139A) that had a comparatively short incubation period in SAMP8 and AKR mice caused an increase in brain MuLV titres that was scrapie strain-specific: in each mouse strain, the greatest effect was with 1 39A, and the least with ME7. The 22A scrapie strain, which has a long incubation period in SAMP8 mice, did not affect MuLV titres in brains of this mouse strain. Previous analyses of scrapie incubation periods in AKR, SAMP8 and another strain derived from an AKR cross (SAMR1) showed an inverse relationship between brain MuLV titres and scrapie incubation periods. This finding, combined with the effect of scrapie on MuLV titres, suggests an interaction between the scrapie infectious process and MuLV replication.

  7. A Ten Year Descriptive Study of Adult Leukaemia at Al-Jomhori Teaching Hospital in Sana'a, Yemen

    Directory of Open Access Journals (Sweden)

    Jameel Al-Ghazaly

    2014-12-01

    Full Text Available Background: There is scarcity of data of the epidemiology of leukaemia in Arab countries including Yemen. Understanding patterns of leukaemia underpins epidemiology and can provide insight into disease etiology. The aim of this research is to determine the epidemiologic pattern of adult leukaemia in Yemen. Methods: The research is a descriptive cross-sectional study. We analyzed the data of 702 adult patients with leukaemia, who were newly diagnosed over a ten-year period between October 1999 and October 2009 at the referral haematology centre in Sana’a at Al-Jomhori Teaching Hospital, according to type of leukaemia, age, sex, geographic distribution and time of diagnosis. Results: Acute Myeloid Leukaemia (AML was found to be the most common (45.1% followed by Chronic Myeloid Leukaemia (CML (26.5%, Acute Lymphoid Leukaemia (ALL (17.7% and Chronic Lymphoid Leukaemia (CLL (10.7%, respectively. There was an almost equal prevalence of AML and CML for males and females but males had significantly more cases of ALL and CLL (p =0.008. A significant variation in geographic pattern showed that the highest number of cases is seen the Central mountainous region and the least number of cases in the South-eastern region which is coastal and lowland (p<0.001. The seasonal variation showed that higher number of ALL cases was seen in the summer months (33% compared with other seasons (21% in the spring, 24.2% in autumn and 21.8% in winter. Conclusions: The pattern of adult leukaemia in Yemen is different from that seen in western countries which could be attributed to different environmental exposure. The geographic pattern indicates a possible role of certain environmental factors which warrant further investigations. The pattern of seasonal variation needs further studies for evaluating the seasonality.

  8. Sudden sensorineural hearing loss as the first manifestation of chronic myeloid leukaemia: case report.

    Science.gov (United States)

    Diao, M; Tian, F; Sun, J

    2014-11-01

    Sudden sensorineural hearing loss rarely occurs in patients with chronic myeloid leukaemia. We present a case report of a patient who presented with sudden sensorineural hearing loss as the first manifestation of chronic myeloid leukaemia, and review the mechanisms responsible for sudden sensorineural hearing loss in leukaemic patients. A 31-year-old female presented to our clinic with unilateral sudden sensorineural hearing loss and tinnitus. Pure tone audiometry revealed profound sensorineural hearing loss in the left ear at all frequencies. During an investigation into her hearing loss, the patient was found to have chronic myeloid leukaemia. Every case of sudden sensorineural hearing loss must be carefully evaluated, and haematological disorders must be considered in the differential diagnosis of sudden hearing loss.

  9. Intussusception: a rare complication in a patient with acute leukaemia after consolidation chemotherapy.

    Science.gov (United States)

    Qasrawi, Ayman; Abu Ghanimeh, Mouhanna; Abughanimeh, Omar; Qasem, Abdulraheem

    2017-02-28

    Intussusception is telescoping of one segment of the gastrointestinal tract into an adjacent one. It is more common in children than adults. When it occurs in adults, it is usually associated with a lead point. Intussusception is very rare in acute leukaemia and has only been reported in few cases. We present a case of an adult woman who presented with intussusception after a cycle of consolidation chemotherapy with high-dose cytarabine for acute myeloid leukaemia. Other causes of acute abdominal pain were excluded, and the diagnosis was established by CT scan of the abdomen and barium enema. No pathological lead points were found intraoperatively. She underwent a right-sided hemicolectomy with complete recovery. To the best of our knowledge, this is only the fourth case of intussusception that has been reported in an adult patient with acute myeloid leukaemia. 2017 BMJ Publishing Group Ltd.

  10. Changing bone marrow micro-environment during development of acute myeloid leukaemia in rats

    DEFF Research Database (Denmark)

    Mortensen, B T; Jensen, P O; Helledie, N;

    1998-01-01

    The Brown Norwegian rat transplanted with promyelocytic leukaemic cells (BNML) has been used as a model for human acute myeloid leukaemia. We have previously shown that both the blood supply to the bone marrow and the metabolic rate decrease in relation to the leukaemic development in these rats....... Here we have investigated how the development and progression of this leukaemia affect oxygenation, pH and proliferation of normal and leukaemic cells in vivo. Bone marrow pH was measured by a needle electrode. Nitroimidazol-theophylline (NITP) was used to identify hypoxic cells, and we applied...... bromodeoxyuridine (BrdUrd) to identify DNA replicating cells. The leukaemia progressed slowly until day 27 after which a rapid deterioration could be observed leading to severe changes over the following 5 d. In whole blood there was evidence of progressing metabolic acidosis. In bone marrow the fraction...

  11. 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...

  12. Impact on learning of an e-learning module on leukaemia: a randomised controlled trial

    Directory of Open Access Journals (Sweden)

    Morgulis Yuri

    2012-05-01

    Full Text Available Abstract Background e-learning resources may be beneficial for complex or conceptually difficult topics. Leukaemia is one such topic, yet there are no reports on the efficacy of e-learning for leukaemia. This study compared the learning impact on senior medical students of a purpose-built e-learning module on leukaemia, compared with existing online resources. Methods A randomised controlled trial was performed utilising volunteer senior medical students. Participants were randomly allocated to Study and Control groups. Following a pre-test on leukaemia administered to both groups, the Study group was provided with access to the new e-learning module, while the Control group was directed to existing online resources. A post-test and an evaluation questionnaire were administered to both groups at the end of the trial period. Results Study and Control groups were equivalent in gender distribution, mean academic ability, pre-test performance and time studying leukaemia during the trial. The Study group performed significantly better than the Control group in the post-test, in which the group to which the students had been allocated was the only significant predictor of performance. The Study group’s evaluation of the module was overwhelmingly positive. Conclusions A targeted e-learning module on leukaemia had a significant effect on learning in this cohort, compared with existing online resources. We believe that the interactivity, dialogic feedback and integration with the curriculum offered by the e-learning module contributed to its impact. This has implications for e-learning design in medicine and other disciplines.

  13. 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.

  14. Tailored therapy of adult acute leukaemia in Jehovah's Witnesses: unjustified reluctance to treat.

    Science.gov (United States)

    Laszlo, Daniele; Agazzi, Alberto; Goldhirsch, Aron; Cinieri, Saverio; Bertolini, Francesco; Rabascio, Cristina; Pruneri, Giancarlo; Calabrese, Liliana; Cocquio, Angela; Martinelli, Giovanni

    2004-04-01

    Treatment of acute leukaemia in adult Jehovah's Witnesses (JW) is challenging because of 'a priori' refusal of most physicians to apply diagnostic and therapeutic procedures to haematological abnormalities resembling acute leukaemia. Rejection of blood transfusions by individuals of this faith is usually blamed to justify this attitude, thus leading to severe personal, medical and psychological distress related to the lack of care. We therefore intended to verify whether a standard (tailored) chemotherapy, without the use of prophylactic blood product transfusions, could be applied during treatment of acute leukaemia under such circumstances. Eleven consecutive JW adult patients with acute leukaemia, all of whom had been denied care in other institutions, were treated at the European Institute of Oncology (EIO) in Milan, Italy. Five had acute lymphoblastic leukaemia (ALL) (one bcr/abl positive), six had acute myeloid leukaemia (AML) with immunophenotype and/or cytogenetic intermediate-high risk features, except one patient with acute promyelocytic leukaemia (APML). Standard induction chemotherapy [cytosine arabinoside (ARA-C) and daunorubicin (DNR) for AML, vincristine (VCR), DNR and prednisone (PDN) for ALL, all-trans retinoic acid (ATRA) and DNR for APML] with the antracycline dose of at least 30 mg/sqm were used. All patients experienced severe anaemia after induction chemotherapy despite erythropoietin. Median haemoglobin nadir for patients with ALL and AML was 4.5 g/dL (range 1.3-6.9) and 5.1 g/dL (range 2.6-6.8), respectively. Median platelet nadir counts for all patients was 14.5 x 10(9))/L (range 1-24). One patient died during induction probably due to haemorrhage. Four of five patients with ALL achieved a complete remission (CR) (including the bcr/abl case) while among patients with AML only the one with APML achieved CR. Three patients (APML = 1 and ALL = 2) are still alive and disease-free. This small series of adult patients with leukaemia illustrates

  15. Atypical Ph negative chronic myeloid leukaemia presenting as sudden profound deafness.

    Science.gov (United States)

    Smith, N; Bain, B; Michaels, L; Craven, E

    1991-01-01

    A patient with atypical Ph negative chronic myeloid leukaemia presented with the sudden onset of profound deafness. He survived only eight months. Detailed histological investigation performed at necropsy showed loss of ganglion cells and afferent nerve fibres in the cochlea and vestibule associated with extensive fibrosis and new bone formation in the labyrinthine spaces. Both leucophoresis and high dose chemotherapy capable of rapid cytoreduction are recommended in patients with chronic myeloid leukaemia with profound hearing loss, as conventional chemotherapy is rarely followed by recovery. Images PMID:1791207

  16. 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.)

  17. Epigenetic silencing of Bim transcription by Spi-1/PU.1 promotes apoptosis resistance in leukaemia.

    Science.gov (United States)

    Ridinger-Saison, M; Evanno, E; Gallais, I; Rimmelé, P; Selimoglu-Buet, D; Sapharikas, E; Moreau-Gachelin, F; Guillouf, C

    2013-09-01

    Deregulation of transcriptional networks contributes to haematopoietic malignancies. The transcription factor Spi-1/PU.1 is a master regulator of haematopoiesis and its alteration leads to leukaemia. Spi-1 overexpression inhibits differentiation and promotes resistance to apoptosis in erythroleukaemia. Here, we show that Spi-1 inhibits mitochondrial apoptosis in vitro and in vivo through the transcriptional repression of Bim, a proapoptotic factor. BIM interacts with MCL-1 that behaves as a major player in the survival of the preleukaemic cells. The repression of BIM expression reduces the amount of BIM-MCL-1 complexes, thus increasing the fraction of potentially active antiapoptotic MCL-1. We then demonstrate that Spi-1 represses Bim transcription by binding to the Bim promoter and by promoting the trimethylation of histone 3 on lysine 27 (H3K27me3, a repressive histone mark) on the Bim promoter. The PRC2 repressive complex of Polycomb is directly responsible for the deposit of H3K27me3 mark at the Bim promoter. SUZ12 and the histone methyltransferase EZH2, two PRC2 subunits bind to the Bim promoter at the same location than H3K27me3, distinct of the Spi-1 DNA binding site. As Spi-1 interacts with SUZ12 and EZH2, these results indicate that Spi-1 modulates the activity of PRC2 without directly recruiting the complex to the site of its activity on the chromatin. Our results identify a new mechanism whereby Spi-1 represses transcription and provide mechanistic insights on the antiapoptotic function of a transcription factor mediated by the epigenetic control of gene expression.

  18. [Sexual behavior characteristics of clients attending the Israel AIDS Task Force anonymous clinic in Tel Aviv].

    Science.gov (United States)

    Bar-On, Yaeli; Perry, Zvi H; Nof, Einav; Shiber, Asher; Risenberg, Klaris; Ben Zion, Itzhak

    2014-09-01

    Until now, research on sexual behavior and HIV in Israel has been carried out mainly on the general population, and focused primarily on defining populations at risk, without adequate consideration given to the reasons bringing these populations to be tested, and their specific sexual behaviors. In Israel, one can choose whether to take an HIV test in confidential centers (giving one's name under medical confidentiality) or in anonymous centers (Israel AIDS Task Force in Tel Aviv and Beer Sheva, Levinsky Clinic in Tel Aviv and Haparsim Clinic in Haifa]. At least 21% of the clients of the anonymous testing centers in Israel belong to a high risk population in contrast to 2.6% in confidential clinics, and so, in this study, we hypothesize that characterization of sexual behavior patterns in anonymous testing centers might enable us to better characterize sexual behavior patterns in high risk populations. In this cross-sectional study, we used questionnaires distributed in the clinics by the Israel AIDS Task Force in order to characterize their clinic's clients. The questionnaires were completed by the Israel AIDS Task Force consultants during the consultation period at which the anonymous test was performed. Data collected included: gender, age, testing history, specific sexual behaviors and reasons for applying for the current test. A total of 926 questionnaires were collected; 29.9% of them were of female patients. The average age was 29.47 years (1±8.66]; 21.3% of the clients were men who have sex with men [MSM]; only 2.3% of the clients belonged to other high risk populations. In all groups, the majority of the patients reported high risk sexual behavior (any sexual contact without a condom) and the average age for the first test was much higher than the average age of first sexual intercourse common in Israel. Women reported more participation in unprotected vaginal intercourse than heterosexual men, and a substantial part of MSM reported performing unprotected

  19. O TelEduc na Amazônia: a experiência a Universidade Federal de Rondônia / The TelEduc in Amazon: the experience of the Federal University of Rondônia

    Directory of Open Access Journals (Sweden)

    Tania Suely Azevedo Brasileiro

    2011-04-01

    Full Text Available Este artigo tem como objetivo relatar a experiência da Universidade Federal de Rondônia – UNIR com o ambiente AVA TelEduc, destacando sua história, bem como a aceitação por alunos e professores das mais variadas disciplinas e cursos desta IFES, além de analisar questões de ordem mais técnica que a Plataforma TelEduc nos apresentou durante os anos em que o ambiente foi adotado como recurso didático-tecnológico nas atividades docentes desde a sala de aula universitária. Nossa experiência com este ambiente data de 2004 e, devido a problemas técnicos, somente volta a funcionar em nossa universidade em 2008, agora como parte de um projeto do Laboratório Didático-Pedagógico Multimídia – Labmídia. Em 2009/2010 o destaque foi a mudança de versão da 3.3.8 para 4.2.1 e adesão dos cursos do PARFOR. Alguns aspectos foram tomados como considerações desta experiência com o TelEduc: boa aceitação do ambiente como recurso tecnológico ao ensino presencial; mostrou-se um ambiente de fácil utilização e robusto; têm ferramentas de aprendizagem interativa que proporcionam aos alunos uma aprendizagem prazerosa; a ferramenta bate-papo pode ser melhorada quanto a inserção de recursos de áudio; o código fonte do TelEduc deve ser reescrito para substituir tags em desuso. Entretanto, o nosso maior desafio continua sendo vencer as dificuldades próprias de viver e trabalhar numa região como a Amazônia, distante de quase tudo, mas, ao mesmo tempo, grandiosa em suas possibilidades, e a adoção de ferramentas da Educação a Distância é estratégica para o desenvolvimento sustentável da região.AbstractThis article aims at describing the Universidade Federal de Rondônia – UNIR with the TelEduc AVA environment, highlighting its history, and the acceptance by students and teachers from various disciplines and courses of IFES, and discuss matters of more technical Platform TelEduc that introduced us during the years when the

  20. Detection of transient and persistent feline leukaemia virus infections.

    Science.gov (United States)

    Jarrett, O; Golder, M C; Stewart, M F

    1982-03-01

    A study was made of cats persistently or transiently viraemic with feline leukaemia virus (FeLV) following experimental oronasal infection. Cats of two ages were exposed to the virus. One group was infected when eight weeks old in the expectation that most of the cats would become persistently viraemic, and the second group when 16 weeks old, so that some would show signs of a transient infection and then recover. The periods following infection when virus was detectable in the blood and in the oropharynx were determined for each group. Three methods for detecting viraemia were compared: virus isolation, immunofluorescence on blood smears and an enzyme-linked immunosorbent assay (ELISA). There was good overall agreement among the three tests in detecting virus-positive cats. Virus was found sooner after infection by virus isolation than by the other methods, and virus appeared in the blood slightly sooner in cats which developed persistent viraemia than in transiently viraemic cats. Infectious FeLV was isolated from the oropharynx of all of the persistently viraemic cats, in most cases simultaneously with virus in the plasma. Virus was also isolated from the mouth of most transiently viraemic cats. Under field conditions such transient excretion of virus lasting only a few days would rarely be detected in a single sampling. This might explain how FeLV is maintained in free range urban cats in the absence of a large number of cats with persistent active FeLV infection. For routine diagnosis, immunofluorescence would appear to offer the best chance of differentiating transient and persistent infections by FeLV.

  1. A novel RT-qPCR assay for quantification of the MLL-MLLT3 fusion transcript in acute myeloid leukaemia

    DEFF Research Database (Denmark)

    Abildgaard, Lotte; Ommen, Hans Beier; Lausen, Birgitte Frederiksen

    2013-01-01

    OBJECTIVES: Patients with acute myeloid leukaemia (AML) of the monocytic lineage often lack molecular markers for minimal residual disease (MRD) monitoring. The MLL-MLLT3 fusion transcript found in patients with AML harbouring t(9;11) is amenable to RT-qPCR quantification but because of the heter......OBJECTIVES: Patients with acute myeloid leukaemia (AML) of the monocytic lineage often lack molecular markers for minimal residual disease (MRD) monitoring. The MLL-MLLT3 fusion transcript found in patients with AML harbouring t(9;11) is amenable to RT-qPCR quantification but because...... of the heterogeneity of translocation break points, the MLL-MLLT3 fusion gene is a challenging target. We hypothesised that MRD monitoring using MLL-MLLT3 as a RT-qPCR marker is feasible in the majority of patients with t(9;11)-positive AML. METHODS: Using a locked nucleic acid probe, we developed a sensitive RT-qPCR...... follow-up. Two patients relapsed, and both were MRD positive in BM after first induction course. A total of three relapses occurred, and they were detected by RT-qPCR 3 wks before haematological relapse was diagnosed. CONCLUSION: This MLL-MLLT3 RT-qPCR assay could be useful in MRD monitoring of a group...

  2. Outcomes of a telemonitoring-based program (telEPOC) in frequently hospitalized COPD patients.

    Science.gov (United States)

    Esteban, Cristóbal; Moraza, Javier; Iriberri, Milagros; Aguirre, Urko; Goiria, Begoña; Quintana, José M; Aburto, Myriam; Capelastegui, Alberto

    2016-01-01

    The increasing prevalence of chronic diseases requires changes in health care delivery. In COPD, telemedicine appears to be a useful tool. Our objective was to evaluate the efficacy (in improving health care-resource use and clinical outcomes) of a telemonitoring-based program (telEPOC) in COPD patients with frequent hospitalizations. We conducted a nonrandomized observational study in an intervention cohort of 119 patients (Galdakao-Usansolo Hospital) and a control cohort of 78 patients (Cruces Hospital), followed up for 2 years (ClinicalTrials.gov identifier: NCT02528370). The inclusion criteria were two or more hospital admissions in the previous year or three or more admissions in the previous 2 years. The intervention group received telemonitoring plus education and controls usual care. Most participants were men (13% women), and the sample had a mean age of 70 years, forced expiratory volume in 1 second of 45%, Charlson comorbidity index score of 3.5, and BODE (body mass index, airflow obstruction, dyspnea, and exercise capacity) index score of 4.1. In multivariate analysis, the intervention was independently related to lower rates of hospital admission (odds ratio [OR] 0.38, 95% confidence interval [CI] 0.27-0.54; Ptelemonitoring and education was able to reduce the health care-resource use and stabilize the clinical condition of frequently admitted COPD patients.

  3. Sapphirine and fluid inclusions in Tel Thanoun mantle xenoliths,Syria

    Science.gov (United States)

    Bilal, Ahmad

    2016-04-01

    Volcanoes along the Syrian rift, which extend a distance of about 1000 km, brought to the surface mantle xenoliths within erupted basalts, during multiples periods of volcanic activity. Xenoliths in early Cretaceous volcanoes originate in the garnet peridotite field of the subcontinental mantle, whereas those in recent Cenozoic volcanoes, the prime object of this study, are issued from shallower levels (spinel peridotite field). The recent discovery of sapphirine-bearing websterite in Tel Thanoun, a small volcanic diatreme inside the larger Quaternary volcanic field (Djebel Al Arab), allows us to estimate the P-T evolution and fluid-rock interaction at the volcanic source. Harzburgites and lherzolites are equilibrated at a temperature of about 1000 °C at a depth of 35-40 km. Sapphirine appears to have formed during cooling, at depth at a temperature of about 900 °C, at a time where spinel exsolution occurred in harzburgite and lherzolite pyroxenes. This occurred in the presence of a high-density pure CO2 fluid phase, still present in primary fluid inclusions. The highly-aluminous sapphirine-bearing protolith might be former garnet websterite (possibly uplifted during cretaceous magmatism), which resided and cooled in the spinel peridotite stability field, and was then dragged and brought to the surface by quaternary basalts.

  4. Arnold Rüütli valimisplatvorm / Arnold Rüütel

    Index Scriptorium Estoniae

    Rüütel, Arnold, 1928-

    2006-01-01

    Ilmunud ka: Äripäev (2006) 13. sept., lk. 23, pealk.: Eesti peab olema inimestele turvaline kodu ; Kesknädal (2006) 13. sept., lk. 4-5, pealk.: Muudame riigi turvaliseks rahvakoduks ; Sakala (2006) 14. sept., lk. 2, pealk.: Eesti olgu inimestele turvaline kodu ; Pärnu Postimees (2006) 14. sept., lk. 15, pealk.: Eesti peab olema inimestele turvaline kodu ; Põhjarannik (2006) 14. sept., lk. 2, Eesti peab olema inimestele turvaline kodu ; Severnoje Poberezhje (2006) 14. sept., lk. 2 ; Vesti Nedeli Den za Dnjom (2006) 15. sept., lk. 20 ; Lääne-Harju Ekspress (2006) 16. sept., lk. 7 ; Hiiu Leht (2006) 19. sept., lk. 4. President Arnold Rüütel rõhutab oma valimisplatvormis, et Eesti ülim eesmärk on rahva püsimajäämine ja oma riigi hoidmine. Kommenteerib Toomas Hendrik Ilves. Lisa: Presidendikultuuri seitse alusmõtet. Ajal. Äripäev kommenteerib Aivar Hundimägi, T. H. Ilvese kommentaar ainult Eesti Päevalehes

  5. Germplasm evaluation of heat tolerance in bread wheat in Tel Hadya, Syria

    Directory of Open Access Journals (Sweden)

    Emeka C Okechukwu

    2016-03-01

    Full Text Available Breeding for heat tolerance in bread wheat (Triticum aestivum L. is a serious global concern due to the increasing threats of high temperature. Thus, 189 wheat genotypes coded from 1 to 189 were evaluated for heat tolerance in normal and late seasons in the International Centre for Agricultural Research in Dry Areas (ICARDA, Tel Hadya, Syria, from 2010 to 2012. The experiments were laid out in alpha lattice designs with two replicates. Data collected on the grain yield, days to heading and maturity, grain filling duration and plant height were subjected to restricted maximum likelihood (REML analysis for generation of the best linear unbiased estimates (BLUEs. Very highly significant effects (p < 0.001 of genotype, season, and genotype by season interaction on grain yield and other traits were obtained. The grain yield and other traits performance of the wheat genotypes were significantly (p < 0.05 higher in the normal season than in the late season. Genotype 148 was among the 30 top grain yielding genotypes in all the environments, while genotypes 172 and 124 were among the top yielding genotypes in all the environments except in late season 2. The relative heat tolerance of the genotypes ranged from -33.69% to -77.95% in late season 1 vs. normal season 1 and -65.28% to -95.83% in late season 2 vs. normal season 2. The high variability obtained in the germplasm underlies sufficient genetic variability for improving heat tolerance in bread wheat.

  6. El teléfono inteligente (smartphone como herramienta pedagógica

    Directory of Open Access Journals (Sweden)

    Javier Organista-Sandoval

    2013-04-01

    Full Text Available Se presenta un estudio sobre cobertura y usos educativos del celular con estudiantes y docentes de dos campi de la UABC. Se seleccionó una muestra al azar con 12% de estudiantes y 24% de docentes, a quienes se les aplicaron una encuesta para precisar la posesión de celular, sus características técnicas, los usos educativos realizados y las ventajas y desventajas de su uso en cursos universitarios. La posesión de teléfono celular se acerca a 97% tanto para estudiantes como para docentes. Los principales usos educativos fueron para comunicación, manejo de información y organización. Las desventajas señaladas fueron, entre otras, distracción y costo elevado de conexión. Las ventajas mayormente mencionadas fueron la bondad de contar con comunicación y acceso a la información en todo momento y lugar. Sin duda, el smartphone tiene gran potencial pedagógico; sin embargo, es necesario ampliar las investigaciones para su adecuada incorporación al proceso educativo universitario.

  7. Arnold Rüütli valimisplatvorm / Arnold Rüütel

    Index Scriptorium Estoniae

    Rüütel, Arnold, 1928-

    2006-01-01

    Ilmunud ka: Äripäev (2006) 13. sept., lk. 23, pealk.: Eesti peab olema inimestele turvaline kodu ; Kesknädal (2006) 13. sept., lk. 4-5, pealk.: Muudame riigi turvaliseks rahvakoduks ; Sakala (2006) 14. sept., lk. 2, pealk.: Eesti olgu inimestele turvaline kodu ; Pärnu Postimees (2006) 14. sept., lk. 15, pealk.: Eesti peab olema inimestele turvaline kodu ; Põhjarannik (2006) 14. sept., lk. 2, Eesti peab olema inimestele turvaline kodu ; Severnoje Poberezhje (2006) 14. sept., lk. 2 ; Vesti Nedeli Den za Dnjom (2006) 15. sept., lk. 20 ; Lääne-Harju Ekspress (2006) 16. sept., lk. 7 ; Hiiu Leht (2006) 19. sept., lk. 4. President Arnold Rüütel rõhutab oma valimisplatvormis, et Eesti ülim eesmärk on rahva püsimajäämine ja oma riigi hoidmine. Kommenteerib Toomas Hendrik Ilves. Lisa: Presidendikultuuri seitse alusmõtet. Ajal. Äripäev kommenteerib Aivar Hundimägi, T. H. Ilvese kommentaar ainult Eesti Päevalehes

  8. NPM1 mutation is a stable marker for minimal residual disease monitoring in acute myeloid leukaemia patients with increased sensitivity compared to WT1 expression*

    DEFF Research Database (Denmark)

    Kristensen, Thomas; Møller, Michael B; Friis, Lone;

    2011-01-01

    Mutation in the NPM1 gene occurs in 60% of acute myeloid leukaemia (AML) patients with normal karyotype. NPM1 mutation is potentially a superior minimal residual disease (MRD) marker compared to WT1 gene overexpression by being specific to the malignant clone, although experimental evidence...... published so far includes very limited numbers of relapsed cases. Also, the stability of the NPM1 mutation has been questioned by reports of the mutation being lost at relapse. In the present study we compared NPM1 mutation and WT1 overexpression as MRD markers in 20 cases of relapsed AML. The 20 patients...... experienced a total of 28 morphological relapses. Karyotypic evolution was detected in 56% of relapses. All relapses were accompanied by high levels of NPM1 mutation, along with high WT1 mRNA levels, thus demonstrating complete stability of both markers during relapse. Detectable NPM1 mutation following...

  9. A novel recombinant Salmonella vaccine enhances the innate immunity of NK cells against acute myeloid leukaemia cells Kasumi-1 in vitro.

    Science.gov (United States)

    Zhang, Bei; Liu, Yuan; Wang, Xiuju; Jiang, Ling; Lu, Zhigang; Zhang, Xing; Li, Kunpeng; Hu, Haiyan

    2013-12-01

    Minor histocompatibility antigen HA-1-specific cytotoxic lymphocyte (CTL) clones have apparent anti-leukaemic efficacy, and the AML/ETO gene is a special fusion gene in leukaemic cells. Thus, we hypothesised that a vaccine targeting HA-1 and AML/ETO could stimulate NK cells to target leukaemia cells. Furthermore, we packaged the vaccine using attenuated Salmonella to enhance its immuno-activity. Expression of the NK cell-activating ligand ULBP2 was notably elevated upon packaging in a co-recombinant group. An AML/ETO single plasmid gave the weakest vaccine. The level of miR-182, which targets ULBP2, significantly decreased with increasing IFN-γ and granzyme B in a co-recombinant group. In summary, DNA vaccines including AML/ETO and HA-1 fragments significantly enhance the innate immunity of NK cells in vitro. © 2013 International Federation for Cell Biology.

  10. Teléfonos móviles: "el secreto mundo privado" en el espacio público

    OpenAIRE

    2011-01-01

    Se propone una revisión teórica de algunos criterios contemporáneos sobre los teléfonos móviles y su influencia en el comportamiento social. Partiendo de la naturaleza del espacio público y privado, se visualiza el espacio híbrido donde se maneja la información a través de los teléfonos móviles. El estudio demuestra que existe poco interés entre los psicólogos latinoamericanos por el análisis de la temática; por consiguiente, se formulan algunas líneas de investigación como propuesta final....

  11. El teléfono celular y los jóvenes sinaloenses. Adopción, usos y adaptaciones

    OpenAIRE

    Ana Luz Ruelas

    2014-01-01

    E n el artículo se discuten los usos y adopciones del teléfono celular por los jóvenes en Culiacán, Sinaloa, a partir de los resultados de una encues - ta aplicada en mayo de 2009, que per - mite afirmar la existencia de formas diferenciadas de adopción que depen - den no solo de la brecha generacional, sino fundamentalmente de la brecha económica.

  12. Human herpes virus-6 seroprevalence and leukaemias: a case-control study. GIMEMA (Gruppo Italiano Malattie Ematologiche dell' Adulto).

