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Sample records for cell-specific leukemia mortality

  1. Analysis of childhood leukemia mortality trends in Brazil, from 1980 to 2010

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    Franciane F. Silva

    2014-12-01

    Full Text Available OBJECTIVE: Leukemias comprise the most common group of cancers in children and adolescents. Studies conducted in other countries and Brazil have observed a decrease in their mortality.This study aimed to evaluate the trend of mortality from leukemia in children under 19 years of age in Brazil, from 1980 to 2010. METHODS: This was an ecological study, using retrospective time series data from the Mortality Information System, from 1980 to 2010. Calculations of mortality rates were performed, including gross, gender-specific, and age-based. For trend analysis, linear and semi-log regression models were used. The significance level was 5%. RESULTS: Mortality rates for lymphoid and myeloid leukemias presented a growth trend, with the exception of lymphoid leukemia among children under 4 years of age (percentage decrease: 1.21% annually, while in the sub-group "Other types of leukemia", a downward trend was observed. Overall, mortality from leukemia tended to increase for boys and girls, especially in the age groups 10-14 years (annual percentage increase of 1.23% for males and 1.28% for females and 15-19 years (annual percentage increase of 1.40% for males and 1.62% for females. CONCLUSIONS: The results for leukemia generally corroborate the results of other similar studies. A detailed analysis by subgroup of leukemia, age, and gender revealed no trends shown in other studies, thus indicating special requirements for each variable in the analysis.

  2. Upregulation of T-Cell-Specific Transcription Factor Expression in Pediatric T-Cell Acute Lymphoblastic Leukemia (T-ALL

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    Müge Sayitoğlu

    2012-12-01

    Full Text Available OBJECTIVE: T-cell acute lymphoblastic leukemia (T-ALL is associated with recurrent chromosomal aberrations and abnormal ectopic gene expression during T-cell development. In order to gain insight into the pathogenesis of T-ALL this study aimed to measure the level of expression of 7 T-cell oncogenes (LMO2, LYL1, TAL1, TLX1, TLX3, BMI1, and CALM-AF10 in pediatric T-ALL patients. METHODS: LMO2, LYL1, TLX1, TLX3, BMI1, TAL1, and CALM-AF10 expression was measured using quantitative real-time PCR in 43 pediatric T-ALL patients. RESULTS: A high level of expression of LMO2, LYL1, TAL1, and BMI1 genes was observed in a large group of T-ALL. Several gene expression signatures indicative of leukemic arrest at specific stages of normal thymocyte development (LYL1 and LMO2 were highly expressed during the cortical and mature stages of T-cell development. Furthermore, upregulated TAL1 and BMI1 expression was observed in all phenotypic subgroups. In all, 6 of the patients had TLX1 and TLX3 proto-oncogene expression, which does not occur in normal cells, and none of the patients had CALM-AF10 fusion gene transcription. Expression of LYL1 alone and LMO2-LYL1 co-expression were associated with mediastinal involvement; however, high-level oncogene expression was not predictive of outcome in the present pediatric T-ALL patient group, but there was a trend towards a poor prognostic impact of TAL1 and/or LMO2 and/or LYL1 protooncogene expression. CONCLUSION: Poor prognostic impact of TAL1 and/or LMO2 and/or LYL1 proto-oncogene expression indicate the need for extensive study on oncogenic rearrangement and immunophenotypic markers in T-ALL, and their relationship to treatment outcome.

  3. The mortality and response rate after FLANG regimen in patients with refractory/relapsed acute leukemia

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    Vali A Mehrzad

    2012-01-01

    Full Text Available Background: Oncologists today are greatly concerned about the treatment of relapsed/refractory acute leukemia. FLANG regimen, combination of novantron, cytarabine, fludarabine, and granulocyte-colony stimulating factor, has been used in treatment of refractory/relapsed acute leukemia since 1990s. The present study has evaluated mortality and response rate of this regimen. Materials and Methods: In this study, 25 patients with refractory/relapsed acute leukemia aged 15-55 years underwent FLANG regimen at Seyed-Al-Shohada Hospital, Isfahan, Iran during 2008-2009. One month later, bone marrow samples were taken to evaluate the responsiveness to treatment. Participants were followed for a year. The data was analyzed by student-t and chi-square tests, logistic, and Cox regression analysis, and Kaplan-Meier curves in SPSS 19. Results: Out of the 25 patients, 8 patients (32% had acute lymphoblastic leukemia (5 refractory and 3 relapsed cases and 17 subjects had acute myeloid leukemia (7 refractory and 10 relapsed cases. According to the bone marrow biopsies taken one month after FLANG regimen, 10 patients (40% had responded to treatment. Five patients of the 10 responders underwent successful bone marrow transplantation (BMT. On the other hand, 13 patients (52%, who had not entered the CR period, died during the follow-up. Logistic regression analysis did not reveal any significant associations between disease type and responsiveness to treatment. Conclusion: This study indicated higher rates of unresponsiveness to treatment while its mortality rate was comparable with other studies. Overall, according to limitations for BMT (as the only chance for cure in Iran, it seems that FLANG therapy is an acceptable choice for these patients.