    Science.gov (United States)

    Gentile, G; Mele, A; Ragona, G; Faggioni, A; Zompetta, C; Tosti, M E; Visani, G; Castelli, G; Pulsoni, A; Monarca, B; Martino, P; Mandelli, F

    1999-06-01

    The relationships between acute myeloid leukaemia (AML), acute lymphocytic leukaemia (ALL), chronic myeloid leukaemia (CML) and refractory anaemia with excess of blasts (RAEB) and human herpes virus (HHV)-6 antibody level were investigated in a multicentre case-control study. An association between increased HHV-6 seropositivity and geometric mean titre ratio with AML was shown: P for trend = 0.022, adjusted odds ratio 1.20, 95% confidence interval 1.07-1.33 respectively. No association was found between HHV-6 and ALL, CML or RAEB.

  13. Evaluation of natural transmission of bovine leukaemia virus within dairy herds of Argentina

    NARCIS (Netherlands)

    Monti, G.E.; Frankena, K.; Jong, de M.C.M.

    2007-01-01

    The purpose of this study was to describe patterns of seroconversion to bovine leukaemia virus and to estimate the main parameters needed for future model building. A longitudinal study was carried out between February 1999 and November 2001 in seven commercial dairy farms in Argentina using 1535

  14. Childhood leukaemia risks: from unexplained findings near nuclear installations to recommendations for future research.

    Science.gov (United States)

    Laurier, D; Grosche, B; Auvinen, A; Clavel, J; Cobaleda, C; Dehos, A; Hornhardt, S; Jacob, S; Kaatsch, P; Kosti, O; Kuehni, C; Lightfoot, T; Spycher, B; Van Nieuwenhuyse, A; Wakeford, R; Ziegelberger, G

    2014-09-01

    Recent findings related to childhood leukaemia incidence near nuclear installations have raised questions which can be answered neither by current knowledge on radiation risk nor by other established risk factors. In 2012, a workshop was organised on this topic with two objectives: (a) review of results and discussion of methodological limitations of studies near nuclear installations; (b) identification of directions for future research into the causes and pathogenesis of childhood leukaemia. The workshop gathered 42 participants from different disciplines, extending widely outside of the radiation protection field. Regarding the proximity of nuclear installations, the need for continuous surveillance of childhood leukaemia incidence was highlighted, including a better characterisation of the local population. The creation of collaborative working groups was recommended for consistency in methodologies and the possibility of combining data for future analyses. Regarding the causes of childhood leukaemia, major fields of research were discussed (environmental risk factors, genetics, infections, immunity, stem cells, experimental research). The need for multidisciplinary collaboration in developing research activities was underlined, including the prevalence of potential predisposition markers and investigating further the infectious aetiology hypothesis. Animal studies and genetic/epigenetic approaches appear of great interest. Routes for future research were pointed out.

  15. Effect of glutathione S-transferases on the survival of patients with acute myeloid leukaemia

    DEFF Research Database (Denmark)

    Autrup, Judith; Hokland, Peter; Pedersen, Lars

    2002-01-01

    The objective of the study was to investigate the effect of genetic polymorphisms in glutathione S-transferases (GST) on the survival of acute myeloid leukaemia patients receiving adriamycin induction therapy. A total of 89 patients were included in the study. Patients who carried at least one GS...

  16. Cost-effectiveness of obinutuzumab for chronic lymphocytic leukaemia in The Netherlands

    NARCIS (Netherlands)

    Blommestein, Hedwig M.; de Groot, Saskia; Aarts, Mieke J.; Vemer, Pepijn; de Vries, Robin; van Abeelen, Annet F. M.; Posthuma, E. F. M. Ward; Uyl-de Groota, Carin A.

    2016-01-01

    Background: Obinutuzumab combined with chlorambucil (GClb) has shown to be superior to rituximab combined with chlorambucil (RClb) and chlorambucil (Clb) in newly diagnosed patients with chronic lymphocytic leukaemia (CLL). This study evaluates the cost-effectiveness per life-year and quality

  17. Cost-effectiveness of obinutuzumab for chronic lymphocytic leukaemia in The Netherlands

    NARCIS (Netherlands)

    H.M. Blommestein (Hedwig); S. de Groot (Saskia); M.J. Aarts (Mieke); P. Vemer (Pepijn); de Vries, R. (Robin); A.F.M. (ANNET) van Abeelen; H.L.A. Posthuma (Hidde); C.A. Uyl-de Groot (Carin)

    2016-01-01

    textabstractBackground Obinutuzumab combined with chlorambucil (GClb) has shown to be superior to rituximab combined with chlorambucil (RClb) and chlorambucil (Clb) in newly diagnosed patients with chronic lymphocytic leukaemia (CLL). This study evaluates the cost-effectiveness per life-year and

  18. T-cell prolymphocytic leukaemia (T-PLL): a rare disease with a grave prognosis.

    Science.gov (United States)

    Vivekanandarajah, Abhirami; Atallah, Jean Paul; Gupta, Shilpi

    2013-05-02

    T-cell prolymphocytic leukaemia (T-PLL) is an extremely uncommon haematological malignancy that has an aggressive course and a grave prognosis. We describe a patient who presented with lymphocytosis, scalp erythema, ascites and splenomegaly and was diagnosed with T-PLL. He was treated with alemtuzumab with a good response and was referred for allogeneic stem cell transplantation.

  19. Clinical presentation of childhood leukaemia : a systematic review and meta-analysis

    NARCIS (Netherlands)

    Clarke, Rachel T; Van den Bruel, Ann; Bankhead, Clare; Mitchell, Christopher D; Phillips, Bob; Thompson, Matthew J

    2016-01-01

    OBJECTIVE: Leukaemia is the most common cancer of childhood, accounting for a third of cases. In order to assist clinicians in its early detection, we systematically reviewed all existing data on its clinical presentation and estimated the frequency of signs and symptoms presenting at or prior to di

  20. 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...

  1. Leukaemia and occupation: a New Zealand Cancer Registry-based case-control Study.

    NARCIS (Netherlands)

    McLean, D.; 't Mannetje, A.; Dryson, E.; Walls, C.; McKenzie, F.; Maule, M.; Cheng, S.; Cunningham, C.; Kromhout, H.; Boffetta, P.; Blair, A.; Pearce, N.

    2009-01-01

    BACKGROUND: To examine the association between occupation and leukaemia. METHODS: We interviewed 225 cases (aged 20-75 years) notified to the New Zealand Cancer Registry during 2003-04, and 471 controls randomly selected from the Electoral Roll collecting demographic details, information on potentia

  2. Transmission of bovine leukaemia virus within dairy herds by simulation modelling

    NARCIS (Netherlands)

    Monti, G.E.; Frankena, K.; Jong, de M.C.M.

    2007-01-01

    In Argentina, bovine leukaemia virus (BLV) infection is common in dairy herds. The country currently has a National Voluntary Control Programme but relatively few farms have enrolled. However, there is increased interest from authorities and farmers to implement regional compulsory programmes but th

  3. Evaluation of natural transmission of bovine leukaemia virus within dairy herds of Argentina

    NARCIS (Netherlands)

    Monti, G.E.; Frankena, K.; Jong, de M.C.M.

    2007-01-01

    The purpose of this study was to describe patterns of seroconversion to bovine leukaemia virus and to estimate the main parameters needed for future model building. A longitudinal study was carried out between February 1999 and November 2001 in seven commercial dairy farms in Argentina using 1535 la

  4. Cost-effectiveness of obinutuzumab for chronic lymphocytic leukaemia in The Netherlands

    NARCIS (Netherlands)

    Blommestein, Hedwig M.; de Groot, Saskia; Aarts, Mieke J.; Vemer, Pepijn; de Vries, Robin; van Abeelen, Annet F. M.; Posthuma, E. F. M. Ward; Uyl-de Groota, Carin A.

    2016-01-01

    Background: Obinutuzumab combined with chlorambucil (GClb) has shown to be superior to rituximab combined with chlorambucil (RClb) and chlorambucil (Clb) in newly diagnosed patients with chronic lymphocytic leukaemia (CLL). This study evaluates the cost-effectiveness per life-year and quality adjust

  5. Geographical and ecological analyses of childhood acute leukaemias and lymphomas in north-west England.

    Science.gov (United States)

    McNally, Richard J Q; Alston, Robert D; Cairns, Donal P; Eden, Osborn B; Birch, Jillian M

    2003-10-01

    Childhood leukaemias and lymphomas have been associated with exposure to environmental factors, including infections, which show geographical variation. This study examined the geographical distribution of the incidence of acute leukaemia and lymphoma using Manchester Children's Tumour Registry (MCTR) data 1976-2000. A total of 910 children were included, all of whom had histologically and/or cytologically verified leukaemia or lymphoma. At the time of their diagnoses, all the children were aged 0-14 years and were resident in the counties of Greater Manchester or Lancashire. Standardized morbidity ratios were calculated. Poisson regression was used to examine the relationship between incidence rates and small-area (census ward) population density, ethnic composition and deprivation index. There was a monotonic relationship between acute lymphoblastic leukaemia (ALL) incidence and population density (P = 0.05). Higher rates were seen in more densely populated areas. There was evidence for a monotonic relationship between the incidence of the mixed cellularity subtype of Hodgkin's disease (HD) and the Townsend deprivation score (P = 0.001). Markedly higher incidence was associated with greater levels of unemployment and household overcrowding. The results for ALL and mixed cellularity HD support the involvement of environmental factors, such as infections, in disease aetiology.

  6. Childhood leukaemia in North West England 1954-1977: epidemiology, incidence and survival.

    Science.gov (United States)

    Birch, J M; Swindell, R; Marsden, H B; Morris Jones, P H

    1981-03-01

    The annual incidence of leukaemia among children aged up to 14 years as estimated by the Manchester Children's Tumour Registry has been analysed for the 24 years 1954-1977. A significant increase in acute lymphoid leukaemia (ALL) was found, while the incidence of acute myeloid leukaemia (AML) remained constant. Other types of leukaemia were too rare to be analysed separately. The increase in ALL was concentrated among boys in the 1--5-year age group. Analysis with respect to initial white-cell count showed the increase to be more pronounced in children with initial white cell counts of 1-5 x 10(4)/microliters. The proportion of cases presenting in Lancashire compared with Greater Manchester did not change during the study period. The distribution of cases with respect to social class and socio-economic group of the parents also remained constant. Due to advances in the treatment of childhood ALL survival improved considerably during the study period and no increase in mortality was seen.

  7. 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

  8. Environmental factors and leukaemia risks of children: an overview; Umweltfaktoren und Leukaemierisiko bei Kindern: eine Uebersicht

    Energy Technology Data Exchange (ETDEWEB)

    Schuez, Joachim [Inst. of Cancer Epidemiology, Danish Cancer Society, Copenhagen (Denmark)

    2008-07-01

    Leukaemia is the most common malignancy in childhood, with an incidence rate in Germany of 5.5 per 100,000 children aged 0 to 14 years per year. Overall, epidemiological studies suggest a rather minor role of environmental factors in the development of childhood leukaemia. Ionising radiation is the only established risk factor; however, it is currently unclear at which doses effects occur. Low doses from terrestrial exposures or related to living close to a nuclear power plant show weak associations in recent epidemiological studies, but the findings can at present not be explained with mechanistic models from radiation biology. The consistent association observed in epidemiological studies between extremely low-frequency magnetic fields and childhood leukaemia risk also lacks a good explanation and it is still not known whether this observation displays an artefact or a causal link. Some pesticides appear to be carcinogenic in experiments, but the results from epidemiological studies are inconsistent. No substantial risk appears to be related to air pollution from road traffic. Recent research focused on working hypotheses related to patterns of infections, in particular that an isolation from infectious stimulation in infancy leads to an immature immune system reacting inappropriately to later common infections. While children being at day care at an early age appear to have a reduced risk of childhood leukaemia, more work needs to be done to clearly identify the agents involved in a putative mechanism. (orig.)

  9. 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

  10. Gemtuzumab-induced orchitis in a patient with refractory acute promyelocytic leukaemia.

    Science.gov (United States)

    Jalil-ur-Rehman; Kelta, Muhammad; Awad, Khalid; Beirouti, Basim Al; Nasser, Shahzad; Aslam, Muhammad

    2012-09-01

    We report the case of a 22-year-old Saudi male patient who was treated extensively in the past with various regimens for acute promyelocytic leukaemia that was refractory to all standard treatments. He was ultimately administered Gemtuzumab to induce remission and subjected to an allogeneic bone marrow transplant. However, he developed orchitis, which has not been previously reported with this agent.

  11. Immunological and molecular biological identification of a true case of T-hairy cell leukaemia

    DEFF Research Database (Denmark)

    Demeter, J; Pálóczi, K; Földi, J

    1990-01-01

    A hairy cell leukaemia (HCL) patient is presented in whom the peripheral blood mononuclear cells (PBMCs) carried suppressor T-cell markers (CD3+, CD2+, CD8+/CD4-, CD38+). Analysis of genomic DNA of PBMNC showed the presence of a monoclonal population of T cells, the T-cell receptor (TCR) beta-cha...

  12. An analysis of prognostic variables in acute lymphocytic leukaemia in a heterogenous South African population

    NARCIS (Netherlands)

    Hesseling, PB; Buurman, M; Oud, C; Nel, ED

    1997-01-01

    The records of all 96 children below the age of 15 years diagnosed with acute lymphoblastic leukaemia at Tygerberg Hospital in the Republic of South African between 1983 and 1995 were reviewed to determine risk factors which may predict poor outcome. Age <2 and > 8 years, and white cell count >20 x

  13. Association of inclusion body myositis with T cell large granular lymphocytic leukaemia

    DEFF Research Database (Denmark)

    Greenberg, Steven A; Pinkus, Jack L; Amato, Anthony A

    2016-01-01

    SEE HOHLFELD AND SCHULZE-KOOPS DOI101093/BRAIN/AWW053 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: Inclusion body myositis and T cell large granular lymphocytic leukaemia are rare diseases involving pathogenic cytotoxic CD8+ T cells. After encountering four patients with both disorders, we prospe...

  14. Experience with alemtuzumab in treatment of chronic lymphocytic leukaemia in the Netherlands.

    NARCIS (Netherlands)

    Gorkom, B.A.P. van; Huisman, C.A.; Wijermans, P.W.; Schipperus, M.R.

    2007-01-01

    BACKGROUND: Alemtuzumab (MabCampath) is a monoclonal antibody against CD52, indicated as third-line treatment of chronic lymphocytic leukaemia (CLL). As most important side effect opportunistic infections are mentioned. It is, however, unknown whether these complications often lead to problems in ge

  15. Epigenetic Guardian: A Review of the DNA Methyltransferase DNMT3A in Acute Myeloid Leukaemia and Clonal Haematopoiesis

    Science.gov (United States)

    Chaudry, Sabah F.

    2017-01-01

    Acute myeloid leukaemia (AML) is a haematological malignancy characterized by clonal stem cell proliferation and aberrant block in differentiation. Dysfunction of epigenetic modifiers contributes significantly to the pathogenesis of AML. One frequently mutated gene involved in epigenetic modification is DNMT3A (DNA methyltransferase-3-alpha), a DNA methyltransferase that alters gene expression by de novo methylation of cytosine bases at CpG dinucleotides. Approximately 22% of AML and 36% of cytogenetically normal AML cases carry DNMT3A mutations and around 60% of these mutations affect the R882 codon. These mutations have been associated with poor prognosis and adverse survival outcomes for AML patients. Advances in whole-exome sequencing techniques have recently identified a large number of DNMT3A mutations present in clonal cells in normal elderly individuals with no features of haematological malignancy. Categorically distinct from other preleukaemic conditions, this disorder has been termed clonal haematopoiesis of indeterminate potential (CHIP). Further insight into the mutational landscape of CHIP may illustrate the consequence of particular mutations found in DNMT3A and identify specific “founder” mutations responsible for clonal expansion that may contribute to leukaemogenesis. This review will focus on current research and understanding of DNMT3A mutations in both AML and CHIP. PMID:28286768

  16. Verificación y gestión de facturas electrónicas en un teléfono Android

    OpenAIRE

    Moreno de Frutos, María José

    2014-01-01

    El trabajo consiste en el desarrollo de una aplicación para los teléfonos Android que ayuda a los usuarios a gestionar sus facturas electrónicas en formato facturae. El treball consisteix en el desenvolupament d'una aplicació per als telèfons Android que ajuda els usuaris a gestionar les seves factures electròniques en format facturae. Master thesis for the ICT Security management program.

  17. An S/T-Q cluster domain census unveils new putative targets under Tel1/Mec1 control

    Directory of Open Access Journals (Sweden)

    Cheung Hannah C

    2012-11-01

    Full Text Available Abstract Background The cellular response to DNA damage is immediate and highly coordinated in order to maintain genome integrity and proper cell division. During the DNA damage response (DDR, the sensor kinases Tel1 and Mec1 in Saccharomyces cerevisiae and ATM and ATR in human, phosphorylate multiple mediators which activate effector proteins to initiate cell cycle checkpoints and DNA repair. A subset of kinase substrates are recognized by the S/T-Q cluster domain (SCD, which contains motifs of serine (S or threonine (T followed by a glutamine (Q. However, the full repertoire of proteins and pathways controlled by Tel1 and Mec1 is unknown. Results To identify all putative SCD-containing proteins, we analyzed the distribution of S/T-Q motifs within verified Tel1/Mec1 targets and arrived at a unifying SCD definition of at least 3 S/T-Q within a stretch of 50 residues. This new SCD definition was used in a custom bioinformatics pipeline to generate a census of SCD-containing proteins in both yeast and human. In yeast, 436 proteins were identified, a significantly larger number of hits than were expected by chance. These SCD-containing proteins did not distribute equally across GO-ontology terms, but were significantly enriched for those involved in processes related to the DDR. We also found a significant enrichment of proteins involved in telophase and cytokinesis, protein transport and endocytosis suggesting possible novel Tel1/Mec1 targets in these pathways. In the human proteome, a wide range of similar proteins were identified, including homologs of some SCD-containing proteins found in yeast. This list also included high concentrations of proteins in the Mediator, spindle pole body/centrosome and actin cytoskeleton complexes. Conclusions Using a bioinformatic approach, we have generated a census of SCD-containing proteins that are involved not only in known DDR pathways but several other pathways under Tel1/Mec1 control suggesting new

  18. Multi-disciplinary study for the exploration of deep low enthalpy geothermal reservoirs, Neuchâtel, Switzerland

    Science.gov (United States)

    Mauri, G.; Abdelfettah, Y.; Negro, F.; Schill, E.; Vuataz, F.

    2011-12-01

    The authorities of the canton of Neuchâtel, in the Western part of Switzerland, are willing to develop geothermal energy for district heating in the two main cities of the canton: Neuchâtel, located along the Lake of Neuchâtel, and La Chaux-de-Fonds situated in a high valley of the Jura Massif. The geology of both areas is linked to the Jura Range and present complex structures, where the landscape is composed of anticlines associated with overthrust faults, which are overcut by strike-slip fault and secondary faulting events. The rock formations go from the Trias, which forms the detachment layer, up to the Quaternary rock. Bedrocks are mainly composed of limestones and marls, which can reach a thickness of several hundreds meters. The three main deep aquifers investigated in this area, from the shallowest (≤ 400 m below surface) to deepest (< 2000 m), are the Malm, the Dogger and the Muschelkalk. The estimated temperatures, based on previous studies, should range between 20 to 65 oC, which are function of depth, elevation and groundwater velocity. The expected low temperature is mainly due to the presence of karstic systems, which drains the heat towards the low elevation of the basin. The present study is based on gravimetry surveys, 3D geological models and 3D gravimetry models to best characterize the underground structures and to find areas where the rock properties would be favourable to geothermal exploitation. This means targets where permeability and porosity are high in the potential aquifers, allowing a significant flow at the future production wells. The results indicate that gravity anomalies are associated with both shallow and deep geological structures in the two exploration sites and that high resolution of dense grid gravity measurements combined with realistic 3D models of the geological structures allow to characterize interesting features for deep geothermal exploration. Gravity corrections were carried out with a computing code using

  19. Border Crossings in Maríe Redonnet's Splendid [Seaside] Hôtel

    Directory of Open Access Journals (Sweden)

    Elizabeth A. Mazza-Anthony

    1996-06-01

    Full Text Available Maríe Redonnet crosses previously established boundaries in Splendid Hôtel and Seaside . Her writing flows across traditional literary genres as she revisits certain motifs, characters, and situations in her novel and play. In addition to crossing the border between the novel and theater, she echoes the works of other authors—specifically Rimbaud and Duras. Moreover, within a particular text Redonnet erases subject boundaries. That is to say, her characters are not individuals; their uniqueness is washed away by a continual ebb and flow of common characteristics and traits. By creating such fluid personae, Redonnet captures the societal homogeneity that is symptomatic of "surmodernity" as defined by Mark Augé: "the acceleration and overabundance of events and space and the individualization of references [are] the three elements of excess with which we have tried to characterize the supermodern condition." As she weaves her "literary" text and intertext she also incorporates elements from other disciplines. Indeed, her references to the cinema as well as to the family photograph obscure conventional distinctions between "high" and "mass" culture. At the same time, Redonnet's blurred boundaries create a sense of longing for the past, or more precisely, for past representations. This element of nostalgia sends the characters and, at times, the reader/spectator into the familiar. Thus, traces of past representations emerge in Redonnet's writing as in a palimpsest. In conclusion, by crossing previously established borders, Maríe Redonnet paints the permeable "supermodern" boundaries among individuals, text/intertext, and photography/film/literature.

  20. Results of a randomized trial in children with Acute Myeloid Leukaemia : Medical Research Council AML12 trial

    NARCIS (Netherlands)

    Gibson, Brenda E. S.; Webb, David K. H.; Howman, Andrew J.; De Graaf, Siebold S. N.; Harrison, Christine J.; Wheatley, Keith

    2011-01-01

    The Medical Research Council Acute Myeloid Leukaemia 12 (MRC AML12) trial (children) addressed the optimal anthracenedione/anthracycline in induction and the optimal number of courses of consolidation chemotherapy. 504 children (

  1. Absence of activated murine leukaemia virus in X-irradiated CBA/H-T6Crc mice

    Energy Technology Data Exchange (ETDEWEB)

    Holmes, H.C.; Tuffrey, M.; Wilson, L.; Barnes, R.D. (Medical Research Council, Harrow (UK). Clinical Research Centre)

    1981-04-01

    CBA/H-T6Crc mice, a substrain that does not normally express demonstrable levels of murine leukaemia virus (MuLV) and has a low natural incidence of leukaemia, were examined for evidence of virus activation at various times following X-irradiation. Although X-irradiation caused a high incidence of leukaemia, no ecotropic, xenotropic or recombinant MuLV was detected by in vitro co-cultivation of bone marrow, spleen and thymus cells from pre-leukaemic and leukaemic animals with selectively permissive cell lines followed by indirect immunofluorescence for MuLV group-specific (gs) antigen. These results therefore, are not consistent with the hypothesis that endogenous viruses are the universal aetiological agents of leukaemia.

  2. Wilms' tumour gene 1 (WT1) in human neoplasia.

    NARCIS (Netherlands)

    Keilholz, U.; Menssen, H.D.; Gaiger, A.; Menke, A.; Oji, Y.; Oka, Y.; Scheibenbogen, C.; Stauss, H.; Thiel, E. van; Sugiyama, H.

    2005-01-01

    The transcription factor Wilms' tumour gene 1 (WT1) is important as a prognostic marker as well as in the detection and monitoring of minimal residual disease in leukaemia and myelodysplastic syndromes. Evidence has accumulated over the past decade to show that WT1 is a key molecule for tumour proli

  3. 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

  4. Les grands hôtels, témoins de l’histoire du tourisme.Le Splendid et Royal Hôtel à Saint-Gervais-les-Bains (Haute-Savoie

    Directory of Open Access Journals (Sweden)

    Mireille Bruston

    2000-09-01

    Full Text Available S’intéresser au bâti pour comprendre les territoires, leur structuration et leur recomposition est souvent très éclairant. L’approche spatiale du tourisme n’échappe pas à ce constat et le cas des grands hôtels et des palaces est particulièrement révélateur de la phase de création des stations touristiques. Derrière l’apparente unité d’un bâti se cache parfois une histoire longue et complexe, qu’il convient de décrypter.

  5. Detection of residual bcr/abl translocation by polymerase chain reaction in chronic myeloid leukaemia patients after bone-marrow transplantation.

    Science.gov (United States)

    Gabert, J; Thuret, I; Lafage, M; Carcassonne, Y; Maraninchi, D; Mannoni, P

    1989-11-11

    The polymerase chain reaction was used to evaluate minimum residual disease in chronic myelogenous leukaemia (CML) patients after bone-marrow transplantation, by amplification of the transcript of the specific bcr/abl hybrid gene. Strict precautions were taken to avoid contamination. Peripheral blood cells from 22 patients transplanted for haematological malignant disorders were analysed. The results were clearcut for positive controls (patients with CML in relapse) and negative controls (patients with malignant disorders other than CML). In 11 of 12 CML patients in clinical and cytogenetic remission the bcr/abl transcript was detected 3 months to 6 years after transplantation. Thus, it appears that cells expressing the bcr/abl mRNA are not eradicated from the blood of CML patients in complete clinical remission even years after bone-marrow transplantation.

  6. Fli-1 overexpression in hematopoietic progenitors deregulates T cell development and induces pre-T cell lymphoblastic leukaemia/lymphoma.

    Directory of Open Access Journals (Sweden)

    Monique F M A Smeets

    Full Text Available The Ets transcription factor Fli-1 is preferentially expressed in hematopoietic tissues and cells, including immature T cells, but the role of Fli-1 in T cell development has not been closely examined. To address this we retrovirally overexpressed Fli-1 in various in vitro and in vivo settings and analysed its effect on T cell development. We found that Fli-1 overexpression perturbed the DN to DP transition and inhibited CD4 development whilst enhancing CD8 development both in vitro and in vivo. Surprisingly, Fli-1 overexpression in vivo eventuated in development of pre-T cell lymphoblastic leukaemia/lymphoma (pre-T LBL. Known Fli-1 target genes such as the pro-survival Bcl-2 family members were not found to be upregulated. In contrast, we found increased NOTCH1 expression in all Fli-1 T cells and detected Notch1 mutations in all tumours. These data show a novel function for Fli-1 in T cell development and leukaemogenesis and provide a new mouse model of pre-T LBL to identify treatment options that target the Fli-1 and Notch1 signalling pathways.

  7. Follow-up of post-transplant minimal residual disease and chimerism in childhood lymphoblastic leukaemia: 90 d to react.

    Science.gov (United States)

    Pochon, Cécile; Oger, Emmanuel; Michel, Gérard; Dalle, Jean-Hugues; Salmon, Alexandra; Nelken, Brigitte; Bertrand, Yves; Cavé, Hélène; Cayuela, Jean-Michel; Grardel, Nathalie; Macintyre, Elizabeth; Margueritte, Geneviève; Méchinaud, Françoise; Rohrlich, Pierre; Paillard, Catherine; Demeocq, François; Schneider, Pascale; Plantaz, Dominique; Poirée, Marilyne; Eliaou, Jean-François; Semana, Gilbert; Drunat, Séverine; Jonveaux, Philippe; Bordigoni, Pierre; Gandemer, Virginie

    2015-04-01

    Relapse after transplantation is a major cause of treatment failure in paediatric acute lymphoblastic leukaemia (ALL). Here, we report the findings of a prospective national study designed to investigate the feasibility of immune intervention in children in first or subsequent remission following myeloablative conditioning. This study included 133 children who received a transplant for ALL between 2005 and 2008. Minimal Residual Disease (MRD) based on T cell receptor/immunoglobulin gene rearrangements was measured on days -30, 30, 90 and 150 post-transplantation. Ciclosporin treatment was rapidly discontinued and donor lymphocyte infusions (DLI) were programmed for patients with a pre- or post-transplant MRD status ≥10(-3) . Only nine patients received DLI. Pre- and post-transplant MRD status, and the duration of ciclosporin were independently associated with 5-year overall survival (OS), which was 62·07% for the whole cohort. OS was substantially higher in patients cleared of MRD than in those with persistent MRD (52·3% vs. 14·3%, respectively). Only pre-transplant MRD status (Hazard Ratio 2·57, P = 0·04) and duration of ciclosporin treatment (P < 0·001) were independently associated with relapse. The kinetics of chimerism were not useful for predicting relapse, whereas MRD monitoring up to 90 d post-transplantation was a valuable prognostic tool to guide therapeutic intervention. © 2014 John Wiley & Sons Ltd.

  8. UJI STABILITAS FISIK, KIMIA DAN BIOLOGIK TERHADAP FORMULASI TERBARU LIPOSOM TETRA ETER LIPID (EPC-TEL 2,5 SEBAGAI PEMBAWA OBAT (Drug Carrier

    Directory of Open Access Journals (Sweden)

    Sri Widia A. Jusman

    2007-12-01

    Full Text Available The Physical, Chemical, and the Biological stability test on Liposome EPC-TEL 2.5 as the newest drug delivery systems (drug carrier, in vitro and in vivo. This experiment is carried out in order to improve the stability of the Liposome EPC-TEL 2.5 physically, chemically, and biologically. As a new formula, this liposome that has contained phosphatidylcholine from egg yolk=EPC and Tetra-ether Lipid (TEL from membrane of Sulfolobus acidocaldarius or Thermoplasma acidophilum had never been tested on their stability. The stability of liposome to carry the drug into the targeted cells or organs is required for determining the therapeutic dose of the drugs. Physically, the test was done by measuring the amount and diameter of liposome after incubating at 4º C, at room temperature, and 37º C. Chemically, the test was also done using the same parameters after introduction of chemical solution of NaCl, CaCl2; MgCl2 at the pH of 5; 7; 9. The measurements was carried out on day 1; 7; and month 1; 2; and 3. Biologically, liposome EPC-TEL 2.5 was injected Intra-Peritoneally to mice to detect the degradation of TEL in their liver, at the minute of 0; 30 ; 60 ; the hour of 2; 4; and 8. The results of these tests were shown that liposome EPC-TEL 2.5 was stable until the last month of 1 at 4º C and 37º C on physical stability test; more stable at the chemical solution of NaCl and CaCl2 at the pH of 5 and 7 until two months; and TEL was degradable in liver of mice.

  9. Potencial sesgo de selección en las encuestas telefónicas: teléfonos fijos y móviles

    Directory of Open Access Journals (Sweden)

    Xavier Garcia-Continente

    2014-03-01

    Full Text Available La aparición del teléfono móvil en las últimas décadas ha hecho disminuir la cobertura de hogares españoles con teléfono fijo. Este estudio analiza características sociodemográficas e indicadores de salud según el tipo de teléfono disponible (sólo móvil frente a fijo o fijo y móvil. Se realizaron dos encuestas telefónicas en muestras españolas (febrero de 2010 y febrero de 2011. Se analizaron diferencias en las principales características sociodemográficas según el tipo de teléfono disponible en el hogar, mediante análisis de regresión logística multivariada. Entre las dos encuestas se obtuvieron 2027 respuestas válidas (1627 en fijos y 400 en móviles. La probabilidad de seleccionar individuos extranjeros, de clase social manual, de menor nivel de estudios y fumadores fue mayor en la población contactada mediante teléfono móvil que mediante fijo. El perfil de la población que sólo dispone de teléfono móvil es diferente al de la que dispone de fijo, por lo que la realización de encuestas telefónicas exclusivamente mediante teléfonos fijos puede conllevar un sesgo de selección.

  10. Outcomes of a telemonitoring-based program (telEPOC in frequently hospitalized COPD patients

    Directory of Open Access Journals (Sweden)

    Esteban C

    2016-11-01

    Full Text Available Cristóbal Esteban,1,2 Javier Moraza,1 Milagros Iriberri,3 Urko Aguirre,2,4 Begoña Goiria,5 José M Quintana,2,4 Myriam Aburto,1 Alberto Capelastegui1 1Pneumology Department, Galdakao-Usansolo Hospital, Galdakao, 2Red de Investigación en Servicios Sanitarios y Enfermedades Crónicas (REDISSEC, Bilbao, 3Pneumology Department, Cruces Hospital, Barakaldo, 4Research Unit, Galdakao-Usansolo Hospital, Galdakao, 5Primary Care Unit, Barrualde Integrated Healthcare Organisation (OSI-Barrualde, Spain Background: The increasing prevalence of chronic diseases requires changes in health care delivery. In COPD, telemedicine appears to be a useful tool. Our objective was to evaluate the efficacy (in improving health care-resource use and clinical outcomes of a telemonitoring-based program (telEPOC in COPD patients with frequent hospitalizations. Materials and methods: We conducted a nonrandomized observational study in an intervention cohort of 119 patients (Galdakao-Usansolo Hospital and a control cohort of 78 patients (Cruces Hospital, followed up for 2 years (ClinicalTrials.gov identifier: NCT02528370. The inclusion criteria were two or more hospital admissions in the previous year or three or more admissions in the previous 2 years. The intervention group received telemonitoring plus education and controls usual care. Results: Most participants were men (13% women, and the sample had a mean age of 70 years, forced expiratory volume in 1 second of 45%, Charlson comorbidity index score of 3.5, and BODE (body mass index, airflow obstruction, dyspnea, and exercise capacity index score of 4.1. In multivariate analysis, the intervention was independently related to lower rates of hospital admission (odds ratio [OR] 0.38, 95% confidence interval [CI] 0.27–0.54; P<0.0001, emergency department attendance (OR 0.56, 95% CI 0.35–0.92; P<0.02, and 30-day readmission (OR 0.46, 95% CI 0.29–0.74; P<0.001, as well as cumulative length of stay (OR 0.58, 95% CI 0

  11. Park size and disturbance: impact on soil heterogeneity - a case study Tel-Aviv- Jaffa.

    Science.gov (United States)

    Zhevelev, Helena; Sarah, Pariente; Oz, Atar

    2015-04-01

    Parks and gardens are poly-functional elements of great importance in urban areas, and can be used for optimization of physical and social components in these areas. This study aimed to investigate alteration of soil properties with land usages within urban park and with area size of park. Ten parks differed by size (2 - 50 acres) were chosen, in random, in Tel-Aviv- Jaffa city. Soil was sampled in four microenvironments ((lawn, path, picnic and peripheral area (unorganized area) of each the park)), in three points and three depth (0-2, 5-10 and 10-20 cm). Penetration depth was measured in all point of sampling. For each soil sample electrical conductivity and organic matter content were determined. Averages of penetration depth drastically increased from the most disturbed microenvironments (path and picnic) to the less disturbed ones (lawn and peripheral). The maximal heterogeneity (by variances and percentiles) of penetration depth was found in the peripheral area. In this area, penetration depth increased with increasing park size, i.e., from 2.6 cm to 3.7 cm in the small and large parks, respectively. Averages of organic matter content and electrical conductivity decreased with soil depth in all microenvironments and increased with decreasing disturbance of microenvironments. Maximal heterogeneity for both of these properties was found in the picnic area. Increase of park size was accompanied by increasing of organic matter content in the upper depth in the peripheral area, i.e., from 2.4% in the small parks to 4.5% in the large ones. In all microenvironments the increasing of averages of all studied soil properties was accompanied by increasing heterogeneity, i.e., variances and upper percentiles. The increase in the heterogeneity of the studied soil properties is attributed to improved ecological soil status in the peripheral area, on the one hand, and to the high anthropogenic pressure in the picnic area, on the other. This means that the urban park offers

  12. miR-664 negatively regulates PLP2 and promotes cell proliferation and invasion in T-cell acute lymphoblastic leukaemia

    Energy Technology Data Exchange (ETDEWEB)

    Zhu, Hong; Miao, Mei-hua; Ji, Xue-qiang; Xue, Jun; Shao, Xue-jun, E-mail: xuejunshao@hotmail.com

    2015-04-03

    MicroRNAs (miRNAs) play important roles in the pathogenesis of many types of cancers by negatively regulating gene expression at posttranscriptional level. However, the role of microRNAs in leukaemia, particularly T-cell acute lymphoblastic leukaemia (T-ALL), has remained elusive. Here, we identified miR-664 and its predicted target gene PLP2 were differentially expressed in T-ALL using bioinformatics methods. In T-ALL cell lines, CCK-8 proliferation assay indicated that the cell proliferation was promoted by miR-664, while miR-664 inhibitor could significantly inhibited the proliferation. Moreover, migration and invasion assay showed that overexpression of miR-664 could significantly promoted the migration and invasion of T-ALL cells, whereas miR-664 inhibitor could reduce cell migration and invasion. luciferase assays confirmed that miR-664 directly bound to the 3'untranslated region of PLP2, and western blotting showed that miR-664 suppressed the expression of PLP2 at the protein levels. This study indicated that miR-664 negatively regulates PLP2 and promotes proliferation and invasion of T-ALL cell lines. Thus, miR-664 may represent a potential therapeutic target for T-ALL intervention. - Highlights: • miR-664 mimics promote the proliferation and invasion of T-ALL cells. • miR-664 inhibitors inhibit the proliferation and invasion of T-ALL cells. • miR-664 targets 3′ UTR of PLP2 in T-ALL cells. • miR-664 negatively regulates PLP2 in T-ALL cells.

  13. Mobile health for early retention in HIV care: a qualitative study in Kenya (WelTel Retain).

    Science.gov (United States)

    Smillie, Kirsten; Van Borek, Natasha; van der Kop, Mia L; Lukhwaro, Abigael; Li, Neville; Karanja, Sarah; Patel, Anik R; Ojakaa, David; Lester, Richard T

    2014-01-01

    Many people newly diagnosed with HIV are lost to follow-up before timely initiation of antiretroviral therapy (ART). A randomised controlled trial (RCT), WelTel Kenya1, demonstrated the effectiveness of the WelTel text messaging intervention to improve clinical outcomes among patients initiating ART. In preparation for WelTel Retain, an RCT that will evaluate the effect of the intervention to retain patients in care immediately following HIV diagnosis, we conducted an informative qualitative study with people living with HIV (n = 15) and healthcare providers (HCP) (n = 5) in October 2012. Study objectives included exploring the experiences of people living with HIV who have attempted to engage in HIV care, the use of cell phones in everyday life, and perceptions of communicating via text message with HCP. Participants were recruited through convenience sampling. Semi-structured, qualitative interviews were conducted and recorded, transcribed verbatim and analysed using NVivo software. Analysis was guided by the Theory of Reasoned Action and the Technology Acceptance Model. Results indicate that while individuals have many motivators for engaging in care after diagnosis, structural and individual barriers including poverty, depression and fear of stigma prevent them from doing so. All participants had access to a mobile phone, and most were comfortable communicating through text messages, or were willing to learn. Both people living with HIV and HCP felt that increased communication via the text messaging intervention has the potential to enable early identification of problems, leading to timely problem solving that may improve retention and engagement in care during the first year after diagnosis.

  14. Propuesta de rehabilitación de la casa de correos y telégrafos central de Badalona

    OpenAIRE

    Torres Sánchez, Victoria

    2015-01-01

    En este proyecto final de grado realizaré una rehabilitación de la casa de Correos y Telégrafos central de Badalona sin efectuar un cambio de uso, dato que se desarrollará en los capítulos siguientes. En una primera parte del trabajo, que he articulado en varios capítulos principales, encontraremos una breve introducción donde se explican los objetivos que se pretenden conseguir y el marco normativo que le afecta. Nos introduciremos en la evolución histórica de Correos y ...

  15. El teléfono celular: una estrategia didáctica para la enseñanza del electromagnetismo

    OpenAIRE

    Domingo Padilla Arzúzar; Isabel Garzón Barragán

    2010-01-01

    Las ondas electromagnéticas, oem, son una temática común en los currículos en las carreras de física e ingenierías. A pesar de ello, la manipulación de artefactos que conducen a que los estudiantes se formen una idea de los efectos de las oem es escasa, en gran medida por la falta de equipos de laboratorio adecuados. Debido a esta problemática, nuestra investigación nos condujo a utilizar el teléfono celular, tc, como instrumento de registro de las oem. Junto con los estudiantes, logramos con...

  16. Changing bone marrow micro-environment during development of acute myeloid leukaemia in rats

    DEFF Research Database (Denmark)

    Mortensen, B T; Jensen, P O; Helledie, N;

    1998-01-01

    cells (from about 45% to 25%), evidently as a result of the severely changed microenvironment. In this study we have demonstrated in vivo the development of an acidic and hypoxic bone marrow hampering normal haemopoiesis during leukaemic growth. Our data support the notion of BNML as a valuable tool......The Brown Norwegian rat transplanted with promyelocytic leukaemic cells (BNML) has been used as a model for human acute myeloid leukaemia. We have previously shown that both the blood supply to the bone marrow and the metabolic rate decrease in relation to the leukaemic development in these rats....... Here we have investigated how the development and progression of this leukaemia affect oxygenation, pH and proliferation of normal and leukaemic cells in vivo. Bone marrow pH was measured by a needle electrode. Nitroimidazol-theophylline (NITP) was used to identify hypoxic cells, and we applied...

  17. Application of genomics for risk stratification of childhood acute lymphoblastic leukaemia: from bench to bedside?

    Science.gov (United States)

    Izraeli, Shai

    2010-10-01

    The remarkable progress in the treatment of childhood acute lymphoblastic leukaemia (ALL) has been based on the adjustment of therapy to subgroups of leukaemia stratified by their prognostic implications. Here, the contribution of the last decade of advanced genomic research on the clinical management of childhood ALL is examined. The application of genomics for routine diagnosis of ALL is feasible but depends on commercial development of appropriate certified platforms. The discovery of several novel high-risk markers, such as deletions in IKZF1 might be integrated into clinical protocols in the near future. Several novel targets for therapy have been identified and have led to phase I/II therapeutic trials. This and any future progress depends on the maintenance of high quality bio-banks including biological material and clinical data of each patient enrolled on a prospective clinical protocol. © 2010 Blackwell Publishing Ltd.

  18. Combination chemotherapy for marrow relapse in children and adolescents with acute lymphocytic leukaemia.

    Science.gov (United States)

    Amadori, S; Spiriti, M A; Meloni, G; Pacilli, L; Papa, G; Mandelli, F

    1981-04-01

    38 children with acute lymphocytic leukaemia (ALL) in haematologic relapse were retreated with vincristine, daunomycin and prednisone (VPD) together with intrathecal methotrexate and prednisone, followed by asparaginase in those patients not in complete remission after 4 weeks. The overall complete remission (CR) rate was 79%; asparaginase was needed to achieve CR in 7 of the 30 responding patients. The median duration of second remission was only 36 weeks, but 6 out of 15 children receiving the COAP-POMP-CART consolidation regimen remain in continuous second remission after 37-260 weeks; 3 of them are currently off all therapy. It is concluded that a prolonged second remission can be achieved in children with ALL in bone marrow relapse by combining intensive chemotherapy with the prevention of meningeal leukaemia.

  19. Treatment-related toxicities in children with acute lymphoblastic leukaemia predisposition syndromes

    DEFF Research Database (Denmark)

    Schmiegelow, K.

    2016-01-01

    Although most children with acute lymphoblastic leukaemia (ALL) do not harbor germline mutations that strongly predispose them to development of this malignancy, large syndrome registries and detailed mapping of exomes or whole genomes of familial leukaemia kindreds have revealed that 3-5% of all...... patients is important in order to adjust therapy and offer genetic counseling and cancer surveillance to mutation carriers in the family. In the coming years large genomic screening projects are expected to reveal further hitherto unrecognised familial ALL syndromes. The treatment of ALL cases harboring...... cancer predisposing mutations can be challenging for both the physician and the patient due to their preexisting symptoms, their reduced tolerance to radio- and/or chemotherapy with enhanced risk of life-threatening organ toxicities, and the paucity of data from ALL patients with the same or similar...

  20. Acute sinusitis and blindness as the first presentation of chronic lymphocytic leukaemia.

    Science.gov (United States)

    Lim, K H; Thomas, G; van Beers, E J; Hosman, A E; Mourits, M P; van Noesel, C J M; Kater, A P; Reinartz, S M

    2014-12-01

    Chronic lymphocytic leukaemia (CLL) is the most frequent form of leukaemia among adults in the Western world, presenting at a median age of 65 years. The diagnosis is usually made incidentally during routine blood examination while the disease is still in its early phase. We report a case of blindness of 24 hours due to acute sinusitis based on CLL localisation in a patient with undiagnosed CLL. Emergency endoscopic sinus surgery and intra- and extra-ocular orbital decompression were performed. The sinusitis resolved after surgery and intravenous antibiotics. Her vision improved within 24 hours and eventually recovered completely after six months. Her CLL remained in an indolent state, needing no active treatment. This case illustrates that blindness from a lymphoproliferative disorder may be treated with emergency endoscopic sinus surgery instead of conventional chemotherapy in order to salvage the vision first, even if the vision is lost for more than 24 hours.

  1. Acute myelomonocytic leukaemia with short-term spontaneous remission in a cat.

    Science.gov (United States)

    Mylonakis, M E; Petanides, T A; Valli, V E; Vernau, W; Koytinas, A F; Michael, R S

    2008-06-01

    A 2-year-old, spayed female domestic shorthair cat was referred with a history of anorexia and depression of 1 week duration. On physical examination, the cat was lethargic and febrile, with splenomegaly, anisocoria and ulcerative stomatitis. A complete blood count (CBC) and a biochemistry profile showed leukocytosis, numerous blast cells in the peripheral blood, thrombocytopenia, hyperglobulinaemia and a positive test for feline leukaemia virus antigen. A diagnosis of acute myelomonocytic leukaemia was made on the basis of the results of bone marrow cytology, histopathology, and immunochemistry (CD3, CD79a, lysozyme, and myeloperoxidase) tests. Following an unexpected 1-month period of clinical and clinicopathological remission without chemotherapy, the cat relapsed and died 1 week later.

  2. Evaluation of natural transmission of bovine leukaemia virus within dairy herds of Argentina

    OpenAIRE

    Monti, G.E.; Frankena, K.; Jong, de, F.

    2007-01-01

    The purpose of this study was to describe patterns of seroconversion to bovine leukaemia virus and to estimate the main parameters needed for future model building. A longitudinal study was carried out between February 1999 and November 2001 in seven commercial dairy farms in Argentina using 1535 lactating cows. Time-interval parameters were analysed using a parametric survival model with shared frailty, time until infection was analysed using a Bayesian interval-censoring survival model and ...

  3. Transmission of bovine leukaemia virus within dairy herds by simulation modelling

    OpenAIRE

    Monti, G.E.; Frankena, K.; Jong, de, F.

    2007-01-01

    In Argentina, bovine leukaemia virus (BLV) infection is common in dairy herds. The country currently has a National Voluntary Control Programme but relatively few farms have enrolled. However, there is increased interest from authorities and farmers to implement regional compulsory programmes but there is scarce quantitative information of the transmission of BLV in cattle herds. This information is a prerequisite to develop effective BLV control strategies. Mathematical modelling offers ways...

  4. Dopamine inhibits proliferation, induces differentiation and apoptosis of K562 leukaemia cells

    Institute of Scientific and Technical Information of China (English)

    HE Qun; YUAN Lin-bo

    2007-01-01

    Background Dopamine exerts its effects mainly in nervous system through D1, D2 or D3 receptors. There are few reports dealing with the effects of dopamine on leukaemia cells. However, some dopamine agonists or antagonists do show biological effects on some types of leukaemia cells. Here, we report the effects of dopamine on the proliferation,differentiation and apoptosis of K562 leukaemia cells.Methods Proliferation was determined by MTT assay and cell counting both in liquid and semisolid cultures.Differentiation was verified by morphology, benzidine staining and flow cytometry. Apoptosis was checked by Hoechst 33258 staining and flow cytometry. The two groups were untreated group and treated group (dopamine 10-9 mol/L-10-4mol/L).Results In liquid culture, MTT assay and colony assay, dopamine inhibited proliferation of K562 cells. Inhibition rate was 29.28% at 10-6 mol/L and 36.10% at 10-5 mol/L after culture for 5 days in MTT assay. In benzidine staining and CD71 expression, dopamine induced K562 cells toward erythroid differentiation by increased 155% at 10-6 mol/L and by 171% at 10-5 mol/L after culture for 5 days in benzidine staining. In Hoechst 33258 staining and flow cytometry,dopamine induced K562 cells toward apoptosis. The sub G1 peak stained by PI was 14.23% at 10-4 mol/L dopamine after culture for 3 days compared with the control (0.81%) in flow cytometry.Conclusion Dopamine inhibites proliferation and induces both differentiation and apoptosis of K562 leukaemia cells.

  5. 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.

  6. Bone marrow aplasia in B cell chronic lymphocytic leukaemia: successful treatment with antithymocyte globulin.

    OpenAIRE

    Singal, R; Winfield, D A; Greaves, M.

    1991-01-01

    Pure red cell aplasia is a rare but well known association of chronic lymphocytic leukaemia (CLL). Pancytopenia due to bone marrow aplasia has not been previously described in CLL. A 42 year old man with B cell CLL became severely pancytopenic with bone marrow aplasia. Bone marrow culture resulted in a greatly reduced colony formation. High dose corticosteroids and intravenous immunoglobulin treatment were unsuccessful. Prompt and complete marrow recovery ensued after administration of antith...

  7. Ionising radiation and risk of death from leukaemia and lymphoma in radiation-monitored workers (INWORKS)

    Energy Technology Data Exchange (ETDEWEB)

    Lorenz, Bernd

    2015-07-01

    Since July 2015 the study ''ionising radiation and risk of death from leukaemia and lymphoma in radiation-monitored workers (INWORKS) - an international cohort study'' is available. INWORKS comprised data from 300.000 occupational exposed and dosimetric monitored persons from France, USA and UK. The contribution is a critical discussion of this study with respect to the conclusion of a strong evidence of positive associations between protracted low-dose irradiation exposure and leukemia.

  8. First light of the VLT planet finder SPHERE - II. The physical properties and the architecture of the young systems PZ Tel and HD 1160 revisited

    CERN Document Server

    Maire, A -L; Ginski, C; Vigan, A; Messina, S; Mesa, D; Galicher, R; Gratton, R; Desidera, S; Kopytova, T G; Millward, M; Thalmann, C; Claudi, R U; Ehrenreich, D; Zurlo, A; Chauvin, G; Antichi, J>; Baruffolo, A; Bazzon, A; Beuzit, J -L; Blanchard, P; Boccaletti, A; de Boer, J; Carle, M; Cascone, E; Costille, A; De Caprio, V; Delboulbe, A; Dohlen, K; Dominik, C; Feldt, M; Fusco, T; Girard, J H; Giro, E; Gisler, D; Gluck, L; Gry, C; Henning, T; Hubin, N; Hugot, E; Jaquet, M; Kasper, M; Lagrange, A -M; Langlois, M; Mignant, D Le; Llored, M; Madec, F; Martinez, P; Mawet, D; Milli, J; Moeller-Nilsson, O; Mouillet, D; Moulin, T; Moutou, C; Origne, A; Pavlov, A; Petit, C; Pragt, J; Puget, P; Ramos, J; Rochat, S; Roelfsema, R; Salasnich, B; Sauvage, J -F; Schmid, H M; Turatto, M; Udry, S; Vakili, F; Wahhaj, Z; Weber, L; Wildi, F

    2015-01-01

    [Abridged] Context. The young systems PZ Tel and HD 1160, hosting known low-mass companions, were observed during the commissioning of the new planet finder SPHERE with several imaging and spectroscopic modes. Aims. We aim to refine the physical properties and architecture of both systems. Methods. We use SPHERE commissioning data and REM observations, as well as literature and unpublished data from VLT/SINFONI, VLT/NaCo, Gemini/NICI, and Keck/NIRC2. Results. We derive new photometry and confirm the nearly daily photometric variability of PZ Tel A. Using literature data spanning 38 yr, we show that the star also exhibits a long-term variability trend. The 0.63-3.8 mic SED of PZ Tel B allows us to revise its properties: spectral type M7+/-1, Teff=2700+/-100 K, log(g)0.66) of PZ Tel B. For e4 MJ) outside 0.5" for the PZ Tel system. We also show that K1-K2 color can be used with YJH low-resolution spectra to identify young L-type companions, provided high photometric accuracy (<0.05 mag) is achieved. Conclusi...

  9. The 1957 MRC report on leukaemia and aplastic anaemia in patients irradiated for ankylosing spondylitis

    Energy Technology Data Exchange (ETDEWEB)

    Smith, Peter G [London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT (United Kingdom)

    2007-12-15

    The estimation of the carcinogenic effects of exposure to low doses of ionizing radiation has depended primarily on extrapolation from effects seen in two populations exposed to relatively high doses-the survivors of the atomic bomb explosions in Japan and patients treated in the UK with x-rays for the arthritic condition ankylosing spondylitis. The study of the leukaemia risk in over 14000 irradiated spondylitis patients was completed in an astonishingly short period of time in the mid-1950s. The full report of the original study has been difficult to access because it was not published in a journal but only as a Special Report of the UK Medical Research Council. To mark 50 years since this publication this full report is reproduced in this issue of the Journal. This accompanying review describes the background to the study, the principal findings and the further follow-up of the population that documented the risks of cancers in addition to leukaemia associated with the x-ray treatment. The architects of the study were a radiobiologist, Michael Court-Brown, and an epidemiologist, Richard Doll. Their very productive study of the leukaemia risk among spondylitics spawned a lifelong collaboration including further seminal studies of the carcinogenic effects of radiation exposure, which are also summarised in the review. (review)

  10. Incidence and predictors of treatment-related mortality in paediatric acute leukaemia in El Salvador

    Science.gov (United States)

    Gupta, S; Bonilla, M; Fuentes, S L; Caniza, M; Howard, S C; Barr, R; Greenberg, M L; Ribeiro, R; Sung, L

    2009-01-01

    Survival rates among children with leukaemia in low-income countries are lower than those in high-income countries. This has been attributed in part to higher treatment-related mortality (TRM). We examined the demographics, treatment, and outcomes of paediatric patients in El Salvador with acute lymphoblastic leukaemia (ALL) or acute myeloid leukaemia (AML) to determine the incidence, causes, and risk factors for TRM. Two trained data managers collected data prospectively; no patients were excluded. Biological, socioeconomic and nutritional predictors were examined. A total of 469 patients with ALL and 78 patients with AML were included. The 2-year cumulative incidence of TRM was significantly higher among children with AML (35.4±6.4%) than those with ALL (12.5±1.7%; P<0.0001). However, the proportion of deaths attributable to the toxicity of treatment did not differ significantly between AML (25/47, 53.2%) and ALL (55/107, 51.4%; P=0.98). Among children with ALL, low monthly income (P=0.04) and low parental education (P=0.02) significantly increased the risk of TRM. Among children with AML, biological, socioeconomic, and nutritional variables were not associated with TRM. In this low-income country, toxic death significantly contributes to mortality in both ALL and AML. A better understanding of the effect of socioeconomic status on TRM may suggest specific strategies for patients with ALL. PMID:19293804

  11. The CD68 protein as a potential target for leukaemia-reactive CTL.

    Science.gov (United States)

    Sadovnikova, E; Parovichnikova, E N; Savchenko, V G; Zabotina, T; Stauss, H J

    2002-10-01

    CD68, a haematopoietic differentiation marker of the monocyte-macrophage lineage, is expressed in various human malignancies including chronic and acute myeloid leukaemia (AML). While the majority of normal CD34(+) cells are negative for CD68 expression, CD34(+) cells from AML patients produce elevated amounts of this protein. The purpose of this study was to identify CTL epitopes in the human CD68 protein. Mouse CD68 was also analysed to search for epitopes that could be used in murine tumor model. Peptides binding to murine H2(b) class I molecules were identified and used to stimulate CTL responses from allogeneic donor mice to avoid immunological tolerance. High avidity CTL clones specific for three different peptide epitopes did not kill CD68-expressing murine target cells, indicating that endogenous antigen processing failed to produce sufficient amounts of these peptides. In contrast, allo-restricted human CTL specific for an HLA-A2-binding peptide of CD68 recognised not only picomolar concentrations of peptide, but also displayed low levels of killing against HLA-A2-positive K562 and THP-1 leukemia cell lines and blast cells from AML patients. These data suggest that human leukaemia cells express limited amounts of CD68-derived peptides, and that high avidity CTL capable of recognising sub-picomolar concentrations of peptides are required for efficient killing of leukaemia cells.

  12. Oncogenic roles of PRL-3 in FLT3-ITD induced acute myeloid leukaemia.

    Science.gov (United States)

    Park, Jung Eun; Yuen, Hiu Fung; Zhou, Jian Biao; Al-Aidaroos, Abdul Qader O; Guo, Ke; Valk, Peter J; Zhang, Shu Dong; Chng, Wee Joo; Hong, Cheng William; Mills, Ken; Zeng, Qi

    2013-09-01

    FLT3-ITD mutations are prevalent mutations in acute myeloid leukaemia (AML). PRL-3, a metastasis-associated phosphatase, is a downstream target of FLT3-ITD. This study investigates the regulation and function of PRL-3 in leukaemia cell lines and AML patients associated with FLT3-ITD mutations. PRL-3 expression is upregulated by the FLT3-STAT5 signalling pathway in leukaemia cells, leading an activation of AP-1 transcription factors via ERK and JNK pathways. PRL-3-depleted AML cells showed a significant decrease in cell growth. Clinically, high PRL-3 mRNA expression was associated with FLT3-ITD mutations in four independent AML datasets with 1158 patients. Multivariable Cox-regression analysis on our Cohort 1 with 221 patients identified PRL-3 as a novel prognostic marker independent of other clinical parameters. Kaplan-Meier analysis showed high PRL-3 mRNA expression was significantly associated with poorer survival among 491 patients with normal karyotype. Targeting PRL-3 reversed the oncogenic effects in FLT3-ITD AML models in vitro and in vivo. Herein, we suggest that PRL-3 could serve as a prognostic marker to predict poorer survival and as a promising novel therapeutic target for AML patients.

  13. Quercus Suber L. Cork Extracts Induce Apoptosis in Human Myeloid Leukaemia HL-60 Cells.

    Science.gov (United States)

    Bejarano, Ignacio; Godoy-Cancho, Belén; Franco, Lourdes; Martínez-Cañas, Manuel A; Tormo, María A

    2015-08-01

    Quercus suber L. cork contains a diversity of phenolic compounds, mostly low molecular weight phenols. A rising number of reports support with convergent findings that polyphenols evoke pro-apoptotic events in cancerous cells. However, the literature related to the anti-cancer bioactivity of Q. suber L. cork extractives (QSE) is still limited. Herein, we aim to describe the antitumor potential displayed by cork extractives obtained by different extraction methods in the human promyelocytic leukaemia cells. In order to quantify the effects of QSE on cancer cells viability, phosphatidylserine exposure, caspase-3 activity, mitochondrial membrane potential and cell cycle were evaluated. The results indicated that the QSE present a time-dependent and dose-dependent cytotoxicity in the human promyelocytic leukaemia cells. Such a noxious effect leads these leukaemia cells to their death through apoptotic processes by altering the mitochondrial outer membrane potential, activating caspase-3 and externalizing phosphatidylserine. However, cells cycle progression was not affected by the treatments. This study contributes to open a new way to use this natural resource by exploiting its anti-cancer properties. Moreover, it opens new possibilities of application of cork by-products, being more efficient in the sector of cork-based agriculture. Copyright © 2015 John Wiley & Sons, Ltd.

  14. Breaking bad news--parents' experience of learning that their child has leukaemia.

    LENUS (Irish Health Repository)

    Oshea, J

    2012-02-03

    This study aimed to seek parents\\' experiences of how they learned their child had leukaemia and therefore identify ways of improving this process. To achieve this task a questionnaire was designed to ask parents about specific elements of the initial interview and give them opportunity to add their thoughts and feelings on the subject. All children with a diagnosis of leukaemia over an eighteen-year period were identified and parents of those children still alive were invited to partake in the study. 49 out of 50 families agreed to participate of which 35 (72%) returned completed questionnaires. The majority 29 (83%) expressed overall satisfaction. Their replies confirmed some findings of previous studies, and also offered some new insights. Examples of new findings or expansion on previous findings include observations on the presence of young children at the initial interview; the importance of the language used in conveying the diagnosis and prognostic information, and a preference for actuarial terms when discussing prognosis. Telling parents their child has leukaemia is a challenging and important task. The experience of parents gives us valuable insights into our own communication skills and highlights areas of possible improvement in this difficult area.

  15. El teléfono celular: una estrategia didáctica para la enseñanza del electromagnetismo

    Directory of Open Access Journals (Sweden)

    Domingo Padilla Arzúzar

    2010-10-01

    Full Text Available Las ondas electromagnéticas, oem, son una temática común en los currículos en las carreras de física e ingenierías. A pesar de ello, la manipulación de artefactos que conducen a que los estudiantes se formen una idea de los efectos de las oem es escasa, en gran medida por la falta de equipos de laboratorio adecuados. Debido a esta problemática, nuestra investigación nos condujo a utilizar el teléfono celular, tc, como instrumento de registro de las oem. Junto con los estudiantes, logramos construir un blindaje electromagnético para el tc y un reflector parabólico, en cuyo foco ubicamos un teléfono con conexión con el pc por el puerto usb para registrar las variaciones de la intensidad de la señal del operador celular.

  16. Application of the new pediatric criteria and Tel Hashomer criteria in heterozygous patients with clinical features of FMF.

    Science.gov (United States)

    Ozçakar, Z Birsin; Yalçınkaya, Fatoş; Cakar, Nilgün; Acar, Banu; Bilgiç, A Evren; Uncu, Nermin; Kara, Nazlı; Ekim, Mesiha; Kasapçopur, Ozgür

    2011-08-01

    Recently, a new set of criteria was established for the diagnosis of familial Mediterranean fever (FMF) in childhood. The aim of this study is to validate the new criteria set among heterozygous patients with clinical features of FMF. The study group consisted of FMF patients, who had a mutation at a single allele, who were followed in four pediatric nephrology-rheumatology centers in Turkey. Patients were evaluated by the new criteria set and also by the Tel Hashomer criteria. According to the new criteria, the diagnosis of FMF was established by the presence of two or more of five criteria (fever, abdominal pain, chest pain, arthritis, family history of FMF). The study group consisted of 110 FMF (54 male, 56 female) patients. Majority of the patients had heterozygous pM694V mutation (65%). The sensitivity of the new criteria set and that of the Tel Hashomer criteria in our study group were found to be 93% and 100%, respectively. In conclusion, this study designates that sensitivity of the new criteria set is also high in patients who had a mutation at a single allele.

  17. Indications of stellar prominence oscillations on fast rotating stars: the cases of HK Aqr and PZ Tel

    CERN Document Server

    Leitzinger, M; Zaqarashvili, T V; Greimel, R; Hanslmeier, A; Lammer, H

    2016-01-01

    We present the analysis of six nights of spectroscopic monitoring of two young and fast rotating late-type stars, namely the dMe star HK Aqr and the dG/dK star PZ Tel. On both stars we detect absorption features reminiscent of signatures of co-rotating cool clouds or prominences visible in H$\\alpha$. Several prominences on HK Aqr show periodic variability in the prominence tracks which follow a sinusoidal motion (indication of prominence oscillations). On PZ Tel we could not find any periodic variability in the prominence tracks. By fitting sinusoidal functions to the prominence tracks we derive amplitudes and periods which are similar to those of large amplitude oscillations seen in solar prominences. In one specific event we also derive a periodic variation of the prominence track in the H$\\beta$ spectral line which shows an anti-phase variation with the one derived for the H$\\alpha$ spectral line. Using these parameters and estimated mass density of a prominence on HK Aqr we derive a minimum magnetic field...

  18. Indications of stellar prominence oscillations on fast rotating stars: the cases of HK Aqr and PZ Tel

    Science.gov (United States)

    Leitzinger, M.; Odert, P.; Zaqarashvili, T. V.; Greimel, R.; Hanslmeier, A.; Lammer, H.

    2016-11-01

    We present the analysis of six nights of spectroscopic monitoring of two young and fast rotating late-type stars, namely the dMe star HK Aqr and the dG/dK star PZ Tel. On both stars, we detect absorption features reminiscent of signatures of corotating cool clouds or prominences visible in Hα. Several prominences on HK Aqr show periodic variability in the prominence tracks which follow a sinusoidal motion (indication of prominence oscillations). On PZ Tel, we could not find any periodic variability in the prominence tracks. By fitting sinusoidal functions to the prominence tracks, we derive amplitudes and periods which are similar to those of large-amplitude oscillations seen in solar prominences. In one specific event, we also derive a periodic variation of the prominence track in the Hβ spectral line which shows an anti-phase variation with the one derived for the Hα spectral line. Using these parameters and estimated mass density of a prominence on HK Aqr, we derive a minimum magnetic field strength of ˜2 G. The relatively low strength of the magnetic field is explained by the large height of this stellar prominence (≥ 0.67 stellar radii above the surface).

  19. The design and qualification of the TEL CLEAN TRACK ACT TM M photomask coating tool at Intel

    Science.gov (United States)

    Jamieson, Andrew; Dam, Thuc; Baik, Ki-Ho; Duerksen, Ken; Eidson, Elie; Akai, Keiji; Hisano, Kazuya; Kohama, Norifumi; Machidori, Shinichi

    2006-05-01

    As photomask complexity has increased, mask manufacturing has become significantly more challenging. Tightening specs on defect performance, resolution, and CD control have pushed mask manufacturing to achieve levels that nearly match wafer capabilities. To meet wafer manufacturing needs, mask production requires high yield and quick turn-around time, resulting in an increased demand for very high equipment reliability. In-line resist coating capability is important to meet these demands; both for robust 2 nd level phase-shift coating processes, and the enablement of advanced 1 st-level process development with new resists and new resist process conditions. Intel Corporation worked with Tokyo Electron Ltd (TEL) to bring one of the first CLEAN TRACK ACT M (ACT M) units through design, acceptance tests and into manufacturing. TEL's CLEAN TRACK ACT M is a resist coating tool based on the CLEAN TRACK ACT12 (ACT 12) wafer manufacturing platform, and contains multiple mask-specific modules including advanced softbake oven units, edge-bead removal modules, and cleaning systems. After setup and optimization, the tool shows impressive performance, (for example, within-plate thickness uniformity of manufacturing performance.

  20. [Patterns of prescription of opioid analgesics in Hôtel-Dieu de France of Beyrouth].

    Science.gov (United States)

    Noufi, P; Khoury, E; Ayoub, E; Naccache, N; Richa, S

    2016-12-01

    participants were unrelated to prescribing, but those with specialty training and use of practice guidelines were more likely to prescribe opioids and were less reluctant to do so. A majority of practitioners felt that opioids are effective for the treatment of chronic nonmalignant pain and that they have the sufficient training to prescribe them adequately; however, they still worry about the long-term prescription of opioids, particularly fearing the psychological dependence this treatment might cause. Using a series of Spearman correlation tests, we found that practitioners who thought they were adequately trained and who believed in the efficacy of long-term opioid treatment were more likely to prescribe them but that the worries about side effects decreased the frequency of prescription. A significant proportion of practitioners do not evaluate addiction risk factors of patients before prescribing opioids. The results concerning the modalities of follow-up of prescription were very heterogeneous with 87% of practitioners not explaining and 65% not screening for adverse effects. We similarly found that the frequency of follow-up and the management of patients who were exhibiting signs of dependence were very diverse. The results of this study were compatible with those of other recent studies about opioid prescription. The doctors practicing in the university hospital Hôtel-Dieu de France de Beyrouth present comparable prescription patterns, independent of their personal or professional characteristics, and they are more confident in their prescription when professionally trained for it. However, they exhibit a notable heterogeneity in their attitudes towards opioids and in their modalities of evaluating patients receiving long-term treatment. These results suggest a need for additional training in the management of this category of drugs. Copyright © 2016. Published by Elsevier Masson SAS.

  1. Spatial variability of soil and vegetation characteristics in an urban park in Tel-Aviv

    Science.gov (United States)

    Sarah, Pariente; Zhevelev, Helena M.; Oz, Atar

    2010-05-01

    Mosaic-like spatial patterns, consisting of divers soil microenvironments, characterize the landscapes of many urban parks. These microenvironments may differ in their pedological, hydrological and floral characteristics, and they play important roles in urban ecogeomorphic system functioning. In and around a park covering 50 ha in Tel Aviv, Israel, soil properties and herbaceous vegetation were measured in eight types of microenvironments. Six microenvironments were within the park: area under Ceratonia siliqua (Cs-U), area under Ficus sycomorus (Fi-U), a rest area under F. sycomorus (Re-U), an open area with bare soil (Oa-S), an open area with biological crusts (Oa-C), and an open area with herbaceous vegetation (Oa-V). Outside the park were two control microenvironments, located, respectively, on a flat area (Co-P) and an inclined open area (Co-S). The soil was sampled from two depths (0-2 and 5-10 cm), during the peak of the growing season (March). For each soil sample, moisture content, organic matter content, CaCO3 content, texture, pH, electrical conductivity, and soluble ions contents were determined in 1:1 water extraction. In addition, prior to the soil sampling, vegetation cover, number of species, and species diversity of herbaceous vegetation were measured. The barbecue fires and visitors in each of the microenvironments were counted. Whereas the soil organic matter and vegetation in Fi-U differed from those in the control(Co-P, Co-S), those in Oa-V were similar to those in the control. Fi-U was characterized by higher values of soil moisture, organic matter, penetration depth, and vegetation cover than Cs-U. Open microenvironments within the park (Oa-S, Oa-C, Oa-V) showed lower values of soil penetration than the control microenvironments. In Oa-V unique types of plants such as Capsella bursa-pastoris and Anagallis arvensis, which did not appear in the control microenvironments, were found. This was true also for Fi-U, in which species like Oxalis pes

  2. Molecular response to imatinib & its correlation with mRNA expression levels of imatinib influx & efflux transporters in patients with chronic myeloid leukaemia in chronic phase

    Directory of Open Access Journals (Sweden)

    Hemant Malhotra

    2015-01-01

    Full Text Available Background & objectives: Imatinib is the standard first-line treatment for chronic myeloid leukaemia (CML patients. About 20 to 30 per cent patients develop resistance to imatinib and fail imatinib treatment. One of the mechanisms proposed is varying expression levels of the drug transporters. This study was aimed to determine the expression levels of imatinib transporter genes (OCT1, ABCB1, ABCG2 in CML patients and to correlate these levels with molecular response. Methods: Sixty three CML chronic phase patients who were on 400 mg/day imatinib for more than two years were considered for gene expression analysis study for OCT1, ABCB1 and ABCG2 genes. These were divided into responders and non-responders. The relative transcript expression levels of the three genes were compared between these two categories. The association between the expression values of these three genes was also determined. Results: No significant difference in the expression levels of OCT1, ABCB1 and ABCG2 was found between the two categories. The median transcript expression levels of OCT1, ABCB1 and ABCG2 genes in responders were 26.54, 10.78 and 0.64 versus 33.48, 7.09 and 0.53 in non-responders, respectively. A positive association was observed between the expression of the ABCB1 and ABCG2 transporter genes (r=0.407, P<0.05 while no association was observed between the expression of either of the ABC transporter genes with the OCT1 gene. Interpretation & conclusions: Our findings demonstrated that the mRNA expression levels of imatinib transporter genes were not correlated with molecular response in CML patients. Further studies need to be done on a large sample of CML patients to confirm these findings.

  3. Eflúvio telógeno pós quadro de dengue - relatos de casos

    Directory of Open Access Journals (Sweden)

    Maria Carolina Coelho Gozzano

    2015-10-01

    Full Text Available Introdução: Eflúvio telógeno (ET é uma forma de alopecia difusa caracterizada pelo aumento do número de fios na fase telógena, como resultado de uma mudança anormal no ciclo folicular, podendo ser crônica ou transitória. ET pode ser desencadeado por: febre, cirurgia, drogas, doenças sistêmicas, estresse, entre outros. Não existe explicação definitiva para o fenômeno, mas sabe-se que as alterações aceleram a entrada dos fios da fase anágena para a fase telógena. Geralmente o ET ocorre cerca de 2 a 3 meses após a ocorrência do fato que a gerou. Diagnóstico do ET é difícil pela ausência de sintomas ou características específicas; eventualmente o cabelo pode tornar-se mais fino e apresentar algum grau de rarefação; não há prurido, descamação ou inflamação; o teste de tração leve dos fios pode ser positivo e o tricograma apresentará mais do que 20% de fios telógenos. Tratamento do ET depende do fator desencadeante e seu controle, mas não há tratamento específico para o eflúvio telógeno. Objetivo: Relatar 11 casos de ET após quadro febril-infeccioso de dengue. Metodologia: Pacientes atendidos em ambulatório diagnosticados com ET, no período de junho a agosto de 2015. Resultados: 10 pacientes do sexo feminino e 1 masculino, referiram queixa de queda de cabelo após quadro de dengue, com início da perda dos fios variando de 1 a 5 meses após o quadro infeccioso (5 casos após 1 mês, 1 caso após 2 meses, 1 caso após 3 meses, 3 casos após 4 meses e 1 caso após 1 mês. Conclusão: ET geralmente é uma doença reativa e reversível. Muitas vezes, após um quadro febril-infeccioso, a queda se resolve de forma espontânea, mas causa grande preocupação pela intensidade e rapidez da instalação da queda. Portanto, identificar e corrigir possíveis causas subjacentes e tranquilizar o paciente são os componentes mais importantes no tratamento.

  4. T cell lymphoblastic leukaemia/lymphoma associated with a microenvironment of thymic asteroid B cells in the bone marrow.

    Science.gov (United States)

    Naresh, Kikkeri N; May, Philippa C; Reid, Alistair G; Marks, Alexandra J; Macdonald, Donald; Kanfer, Ed

    2010-10-01

      Asteroid B cells are a component of normal thymus. It is currently unclear whether these cells are identifiable in T cell lymphoblastic leukaemia/lymphoma (T-ALL/LBL) of the thymus. The aim of this study was to identify asteroid B cells both in thymic and extrathymic tissue involved by T-ALL/LBL.   Thymic, lymph node (LN) and bone marrow trephine biopsy (BMTB) samples from eight patients with T-ALL/LBL were reviewed. All had been investigated by immunohistochemistry and one by fluorescent in situ hybridization (FISH). The BMTB samples of two of eight T-ALL/LBLs and LN sample in one of them showed the presence of asteroid-shaped B cells with dendritic cytoplasmic processes. These B cells also expressed CD23 and the features were akin to the unique thymic asteroid B cells. Both patients had aggressive/resistant disease. Cytogenetic analysis in one showed a complex translocation involving the T cell receptor beta (TCRB) gene at 7q35 and a distal region of 9q known to harbour the NOTCH1 gene.   This is the first report of T-ALL/LBL documenting the presence of an asteroid B cell-rich microenvironment at bone marrow and LN sites. In this small subset, T-ALL/LBL cells are possibly dependent upon asteroid B cells, and whether targeting of asteroid B cells with anti-CD20 monoclonal antibody in such cases will result in clinical benefit remains to be determined. © 2010 Blackwell Publishing Limited.

  5. Maintenance treatment with azacytidine for patients with high-risk myelodysplastic syndromes (MDS) or acute myeloid leukaemia following MDS in complete remission after induction chemotherapy

    DEFF Research Database (Denmark)

    Grövdal, Michael; Karimi, Mohsen; Khan, Rasheed

    2010-01-01

    This prospective Phase II study is the first to assess the feasibility and efficacy of maintenance 5-azacytidine for older patients with high-risk myelodysplastic syndrome (MDS), chronic myelomonocytic leukaemia and MDS-acute myeloid leukaemia syndromes in complete remission (CR) after induction...

  6. Leukaemia incidence and survival in children and adolescents in Europe during 1978-1997. Report from the Automated Childhood Cancer Information System project

    NARCIS (Netherlands)

    Coebergh, J. W. W.; Reedijk, A. M. J.; de Vries, E.; Martos, C.; Jakab, Z.; Steliarova-Foucher, E.; Kamps, W. A.

    2006-01-01

    Leukaemias constitute approximately one-third of cancers in children (age 0-14 years) and 10% in adolescents (age 15-19 years). Geographical patterns (1988-1997) and time trends (1978-1997) of incidence and survival from leukaemias in children (n = 29,239) and adolescents (n = 1929) were derived fro

  7. Treatment for myeloid leukaemia of Down syndrome: population-based experience in the UK and results from the Medical Research Council AML 10 and AML 12 trials.

    NARCIS (Netherlands)

    Rao, A.; Hills, R.K.; Stiller, C.; Gibson, B.E.; Graaf, S.S.N. de; Hann, I.M.; O'Marcaigh, A.; Wheatley, K.; Webb, D.K.

    2006-01-01

    Down syndrome (DS) children are at an increased risk of developing myelodysplasia and acute myeloid leukaemia (AML). We retrospectively analysed the population-based data on 81 children with myeloid leukaemia of Down syndrome (ML-DS) from the UK National Registry of Childhood Tumours and experience

  8. Low frequency of MLL-partial tandem duplications in paediatric acute myeloid leukaemia using MLPA as a novel DNA screenings technique.

    NARCIS (Netherlands)

    Balgobind, B.V.; Hollink, I.H.; Reinhardt, D.; Wering, E.R. van; Graaf, S.S.N. de; Baruchel, A.; Stary, J.; Beverloo, H.B.; Greef, G.E. de; Pieters, R.; Zwaan, C.M.; Heuvel-Eibrink, M.M. van den

    2010-01-01

    Mixed-lineage leukaemia (MLL)-partial tandem duplications (PTDs) are found in 3-5% of adult acute myeloid leukaemia (AML), and are associated with poor prognosis. In adult AML, MLL-PTD is only detected in patients with trisomy 11 or internal tandem duplications of FLT3 (FLT3-ITD). To date, studies i

  9. Ciberacoso mediante teléfono móvil e Internet en las relaciones de noviazgo entre jóvenes

    OpenAIRE

    Roberto Martínez Pecino; Mercedes Durán Segura

    2015-01-01

    El ciberacoso es un fenómeno ampliamente analizado entre adolescentes, sin embargo en España ha sido poco estudiado entre jóvenes y particularmente en sus relaciones de noviazgo. Empleando una metodología cuantitativa este estudio analiza el ciberacoso mediante el teléfono móvil e Internet en las relaciones de noviazgo en una muestra compuesta por 336 estudiantes universitarios. El análisis de resultados indica que un 57,2% declara haber sido victimizado por su pareja mediante el teléfono móv...

  10. Tel-Aviv a cent ans ! 1909-2009 : un siècle de globalisation au Proche-Orient

    Directory of Open Access Journals (Sweden)

    Caroline Rozenholc

    2009-03-01

    Full Text Available En mettant en perspective les grandes étapes du développement de Tel-Aviv, cet article propose de lire la capitale économique et culturelle d’Israël comme un lieu d’ancrage des idéologies du 20ème siècle européen au Proche-Orient. Sans faire l’impasse sur la mondialisation à l’œuvre dans la ville aujourd’hui, cette réflexion se déploie autour de la l’inscription récente de Tel-Aviv au patrimoine mondial de l’humanité. D’un quartier de Jaffa, Tel-Aviv est devenue la « Ville Blanche », la ville du Bauhaus, la vitrine des tendances du mouvement moderne en architecture. L’enchaînement raisonné de ces différents moments permet de mettre à jour la manière dont cette ville « sans histoire » est entrée de plain-pied dans l’Histoire. Ainsi, des maisons d’un étage qui marquent la naissance de la ville, à la tour de verre et d’aluminium de « l’architecte du blanc », Richard Meir, en passant par la reconnaissance de la ville comme inflexion « locale » d’une proposition architecturale internationale, Tel-Aviv se révèle comme un laboratoire exceptionnel de l’articulation local/global. Et l’engouement des architectes les plus prestigieux pour la ville ne fait que réactualiser Tel-Aviv comme lieu où jouent ces assemblages complexes d’espaces et de temporalités.Putting Tel Aviv’s development into perspective, this contribution suggests “reading” Israel’s economical and cultural capital – Tel-Aviv – as the successful implementation of 20th century European ideologies in the Middle East, Jaffa, Palestine. The starting point of this paper is the proclamation of Tel-Aviv as a World Cultural Heritage site for its unique urban and historical fabric, commonly known as the “White City” or the Bauhaus City. But how this city – generally considered as “devoid of history” – too set foot in History? And how from the one storey houses of the first neighborhood of Tel

  11. Child leukaemia and low frequency electromagnetic fields; Les leucemies de l'enfant et les champs electromagnetiques basse frequence

    Energy Technology Data Exchange (ETDEWEB)

    Clavel, J.

    2009-07-01

    The author discusses the possible causes of child leukaemia: exposure to natural ionizing radiation (notably radon), to pesticides, and to hydrocarbons emitted by road traffic. Some studies suggested that an inadequate reaction of the immune system to an ordinary infection could result in leukaemia. Other factors are suspected, notably extremely low frequency electromagnetic fields, the influence of which is then discussed by the author. She evokes and discusses results of different investigations on this topic which have been published since the end of the 1970's. It appears that a distance less than 50 meters from high voltage lines or the vicinity of transformation stations may double the risk of child leukaemia

  12. Integrating multiple immunogenetic data sources for feature extraction and mining somatic hypermutation patterns: the case of "towards analysis" in chronic lymphocytic leukaemia.

    Science.gov (United States)

    Kavakiotis, Ioannis; Xochelli, Aliki; Agathangelidis, Andreas; Tsoumakas, Grigorios; Maglaveras, Nicos; Stamatopoulos, Kostas; Hadzidimitriou, Anastasia; Vlahavas, Ioannis; Chouvarda, Ioanna

    2016-06-06

    Somatic Hypermutation (SHM) refers to the introduction of mutations within rearranged V(D)J genes, a process that increases the diversity of Immunoglobulins (IGs). The analysis of SHM has offered critical insight into the physiology and pathology of B cells, leading to strong prognostication markers for clinical outcome in chronic lymphocytic leukaemia (CLL), the most frequent adult B-cell malignancy. In this paper we present a methodology for integrating multiple immunogenetic and clinocobiological data sources in order to extract features and create high quality datasets for SHM analysis in IG receptors of CLL patients. This dataset is used as the basis for a higher level integration procedure, inspired form social choice theory. This is applied in the Towards Analysis, our attempt to investigate the potential ontogenetic transformation of genes belonging to specific stereotyped CLL subsets towards other genes or gene families, through SHM. The data integration process, followed by feature extraction, resulted in the generation of a dataset containing information about mutations occurring through SHM. The Towards analysis performed on the integrated dataset applying voting techniques, revealed the distinct behaviour of subset #201 compared to other subsets, as regards SHM related movements among gene clans, both in allele-conserved and non-conserved gene areas. With respect to movement between genes, a high percentage movement towards pseudo genes was found in all CLL subsets. This data integration and feature extraction process can set the basis for exploratory analysis or a fully automated computational data mining approach on many as yet unanswered, clinically relevant biological questions.

  13. Estrategias de flexibilidad productiva y cambio tecnológico en Teléfonos de México

    OpenAIRE

    Gabriel Pérez; Gerardo Tunal

    2003-01-01

    El presente artículo analiza cómo se dio el proceso de reestructuración productiva y flexibilidad laboral en Teléfonos de México, S.A. de C.V. (Telmex) a partir de los años ochenta. Específicamente se examina cómo se da éste a través de la firma de un convenio de concertación para la apertura y la competencia; los cambios en algunas cláusulas de los Contratos Colectivos de Trabajo (CCT) derivadas de la puesta en marchar de un convenio de productividad; la compactación de especialidades; las e...

  14. TEL (Tecnology – Enhanced - Learning), sobre plataformas móviles para gamificación potenciada con realidad aumentada

    OpenAIRE

    Hermoso García, Cristina

    2016-01-01

    Dentro del amplio campo de la Innovación Educativa, y atendiendo al específico de las Tecnologías para Potenciación del Aprendizaje (TEL), ya en los años 80 se empezaba a habla de “gamificar”, pero no fue hasta el año 2008 que se dio a conocer el término gamificación, desde entonces esta técnica ha ido en auge y cada vez más se va instalando en nuestra vida diaria, aunque no nos demos cuenta. La finalidad de este trabajo no es otra que usar dicha técnica, La Gamificación, en el ámbito educ...

  15. Tels des astres éteints de Léonora Miano : habiter un nom, habiter une peau

    Directory of Open Access Journals (Sweden)

    Myriam Mallart Brussosa

    2013-11-01

    Full Text Available In her novel Tels des astres éteints, Léonora Miano creates an onomastic game haunted by questions of belonging and identity. Overinvested with meaning, the forenames of the three protagonists, all products of the African diaspora, reveal something of their past lives and their destinies. The lack of a surname also testifies to their deracination, sought after or suffered. The « intimate drama » of these drifters, which flirts with madness, even, is expressed in part by the issue of naming, enabling the writer to speak of the difficulty of inhabiting a «black skin» today, but above all revealing the impossibility of defining any identity.

  16. Forced recombination of psi-modified murine leukaemia virus-based vectors with murine leukaemia-like and VL30 murine endogenous retroviruses

    DEFF Research Database (Denmark)

    Mikkelsen, J G; Lund, Anders Henrik; Duch, M;

    1999-01-01

    -impaired Akv-MLV-derived vectors, we here examine putative genetic interactions between vector RNAs and copackaged endogenous retroviral RNAs of the murine leukaemia virus (MLV) and VL30 retroelement families. We show (i) that MLV recombination is not blocked by nonhomology within the 5' untranslated region...... harbouring the supposed RNA dimer-forming cis -elements and (ii) that copackaged retroviral RNAs can recombine despite pronounced sequence dissimilarity at the cross-over site(s) and within parts of the genome involved in RNA dimerization, encapsidation and strand transferring during reverse transcription....... We note that recombination-based rescue of primer binding site knock-out retroviral vectors may constitute a sensitive assay to register putative genetic interactions involving endogenous retroviral RNAs present in cells of various species....

  17. BCR-ABL DERIVED PEPTIDE VACCINES FOR CHRONIC MYELOID LEUKAEMIA

    Directory of Open Access Journals (Sweden)

    M. Bocchia

    2012-01-01

    Full Text Available Chronic Myeloid Leukemia (CML is a myeloproliferative pluripotent stem cell disorder characterized by the presence of a cytogenetic hallmark, the Philadelphia (Ph chromosome, and accounts for 15% of adult leukemias. The disease progresses from a chronic phase through an accelerated phase to a blast phase and its natural course accounts for a median 4 years survival1. The Ph chromosome is derived by a reciprocal translocation termed t(9;22 in which the c-abl oncogene has moved from chromosome 9 into the breakpoint cluster region (bcr, within the bcr gene on chromosome 22, resulting in a chimeric bcr-abl fusion gene that encodes a 210 KD protein (p210 with constitutive tyrosine kinase activity. Two major alternative chimeric p210 can result from this fusion gene: p210-b2a2 where the junction occurs between bcr exon 2 (b2 and abl exon 2 (a2 and p210-b3a2 where the the junction occurs between bcr exon 3 (b3 and abl exon 2 (a2. About 40% of CML patients harbor the p210-b2a2 and about 60% of them show the p210-b3a2.

  18. Pch2 acts through Xrs2 and Tel1/ATM to modulate interhomolog bias and checkpoint function during meiosis.

    Directory of Open Access Journals (Sweden)

    Hsuan-Chung Ho

    2011-11-01

    Full Text Available Proper segregation of chromosomes during meiosis requires the formation and repair of double-strand breaks (DSBs to form crossovers. Repair is biased toward using the homolog as a substrate rather than the sister chromatid. Pch2 is a conserved member of the AAA(+-ATPase family of proteins and is implicated in a wide range of meiosis-specific processes including the recombination checkpoint, maturation of the chromosome axis, crossover control, and synapsis. We demonstrate a role for Pch2 in promoting and regulating interhomolog bias and the meiotic recombination checkpoint in response to unprocessed DSBs through the activation of axial proteins Hop1 and Mek1 in budding yeast. We show that Pch2 physically interacts with the putative BRCT repeats in the N-terminal region of Xrs2, a member of the MRX complex that acts at sites of unprocessed DSBs. Pch2, Xrs2, and the ATM ortholog Tel1 function in the same pathway leading to the phosphorylation of Hop1, independent of Rad17 and the ATR ortholog Mec1, which respond to the presence of single-stranded DNA. An N-terminal deletion of Xrs2 recapitulates the pch2Δ phenotypes for signaling unresected breaks. We propose that interaction with Xrs2 may enable Pch2 to remodel chromosome structure adjacent to the site of a DSB and thereby promote accessibility of Hop1 to the Tel1 kinase. In addition, Xrs2, like Pch2, is required for checkpoint-mediated delay conferred by the failure to synapse chromosomes.

  19. Increased cellular hypoxia and reduced proliferation of both normal and leukaemic cells during progression of acute myeloid leukaemia in rats

    DEFF Research Database (Denmark)

    Jensen, P O; Mortensen, B T; Hodgkiss, R J;

    2000-01-01

    The microenvironmental changes in the bone marrow, spleen and liver during progression of the transplantable promyelocytic leukaemia in the Brown Norwegian rat (BNML) have been studied. We used flow cytometry to estimate cellular hypoxia and proliferation based on in vivo pulse-labelling with a m......The microenvironmental changes in the bone marrow, spleen and liver during progression of the transplantable promyelocytic leukaemia in the Brown Norwegian rat (BNML) have been studied. We used flow cytometry to estimate cellular hypoxia and proliferation based on in vivo pulse...

  20. Characterisation and Clinical Significance of FLT3-ITD and non-ITD in Acute Myeloid Leukaemia Patients in Kelantan, Northeast Peninsular Malaysia.

    Science.gov (United States)

    Yunus, Noraini Mat; Johan, Muhammad Farid; Ali Nagi Al-Jamal, Hamid; Husin, Azlan; Hussein, Abdul Rahim; Hassan, Rosline

    2015-01-01

    Mutations of the FMS-like tyrosine kinase-3 (FLT3) receptor gene may promote proliferation via activation of multiple signaling pathways. FLT3-internal tandem duplication (FLT3-ITD) is the most common gene alteration found in patients diagnosed with acute myeloid leukaemia (AML) and has been associated with poor prognosis. We performed mutational analysis of exons 14-15 and 20 of the FLT3 gene in 54 AML patients using PCR-CSGE (conformational sensitive gel electrophoresis) followed by sequencing analysis to characterise FLT3 mutations in adult patients diagnosed with AML at Hospital USM, Kelantan, Northeast Peninsular Malaysia. FLT3 exon 14-15 mutations were identified in 7 of 54 patients (13%) whereas no mutation was found in FLT3 exon 20. Six ITDs and one non-ITD mutation were found in exon 14 of the juxtamembrane (JM) domain of FLT3. FLT3-ITD mutations were associated with a significantly higher blast percentage (p-value=0.008) and white blood cell count (p-value=0.023) but there was no significant difference in median overall survival time for FLT3-ITD+/FLT3-ITD- within 2 years (p-value=0.374). The incidence of FLT3-ITD in AML patients in this particular region of Malaysia is low compared to the Western world and has a significant association with WBC and blast percentage.

  1. Abscopal induction of leukaemia and osteosarcoma following administration of alpha-emitting radionuclides

    Energy Technology Data Exchange (ETDEWEB)

    Lord, B.I. (Paterson Institute for Cancer Research, Christie Hospital Manchester, Manchester (United Kingdom))

    2008-12-15

    Alpha-particle-emitting, bone-seeking radionuclides can induce leukaemia and/ or osteosarcoma in mice. Furthermore, plutonium-239, given to male mice before mating with normal females, while not directly leading to leukaemia in the progeny does lead to enhanced susceptibility to leukaemogenic agents. In the first case, the amounts of radionuclide are very small in experimental terms; and zero in the case of transgenerational activity. In both cases, the development of the disorders is remote in time and location relative to that of the contaminating radionuclide, making interpretation of the mechanisms and estimation of radiation risk problematic. It is necessary, then, to address questions involving the basis of haemopoiesis itself. Cellular kinetics of the development of blood from the pluripotent stem cells to the mature functional cells are outlined, describing compensatory proliferation mechanisms and extensive movement of cells throughout the marrow space. The locations of potential oncogenic target cells are identified and the nature of the stromal microenvironment that regulates haemopoiesis is defined. Plutonium-239, given to male mice, targets spermatogenesis at the stem cell level leaving unidentified damage that is inherited by his offspring. This leaves the offspring susceptible to a leukaemogenic agent encountered later in life. The characteristics of this, corroborated by consideration of the cellular kinetics, are of an inherited genomic instability. Cells of the microenvronment, inheriting the same genetic damage, probably act in the role of an enhancing 'bystander'. In adult mice, the mechanisms are different. Bone turnover results in radioactivity being gradually transported through the marrow by long-lived macrophages. A model based on temporal microdistributions of activity, defining specific target cell regions, is able to illustrate that considering bone marrow as a uniform mass of cells is inadequate to describe the observed

  2. Self-Esteem and Academic Difficulties in Preadolescents and Adolescents Healed from Paediatric Leukaemia

    Science.gov (United States)

    Tremolada, Marta; Taverna, Livia; Bonichini, Sabrina; Basso, Giuseppe; Pillon, Marta

    2017-01-01

    Adolescents with cancer may demonstrate problems in their self-esteem and schooling. This study aims to screen the preadolescents and adolescents more at risk in their self-esteem perception and schooling difficulties post-five years from the end of therapy. Twenty-five paediatric ex-patients healed from leukaemia were recruited at the Haematology-Oncologic Clinic (University of Padua). The mean age of the children was 13.64 years (Standard Deviation (SD)) = 3.08, range = 10–19 years), most were treated for acute lymphoblastic leukaemia (ALL) (84%) and relatively equally distributed by gender. They filled in the Multidimensional Self-Esteem Test, while parents completed a questionnaire on their child’s schooling. Global self-esteem was mostly below the 50 percentile (58.5%), especially regarding interpersonal relationships (75%). An independent sample t-test showed significant mean differences on the emotionality scale (t = 2.23; degree of freedom (df) = 24; p = 0.03) and in the bodily experience scale (t = 3.02; df = 24; p = 0.006) with survivors of Acute Myeloid Leukaemia (AML) having lower scores. An Analysis of Variance (ANOVA) showed significant mean differences in the bodily experience scale (F = 12.31; df = 2, p = 0.0001) depending on the survivors’ assigned risk band. The parent reports showed that 43.5% of children had difficulties at school. Childhood AML survivors with a high-risk treatment were more at risk in their self-esteem perceptions. Preventive interventions focusing on self-esteem and scholastic wellbeing are suggested in order to help their return to their normal schedules. PMID:28538707

  3. Nutritional status and dietary intake of children with acute leukaemia during induction or consolidation chemotherapy.

    Science.gov (United States)

    Tan, S Y; Poh, B K; Nadrah, M H; Jannah, N A; Rahman, J; Ismail, M N

    2013-07-01

    The assessment of nutritional status among paediatric patients is important for the planning and execution of nutritional strategies that strive to optimise the quality of life and growth among sick children. The present study aimed to evaluate the nutritional status and dietary intake among children with acute leukaemia. This cross-sectional study included 53 paediatric patients aged 3-12 years old, who were diagnosed with either acute lymphoblastic leukaemia or acute myelogenous leukaemia and were undergoing chemotherapy treatments (induction or consolidation phase). Patients were matched for sex, age (±6 months) and ethnicity with healthy children as controls. Weight, height, body mass index, waist circumference, mid-upper arm circumference, triceps skinfold thickness, mid-upper arm muscle area and fat area were determined. Dietary intake was assessed using 3-day food records. Anthropometric variables were generally higher among patients compared to controls, although the differences were not statistically significant (P > 0.05). The prevalence of overnutrition among patients according to body mass index-for-age, waist circumference-for-age, mid-upper arm circumference-for-age and triceps skinfold-for-age were 24.5%, 29.1%, 17.0% and 30.2%, respectively. Mean energy [5732 ± 1958 kJ (1370 ± 468 kcal) versus 6945 ± 1970 kJ (1660 ± 471 kcal), P Nutrition and Dietetics © 2013 The British Dietetic Association Ltd.

  4. Self-Esteem and Academic Difficulties in Preadolescents and Adolescents Healed from Paediatric Leukaemia.

    Science.gov (United States)

    Tremolada, Marta; Taverna, Livia; Bonichini, Sabrina; Basso, Giuseppe; Pillon, Marta

    2017-05-24

    Adolescents with cancer may demonstrate problems in their self-esteem and schooling. This study aims to screen the preadolescents and adolescents more at risk in their self-esteem perception and schooling difficulties post-five years from the end of therapy. Twenty-five paediatric ex-patients healed from leukaemia were recruited at the Haematology-Oncologic Clinic (University of Padua). The mean age of the children was 13.64 years (Standard Deviation (SD)) = 3.08, range = 10-19 years), most were treated for acute lymphoblastic leukaemia (ALL) (84%) and relatively equally distributed by gender. They filled in the Multidimensional Self-Esteem Test, while parents completed a questionnaire on their child's schooling. Global self-esteem was mostly below the 50 percentile (58.5%), especially regarding interpersonal relationships (75%). An independent sample t-test showed significant mean differences on the emotionality scale (t = 2.23; degree of freedom (df) = 24; p = 0.03) and in the bodily experience scale (t = 3.02; df = 24; p = 0.006) with survivors of Acute Myeloid Leukaemia (AML) having lower scores. An Analysis of Variance (ANOVA) showed significant mean differences in the bodily experience scale (F = 12.31; df = 2, p = 0.0001) depending on the survivors' assigned risk band. The parent reports showed that 43.5% of children had difficulties at school. Childhood AML survivors with a high-risk treatment were more at risk in their self-esteem perceptions. Preventive interventions focusing on self-esteem and scholastic wellbeing are suggested in order to help their return to their normal schedules.

  5. Glocalized New Age Spirituality: A Mental Map of the New Central Bus Station in Tel Aviv, Deciphered through Its Visual Codes and Based on Ethno-Visual Research

    Science.gov (United States)

    Ben-Peshat, Malka; Sitton, Shoshana

    2011-01-01

    We present here the findings of an ethno-visual research study involving the creation of a mental map of images, artifacts and practices in Tel Aviv's New Central Bus Station. This huge and complex building, part bus station, part shopping mall, has become a stage for multicultural encounters and interactions among diverse communities of users.…

  6. Kuidas teile meeldis presidendi kõne ja millise mulje jättis kultuuriprogramm? / Arnold Rüütel, Peeter Kreitzberg, Tunne Kelam ... [jt.

    Index Scriptorium Estoniae

    2009-01-01

    Presidendi iseseisvuspäeva kõne ja vastuvõtu kohta avaldavad arvamust president Arnold Rüütel, Euroopa Parlamendi saadik Tunne Kelam, peapiiskop Andres Põder, Riigikogu liikmed Peeter Kreitzberg, Lembit Kaljuvee, Ene Ergma, Hannes Rumm, Toomas Varek ja Indrek Saar, vabadusvõitleja Enn Tarto, Rakvere lihakombinaadi direktor Anne Mere ja aktiivne vabatahtlik Rakverest Liis Lill

  7. The Dialectics of Assimilation and Multiculturalism: The Case of Children of Refugees and Migrant Workers in the Bialik-Rogozin School, Tel Aviv

    Science.gov (United States)

    Dvir, Nurit; Aloni, Nimrod; Harari, Dor

    2015-01-01

    This paper focuses on children of refugees and migrant workers from 48 countries who study together in one multicultural school in the city of Tel Aviv, Israel. The context of our study is the current ethos of globalisation and within it the phenomenon of vast migrations and creation of intercultural social realities. The aims of the study were to…

  8. Tähtis kokkuvõtteid teha : EPA - 35 / Minna Klementi, Arnold Rüütel, Nikolai Kozlov ... [jt.] ; [intervjueerinud] Tiina Siimets

    Index Scriptorium Estoniae

    1986-01-01

    Küsimustele vastavad EPA endised rektorid Minna Klementi ja Arnold Rüütel, rektor Nikolai Kozlov, ATK esimees Heino Veldi, ATK esimehe esimene asetäitja, ENSV minister Vello Lind, ATK esimehe asetäitja Jüri Kulbin, ATK esimehe asetäitja, EPA põllumajandusloomade aretuse kateedri professori kt. Olev Saveli

  9. Rüütel, Ergma ja Parts kutsusid rahvast üles hääletama ELi poolt / Katrin Lust

    Index Scriptorium Estoniae

    Lust, Katrin

    2003-01-01

    President Arnold Rüütel, Riigikogu esimees Ene Ergma ja peaminister Juhan Parts tegid ühisavalduse - meie hääletame Euroopa Liidu poolt. Uurimiskeskuse Vaba Euroopa direktori Martin Helme, euroskeptik Jaanus Raidali, Res Publica meediajuhi Allan Tankleri, suhtekorraldaja Kristina Kallase ja ELi teabekeskuse nõuniku Paavo Palki kommentaarid

  10. President Arnold Rüütel andis president George W. H. Bushile üle Maarjamaa Risti / Kärt Ulman

    Index Scriptorium Estoniae

    Ulman, Kärt

    2005-01-01

    President Arnold Rüütel andis New Yorgis endisele USA presidendile Georg Bushile Eesti iseseisvuspüüdluste toetamise eest Maarjamaa Risti I klassi ordeni. Vt. samas lühiintervjuud president George W. H. Bushiga. Töövisiit New Yorki 13.-17.09.2005

  11. Expanding the Scope of Anatomical Sciences: The Case of "Human Evolution--The Fossil Evidence" Course at the Sackler School of Medicine, Tel-Aviv University

    Science.gov (United States)

    Notzer, Netta; Abramovitz, Ruth

    2012-01-01

    The Anatomy Department at Tel-Aviv University Medical School offers its students an elective course of 26 didactic hours on human evolution. The course is open to students from all faculties, who must fulfill all academic requirements, without a prerequisite of a background in anatomy. Approximately 120 students attend annually, a third of them…

  12. Rüütel, Ergma ja Parts kutsusid rahvast üles hääletama ELi poolt / Katrin Lust

    Index Scriptorium Estoniae

    Lust, Katrin

    2003-01-01

    President Arnold Rüütel, Riigikogu esimees Ene Ergma ja peaminister Juhan Parts tegid ühisavalduse - meie hääletame Euroopa Liidu poolt. Uurimiskeskuse Vaba Euroopa direktori Martin Helme, euroskeptik Jaanus Raidali, Res Publica meediajuhi Allan Tankleri, suhtekorraldaja Kristina Kallase ja ELi teabekeskuse nõuniku Paavo Palki kommentaarid

  13. Expanding the Scope of Anatomical Sciences: The Case of "Human Evolution--The Fossil Evidence" Course at the Sackler School of Medicine, Tel-Aviv University

    Science.gov (United States)

    Notzer, Netta; Abramovitz, Ruth

    2012-01-01

    The Anatomy Department at Tel-Aviv University Medical School offers its students an elective course of 26 didactic hours on human evolution. The course is open to students from all faculties, who must fulfill all academic requirements, without a prerequisite of a background in anatomy. Approximately 120 students attend annually, a third of them…

  14. The Dialectics of Assimilation and Multiculturalism: The Case of Children of Refugees and Migrant Workers in the Bialik-Rogozin School, Tel Aviv

    Science.gov (United States)

    Dvir, Nurit; Aloni, Nimrod; Harari, Dor

    2015-01-01

    This paper focuses on children of refugees and migrant workers from 48 countries who study together in one multicultural school in the city of Tel Aviv, Israel. The context of our study is the current ethos of globalisation and within it the phenomenon of vast migrations and creation of intercultural social realities. The aims of the study were to…

  15. The N-terminus of murine leukaemia virus p12 protein is required for mature core stability.

    Directory of Open Access Journals (Sweden)

    Darren J Wight

    2014-10-01

    Full Text Available The murine leukaemia virus (MLV gag gene encodes a small protein called p12 that is essential for the early steps of viral replication. The N- and C-terminal regions of p12 are sequentially acting domains, both required for p12 function. Defects in the C-terminal domain can be overcome by introducing a chromatin binding motif into the protein. However, the function of the N-terminal domain remains unknown. Here, we undertook a detailed analysis of the effects of p12 mutation on incoming viral cores. We found that both reverse transcription complexes and isolated mature cores from N-terminal p12 mutants have altered capsid complexes compared to wild type virions. Electron microscopy revealed that mature N-terminal p12 mutant cores have different morphologies, although immature cores appear normal. Moreover, in immunofluorescent studies, both p12 and capsid proteins were lost rapidly from N-terminal p12 mutant viral cores after entry into target cells. Importantly, we determined that p12 binds directly to the MLV capsid lattice. However, we could not detect binding of an N-terminally altered p12 to capsid. Altogether, our data imply that p12 stabilises the mature MLV core, preventing premature loss of capsid, and that this is mediated by direct binding of p12 to the capsid shell. In this manner, p12 is also retained in the pre-integration complex where it facilitates tethering to mitotic chromosomes. These data also explain our previous observations that modifications to the N-terminus of p12 alter the ability of particles to abrogate restriction by TRIM5alpha and Fv1, factors that recognise viral capsid lattices.

  16. The N-Terminus of Murine Leukaemia Virus p12 Protein Is Required for Mature Core Stability

    Science.gov (United States)

    Wight, Darren J.; Boucherit, Virginie C.; Wanaguru, Madushi; Elis, Efrat; Hirst, Elizabeth M. A.; Li, Wilson; Ehrlich, Marcelo; Bacharach, Eran; Bishop, Kate N.

    2014-01-01

    The murine leukaemia virus (MLV) gag gene encodes a small protein called p12 that is essential for the early steps of viral replication. The N- and C-terminal regions of p12 are sequentially acting domains, both required for p12 function. Defects in the C-terminal domain can be overcome by introducing a chromatin binding motif into the protein. However, the function of the N-terminal domain remains unknown. Here, we undertook a detailed analysis of the effects of p12 mutation on incoming viral cores. We found that both reverse transcription complexes and isolated mature cores from N-terminal p12 mutants have altered capsid complexes compared to wild type virions. Electron microscopy revealed that mature N-terminal p12 mutant cores have different morphologies, although immature cores appear normal. Moreover, in immunofluorescent studies, both p12 and capsid proteins were lost rapidly from N-terminal p12 mutant viral cores after entry into target cells. Importantly, we determined that p12 binds directly to the MLV capsid lattice. However, we could not detect binding of an N-terminally altered p12 to capsid. Altogether, our data imply that p12 stabilises the mature MLV core, preventing premature loss of capsid, and that this is mediated by direct binding of p12 to the capsid shell. In this manner, p12 is also retained in the pre-integration complex where it facilitates tethering to mitotic chromosomes. These data also explain our previous observations that modifications to the N-terminus of p12 alter the ability of particles to abrogate restriction by TRIM5alpha and Fv1, factors that recognise viral capsid lattices. PMID:25356837

  17. 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...

  18. Incidence trends and ethnic patterns for childhood leukaemia in Hawaii: 1960-1984.

    OpenAIRE

    Goodman, M. T.; Yoshizawa, C. N.; Kolonel, L. N.

    1989-01-01

    We analysed data obtained from the Hawaii Tumor Registry, a population-based participant in the Surveillance, Epidemiology, and End Results (SEER) programme that monitors cancer incidence and mortality for the entire state. A total of 138 males and 116 females, under the age of 15, were diagnosed with leukaemia between 1960 and 1984, with average annual age-adjusted incidence rates of 49.6 and 44.8 per million, respectively. Time trend analysis by 5-year calendar periods revealed an increasin...

  19. The inhibition of DNA synthesis in chronic lymphocytic leukaemia cells by chlorambucil in vitro.

    Science.gov (United States)

    Bentley, D. P.; Blackmore, J. A.

    1992-01-01

    The inhibition of 3H-thymidine incorporation into the DNA of mitogen-stimulated lymphocytes from patients with chronic lymphocytic leukaemia by chlorambucil was measured in vitro and the results related to clinical drug resistance. The assay proved to be both sensitive and specific showing a clear separation of those patients with responsive disease from those with disease resistant to treatment. There was evidence of primary drug resistance in untreated patients. In almost all patients who received treatment this led to increasing resistance to chlorambucil in vitro. The assay is predictive of clinical responsiveness and provides a potential means whereby new therapeutic agents and treatment modifiers may be investigated. PMID:1739612

  20. The Uptake and Utilization of Chlorambucil by Lymphocytes from Patients with Chronic Lymphocytic Leukaemia

    Science.gov (United States)

    Hill, Bridget T.; Harrap, K. R.

    1972-01-01

    It has been shown that lymphocytes isolated from the peripheral blood of patients with chronic lymphocytic leukaemia do not modify the mustard group of chlorambucil, as has been demonstrated previously in Yoshida ascites cells. However, lymphocytes from patients with an unsatisfactory clinical course or poor response to treatment were able to modify the aromatic region of the drug molecule; little change occurred in the aromatic absorption of intracellular chlorambucil in patients who responded to treatment. This simple test may provide a rapid assessment of a patient's potential response to chemotherapy. PMID:4647395

  1. Human retroviruses in leukaemia and AIDS: reflections on their discovery, biology and epidemiology.

    Science.gov (United States)

    Karpas, Abraham

    2004-11-01

    The study of retroviruses has had a profound impact by unveiling an unusual form of viral replication: the multiplication of RNA viruses via a proviral DNA, for which Jan Svoboda provided the experimental model over forty years ago. In 1970 Temin, Mizutani and Baltimore discovered that this group of viruses contains a unique enzyme catalysing the synthesis of a DNA copy of the viral RNA: reverse transcriptase (RT). The discovery of RT has itself had an enormous impact on molecular biology in general, but also stimulated many premature claims of its detection in human disease. Claims by Gallo's laboratory that the cytoplasm of human leukaemia cells contained RT proved to be unfounded, as did his report in collaboration with Weiss that myeloid leukaemia contained HL23 virus, this organism proving not to be human but a laboratory contaminant of three monkey viruses. Conclusive demonstration of a retroviral involvement in human leukaemia was first provided in 1981 by Hinuma and his associates, showing that adult T-cell leukaemia (ATL), a rare form of leukaemia endemic to south-west Japan, is caused by a new retrovirus (ATLV). Other publications in December 1980 and through 1981 claimed the discovery of a new human T-cell leukaemia virus involved in mycosis fungoides (MF) and Sézary's syndrome (SS). This virus was termed HTLV by Gallo. The nucleotide sequence of ATLV is strongly conserved, that of my 1983 isolate from a black British ATL patient being practically identical with the Japanese virus isolates. After AIDS was recognised in 1981 by Gottlieb and coworkers as a new human disease, several papers were published by Gallo and his associates during 1983-4, invoking the oncovirus responsible for adult T-cell leukaemia as the cause of AIDS. In 1983 the French scientist Barré-Sinoussi and her colleagues succeeded in isolating a new agent in the disease, a lentivirus, which they named LAV. The French immunologist Klatzmann and his colleagues discovered that LAV killed

  2. Boronated monoclonal antibodies for potential neutron capture therapy of malignant melanoma and leukaemia

    Energy Technology Data Exchange (ETDEWEB)

    Tamat, S.R.; Patwardhan, A.; Moore, D.E.; Kabral, A.; Bradstock, K.; Hersey, P.; Allen, B.J.

    The authors report a preparation and characterisation of boronated melanoma and leukaemia antibodies and the separation from native antibody by anion exchange liquid chromatography. Two types of biodistribution experiments were performed with the boronated melanoma antibody 225.28S using Balb/c derived nude mice in which melanoma tumours had been raised in the thigh by subcutaneous injection of a human malignant melanoma cell line, designated CMC. From these experiments, one may conclude that the boronated antibody has the ability to localise in the melanoma following systemic injection, but more efficient use of the preparation is achieved with perilesional administration.

  3. Therapeutic leukapheresis in hyperleucocytic leukaemias: lack of correlation between degree of cytoreduction and early mortality rate.

    Science.gov (United States)

    Porcu, P; Danielson, C F; Orazi, A; Heerema, N A; Gabig, T G; McCarthy, L J

    1997-08-01

    The clinical and laboratory data of 48 leukapheresis-treated patients with hyperleucocytic leukaemia (HL) was reviewed to assess the correlation between the degree of leucoreduction and early mortality. Leukapheresis resulted in > 50% leucoreductions and postapheresis WBC counts < 100 x 10(9)/l in most patients (64.5%). Patients presenting with neurological, respiratory or renal complications had higher early mortality rates than patients without such complications, despite similar initial WBC counts and comparable leucoreductions. Thus, in these patients, more efficient leucoreduction was not associated with improved early survival.

  4. Acute myeloid leukaemia presenting as bilateral proptosis in a young child

    Directory of Open Access Journals (Sweden)

    Charudutt Kalamkar

    2016-06-01

    Full Text Available Myeloid sarcoma is an extramedullary manifestation of acute myeloid leukaemia (AML. Aims We are reporting a paediatric case presenting with bilateral proptosis, which we were able to diagnose with peripheral blood smear (PBS examination. Methods Case Report Results This case highlights the utility of simple routinely available PBS test in diagnosing this rare disease. Conclusion Our case highlights the importance of haemogram and peripheral blood smear in the initial evaluation of proptosis. Correct diagnosis of this rare entity is vital especially in cases where (myeloid sarcoma MS is the presenting feature of AML.

  5. The effect of weekly text-message communication on treatment completion among patients with latent tuberculosis infection: study protocol for a randomised controlled trial (WelTel LTBI).

    Science.gov (United States)

    van der Kop, Mia L; Memetovic, Jasmina; Patel, Anik; Marra, Fawziah; Sadatsafavi, Mohsen; Hajek, Jan; Smillie, Kirsten; Thabane, Lehana; Taylor, Darlene; Johnston, James; Lester, Richard T

    2014-04-09

    Interventions to improve adherence to treatment for latent tuberculosis infection (LTBI) are necessary to improve treatment completion rates and optimise tuberculosis (TB) control efforts. The high prevalence of cell phone use presents opportunities to develop innovative ways to engage patients in care. A randomised controlled trial (RCT), WelTel Kenya1, demonstrated that weekly text messages improved antiretroviral adherence and clinical outcomes among patients initiating HIV treatment. The aim of this study is to determine whether the WelTel intervention can improve treatment completion among patients with LTBI and to evaluate the intervention's cost-effectiveness. This open, two-site, parallel RCT (WelTel LTBI) will be conducted at TB clinics in Vancouver and New Westminster, British Columbia, Canada. Over 2 years, we aim to recruit 350 individuals initiating a 9-month isoniazid regimen. Participants will be randomly allocated to an intervention or control (standard care) arm in a 1:1 ratio. Intervention arm participants will receive a weekly text-message 'check-in' to which they will be asked to respond within 48 h. A TB clinician will follow-up instances of non-response and problems that are identified. Participants will be followed until treatment completion (up to 12 months) or discontinuation. The primary outcome is self-reported treatment completion (taking ≥80% of doses within 12 months). Secondary outcomes include daily adherence (percentage of days participants used medication as prescribed) and time to treatment completion. Patient satisfaction with the intervention will be evaluated, and the intervention's cost-effectiveness will be analysed through decision-analytic modelling. Ethical approval has been obtained from the University of British Columbia. This trial will test the efficacy and cost-effectiveness of the WelTel intervention to improve treatment completion among patients with LTBI. Trial results and economic evaluation will help inform

  6. Inhibition of CK2{alpha} and PI3K/Akt synergistically induces apoptosis of CD34+CD38- leukaemia cells while sparing haematopoietic stem cells.

    Science.gov (United States)

    Cheong, June-Won; Min, Yoo Hong; Eom, Ju In; Kim, Soo Jeong; Jeung, Hoi Kyung; Kim, Jin Seok

    2010-11-01

    The CD34(+)CD38(-) leukaemia cell population contains leukaemia stem cells (LSCs) responsible for treatment failure in acute myeloid leukaemia (AML) and, thus, novel therapies are required to eradicate LSCs without harming healthy haematopoietic stem cells (HSC). The present study evaluated the effects of co-treatment with LY294002 (a PI3K/Akt inhibitor) and apigenin (a CK2 inhibitor) (LY/Api) at subtoxic concentrations on leukaemia cell lines and primary AML cells. LY/Api synergistically induced apoptosis in leukaemia cells, especially CD34(+)CD38(-) leukaemia cells. However, these effects were negligible in HSCs. LY/Api-induced apoptosis was accompanied by activation of caspase cascades and disruption of mitochondrial membrane potential. Caspase inhibitor or Akt overexpression abrogated this synergistic induction in apoptosis by LY/Api. LY/Api also led to remarkable down-regulation of anti-apoptotic proteins including Bcl-xL and NF-κB in CD34(+)CD38(-) leukaemia cells, but not in healthy hematopoietic stem cells. Inhibition of both CK2 and PI3K/Akt pathways may be a promising LSCs-targeted therapeutic strategy for AML.

  7. Research on potential radiation risks in areas with nuclear power plants in Japan: leukaemia and malignant lymphoma mortality between 1972 and 1997 in 100 selected municipalities

    Energy Technology Data Exchange (ETDEWEB)

    Yoshimoto, Yasuhiko [Research Centre for Radiation Safety, National Institute of Radiological Sciences, Anagawa 4-9-1, Inage-ward, Chiba 263-8555 (Japan); Yoshinaga, Shinji [Research Centre for Radiation Safety, National Institute of Radiological Sciences, Anagawa 4-9-1, Inage-ward, Chiba 263-8555 (Japan); Yamamoto, Kazuhide [Research Centre for Radiation Safety, National Institute of Radiological Sciences, Anagawa 4-9-1, Inage-ward, Chiba 263-8555 (Japan); Fijimoto, Kenzo [Research Centre for Radiation Safety, National Institute of Radiological Sciences, Anagawa 4-9-1, Inage-ward, Chiba 263-8555 (Japan); Nishizawa, Kanae [Research Centre for Charged Particle Therapy, National Institute of Radiological Sciences, Anagawa 4-9-1, Inage-ward, Chiba 263-8555 (Japan); Sasaki, Yasuhito [Board of Executive Directors, National Institute of Radiological Sciences, Anagawa 4-9-1, Inage-ward, Chiba 263-8555 (Japan)

    2004-12-01

    The results of a geographical correlation study using Poisson regression analysis are reported for leukaemia and malignant lymphoma mortality between 1972 and 1997 in 100 selected Japanese municipalities with or without a nuclear power plant (NPP). The data did not support social concerns of an increased risk of malignant lymphoma in the vicinity of Japanese NPPs. However, some estimates of overall excess relative risk (ERR; relative risk minus one) were statistically significantly positive for leukaemia mortality in 20 NPP municipalities compared with mortality in the remaining 80 control areas, taking into account a minimum two-year latency following the start of commercial operation. One estimate was 0.228 (95% CI: 0.074-0.404) from a simple area adjustment using the mortality in all Japan as the external baseline rate. This superficial increase is not due to leukaemia among young people, aged less than 25 years at death. The ERR estimate for ages at death of 50-74 years was confounded to be positive for leukaemia and distorted to be negative for malignant lymphoma. For leukaemia, a positive ERR estimate was seen, especially for females and during specific periods. Confounding of the ERR estimate for two causes was also seen in some NPP areas including a high adult T-cell leukaemia (ATL) area. Temporal area variations associated with ATL misclassification and a temporal increasing trend of leukaemia mortality in the elderly caused the confounding effects. Our findings do not support the hypothesis of a leukaemogenic impact of NPPs in Japan.

  8. Gene

    Data.gov (United States)

    U.S. Department of Health & Human Services — Gene integrates information from a wide range of species. A record may include nomenclature, Reference Sequences (RefSeqs), maps, pathways, variations, phenotypes,...

  9. Coffee and tea consumption and risk of leukaemia in an adult population: A reanalysis of the Italian multicentre case-control study.

    Science.gov (United States)

    Parodi, Stefano; Merlo, Domenico Franco; Stagnaro, Emanuele

    2017-04-01

    Coffee and tea are the most frequently consumed beverages in the world. Their potential effect on the risk of developing different types of malignancies has been largely investigated, but studies on leukaemia in adults are scarce. The present investigation is aimed at evaluating the potential role of regular coffee and tea intake on the risk of adult leukaemia by reanalysing a large population based case-control study carried out in Italy, a country with a high coffee consumption and a low use of green tea. Interviewed subjects, recruited between 1990 and 1993 in 11 Italian areas, included 1771 controls and 651 leukaemia cases. Association between Acute Myeloid Leukaemia (AML), Acute Lymphoid Leukaemia, Chronic Myeloid Leukaemia, Chronic Lymphoid Leukaemia, and use of coffee and tea was evaluated by standard logistic regression. Odds Ratios (OR) were estimated adjusting for the following potential confounders: gender, age, residence area, smoking habit, educational level, previous chemotherapy treatment, alcohol consumption and exposure to electromagnetic fields, radiation, pesticides and aromatic hydrocarbons. No association was observed between regular use of coffee and any type of leukaemia. A small protective effect of tea intake was found among myeloid malignancies, which was more evident among AML (OR=0.68, 95%CI: 0.49-0.94). However, no clear dose-response relation was found. The lower risk of leukaemia among regular coffee consumers, reported by a few of previous small studies, was not confirmed. The protective effect of tea on the AML risk is only partly consistent with results from other investigations. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Las residencias de Carlos III el Noble en París a comienzos del siglo XV : el Hôtel de Clisson y el Hôtel de Navarre

    Directory of Open Access Journals (Sweden)

    María NARBONA CÁRCELES

    2009-05-01

    Full Text Available Uno de los temas que atañen a la itinerancia cortesana es el de la instalación en una gran ciudad. Y, entre las grandes capitales del momento, París se mostraba indiscutiblemente como lugar de paso o de destino privilegiado de muchos de estos príncipes «itinerantes». Carlos III el Noble, rey de Navarra (1387-1425, fue uno de los grandes príncipes foráneos que frecuentaron París, realizando allí durante largas estancias, entre 1378 y 1411, de las cuales se ha conservado una interesante documentación. La cuestión del alojamiento del rey de Navarra en París, a partir de los documentos conservados tanto en los archivos franceses como en los navarros, será el tema de este trabajo. Además, la reaparición de un «Hôtel de Navarre» en París en los últimos años del siglo XIV, se presenta como un claro síntoma de la presencia de nuevo de los Navarra-Évreux en el seno de la corte francesa.L’un des sujets concernant l’itinérance de la cour est celui de l’installation dans une grande ville. Et, parmi les grandes capitales du moment, Paris était, de façon indiscutable, le lieu de passage ou de destination privilégiée de beaucoup de ces princes « itinérants ». Charles III, le Noble, roi de Navarre (1387-1425, a été l’un de ces princes étrangers qui l’ont fréquentée, y demeurant pendant des longs séjours, entre 1378 et 1411, pour lesquels on conserve une intéressante documentation. La question abordée ici sera celle du logement du roi de Navarre à Paris, à partir des documents conservés autant dans des archives françaises que navarraises. De plus, la réapparition d’un « Hôtel de Navarre » à Paris dans les dernières années du XIVe siècle, est un clair symptôme de la présence, à nouveau, des Navarre-Évreux au sein de la cour de France.

  11. Central nervous system lesions in adult T-cell leukaemia: MRI and pathology

    Energy Technology Data Exchange (ETDEWEB)

    Kitajima, M.; Korogi, Y.; Shigematsu, Y.; Liang, L.; Takahashi, M. [Department of Radiology, Kumamoto University School of Medicine, Honjo, Kumamoto (Japan); Matsuoka, M. [Second Division of Internal Medicine, Kumamoto University School of Medicine, Honjo, Kumamoto (Japan); Yamamoto, T. [Department of Pathology, Kumamoto University School of Medicine, Honjo, Kumamoto (Japan); Jhono, M. [Department of Dermatology, Kumamoto University School of Medicine, Honjo, Kumamoto (Japan); Eto, K. [The National Institute for Minamata Disease, Minamata (Japan)

    2002-07-01

    Adult T-cell leukaemia (ATL) is a T-cell lymphoid neoplasm caused by human T-cell leukaemia virus type I (HTLV-I). Radiological findings in central nervous system (CNS) involvement have not been well characterised. We reviewed the MRI of 18 patients with ATL who developed new neurological symptoms or signs, and pathology specimens from a 53-year-old woman who died of ATL. MRI findings were divided into three categories: definite, probable, and other abnormal. Definite and probable findings were defined as ATL-related. The characteristic findings were multiple parenchymal masses with or without contrast enhancement adjacent to cerebrospinal fluid (CSF) spaced and the deep grey matter of both cerebral hemispheres, plus leptomeningeal lesion. One patient had both cerebral and spinal cord lesions. Other abnormal findings in eight patients included one case of leukoencephalopathy caused by methotrexate. The histology findings consisted of clusters of tumour cells along perivascular spaces, and scattered infiltration of the parenchyma, with nests of tumour cells. Leptomeningeal infiltration by tumour spread into the parenchyma and secondary degeneration of the neuronal tracts was observed. MRI was useful for detecting CNS invasion by ATL and differentiating it from other abnormalities. The MRI findings seemed to correlate well with the histological changes. (orig.)

  12. A multicentre trial of live attenuated varicella vaccine in children with leukaemia in remission.

    Science.gov (United States)

    Gershon, A A; Steinberg, S; Gelb, L; Galasso, G; Borkowsky, W; LaRussa, P; Ferrara, A

    1985-01-01

    Two hundred forty children with acute leukaemia in remission for at least 1 year were immunized with live attenuated varicella vaccine. All were susceptible to varicella before immunization. There was a seroconversion to varicella-zoster virus in approximately 85% after 1 dose, and in 97% after 2 doses. The major side effect was mild to moderate rash, seen mainly in children with maintenance chemotherapy suspended for 1 week before and 1 week after vaccination. Vaccinees with rash were at some risk (10%) to transmit vaccine virus to varicella susceptibles with whom they had close contact. Twenty-nine vaccinees were subsequently exposed to varicella in their households. The attack rate of clinical varicella in these vaccinees was 21%, which is significantly lower than the 80%-90% attack rate occurring in varicella susceptibles after household exposure. All these breakthrough cases of varicella were mild, even in leukaemics receiving chemotherapy. Varicella vaccine was approximately 80% effective in preventing clinical varicella in children with leukaemia and completely effective in preventing severe varicella in this high-risk group.

  13. Mechanosensitive channel activity and F-actin organization in cholesterol-depleted human leukaemia cells.

    Science.gov (United States)

    Morachevskaya, Elena; Sudarikova, Anastasiya; Negulyaev, Yuri

    2007-04-01

    This study focuses on the functional role of cellular cholesterol in the regulation of mechanosensitive cation channels activated by stretch in human leukaemia K562 cells. The patch-clamp method was employed to examine the effect of methyl-beta-cyclodextrin (MbetaCD), a synthetic cholesterol-sequestering agent, on stretch-activated single currents. We found that cholesterol-depleting treatment with MbetaCD resulted in a suppression of the activity of mechanosensitive channels without a change in the unitary conductance. The probability that the channel was open significantly decreased after treatment with MbetaCD. Fluorescent microscopy revealed F-actin reorganization, possibly involving actin assembly, after incubation of the cells with MbetaCD. We suggest that suppression of mechanosensitive channel activation in cholesterol-depleted leukaemia cells is due to F-actin rearrangement, presumably induced by lipid raft destruction. Our observations are consistent with the notion that stretch-activated cation channels in eukaryotic cells are regulated by the membrane-cytoskeleton complex rather than by tension developed purely in the lipid bilayer.

  14. Study of clinical, haematological and cytogenetic profile of patients with acute erythroid leukaemia

    Science.gov (United States)

    Linu, Jacob Abraham; Udupa, MS Namratha; Madhumathi, DS; Lakshmaiah, KC; Babu, K Govind; Lokanatha, D; Babu, MC Suresh; Lokesh, KN; Rajeev, LK; Rudresha, AH

    2017-01-01

    Background Acute erythroid leukaemia (AEL) is a rare subtype of acute myeloid leukaemia (AML), constituting cytogenetic profile of this disease, considering the rarity of its occurrence and poor prognosis. Materials and methods This study was done by retrospective analysis of data from 32 case files of patients diagnosed with AEL. Clinical details noted down were the demographic profile, peripheral blood smear details and bone marrow examination details: (1) blasts-erythroblasts and myeloblasts, (2) dysplasia in the cell lineages and (3) cytogenetic abnormalities. Results The most common presenting symptom was fever. Pancytopenia at presentation was seen in 81.25% of patients. Dysplasia was observed in bone marrow in 100% of erythroblasts and in 40% of myeloblasts in erythroid/myeloid subtype. In pure myeloid subtype, myeloid and megakaryocytic dysplasias were not obvious. Complex karyotype was noticed only in patients of pEL. Conclusion AEL is a rare group of heterogeneous diseases with many neoplastic and non-neoplastic conditions mimicking the diagnosis. The clinical presentation and cytogenetics are also non-specific, presenting additional challenges to the diagnosis. PMID:28144286

  15. Discovery of two aminoglycoside antibiotics as inhibitors targeting the menin-mixed lineage leukaemia interface.

    Science.gov (United States)

    Li, Lianchun; Zhou, Ran; Geng, Heji; Yue, Liyan; Ye, Fei; Xie, Yiqian; Liu, Jingqiu; Kong, Xiangqian; Jiang, Hualiang; Huang, Jiandong; Luo, Cheng

    2014-05-01

    Menin functions as an oncogenic cofactor of mixed lineage leukaemia (MLL) fusion proteins in leukaemogenesis. The menin-MLL interface is a potential therapeutic target in acute leukaemia cases. In this study, approximately 900 clinical compounds were evaluated and ranked using pharmacophore-based virtual screening, the top 29 hits were further evaluated by biochemical analysis to discover the inhibitors that target the menin-MLL interface. Two aminoglycoside antibiotics, neomycin and tobramycin, were identified as menin-MLL inhibitors with binding affinities of 18.8 and 59.9 μM, respectively. The results of thermal shift assay validated the direct interactions between the two antibiotics and menin. The results of isothermal titration calorimetry showed that the equilibrium dissociation constant between menin and neomycin was approximately 15.6 μM. We also predicted the binding modes of inhibitors at the menin-MLL interface through molecular docking analysis. The results indicated that neomycin and tobramycin competitively occupy the binding site of MLL. This study has shed light on the development of powerful probes and new therapies for MLL-mediated leukaemogenesis. Copyright © 2014 Elsevier Ltd. All rights reserved.

  16. 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.

  17. Versatility and nuances of the architecture of haematopoiesis - Implications for the nature of leukaemia.

    Science.gov (United States)

    Brown, Geoffrey; Hughes, Philip J; Ceredig, Rhodri; Michell, Robert H

    2012-01-01

    For many years there was a widely accepted picture of how a haematopoietic stem cell (HSC) gives rise to the multiple types of blood and immune cells. This described the general nature of stem and progenitor cells and the pathways of cell development. Recent years have seen many attempts to re-draw the map of haematopoiesis. These have become increasingly complex, and they often envisage multiples routes to some cell types. The 'established' view that self-renewal in haematopoiesis only occurs in HSCs has been challenged by the recognition of self-renewing HSC-derived progenitor cells that display at least some fate restriction. This evolution of how normal haematopoiesis is viewed has inevitable implications for understanding the origins, disease progression and classification of the leukaemias. In essence, some progenitor cells are now seen as possessing a larger repertoire of routes to end-fates than was previously thought. This leads one to ask whether leukaemia stem cells are equally or less versatile than their normal counterparts? Copyright © 2011 Elsevier Ltd. All rights reserved.

  18. Structural biology contributions to the discovery of drugs to treat chronic myelogenous leukaemia

    Energy Technology Data Exchange (ETDEWEB)

    Cowan-Jacob, Sandra W., E-mail: sandra.jacob@novartis.com; Fendrich, Gabriele; Floersheimer, Andreas; Furet, Pascal; Liebetanz, Janis; Rummel, Gabriele; Rheinberger, Paul; Centeleghe, Mario; Fabbro, Doriano; Manley, Paul W. [Novartis Institutes for Biomedical Research, Basel (Switzerland)

    2007-01-01

    A case study showing how the determination of multiple cocrystal structures of the protein tyrosine kinase c-Abl was used to support drug discovery, resulting in a compound effective in the treatment of chronic myelogenous leukaemia. Chronic myelogenous leukaemia (CML) results from the Bcr-Abl oncoprotein, which has a constitutively activated Abl tyrosine kinase domain. Although most chronic phase CML patients treated with imatinib as first-line therapy maintain excellent durable responses, patients who have progressed to advanced-stage CML frequently fail to respond or lose their response to therapy owing to the emergence of drug-resistant mutants of the protein. More than 40 such point mutations have been observed in imatinib-resistant patients. The crystal structures of wild-type and mutant Abl kinase in complex with imatinib and other small-molecule Abl inhibitors were determined, with the aim of understanding the molecular basis of resistance and to aid in the design and optimization of inhibitors active against the resistance mutants. These results are presented in a way which illustrates the approaches used to generate multiple structures, the type of information that can be gained and the way that this information is used to support drug discovery.

  19. Bloodstream infection caused by Acinetobacter junii in a patient with acute lymphoblastic leukaemia after allogenic haematopoietic cell transplantation.

    Science.gov (United States)

    Cayô, Rodrigo; Yañez San Segundo, Lucrecia; Pérez del Molino Bernal, Inmaculada Concepción; García de la Fuente, Celia; Bermúdez Rodríguez, Maria Aranzazu; Calvo, Jorge; Martínez-Martínez, Luis

    2011-03-01

    Acinetobacter junii is a rare human pathogen associated with bacteraemia in neonates and paediatric oncology patients. We present a case of A. junii causing bacteraemia in an adult transplant patient with leukaemia. The correct identification of Acinetobacter species can highlight the clinical significance of the different species of this genus.

  20. Quality of life of patients with chronic lymphocytic leukaemia in the Netherlands: results of a longitudinal multicentre study

    NARCIS (Netherlands)

    K.M. Holtzer-Goor (Kim M.); M.R. Schaafsma (Martijn); P. Joosten (Peter); H.L.A. Posthuma (Hidde); S. Wittebol (Shulamit); P.C. Huijgens (Peter); V. Mattijssen (V.); G. Vreugdenhil (Gerard); H. Visser (Hein); W.G. Peters (Wim); Z. Erjavec (Zoran); P.W. Wijermans (Pierre); S.M.G.J. Daenen (Simon); K.G. van der Hem (K.); M.H.J. van Oers (Marinus); C.A. Uyl-de Groot (Carin)

    2015-01-01

    textabstractPurpose: To describe the health-related quality of life (HRQoL) of an unselected population of patients with chronic lymphocytic leukaemia (CLL) including untreated patients. Methods: HRQoL was measured by the EORTC QLQ-C30 including the CLL16 module, EQ-5D, and VAS in an observational

  1. Quality of life of patients with chronic lymphocytic leukaemia in the Netherlands : results of a longitudinal multicentre study

    NARCIS (Netherlands)

    Holtzer-Goor, K. M.; Schaafsma, M. R.; Joosten, P.; Posthuma, E. F. M.; Wittebol, S.; Huijgens, P. C.; Mattijssen, E. J. M.; Vreugdenhil, G.; Visser, H.; Peters, W. G.; Erjavec, Z.; Wijermans, P. W.; Daenen, S. M. G. J.; van der Hem, K. G.; van Oers, M. H. J.; Uyl-de Groot, C. A.

    2015-01-01

    To describe the health-related quality of life (HRQoL) of an unselected population of patients with chronic lymphocytic leukaemia (CLL) including untreated patients. HRQoL was measured by the EORTC QLQ-C30 including the CLL16 module, EQ-5D, and VAS in an observational study over multiple years. All

  2. Label-free imaging and identification of typical cells of acute myeloid leukaemia and myelodysplastic syndrome by Raman microspectroscopy

    NARCIS (Netherlands)

    Vanna, R.; Ronchi, P.; Lenferink, A.T.M.; Terstappen, L.W.M.M.; Tresoldi, C.; Morasso, C.; Mehn, D.; Bedoni, M.; Ciceri, F.; Otto, C.; Gramatica, F.

    2015-01-01

    In clinical practice, the diagnosis and classification of acute myeloid leukaemia (AML) and myelodysplastic syndrome (MDS) start from the manual examination of stained smears of bone marrow (BM) and peripheral blood (PB) by using an optical microscope. This step is subjective and scarcely reproducib

  3. Prolonged bone marrow T1-relaxation in acute leukaemia. In vivo tissue characterization by magnetic resonance imaging

    DEFF Research Database (Denmark)

    Thomsen, C; Sørensen, P G; Karle, H

    1987-01-01

    osseous tissue. Nine patients with acute leukaemia, one patient with myelodysplastic syndrome, and ten normal volunteers were included in the study. The T1- and T2-relaxation processes were measured in the lumbar spine bone marrow using a wholebody superconductive MR-scanner operating at 1.5 Tesla...

  4. An update on imatinib mesylate therapy in chronic myeloid leukaemia patients in a teaching hospital in Malaysia.

    Science.gov (United States)

    Bee, P C; Gan, G G; Tai, Y T; Haris, A R; Chin, E; Veera, S N

    2012-01-01

    The introduction of imatinib mesylate in 1998 has changed the management of chronic myeloid leukaemia. It is now the first-line therapy for newly diagnosed chronic myeloid leukaemia patients worldwide. However, its long-term survival benefit still needs to be established in clinical setting among Asian patients. All chronic myeloid leukaemia patients in the chronic phase who were on imatinib mesylate therapy were retrospectively reviewed. Data was collected through a review of case notes, which was then processed, managed and analysed. A total of 44 patients were included in the study. The cumulative rates of complete haematological response, major cytogenetic response and major molecular response were 93.2%, 75.0% and 34.2%, respectively. The overall survival and event-free survival at five years were 86.0% and 84.9%, respectively. 31.8% of the patients developed anaemia, 29.5% neutropenia and 27.3% thrombocytopenia. A total of 43.2% of patients developed non-haematological side effects. Higher dosage (> 600 mg) and smaller body size (< 60 kg) were risk factors for haematological side effects. Patients with major cytogenetic response and absence of thrombocytopenia had better survival. The majority of our chronic myeloid leukaemia patients did well with imatinib therapy. The adverse effects in our patients were tolerable, and no patient had to stop treatment permanently.

  5. CD27-triggering on primary plasma cell leukaemia cells has anti-apoptotic effects involving mitogen activated protein kinases

    NARCIS (Netherlands)

    Guikema, JEJ; Vellenga, E; Abdulahad, WH; Hovenga, S; Bos, NA

    2004-01-01

    Primary plasma cell leukaemia (PCL) is a rare plasma cell malignancy, which is related to multiple myeloma (MM) and is characterized by a poor prognosis. In a previous study we demonstrated that PCL plasma cells display a high expression of CD27, in contrast to MM plasma cells. The present study was

  6. Prevention of infection in children with acute leukaemia - No major difference between total and selective bowel decontamination

    NARCIS (Netherlands)

    Muis, N; Kamps, WA

    1996-01-01

    To evaluate the effect of total bowel decontamination (TD) and selective bowel decontamination (SD) in a non-protective environment clinical and laboratory data of children treated for acute leukaemia between 1983 and 1991 were analysed retrospectively. From 1983 until 1989 34 patients [18 acute non

  7. Variation in survival of European children with acute lymphoblastic leukaemia, diagnosed in 1978-1992 : the EUROCARE study

    NARCIS (Netherlands)

    Coebergh, JW; Pastore, G; Gatta, G; Corazziari, [No Value; Kamps, W

    2001-01-01

    The aim of this study was to provide a comparative description of geographical variations and time trends in the population-based survival of European children with acute lymphoblastic leukaemia (ALL). Data on 13 344 newly diagnosed children (0-14 years) with ALL were included in the EUROCARE study

  8. A combination therapy with fludarabine, mitoxantrone and rituximab induces complete immunophenotypical remission in B-cell prolymphocytic leukaemia

    OpenAIRE

    Tempescul, Adrian; Feuerbach, Johanna; Ianotto, Jean-Christophe; Dalbies, Florence; Marion, Veronique; Bris, Marie-Josée; De Braekeleer, Marc; Berthou, Christian

    2008-01-01

    A combination therapy with fludarabine, mitoxantrone and rituximab induces complete immunophenotypical remission in B-cell prolymphocytic leukaemia phone: +33-298-223504 (Tempescul, Adrian) (Tempescul, Adrian) Department of Clinical Hematology, Institute of Cancerology and Hematology - CHU Morvan, Avenue Foch - 29609 - Brest - FRANCE (Tempescul, Adrian) Department of Clinical Hematology, Institute of Cancerology and Hematology - CHU Morvan, Avenue Foch - 2...

  9. Ibrutinib for previously untreated and relapsed or refractory chronic lymphocytic leukaemia with TP53 aberrations

    DEFF Research Database (Denmark)

    Farooqui, Mohammed Z H; Valdez, Janet; Martyr, Sabrina

    2015-01-01

    BACKGROUND: Patients with chronic lymphocytic leukaemia (CLL) with TP53 aberrations respond poorly to first-line chemoimmunotherapy, resulting in early relapse and short survival. We investigated the safety and activity of ibrutinib in previously untreated and relapsed or refractory CLL with TP53...

  10. Insulin growth factor 1 receptor expression is associated with NOTCH1 mutation, trisomy 12 and aggressive clinical course in chronic lymphocytic leukaemia.

    Directory of Open Access Journals (Sweden)

    Francesco Maura

    Full Text Available IGF1R is emerging as an important gene in the pathogenesis of many solid and haematological cancers and its over-expression has been reported as frequently associated with aggressive disease and chemotherapy resistance. In this study we performed an investigation of the role of IGF1R expression in a large and representative prospective series of 217 chronic lymphocytic leukaemia (CLL patients enrolled in the multicentre O-CLL1 protocol (clinicaltrial.gov #NCT00917540. High IGF1R gene expression was significantly associated with IGHV unmutated (IGHV-UM status (p<0.0001, high CD38 expression (p<0.0001, trisomy 12 (p<0.0001, and del(11(q23 (p=0.014. Interestingly, higher IGF1R expression (p=0.002 characterized patients with NOTCH1 mutation (c.7541_7542delCT, identified in 15.5% of cases of our series by next generation sequencing and ARMS-PCR. Furthermore, IGF1R expression has been proven as an independent prognostic factor associated with time to first treatment in our CLL prospective cohort. These data suggest that IGF1R may play an important role in CLL biology, in particular in aggressive CLL clones characterized by IGHV-UM, trisomy 12 and NOTCH1 mutation.

  11. Insulin Growth Factor 1 Receptor Expression Is Associated with NOTCH1 Mutation, Trisomy 12 and Aggressive Clinical Course in Chronic Lymphocytic Leukaemia

    Science.gov (United States)

    Maura, Francesco; Mosca, Laura; Fabris, Sonia; Cutrona, Giovanna; Matis, Serena; Lionetti, Marta; Agnelli, Luca; Barbieri, Marzia; D’Anca, Marianna; Manzoni, Martina; Colombo, Monica; Massucco, Carlotta; Reverberi, Daniele; Gentile, Massimo; Recchia, Anna Grazia; Bossio, Sabrina; Ilariucci, Fiorella; Musolino, Caterina; Di Raimondo, Francesco; Cortelezzi, Agostino; Morabito, Fortunato; Ferrarini, Manlio; Neri, Antonino

    2015-01-01

    IGF1R is emerging as an important gene in the pathogenesis of many solid and haematological cancers and its over-expression has been reported as frequently associated with aggressive disease and chemotherapy resistance. In this study we performed an investigation of the role of IGF1R expression in a large and representative prospective series of 217 chronic lymphocytic leukaemia (CLL) patients enrolled in the multicentre O-CLL1 protocol (clinicaltrial.gov #NCT00917540). High IGF1R gene expression was significantly associated with IGHV unmutated (IGHV-UM) status (p<0.0001), high CD38 expression (p<0.0001), trisomy 12 (p<0.0001), and del(11)(q23) (p=0.014). Interestingly, higher IGF1R expression (p=0.002) characterized patients with NOTCH1 mutation (c.7541_7542delCT), identified in 15.5% of cases of our series by next generation sequencing and ARMS-PCR. Furthermore, IGF1R expression has been proven as an independent prognostic factor associated with time to first treatment in our CLL prospective cohort. These data suggest that IGF1R may play an important role in CLL biology, in particular in aggressive CLL clones characterized by IGHV-UM, trisomy 12 and NOTCH1 mutation. PMID:25786252

  12. Effects of bioactive compounds from carrots (Daucus carota L.), polyacetylenes, beta-carotene and lutein on human lymphoid leukaemia cells.

    Science.gov (United States)

    Zaini, Rana G; Brandt, Kirsten; Clench, Malcolm R; Le Maitre, Christine L

    2012-07-01

    New therapies for leukaemia are urgently needed. Carrots have been suggested as a potential treatment for leukaemia in traditional medicine and have previously been studied in other contexts as potential sources of anticancer agents. Indicating that carrots may contain bioactive compounds, which may show potential in leukaemia therapies. This study investigated the effects of five fractions from carrot juice extract (CJE) on human lymphoid leukaemia cell lines, together with five purified bioactive compounds found in Daucus carota L, including: three polyacetylenes (falcarinol, falcarindiol and falcarindiol-3-acetate) and two carotenoids (beta-carotene and lutein). Their effects on induction of apoptosis using Annexin V/PI and Caspase 3 activity assays analysed via flow cytometry and inhibition of cellular proliferation using Cell Titer Glo assay and cell cycle analysis were investigated. Treatment of all three lymphoid leukaemia cell lines with the fraction from carrot extracts which contained polyacetylenes and carotenoids was significantly more cytotoxic than the 4 other fractions. Treatments with purified polyacetylenes also induced apoptosis in a dose and time responsive manner. Moreover, falcarinol and falcarindiol-3-acetate isolated from Daucus carota L were more cytotoxic than falcarindiol. In contrast, the carotenoids showed no significant effect on either apoptosis or cell proliferation in any of the cells investigated. This suggests that polyacetylenes rather than beta-carotene or lutein are the bioactive components found in Daucus carota L and could be useful in the development of new leukemic therapies. Here, for the first time, the cytotoxic effects of polyacetylenes have been shown to be exerted via induction of apoptosis and arrest of cell cycle.

  13. Association of nitric oxide synthase 3 (NOS3) 894 G>T polymorphism with prognostic outcomes of anthracycline in Chinese patients with acute myeloid leukaemia.

    Science.gov (United States)

    He, Hui; Xu, Ya-Jing; Yin, Ji-Ye; Li, Xi; Qu, Jian; Xu, Xiao-Jing; Liu, Zhuo-Gang; Zhou, Fan; Zhai, Ming; Li, Yan; Zhou, Hong-Hao; Liu, Zhao-Qian

    2014-06-01

    The aim of the present study was to investigate the influence of the nitric oxide synthase 3 (NOS3) 894 G>T polymorphism on prognostic outcomes of anthracycline in Chinese patients with de novo intermediate-risk acute myeloid leukaemia (AML) and to examine the gene expression level in relation to genetic variation. In all, 225 Chinese patients with intermediate-risk AML (at the complete remission stage) treated with anthracycline were enrolled in the study. The 894 G>T polymorphism of the NOS3 gene was analysed by allele-specific matrix-assisted laser desorption ionization time-of-flight. Expression of NOS3 mRNA was tested in 72 patients of known genotype for NOS3 894 G>T. The clinical characteristics of these patients were obtained from medical records. Survival analysis showed that patients with AML (GG genotype) had a longer overall survival (OS; P = 0.006). After adjusting for age, gender, leucocyte count, haemoglobin level, platelet level, French, American and Britain (FAB) classification, lactate dehydrogenase levels, Eastern Cooperative Oncology Group Performance Status, nucleophosmin gene and fms-related tyrosine kinase 3 gene, multivariate survival analysis showed that the NOS3 894 G>T polymorphism appeared to be a predicting factor for OS (P = 0.014; hazard ratio = 1.856). However, no significant associations between the NOS3 894 G>T polymorphism and relapse-free survival and relapse in patients with AML were observed. Gene expression levels were significantly higher in patients with the GG genotype than in patients with the GT and TT genotypes (P = 0.033). The findings suggest that the NOS3 894 G>T variant may be a biomarker for the prediction of OS in Chinese patients with AML. © 2014 Wiley Publishing Asia Pty Ltd.

  14. mTEL-cFms激酶结构域融合蛋白真核表达载体的构建及其对信号转导和转录激活因子核转位的影响%Establishment of mTEL-cFmskd eukaryotic expression vector and its effect on STAT1/3 nuclear translocation

    Institute of Scientific and Technical Information of China (English)

    杨胜乾; 龙隆; 李微; 王莉莉

    2011-01-01

    OBJECTIVE To construct a eukaryotic expression vector of mTEL-cFmskd and study its effect on nuclear translocation of the signal transducer and activator of transcription 1/3 ( STAT1/3 ). METHODS By recombinant DNA technology, the DNA sequence of polypeptide for myristoylation of human c-Src, helix-loop-helix domain of human TEL, kinase domain of macro-phage colony-stimulating factor receptor and c-Myc tag were inserted into pCORON/neo plasmid to generate pCORON/neo-HcSrc-Tel-cfmskd-Myc eukaryotic expression vector. The mTEL-cFmskd expression vector pCORON/neo-HcSrc-Tel-cfmskd-Myc and the c-Fms expression vector pCORON/ neo-cfms were transfected into U2OS ( expressing GFP-STAT1 ) and BHK ( expressing EGFP-STAT3) cells. After 24 h, the cells were fixed, stained and then imaged on the IN Cell Analyzer 1000. The image was analyzed using the Nuclear Trafficking Analysis Module. RESULTS Restriction enzyme digestion and plasmid sequencing confirmed the successful construction of pCORON/neo-HcSrc-Tel-cfmskd-Myc plasmid. mTEL-cFmskd was expressed in cells, and caused nuclear translocation of GFP-STAT1 and EGFP-STAT3 24 h after transfection. C-Fms inhibitors GW2580 and Sutent could block the nuclear translocation of EGFP-STAT3 by mTEL-cFmskd. CONCLUSION mTEL-cFmskd expression vector pCORON/neo-HcSrc-Tel-cfmskd-Myc is successfully constructed and functional mTEL-cFmskd is expressed in GFP-STAT1_U2OS and EGFP-STAT3_BHK cells.%目的 构建激酶盘真核表达载体,观察豆蔻酰化的TEL转录调节因子HLH结构域与c-Fms激酶结构域融合蛋白( mTEL-cFmskd)的表达对信号转导和转录激活因子1(STAT1)和STAT3核转位的影响.方法 利用DNA重组技术,将人的c-Src豆蔻酰化多肽、TEL转录调节因子HLH结构域、c-Fms激酶结构域以及c-Myc标签的DNA序列克隆在pCORON/neo载体上,构建pCORON/neo-HcSrc-Tel-cfmskd-Myc真核表达载体.将载体转染至稳定表达GFP-STAT1的人骨肉瘤细胞(U2OS)和稳定表达EGFP-STAT3

  15. First-line chemoimmunotherapy with bendamustine and rituximab versus fludarabine, cyclophosphamide, and rituximab in patients with advanced chronic lymphocytic leukaemia (CLL10)

    DEFF Research Database (Denmark)

    Eichhorst, Barbara; Fink, Anna-Maria; Bahlo, Jasmin

    2016-01-01

    BACKGROUND: Chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab is the standard therapy for physically fit patients with advanced chronic lymphocytic leukaemia. This international phase 3 study compared the efficacy and tolerance of the standard therapy with a potentially less to...

  16. Estrategias de flexibilidad productiva y cambio tecnológico en Teléfonos de México

    Directory of Open Access Journals (Sweden)

    Gabriel Pérez

    2003-01-01

    Full Text Available El presente artículo analiza cómo se dio el proceso de reestructuración productiva y flexibilidad laboral en Teléfonos de México, S.A. de C.V. (Telmex a partir de los años ochenta. Específicamente se examina cómo se da éste a través de la firma de un convenio de concertación para la apertura y la competencia; los cambios en algunas cláusulas de los Contratos Colectivos de Trabajo (CCT derivadas de la puesta en marchar de un convenio de productividad; la compactación de especialidades; las estrategias de desarrollo, y del papel que jugó el Sindicato de Telefonistas de la República Mexicana (STRM. Asimismo, se estudia el impacto que tuvo la puesta en marcha de políticas de flexibilización laboral en la contratación colectiva de Telmex y los alcances del proceso de modernización, con la finalidad de hacer algunas reflexiones generales sobre la reestructuración productiva emprendida por esta empresa.

  17. Agenda setting en medios ecuatorianos. Diarios El Universo, El Mercurio, El Comercio y El Telégrafo

    Directory of Open Access Journals (Sweden)

    D Calva Cabrera

    2013-09-01

    Full Text Available Introducción. Tomando como base fundamental los conceptos de la agenda setting el estudio busca conocer la línea que siguen los cuatro medios de comunicación de Ecuador (El Universo, El Telégrafo, El Comercio y El Mercurio para el establecimiento cotidiano de sus temarios periodísticos. Metodología. Se trabajó con el análisis de contenido a través de una semana compuesta entre el 16 de abril al 18 de mayo de 2012, usando como instrumento una ficha de investigación que comprende nueve apartados. Resultados. Se destacan las entidades públicas como los principales motores de la información; las rutinas productivas cotidianas de los medios resultan favorecedoras frente al periodismo de investigación; y las noticias breves tienen mayor número de publicaciones en dichos periódicos objeto de estudio. Discusión. La falta de periodismo de investigación es notoria en los casos de estudio. Los periodistas prefieren hacer rutinas cotidianas en especial con organismos o entidades públicas en donde permanentemente encuentran hechos noticiosos. Conclusiones. Los medios de comunicación están constantemente monitoreados para conocer la importancia que le brindan a la labor periodística. Las empresas informativas suelen moverse atendiendo a determinados intereses de grupos específicos.

  18. TelCoVis: Visual Exploration of Co-occurrence in Urban Human Mobility Based on Telco Data.

    Science.gov (United States)

    Wu, Wenchao; Xu, Jiayi; Zeng, Haipeng; Zheng, Yixian; Qu, Huamin; Ni, Bing; Yuan, Mingxuan; Ni, Lionel M

    2016-01-01

    Understanding co-occurrence in urban human mobility (i.e. people from two regions visit an urban place during the same time span) is of great value in a variety of applications, such as urban planning, business intelligence, social behavior analysis, as well as containing contagious diseases. In recent years, the widespread use of mobile phones brings an unprecedented opportunity to capture large-scale and fine-grained data to study co-occurrence in human mobility. However, due to the lack of systematic and efficient methods, it is challenging for analysts to carry out in-depth analyses and extract valuable information. In this paper, we present TelCoVis, an interactive visual analytics system, which helps analysts leverage their domain knowledge to gain insight into the co-occurrence in urban human mobility based on telco data. Our system integrates visualization techniques with new designs and combines them in a novel way to enhance analysts' perception for a comprehensive exploration. In addition, we propose to study the correlations in co-occurrence (i.e. people from multiple regions visit different places during the same time span) by means of biclustering techniques that allow analysts to better explore coordinated relationships among different regions and identify interesting patterns. The case studies based on a real-world dataset and interviews with domain experts have demonstrated the effectiveness of our system in gaining insights into co-occurrence and facilitating various analytical tasks.

  19. Polars Changing State: Multiwavelength Long Term Photometry and Spectroscopy of QS Tel, V834 Cen, and BL Hyi

    CERN Document Server

    Gerke, J R; Walter, F M; Gerke, Jill R.; Howell, Steve B.; Walter, Frederick M.

    2006-01-01

    Long term optical and near-infrared photometric and blue spectroscopic observations were obtained for QS Tel, V834 Cen, and BL Hyi. The optical light curves of all three polars displayed large magnitude changes during our observations. These same high/low state transitions were also apparent in near-infrared JHK photometry, though with decreased amplitude. The color of the polar with respect to its state was examined and found not to be a good indicator of the instantaneous state. During low to high state transitions, a nearly constant magnitude difference was observed in all three polars. This $\\Delta$m value was found to be consistent with the level expected to occur if accretion onto the white dwarf reached the Eddington luminosity during the high state. The high state Balmer decrement was measured for each star and used to estimate that the temperature of the emission line forming region was ~12,000K with N$_H$ near 12.8 dex. No relationship between the Balmer emission line strength and the white dwarf ma...

  20. Breast Imaging Utilizing Dedicated Gamma Camera and (99m)Tc-MIBI: Experience at the Tel Aviv Medical Center and Review of the Literature Breast Imaging.

    Science.gov (United States)

    Even-Sapir, Einat; Golan, Orit; Menes, Tehillah; Weinstein, Yuliana; Lerman, Hedva

    2016-07-01

    The scope of the current article is the clinical role of gamma cameras dedicated for breast imaging and (99m)Tc-MIBI tumor-seeking tracer, as both a screening modality among a healthy population and as a diagnostic modality in patients with breast cancer. Such cameras are now commercially available. The technology utilizing a camera composed of a NaI (Tl) detector is termed breast-specific gamma imaging. The technology of dual-headed camera composed of semiconductor cadmium zinc telluride detectors that directly converts gamma-ray energy into electronic signals is termed molecular breast imaging. Molecular breast imaging system has been installed at the Department of Nuclear medicine at the Tel Aviv Sourasky Medical Center, Tel Aviv in 2009. The article reviews the literature well as our own experience. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Adult acute lymphoblastic leukaemia in Denmark. A national population-based retrospective study on acute lymphoblastic leukaemia in Denmark 1998-2008

    DEFF Research Database (Denmark)

    Toft, Nina; Schmiegelow, Kjeld; Klausen, Tobias W

    2012-01-01

    with historical controls, we performed a retrospective national population-based study of adult ALL between 1998 and 2008. Patients were identified through the Danish Patobank and the Danish Cancer Registry; data was collected from patient files, and included 277 patients (median age, 47 years, range 15-91 years......Since July 2008, children and adults 1-45 years, diagnosed with acute lymphoblastic leukaemia (ALL) in Denmark have been treated according to the common Nordic Society for Paediatric Haematology and Oncology ALL2008 protocol. To explore whether this strategy will improve survival compared......). The 5-year projected event-free survival (pEFS(5y) ) and overall survival (pOS(5y) ) for the whole cohort was 27·5% [95% confidence interval (CI) 22·4-33·6] and 34·1% (95% CI 28·7-40·4), respectively. No patient above 65 years survived beyond 5 years from diagnosis. For patients receiving curatively...

  2. Ciberacoso mediante teléfono móvil e Internet en las relaciones de noviazgo entre jóvenes

    Directory of Open Access Journals (Sweden)

    Roberto Martínez Pecino

    2015-01-01

    Full Text Available El ciberacoso es un fenómeno ampliamente analizado entre adolescentes, sin embargo en España ha sido poco estudiado entre jóvenes y particularmente en sus relaciones de noviazgo. Empleando una metodología cuantitativa este estudio analiza el ciberacoso mediante el teléfono móvil e Internet en las relaciones de noviazgo en una muestra compuesta por 336 estudiantes universitarios. El análisis de resultados indica que un 57,2% declara haber sido victimizado por su pareja mediante el teléfono móvil, y un 27,4% a través de Internet. El porcentaje de chicos victimizados fue mayor que el de las chicas. Un 47,6% declara haber acosado a su pareja a través del teléfono móvil, y un 14% a través de Internet. El porcentaje de chicos que lo ejerció fue superior al de las chicas. Los análisis de regresión muestran la relación entre haber sido victimizado por la pareja a través de uno de estos medios y el ejercicio del ciberacoso hacia la pareja mediante el mismo medio tecnológico. Los efectos de interacción ponen de manifiesto que los chicos victimizados a través del teléfono móvil o de Internet se implican, en mayor medida que las chicas victimizadas, como agresores en este fenómeno. Los resultados sugieren una modernización en los tipos de violencia que experimenta la juventud en sus relaciones de pareja.

  3. Narraciones escritas en niños con Trastorno Específico del Lenguaje (TEL / Written Narration in Specific Language Impairment (SLI

    Directory of Open Access Journals (Sweden)

    Manuel Soriano-Ferrer

    2012-12-01

    Full Text Available El presente estudio examinó las narraciones escritas, así como la influencia de las variables lingüísticas sobre la competencia narrativa de los niños con Trastorno Específico del Lenguaje (TEL. Veinticinco niños con TEL y 25 niños con desarrollo normal del lenguaje, equilibrados en edad e inteligencia, realizaron una tarea de narración escrita. Los resultados indican que ambos grupos difieren en la producción de narraciones. Los niños con TEL no solo escribieron historias más cortas, sino también de menor organización y coherencia. Además cometieron significativamente más errores de ortografía natural y de sintaxis. Los análisis de regresión jerárquica mostraron que diferentes medidas lingüísticas –memoria secuencial auditiva, comprensión auditiva y expresión verbal– tienen un peso predictivo de lacompetencia narrativa.

  4. PfAP2Tel, harbouring a non-canonical DNA-binding AP2 domain, binds to Plasmodium falciparum telomeres.

    Science.gov (United States)

    Sierra-Miranda, Miguel; Vembar, Shruthi S; Delgadillo, Dulce María; Ávila-López, P A; Vargas, Miguel; Hernandez-Rivas, Rosaura

    2017-04-04

    The telomeres of the malaria parasite Plasmodium falciparum are essential not only for chromosome end maintenance during blood stage development in humans but also to generate genetic diversity by facilitating homologous recombination of subtelomeric, multigene virulence families such as var and rifin. However, other than the telomerase PfTERT, proteins that act at P. falciparum telomeres are poorly characterized. To isolate components that bind to telomeres, we performed oligonucleotide pulldowns and electromobility shift assays with a telomeric DNA probe and identified a non-canonical member of the ApiAP2 family of transcription factors, PfAP2Tel (encoded by PF3D7_0622900), as a component of the P. falciparum telomere-binding protein complex. PfAP2Tel is expressed throughout the intra-erythrocytic life cycle and localizes to the nuclear periphery, co-localizing with telomeric clusters. Furthermore, EMSAs using the recombinant protein demonstrated direct binding of PfAP2Tel to telomeric repeats in vitro, while genome-wide chromatin immunoprecipitation followed by next generation sequencing (ChIP-seq) corroborated the high specificity of this protein to telomeric ends of all 14 chromosomes in vivo. Taken together, our data describe a novel function for ApiAP2 proteins at chromosome ends and open new avenues to study the molecular machinery that regulates telomere function in P. falciparum.

  5. Gene therapy: X-SCID transgene leukaemogenicity.

    Science.gov (United States)

    Thrasher, Adrian J; Gaspar, H Bobby; Baum, Christopher; Modlich, Ute; Schambach, Axel; Candotti, Fabio; Otsu, Makoto; Sorrentino, Brian; Scobie, Linda; Cameron, Ewan; Blyth, Karen; Neil, Jim; Abina, Salima Hacein-Bey; Cavazzana-Calvo, Marina; Fischer, Alain

    2006-09-21

    Gene therapy has been remarkably effective for the immunological reconstitution of patients with severe combined immune deficiency, but the occurrence of leukaemia in a few patients has stimulated debate about the safety of the procedure and the mechanisms of leukaemogenesis. Woods et al. forced high expression of the corrective therapeutic gene IL2RG, which encodes the gamma-chain of the interleukin-2 receptor, in a mouse model of the disease and found that tumours appeared in a proportion of cases. Here we show that transgenic IL2RG does not necessarily have potent intrinsic oncogenic properties, and argue that the interpretation of this observation with respect to human trials is overstated.

  6. Identification of TEL-AML1 (ETV6-RUNX1 associated DNA and its impact on mRNA and protein output using ChIP, mRNA expression arrays and SILAC

    Directory of Open Access Journals (Sweden)

    Yvonne Linka

    2014-12-01

    Full Text Available The contribution of the most common reciprocal translocation in childhood B-cell precursor leukemia t(12;21(p13;q22 to leukemia development is still under debate. Direct as well as secondary indirect effects of the TEL-AML1 fusion protein are commonly recorded by using cell lines and patient samples, often bearing the TEL-AML1 fusion protein for decades. To identify direct targets of the fusion protein a short-term induction of TEL-AML1 is needed. We here describe in detail the experimental procedure, quality controls and contents of the ChIP, mRNA expression and SILAC datasets associated with the study published by Linka and colleagues in the Blood Cancer Journal [1] utilizing a short term induction of TEL-AML1 in an inducible precursor B-cell line model.

  7. 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...

  8. Detection of Bovine Leukaemia Virus Antibodies and Proviral DNA in Colostrum Replacers.

    Science.gov (United States)

    Choudhury, B; Finnegan, C; Phillips, A; Horigan, M; Pollard, T; Steinbach, F

    2015-10-01

    Great Britain has been bovine leukaemia virus (BLV) disease free since 1999. We recently reported three separate incidents of BLV seropositivity on farms with home-reared cattle due to the use of colostrum replacer rather than infection with BLV (Emerg. Infect. Dis., 19, 2013, 1027). These cases were all linked via the use of the same brand of colostrum replacer. Here, we investigate further by examining multiple brands of colostrum replacer for proviral DNA and BLV antibodies. BLV antibodies were detected in 7 of the colostrum replacers tested, with PCR concurring in two cases. Thus, the use of these BLV antibody-positive colostrum replacers may also lead to false-positive serological diagnostics.

  9. Arthroplasties of hips and knees ankylosis in an adolescent with acute lymphoblastic leukaemia.

    Directory of Open Access Journals (Sweden)

    Dipo Samuel OLABUMUYI

    2011-10-01

    Full Text Available Acute lymphoblastic leukaemia (ALL is the most common malignancy in children, representing one third of all paediatric malignancies. Patients are often at high risk for complications due aggressive chemotherapy regimes required for treatment. Musculoskeletal complications include septic arthritis, osteonecrosis, osteoporosis, avascular necrosis and bony ankylosis. We report the case of a 16-year-old boy with ALL who developed osteonecrosis of multiple bones on a background of septicaemia, resulting in bony ankylosis of both hips and knees. He was treated with bilateral conversion of ankylosed hips (one hip to total hip replacement, the second hip to Girdlestone arthroplasty and bilateral ankylosed knees to total knee replacements. He remained well in remission five years after the last surgery. Our case highlights he possible musculoskeletal complications of ALL. 

  10. The development of integrated haematopathology laboratories: a new approach to the diagnosis of leukaemia and lymphoma.

    Science.gov (United States)

    Richards, S J; Jack, A S

    2003-12-01

    The diagnosis and monitoring of leukaemia and lymphoma requires the effective integration of a wide range of diagnostic techniques and expertise. The need to develop this type of service that crosses traditional boundaries of laboratory specialities is being recommended in national guidance. The Haematological Malignancy Diagnostic Service based within the Leeds Teaching Hospitals NHS Trust was established in 1993 to provide specialist laboratory services for the diagnosis of haematological malignancy for Yorkshire and Humberside in the UK. The department uses a wide range of methodologies including morphology, immunocytochemistry, flow cytometry and molecular genetics [fluorescent in situ hybridization (FISH) and polymerase chain reaction (PCR)] in a systematic and co-ordinated way. We describe how the department was established, its current working practices and highlight the advantages of an integrated laboratory for diagnosis of tumours of the haematopoietic system.

  11. Amphotropic murine leukaemia virus envelope protein is associated with cholesterol-rich microdomains

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    Pedersen Lene

    2005-04-01

    Full Text Available Abstract Background Cholesterol-rich microdomains like lipid rafts were recently identified as regions within the plasma membrane, which play an important role in the assembly and budding of different viruses, e.g., measles virus and human immunodeficiency virus. For these viruses association of newly synthesized viral proteins with lipid rafts has been shown. Results Here we provide evidence for the association of the envelope protein (Env of the 4070A isolate of amphotropic murine leukaemia virus (A-MLV with lipid rafts. Using density gradient centrifugation and immunocytochemical analyses, we show that Env co-localizes with cholesterol, ganglioside GM1 and caveolin-1 in these specific regions of the plasma membrane. Conclusions These results show that a large amount of A-MLV Env is associated with lipid rafts and suggest that cholesterol-rich microdomains are used as portals for the exit of A-MLV.

  12. Diagnostic & prognostic role of microRNAs in paediatric acute myeloid leukaemia

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    Sachin Kumar

    2016-01-01

    Full Text Available Dysregulation in microRNAs (miRNAs expression has been observed in distinct acute myeloid leukaemia (AML subtypes, and their potential as an effective diagnostic and prognostic biomarker is slowly being realized. Certain miRNAs have been found to be associated with various cytogenetic and molecular abnormalities of prognostic significance in AML. Experimental evidences have indicated the potential of modulating miRNA expression as an effective antileukaemic strategy. This has opened a new window for miRNAs-based targeted therapies. In this review, we present results of some studies analyzing the dysregulation in miRNAs expression pattern in paediatric AML and also discuss their use as diagnostic and prognostic markers.

  13. Chronic Myeloid Leukaemia Presenting as Bilateral Retinal Haemorrhages with Multiple Retinal Infiltrates.

    Science.gov (United States)

    Rane, Priyanka Ramkrishna; Barot, Rakesh K; Gohel, Devadatta Jayantilal; Bhagat, Nupur

    2016-05-01

    Chronic Myeloid Leukaemia (CML) causes retinopathy manifesting as venous dilation and tortuosity, perivascular sheathing, retinal haemorrhages, microaneurysms, cotton-wool spots and optic nerve infiltration. Retina is the most commonly involved intraocular structure in CML. However, retinal involvement is a rare form of presentation of CML and few cases have been reported. We report a case of CML presenting as unilateral sudden visual loss. Fundus showed multiple white centered retinal haemorrhages in both eyes with unilateral macular oedema. Blood work-up showed raised WBC count, high platelet count and low Haemoglobin. Cytological analysis of bone marrow biopsy confirmed Philadelphia chromosome. After a course of Imatinib, visual acuity improved and haemorrhages resolved with normalization of macular thickness. In our case, patient presented early, leading to early detection producing better visual prognosis. This highlights the importance of detailed hematological work up in patients with retinal involvement to rule out leukaemic retinopathy.

  14. Fetal liver transplantation in 2 patients with acute leukaemia after total body irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Lucarelli, G.; Izzi, T.; Porcellini, A.; Delfini, C.; Galimberti, M.; Moretti, L.; Polchi, P.; Agostinelli, F.; Andreani, M.; Manna, M. (Haematological Department, Pesaro Hospital, Pesaro, Italy)

    1982-01-01

    2 patients with acute leukaemia in relapse were transplanted with fetal liver cells following a conditioning regimen of cyclophosphamide (120 mg/kg) and total body irradiation (1000 r). Each patient achieved a remission with haematopoietic recovery that was rapid in one case and delayed in the other. In one case there was evidence of chimerism as demonstrated by the presence of the XYY karyotype of the donor fetus in 20 % of marrow metaphases, by the presence of double Y bodies in the peripheral blood, by the appearance of new HLA-antigens, and by red cell isoenzyme phenotypes of donor origin. In the second case there was prompt haemotopoietic recovery and the appearance of red cell isoenzyme phenotypes of donor origin. Survival was 153 and 30 d, respectively, and both patients died of interstitial pneumonia without evidence of graft versus host disease.

  15. Lung function after allogeneic bone marrow transplantation for leukaemia or lymphoma

    DEFF Research Database (Denmark)

    Nysom, K; Holm, K; Hesse, B

    1996-01-01

    Longitudinal data were analysed on the lung function of 25 of 29 survivors of childhood leukaemia or lymphoma, who had been conditioned with cyclophosphamide and total body irradiation before allogeneic bone marrow transplantation, to test whether children are particularly vulnerable to pulmonary...... damage after transplantation. None developed chronic graft-versus-host disease. Transfer factor and lung volumes were reduced immediately after bone marrow transplantation, but increased during the following years. However, at the last follow up, 4-13 years (median 8) after transplantation, patients had...... to their age at bone marrow transplantation. In conclusion, patients had subclinical restrictive pulmonary disease at a median of eight years after total body irradiation and allogeneic bone marrow transplantation....

  16. Auricular Oedema and Dyshidrotic Eczema in a Patient with Acute Myeloid Leukaemia Treated with Cytarabine

    Directory of Open Access Journals (Sweden)

    K. Brandt

    2010-10-01

    Full Text Available Cytarabine is an effective drug in the treatment of haematological malignancies. The therapy is associated with various complications. Frequencies of dermatological side-effects range from 2–72% and occur most commonly after high-dose regimens. Although most cutaneous reactions are mild and resolve spontaneously within several days, they may result in an increased risk of infection and alterations in comfort. In some cases, severe life-threatening reactions have been reported. Here we describe the case of a patient with acute myeloid leukaemia, who developed severe exceptional skin toxicity in terms of auricular oedema and palmar dyshidrotic eczema after the application of low-dose cytarabine. Re-administration of the drug resulted in reduced skin toxicity during further cycles of chemotherapy. Negative epicutaneous patch-testing supported the existence of cytarabine-provoked toxicity.

  17. Population preference values for treatment outcomes in chronic lymphocytic leukaemia: a cross-sectional utility study

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    Meiklejohn David

    2010-05-01

    Full Text Available Abstract Background Given that treatments for chronic lymphocytic leukaemia (CLL are palliative rather than curative, evaluating the patient-perceived impacts of therapy is critical. To date, no utility (preference studies from the general public or patient perspective have been conducted in CLL. The objective of this study was to measure preferences for health states associated with CLL treatment. Methods This was a cross-sectional study of 89 members of the general population in the UK (England and Scotland. Using standard gamble, each participant valued four health states describing response status, six describing treatment-related toxicities based on Common Toxicity Criteria, and two describing line of treatment. The health states incorporated standardized descriptions of treatment response (symptoms have "improved," "stabilized," or "gotten worse", swollen glands, impact on daily activities, fatigue, appetite, and night sweats. Utility estimates ranged from 0.0, reflecting dead, to 1.0, reflecting full health. Results Complete response (CR was the most preferred health state (mean utility, 0.91, followed by partial response (PR, 0.84; no change (NC, 0.78; and progressive disease (PD, 0.68. Among the toxicity states, grade I/II nausea and nausea/vomiting had the smallest utility decrements (both were -0.05, and grade III/IV pneumonia had the greatest decrement (-0.20. The utility decrements obtained for toxicity states can be subtracted from utilities for CR, PR, NC, and PD, as appropriate. The utilities for second- and third-line treatments, which are attempted when symptoms worsen, were 0.71 and 0.65, respectively. No significant differences in utilities were observed by age, sex, or knowledge/experience with leukaemia. Conclusions This study reports UK population utilities for a universal set of CLL health states that incorporate intended treatment response and unintended toxicities. These utilities can be applied in future cost

  18. Organ irradiation and combination chemotherapy in treatment of acute lymphocytic leukaemia in children.

    Science.gov (United States)

    Lanzkowsky, P; Shende, A; Aral, I; Saluja, G

    1975-01-01

    Lanzkowsky, P., Shende, A., Aral, I., Saluja, G. (1975). Archives of Disease in Childhood, 50, 685. Organ irradiation and combination chemotherapy in treatment of acute lymphocytic leukaemia in children. A total of 30 consecutive children with acute lymphocytic leukaemia (ALL) were treated from June 1971 until December 1974. Remission was induced with the use of vincristine and prednisone. After induction of remission, cranial irradiation and intrathecal methotrexate were given. Then the liver, spleen, and kidney were irradiated and 6-mercaptopurine, cyclophosphamide, and methotrexate were administered during the maintenance phase. Pulsed doses of vincristine and prednisone were administered at 10- to 12-week intervals. The patients were subdivided into two groups based on their initial white blood cell (WBC) counts: a standard risk group with an initial WBC count of less than 25 000/mm3 (25 X 10(9)/1) and a high risk group with an initial WBC count greater than 25 000/mm3 (25 X 10(9)/1). Of the 30 children entered in this study one standard risk patient died in the induction phase before attaining remission. Analysis of the results is therefore based on the remaining 29 patients, 22 standard risk and 7 high risk patients, who attained complete remission. Survival rates in continuous remission were found to be 43% of the high risk group, 88% for the standard risk group, and 77% for the combined group. Analysis of the data indicates that this therapy is unsatisfactory in high risk ALL. The results to date of this therapy for standard risk are sufficiently encouraging to continue its use in this subgroup of patients. PMID:1059384

  19. Obinutuzumab: a review of its use in patients with chronic lymphocytic leukaemia.

    Science.gov (United States)

    Hoy, Sheridan M

    2015-02-01

    Obinutuzumab (Gazyva(®); Gazyvaro(®)) is an intravenously administered, glycoengineered, humanized, type II, anti-CD20 monoclonal antibody of the IgG1 subclass. It is available in the EU and the USA as combination therapy with oral chlorambucil in adults with previously untreated chronic lymphocytic leukaemia (CLL). In a multinational phase III study in this patient population, obinutuzumab plus chlorambucil significantly prolonged progression-free survival compared with oral chlorambucil alone and intravenous rituximab plus oral chlorambucil. Significant advantages with obinutuzumab plus chlorambucil over chlorambucil alone and rituximab plus chlorambucil were also observed in event-free survival, the time to a new anti-leukaemia treatment and overall response. The overall survival benefit with obinutuzumab plus chlorambucil is as yet unclear, although the most recent analysis suggests a benefit over chlorambucil alone. In the phase III study, obinutuzumab plus chlorambucil had a manageable tolerability profile in accordance with what would be expected for an anti-CD20 antibody. Neutropenia and infusion-related reactions were the most frequently reported grade 3 or higher treatment-emergent adverse events. In the majority of patients, infusion-related reactions were mild to moderate in severity and occurred predominantly during the first infusion and were managed by slowing or temporarily halting the infusion. Thus, current evidence suggests that obinutuzumab plus chlorambucil is a welcome addition to the treatment options currently available for adults with previously untreated CLL and is recommended by the National Comprehensive Cancer Network guidelines as the preferred first option for some, including those with comorbidities.

  20. TESTIN Induces Rapid Death and Suppresses Proliferation in Childhood B Acute Lymphoblastic Leukaemia Cells.

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    Robert J Weeks

    Full Text Available Childhood acute lymphoblastic leukaemia (ALL is the most common malignancy in children. Despite high cure rates, side effects and late consequences of the intensive treatments are common. Unquestionably, the identification of new therapeutic targets will lead to safer, more effective treatments. We identified TES promoter methylation and transcriptional silencing as a very common molecular abnormality in childhood ALL, irrespective of molecular subtype. The aims of the present study were to demonstrate that TES promoter methylation is aberrant, to determine the effects of TES re-expression in ALL, and to determine if those effects are mediated via TP53 activity.Normal fetal and adult tissue DNA was isolated and TES promoter methylation determined by Sequenom MassARRAY. Quantitative RT-PCR and immunoblot were used to confirm re-expression of TES in ALL cell lines after 5'-aza-2'-deoxycytidine (decitabine exposure or transfection with TES expression plasmids. The effects of TES re-expression on ALL cells were investigated using standard cell proliferation, cell death and cell cycle assays.In this study, we confirm that the TES promoter is unmethylated in normal adult and fetal tissues. We report that decitabine treatment of ALL cell lines results in demethylation of the TES promoter and attendant expression of TES mRNA. Re-expression of TESTIN protein in ALL cells using expression plasmid transfection results in rapid cell death or cell cycle arrest independent of TP53 activity.These results suggest that TES is aberrantly methylated in ALL and that re-expression of TESTIN has anti-leukaemia effects which point to novel therapeutic opportunities for childhood ALL.

  1. Evaluación de la longitud de los telómeros en caballos, mediante el uso de la reacción en cadena de la polimerasa cuantitativa

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    L. Sanmartín-Sánchez

    2014-06-01

    Full Text Available Introducción: Los telómeros son estructuras de los cromosomas eucariotas, que juegan un importante papel en el mantenimiento de la estabilidad e integridad celular, estableciéndose como uno de los posibles biomarcadores del envejecimiento celular en el hombre y otras especies. Objetivos: Evaluar la posibilidad del uso de la técnica de la reacción en cadena de la polimerasa cuantitativa (qPCR para calcular la longitud relativa de los telómeros en caballos y asociarla con factores como la edad, la raza y el y el sexo. Material y métodos: Se amplificó una secuencia repetitiva correspondiente a los telómeros, junto con otra de un gen de copia única (Interleukina-2, en muestras de sangre de 175 caballos de tres razas, de distintos grupos de edad y de ambos sexos. Se calculó la longitud relativa de los telómeros de cada individuo a través dos variables de respuesta: la diferencia entre el número de ciclos de cuantificación entre telómeros e Interleukina-2 (Dif Cq y la ratio entre ambos valores (T/S ratio. Resultados: La variable Dif Cq presenta una asociación más fuerte con la edad que la variable T/S ratio. Se observó una correlación negativa entre la edad y la longitud de los telómeros (R= -0,31, p<0,05. Conclusión: La técnica de qPCR es aplicable para determinar la longitud relativa de los telómeros en caballos. Los individuos mayores de 20 años presentan telómeros acortados, aunque no se encontró un efecto significativo ni de la raza, ni del sexo.

  2. Myeloid leukaemia frequency after protracted exposure to ionizing radiation: experimental confirmation of the flat dose-response found in ankylosing spondylitis after a single treatment course with x-rays

    Energy Technology Data Exchange (ETDEWEB)

    Mole, R.H.; Major, I.R. (Medical Research Council, Harwell (UK). Radiobiological Research Unit)

    1983-01-01

    The dose-response for leukaemia induction by exposure to ionizing radiation protracted over several weeks was largely independent of dose not only in X-rayed patients with ankylosing spondylitis but also in experimentally ..gamma..-rayed CBA/H mice. In the experiment the induced leukaemia frequency of acute myeloid leukaemia was independent of a several thousand-fold variation in physical dose rate. Any difference in leukaemia induction between brief and protracted exposures must therefore depend on specifically biological consequences of protracted exposures. Experimental analysis is required to provide the guides for inference about risks of low level exposure from observations on relatively heavily irradiated populations.

  3. An ultra-deep sequencing strategy to detect sub-clonal TP53 mutations in presentation chronic lymphocytic leukaemia cases using multiple polymerases.

    Science.gov (United States)

    Worrillow, L; Baskaran, P; Care, M A; Varghese, A; Munir, T; Evans, P A; O'Connor, S J; Rawstron, A; Hazelwood, L; Tooze, R M; Hillmen, P; Newton, D J

    2016-10-06

    Chronic lymphocytic leukaemia (CLL) is the most common clonal B-cell disorder characterized by clonal diversity, a relapsing and remitting course, and in its aggressive forms remains largely incurable. Current front-line regimes include agents such as fludarabine, which act primarily via the DNA damage response pathway. Key to this is the transcription factor p53. Mutations in the TP53 gene, altering p53 functionality, are associated with genetic instability, and are present in aggressive CLL. Furthermore, the emergence of clonal TP53 mutations in relapsed CLL, refractory to DNA-damaging therapy, suggests that accurate detection of sub-clonal TP53 mutations prior to and during treatment may be indicative of early relapse. In this study, we describe a novel deep sequencing workflow using multiple polymerases to generate sequencing libraries (MuPol-Seq), facilitating accurate detection of TP53 mutations at a frequency as low as 0.3%, in presentation CLL cases tested. As these mutations were mostly clustered within the regions of TP53 encoding DNA-binding domains, essential for DNA contact and structural architecture, they are likely to be of prognostic relevance in disease progression. The workflow described here has the potential to be implemented routinely to identify rare mutations across a range of diseases.

  4. A single nucleotide polymorphism in cBIM is associated with a slower achievement of major molecular response in chronic myeloid leukaemia treated with imatinib.

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    Vanessa Augis

    Full Text Available PURPOSE: BIM is essential for the response to tyrosine-kinase inhibitors (TKI in chronic myeloid leukaemia (CML patients. Recently, a deletion polymorphism in intron 2 of the BIM gene was demonstrated to confer an intrinsic TKI resistance in Asian patients. The present study aimed at identifying mutations in the BIM sequence that could lead to imatinib resistance independently of BCR-ABL mutations. EXPERIMENTAL DESIGN: BIM coding sequence analysis was performed in 72 imatinib-treated CML patients from a French population of our centre and in 29 healthy controls (reference population as a case-control study. Real-time quantitative PCR (RT qPCR was performed to assess Bim expression in our reference population. RESULTS: No mutation with amino-acid change was found in the BIM coding sequence. However, we observed a silent single nucleotide polymorphism (SNP c465C>T (rs724710. A strong statistical link was found between the presence of the T allele and the high Sokal risk group (p = 0.0065. T allele frequency was higher in non responsive patients than in the reference population (p = 0.0049. Similarly, this T allele was associated with the mutation frequency on the tyrosine kinase domain of BCR-ABL (pT SNP of BIM could be useful for predicting the outcome of imatinib-treated CML patients.

  5. Genomic variability and alternative splicing generate multiple PML/RAR alpha transcripts that encode aberrant PML proteins and PML/RAR alpha isoforms in acute promyelocytic leukaemia.

    Science.gov (United States)

    Pandolfi, P P; Alcalay, M; Fagioli, M; Zangrilli, D; Mencarelli, A; Diverio, D; Biondi, A; Lo Coco, F; Rambaldi, A; Grignani, F

    1992-01-01

    The acute promyelocytic leukaemia (APL) 15;17 translocation generates a PML/RAR alpha chimeric gene which is transcribed as a fusion PML/RAR alpha mRNA. Molecular studies on a large series of APLs revealed great heterogeneity of the PML/RAR alpha transcripts due to: (i) variable breaking of chromosome 15 within three PML breakpoint cluster regions (bcr1, bcr2 and bcr3), (ii) alternative splicings of the PML portion and (iii) alternative usage of two RAR alpha polyadenylation sites. Nucleotide sequence analysis predicted two types of proteins: multiple PML/RAR alpha and aberrant PML. The PML/RAR alpha proteins varied among bcr1, 2 and 3 APL cases and within single cases. The fusion proteins contained variable portions of the PML N terminus joined to the B-F RAR alpha domains; the only PML region retained was the putative DNA binding domain. The aberrant PML proteins lacked the C terminus, which had been replaced by from two to ten amino acid residues from the RAR alpha sequence. Multiple PML/RAR alpha isoforms and aberrant PML proteins were found to coexist in all APLs. These findings indicate that two potential oncogenic proteins are generated by the t(15;17) and suggest that the PML activation pathway is altered in APLs. Images PMID:1314166

  6. Allergy and acute leukaemia in children with Down syndrome: a population study. Report from the Mexican inter-institutional group for the identification of the causes of childhood leukaemia

    Science.gov (United States)

    Núñez-Enríquez, J C; Fajardo-Gutiérrez, A; Buchán-Durán, E P; Bernáldez-Ríos, R; Medina-Sansón, A; Jiménez-Hernández, E; Amador-Sanchez, R; Peñaloza-Gonzalez, J G; Paredes-Aguilera, R; Alvarez-Rodriguez, F J; Bolea-Murga, V; de Diego Flores-Chapa, J; Flores-Lujano, J; Bekker-Mendez, V C; Rivera-Luna, R; del Carmen Rodriguez-Zepeda, M; Rangel-López, A; Dorantes-Acosta, E M; Núñez-Villegas, N; Velazquez-Aviña, M M; Torres-Nava, J R; Reyes-Zepeda, N C; Cárdenas-Cardos, R; Flores-Villegas, L V; Martinez-Avalos, A; Salamanca-Gómez, F; Gorodezky, C; Arellano-Galindo, J; Mejía-Aranguré, J M

    2013-01-01

    Background: Allergies have been described as protective factors against the development of childhood acute leukaemia (AL). Our objective was to investigate the associations between allergy history and the development of AL and acute lymphoblastic leukaemia (ALL) in children with Down syndrome (DS). Methods: A case–control study was performed in Mexico City. The cases (n=97) were diagnosed at nine public hospitals, and the controls (n=222) were recruited at institutions for children with DS. Odds ratios (OR) were calculated. Results: Asthma was positively associated with AL development (OR=4.18; 95% confidence interval (CI): 1.47–11.87), whereas skin allergies were negatively associated (OR=0.42; 95% CI: 0.20–0.91). Conclusion: Our findings suggest that allergies and AL in children with DS share biological and immune mechanisms. To our knowledge, this is the first study reporting associations between allergies and AL in children with DS. PMID:23695017

  7. [Etiology of maxillofacial trauma--a 10-year survey at the Chaim Sheba Medical Center, Tel-Hashomer].

    Science.gov (United States)

    Yoffe, Tal; Shohat, Izhar; Shoshani, Yzhak; Taicher, Shlomo

    2008-03-01

    The management of cranio-maxillofacial trauma includes treatment of facial bone fractures, dentoalveolar trauma, and soft tissue injuries. Integration of several specialties is often needed due to the proximity of the cranial bones to important organs such as the eyeballs, the nose, the ears, and the brain. The epidemiology of facial fractures varies in type, severity, and cause depending on the population studied. The differences between populations in the causes of maxillofacial fractures may be the result of risk factors and cultural differences between countries but are more likely to be influenced by the injury severity. Many epidemiologic investigations of maxillofacial fractures have appeared in the scientific literature over the years. Six main causes of injury were identified: motor vehicle accidents, occupational accidents, sport accidents, falls, assaults, and gun shot wounds. However, few reports, representing continuous long-term data on maxillofacial fractures in the state of Israel, are to be found. This study was undertaken to provide information regarding gender, age, etiology and diagnosis of patients with maxillofacial fractures, gleaned from our experience in the last 10 years (1996-2005), and to compare this information to the findings from the years 1985-1995, at the Department of Oral and Maxillofacial Surgery in the Chaim Sheba Medical Center, Tel Hashomer. The present study reviews retrospectively hospital records of 775 patients. Data regarding the 753 patients treated at the department in the years 1985-1995 was taken from previous publication. The diagnosis was based on radiographic data and clinical examination. The statistical analysis was carried out by the Statistics Department of Tel Aviv University. The majority of patients (74.2%) were males, the average age was 33.4 years, and the largest subgroup of patients (34%) was in the third decade of life. The most common cause of injury was falls (35%), followed by motor vehicle

  8. Bruyères-le-Châtel Neutron Evaluations of Actinides with the TALYS Code: The Fission Channel

    Science.gov (United States)

    Romain, P.; Morillon, B.; Duarte, H.

    2016-01-01

    For several years, various neutron evaluations of plutonium and uranium isotopes have been performed at Bruyères-le-Châtel (BRC), from 1 keV up to 30 MeV. Since only nuclear reaction models have been used to produce these evaluations, our approach was named the "Full Model" approach. Total, shape elastic and direct inelastic cross sections were obtained from the coupled channels model using a dispersive optical potential developed for actinides, with a large enough coupling scheme including the lowest octupolar band. All other cross sections were calculated using the Hauser-Feshbach theory (TALYS code) with a pre-equilibrium component above 8-10 MeV. In this paper, we focus our attention on the fission channel. More precisely, we will present the BRC contribution to fission modeling and the philosophy adopted in our "Full Model" approach. Performing evaluations with the "Full Model" approach implies the optimization of a large number of model parameters. With increasing neutron incident energy, many residual nuclei produced by nucleon emission also lead to fission. All available experimental data assigned to various fission mechanisms of the same nucleus were used to determine fission barrier parameters. For uranium isotopes, triple-humped fission barriers were required in order to reproduce accurately variations of the experimental fission cross sections. Our BRC fission modeling has shown that the effects of the class II or class III states located in the wells of the fission barrier sometimes provide an anti-resonant transmission rather than a resonant one. Consistent evaluations were produced for a large series of U and Pu isotopes. Resulting files were tested against integral data.

  9. Reflectance spectroscopy of indoor settled dust in Tel Aviv, Israel: comparison between the spring and the summer seasons

    Directory of Open Access Journals (Sweden)

    A. A. Chudnovsky

    2007-07-01

    Full Text Available The influence of mineral and anthropogenic dust components on the VIS-NIR-SWIR spectral reflectance of artificial laboratory dust mixtures was evaluated and used in combination with Partial Least Squares (PLS regression to construct a model that correlates the dust content with its reflectance. Small amounts of dust (0.018–0.33 mg/cm2 were collected using glass traps placed in different indoor environments in Tel Aviv, Israel during the spring and summer of 2005. The constructed model was applied to reflectance spectroscopy measurements derived from the field dust samples to assess their mineral content. Additionally, field samples were examined using Principal Component Analysis (PCA to identify the most representative spectral pattern for each season. Across the visible range of spectra two main spectral shapes were observed, convex and concave, though spectra exhibiting hybrid shapes were also seen. Spectra derived from spring season dust samples were characterized mostly by a convex shape, which indicates a high mineral content. In contrast, the spectra generated from summer samples were characterized generally by a concave shape, which indicates a high organic matter content. In addition to this seasonal variation in spectral patterns, spectral differences were observed associated with the dwelling position in the city. Samples collected in the city center showed higher organic content, whereas samples taken from locations at the city margins, near the sea and next to open areas, exhibited higher mineral content. We conclude that mineral components originating in the outdoor environment influence indoor dust loads, even when considering relatively small amounts of indoor settled dust. The sensitive spectral-based method developed here has potentially many applications for environmental researchers and policy makers concerned with dust pollution.

  10. A Study of the CryoTel® DS 1.5 Cryocooler for Higher Cooling Capacity

    Science.gov (United States)

    Kim, Yongsu; Wade, Jimmy; Wilson, Kyle

    2015-12-01

    The CryoTel® DS 1.5 is a split type Stirling cryocooler which was developed by Sunpower for systems requiring compact size, high efficiency, and high reliability. The DS 1.5 has a nominal lift of 1.5 watts at 77 K with 30 watts of input power. The cooler design includes gas bearings on the pistons and displacer for non-contact operation, and achieves low vibration by using dual-opposed pistons inside the wave generator, and a passive balancer on the cold head to offset the displacer motion. The efficiency of the DS 1.5 is ranked highly compared to other cryocoolers at 14.2% Carnot efficiency, but there are many customers who want more lift with the same size and reliability. Therefore, Sunpower performed a study on the feasibility of maximizing the lift of the DS 1.5 without increasing its size. This paper describes the analysis and test results of increasing the cooler power density by using a higher operating frequency and charge pressure. Prototype testing showed good agreement with the model. Testing performed at various frequencies and charge pressures with a few internal component changes resulted in a maximum lift of 2.1 watts with an input power of 43 watts, achieving 13.9% of Carnot. The prototype high-capacity DS 1.5 achieved 0.6 watts more lift with only a slight decrease in efficiency, and with less than 0.2% cooler mass increase. The impact on the cooldown time on a thermal mass system was tested and the cool-down time was 37% faster while consuming less input energy during that time. Sunpower plans to build more units to gain a broader range of performance data and will then decide whether to proceed with a commercial product.

  11. Medical condition and care of undocumented migrants in ambulatory clinics in Tel Aviv, Israel: assessing unmet needs.

    Science.gov (United States)

    Mor, Zohar; Raveh, Yuval; Lurie, Ido; Leventhal, Alex; Gamzu, Roni; Davidovitch, Nadav; Benari, Orel; Grotto, Itamar

    2017-07-14

    Approximately 150,000 undocumented migrants (UM) who are medically uninsured reside in Israel, including ~50,000 originating from the horn of Africa (MHA). Free medical-care is provided by two walk-in clinics in Tel-Aviv. This study aims to compare the medical complaints of UM from different origins, define their community health needs and assess gaps between medical needs and available services. This cross-sectional study included a random sample of 610 UM aged 18-64 years, who were treated in these community clinics between 2008 and 2011. The study compared UM who had complex medical conditions which necessitated referral to more equipped medical settings with UM having mild/simple medical conditions, who were treated at the clinics. MHA were younger, unemployed and more commonly males compared with UM originating from other countries. MHA also had longer referral-delays and visited the clinics less frequently. UM with complex medical conditions were more commonly females, had chronic diseases and demonstrated longer referral-delays than those who had mild/simple medical conditions. The latter more commonly presented with complained of respiratory, muscular and skeletal discomfort. In multivariate analysis, the variables which predicted complex medical conditions included female gender, chronic illnes and self-referral to the clinics. The ambulatory clinics were capable of responding to mild/simple medical conditions. Yet, the health needs of women and migrants suffering from complex medical conditions and chronic diseases necessitated referrals to secondary/tertiary medical settings, while jeopardizing the continuity of care. The health gaps can be addressed by a more holistic social approach, which includes integration of UM in universal health insurance.

  12. Prevalencia del uso de teléfonos móviles durante la conducción de vehículos

    Directory of Open Access Journals (Sweden)

    Astrain I.

    2003-01-01

    Full Text Available Objetivo: El objetivo del estudio fue estimar la prevalencia del uso de teléfono móvil durante la conducción de vehículos en la ciudad de Lleida. Métodos: Se seleccionó una muestra aleatoria de 1.536 automóviles en 6 cruces regulados por semáforos de la ciudad de Lleida (3 con tráfico urbano y 3 con tráfico interurbano. Se excluyeron ciclistas, motoristas y automóviles de autoescuelas. Las variables estudiadas fueron uso de teléfono móvil, sexo, edad (18-40; 41-60; > 61 años, ir acompañado en el vehículo, tipo de cruce (tráfico urbano/tráfico interurbano, día de la semana (laborable/festivo y hora del día (punta/no punta. Se calculó la prevalencia del uso de teléfono móvil en porcentajes con un intervalo de confianza (IC del 95%. La relación de la variable dependiente (uso de teléfono móvil con el resto de variables independientes se estudió con la odds ratio (OR y con IC del 95%. Resultados: Se realizaron 1.536 observaciones directas y se detectó uso de teléfono móvil en 50 conductores. La prevalencia fue del 3,3% (IC del 95%, 2,4-4,3. Esta prevalencia fue superior en los varones (OR = 2,2; IC del 95%, 1,0-5,7 en los mayores de 60 años (OR = 2,2; IC del 95%, 0,5-8,4 y en el grupo de 18-40 años (OR = 1,5; IC del 95%, 0,8-3,0, en conductores sin acompañante (OR = 3,0; IC del 95%, 1,5-6,3, en cruces urbanos (OR = 2,7; IC del 95%, 1,2-5,9, en días laborables (OR = 2,0; IC del 95%, 0,9-4,4 y en horas punta (OR = 1,4; IC del 95%, 0,8-2,4. Conclusiones: La prevalencia del uso de teléfono móvil durante la conducción se considera elevada por el incremento del riesgo de accidentes. El perfil de los usuarios se corresponde con varones de 18 a 40 años o mayores de 61, en circuitos urbanos, sin acompañante, en días laborables y horas punta. Se recomienda tomar medidas para reducir el uso de teléfono móvil durante la conducción.

  13. Progress and problems with the use of viral vectors for gene therapy.

    Science.gov (United States)

    Thomas, Clare E; Ehrhardt, Anja; Kay, Mark A

    2003-05-01

    Gene therapy has a history of controversy. Encouraging results are starting to emerge from the clinic, but questions are still being asked about the safety of this new molecular medicine. With the development of a leukaemia-like syndrome in two of the small number of patients that have been cured of a disease by gene therapy, it is timely to contemplate how far this technology has come, and how far it still has to go.

  14. Activity of Bruton's tyrosine-kinase inhibitor ibrutinib in patients with CD117-positive acute myeloid leukaemia: a mechanistic study using patient-derived blast cells.

    Science.gov (United States)

    Rushworth, Stuart A; Pillinger, Genevra; Abdul-Aziz, Amina; Piddock, Rachel; Shafat, Manar S; Murray, Megan Y; Zaitseva, Lyubov; Lawes, Matthew J; MacEwan, David J; Bowles, Kristian M

    2015-05-01

    Roughly 80% of patients with acute myeloid leukaemia have high activity of Bruton's tyrosine-kinase (BTK) in their blast cells compared with normal haemopoietic cells, rendering the cells sensitive to the oral BTK inhibitor ibrutinib in vitro. We aimed to develop the biological understanding of the BTK pathway in acute myeloid leukaemia to identify clinically relevant diagnostic information that might define a subset of patients that should respond to ibrutinib treatment. We obtained acute myeloid leukaemia blast cells from unselected patients attending our UK hospital between Feb 19, 2010, and Jan 20, 2014. We isolated primary acute myeloid leukaemia blast cells from heparinised blood and human peripheral blood mononuclear cells to establish the activity of BTK in response to CD117 activation. Furthermore, we investigated the effects of ibrutinib on CD117-induced BTK activation, downstream signalling, adhesion to primary bone-marrow mesenchymal stromal cells, and proliferation of primary acute myeloid leukaemia blast cells. We used the Mann-Whitney U test to compare results between groups. We obtained acute myeloid leukaemia blast cells from 29 patients. Ibrutinib significantly inhibited CD117-mediated proliferation of primary acute myeloid leukaemia blast cells (p=0·028). CD117 activation increased BTK activity by inducing phosphorylated BTK in patients with CD117-positive acute myeloid leukaemia. Furthermore, ibrutinib inhibited CD117-induced activity of BTK and downstream kinases at a concentration of 100 nM or more. CD117-mediated adhesion of CD117-expressing blast cells to bone-marrow stromal cells was significantly inhibited by Ibrutinib at 500 nM (p=0·028) INTERPRETATION: As first-in-man clinical trials of ibrutinib in patients with acute myeloid leukaemia commence, the data suggest not all patients will respond. Our findings show that BTK has specific pro-tumoural biological actions downstream of surface CD117 activation, which are inhibited by ibrutinib

  15. Fish oil supplementation is beneficial on caloric intake, appetite and mid upper arm muscle circumference in children with leukaemia.

    Science.gov (United States)

    Abu Zaid, Zalina; Shahar, Suzana; Jamal, A Rahman A; Mohd Yusof, Noor Aini

    2012-01-01

    A randomised trial was carried out to determine the effect of supplementation of fish oil among 51 children with leukaemia aged 4 to 12 years on appetite level, caloric intake, body weight and lean body mass. They were randomly allocated into the trial group (TG) and the control group (CG). At baseline, 30.8% of TG subjects and 44.0% of CG subjects were malnourished and 7.7% of subject from TG and 28.0% from CG were classified as stunted. The majority of subjects from TG and CG were in the mild malnutrition category for mid upper arm muscle circumference (MUAMC)-for-age. The TG group showed significant increment in MUAMC (0.13 cm vs -0.09 cm) compared with CG at 8 weeks (pappetite level (0.12±0.33) (pappetite level, caloric intake and MUAMC among children with leukaemia.

  16. A Fatal Case of Acute Myeloid Leukaemia-Methotrexate Related or Primary Autoimmune Disease Related: A Rare Case Report.

    Science.gov (United States)

    Agarwal, Saurabh; Kaeley, Nidhi; Gupta, Priyanka; Gupta, Vibha; Bhatia, Rohan

    2016-03-01

    Methotrexate is being used for many years in the treatment of chronic medical disorders e.g. rheumatoid arthritis since 1951. It has been associated with various systemic toxicities and complications including bone marrow suppression and lymphomas. The development of leukaemia in a patient of chronic rheumatoid arthritis is either related with the primary disease or due to the drugs which are used in the treatment like cyclophosphamide. In our present case, a 70-year-old female who was a known case of Rheumatoid Arthritis (RA) and was on methotrexate once a week orally for the past 20 years presented with complaints of loss of appetite, loss of weight and anaemia since 2 months. After thorough examination and investigation, she was diagnosed with acute myeloid leukaemia (AML-M4) with bilateral chest consolidation.

  17. Treatment of adult lymphoblastic leukaemia using cyclical chemotherapy with three combinations of four drugs (COAP, POMP, TRAP schedule).

    Science.gov (United States)

    Proctor, S J; Finney, R; Walker, W; Thompson, R B

    1981-01-01

    Seventeen adult patients with previously untreated acute lymphoblastic leukaemia (ALL) were entered into a schedule of chemotherapy in which 3 combinations, each of 4 drugs, were administered in a predetermined cyclical rotation in combination with cranial irradiation and intrathecal injections of methotrexate. Of the 17 patients, 16 completed induction therapy and 15 (94%) entered remission. The only patient with T-ALL died before receiving any therapy. The median survival for all patients (17) was 22 months. Meningeal leukaemia did not occur during the haematological remission phase although 3 patients developed this complication following relapse. The authors conclude that the addition of cyclophosphamide and cytosine arabinoside to vincristine/prednisone provides excellent remission induction but the aggressive maintenance schedule employed has not led to significant long-term survival.

  18. Increased cellular hypoxia and reduced proliferation of both normal and leukaemic cells during progression of acute myeloid leukaemia in rats

    DEFF Research Database (Denmark)

    Jensen, P O; Mortensen, B T; Hodgkiss, R J

    2000-01-01

    The microenvironmental changes in the bone marrow, spleen and liver during progression of the transplantable promyelocytic leukaemia in the Brown Norwegian rat (BNML) have been studied. We used flow cytometry to estimate cellular hypoxia and proliferation based on in vivo pulse-labelling with a m......The microenvironmental changes in the bone marrow, spleen and liver during progression of the transplantable promyelocytic leukaemia in the Brown Norwegian rat (BNML) have been studied. We used flow cytometry to estimate cellular hypoxia and proliferation based on in vivo pulse......-labelling with a mixture of 2-nitroimidazole linked to theophylline (NITP) and bromodeoxyuridine (BrdUrd). The leukaemic cells were identified with the RM124 antibody. In rats inoculated with leukaemic cells the fraction of RM124+ cells was significantly increased from day 20 onwards in the spleen and from day 27...

  19. Dose intensification in acute myeloid leukaemia: greater effectiveness at lower cost. Principal report of the Medical Research Council's AML9 study. MRC Leukaemia in Adults Working Party.

    Science.gov (United States)

    Rees, J K; Gray, R G; Wheatley, K

    1996-07-01

    Between 1984 and 1990, 972 patients aged 1-79 years with acute myeloid leukaemia (AML), from 85 British hospitals, were entered into the MRC's 9th AML trial. Patients were randomized between DAT 1 + 5 (daunorubicin for 1 d, with cytarabine and 6-thioguanine for 5 d) and DAT 3 + 10 (same dose drugs for 3 and 10 d respectively) as induction therapy. The 63% who achieved complete remission (CR) were randomized to receive two courses of DAT 2 + 7 alternating with two courses of either MAZE (m-AMSA, 5-azacytidine, etoposide) or COAP (cyclophosphamide, vincristine, cytarabine, prednisone). Finally, those still in CR were randomized to receive either 1 year of maintenance treatment with eight courses of cytarabine and thioguanine followed by four courses of COAP, or no further cytotoxic therapy. Resistance to induction therapy was less common with the DAT 3 + 10 regimen than with DAT 1 + 5 (13% v 23%; P = 0.0001) and hence, despite a 5% increase in the risk of induction death, the CR rate was higher (66% v 61%; P = 0.15). Moreover, CR was achieved more rapidly with DAT 3 + 10 (median 34 v 46 d; P COAP. 5-year survival was not significantly higher with MAZE (37% v 31%). Finally, although 1 year of outpatient maintenance treatment appeared to delay, but not prevent, recurrence it did not improve 5-year survival which was non-significantly worse for those allocated maintenance treatment (41% v 44%). We conclude that the more intensive induction regimen, DAT 3 + 10, is not only more effective than DAT 1 + 5, even for older patients, but is also less expensive; intensive post-remission therapy with MAZE achieves better leukaemic control but at the cost of substantial toxicity; whereas low-level maintenance therapy confers no apparent advantage in survival as well as being inconvenient and costly.

  20. Heterogeneity in the therapeutic approach to relapsed elderly patients with acute myeloid leukaemia: a survey from the Gruppo Italiano Malattie Ematologiche dell' Adulto (GIMEMA) Acute Leukaemia Working Party.

    Science.gov (United States)

    Ferrara, Felicetto; Fazi, Paola; Venditti, Adriano; Pagano, Livio; Amadori, Sergio; Mandelli, Franco

    2008-06-01

    The percentage of long-term survivors in acute myeloid leukaemia (AML) in the elderly does not exceed 10-15% of patients enrolled into clinical trials because of lower complete remission (CR) rates and higher incidence of relapse. However, few data are available as the treatment of elderly patients with relapsed disease is concerned. The aim of this study was of collecting data on criteria adopted for the treatment of these patients. A questionnaire was e-mailed to 32 haematologic institutions involved in the Gruppo Italiano per le Malattie Ematologiche dell'Adulto (GIMEMA) group. Questions to be addressed regarded: (1) per cent of relapsed elderly patients treated with aggressive salvage chemotherapy; (2) the selection criteria adopted for inclusion into intensive reinduction; (3) the specific treatment adopted; (4) the treatment given to patients not eligible for intensive salvage. Per cent of patients enrolled into aggressive salvage regimens varied from 10 to 80% (median 50%). The most frequent factor influencing the therapeutic choice was performance status (97%). Additional factors were age >70 years (44%) and duration of first CR (53%). Fludarabine including regimens were most frequently used as aggressive salvage therapy (59%), while gemtuzumab ozogamicin was adopted in various combinations at 11 out of 32 institutions (34%). For patients not eligible to aggressive therapy, the most frequent approach included hydroxyurea (59%). Low dose ARA-C (LDARA-C) was adopted at five centres: as single agent (n = 1), with 6-thioguanine (n = 1), with vitamin D3 and all-trans retinoic acid (ATRA) (n = 2), or with ATRA alone (n = 1). The FLT3 inhibitor CEP-701 was used at one centre. We conclude that the treatment of AML in elderly relapsed patients is extremely heterogeneous. A marked selection is operated as to inclusion into aggressive salvage regimens and only a small minority of patients are offered experimental approaches.