  4. Mortalidade por leucemias relacionada à industrialização Mortality by industrialization-related leukemias

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    Carmen Helena Seoane Leal

    2002-08-01

    Full Text Available OBJETIVO: Analisar a distribuição espacial da mortalidade por leucemia na população, buscando identificar agregados e estabelecer sua relação com os níveis de industrialização. MÉTODOS: O estudo foi realizado nas 43 regiões de governo do Estado de São Paulo, no qüinqüênio 1991-1995. Foi construído um "índice de industrialização relativo à leucemia" (IIRL baseado no número de indústrias e empregos industriais por 100.000 habitantes, valor adicionado fiscal, variedade de ramos industriais e indústrias com potenciais exposições de risco para a leucemia. O IIRL foi distribuído em cinco categorias. Verificaram-se os coeficientes padronizados de mortalidade por leucemia em cada uma das regiões, também distribuídos em cinco categorias e comparados ao mapa IIRL. RESULTADOS: As regiões mais industrializadas em ordem decrescente foram Campinas, Piracicaba, Jundiaí, Sorocaba e São Paulo. Não foi encontrada associação entre mortalidade, por nenhum tipo de leucemia, e industrialização. A região de Jales foi a que apresentou o mais alto coeficiente padronizado de mortalidade por leucemia. CONCLUSÕES: A distribuição da mortalidade por leucemia ocorreu de forma homogênea no Estado de São Paulo, não apresentando correlação com o nível de industrialização. Entretanto, aspectos relacionados ao método epidemiológico adotado -- estudo ecológico -- e ao uso do parâmetro "mortalidade por leucemia", doença cujo prognóstico tem mudado muito nas últimas décadas, limitaram a interpretação dos resultados.OBJECTIVE: To analyze the spatial distribution of mortality by leukemia in the population, looking for clusters, and to establish an association with the level of industrialization. METHOD: The study was carried out in 43 state regions of the state of São Paulo, Brazil, in the period between 1991 and 1995. It was created an Index of Industrialization-Related Leukemia (IIRL based on number of manufactures and

  5. Leukemia

    Science.gov (United States)

    Leukemia is cancer of the white blood cells. White blood cells help your body fight infection. Your blood cells form in your bone marrow. In leukemia, the bone marrow produces abnormal white blood cells. ...

  6. The role of acuity of illness at presentation in early mortality in black children with acute myeloid leukemia.

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    Winestone, Lena E; Getz, Kelly D; Miller, Tamara P; Wilkes, Jennifer J; Sack, Leah; Li, Yimei; Huang, Yuan-Shung; Seif, Alix E; Bagatell, Rochelle; Fisher, Brian T; Epstein, Andrew J; Aplenc, Richard

    2017-02-01

    Black patients with acute myeloid leukemia (AML) experience higher mortality than White patients. We compared induction mortality, acuity of illness prior to chemotherapy, and insurance type between Black and White patients to assess whether acuity of presentation mediates the disparity. Within a retrospective cohort of 1,122 children with AML treated with two courses of standard induction chemotherapy between 2004 and 2014 in the Pediatric Health Information System (PHIS) database, the association between race (Black versus White) and inpatient mortality during induction was examined. Intensive Care Unit (ICU)-level resource utilization during the first 72 hours following admission for initial AML chemotherapy was evaluated as a potential mediator. The total effect of race on mortality during Induction I revealed a strong association (unadjusted HR 2.75, CI: 1.18, 6.41). Black patients had a significantly higher unadjusted risk of requiring ICU-level resources within the first 72 hours after initial presentation (17% versus 11%; RR 1.52, CI: 1.04, 2.24). Mediation analyses revealed the indirect effect of race through acuity accounted for 61% of the relative excess mortality during Induction I. Publicly insured patients experienced greater induction mortality than privately insured patients regardless of race. Black patients with AML have significantly greater risk of induction mortality and are at increased risk for requiring ICU-level resources soon after presentation. Higher acuity amongst Black patients accounts for a substantial portion of the relative excess mortality during Induction I. Targeting factors affecting acuity of illness at presentation may lessen racial disparities in AML induction mortality.

  7. Reduced-intensity conditioning lowers treatment-related mortality of allogeneic stem cell transplantation for chronic lymphocytic leukemia : a population-matched analysis

    NARCIS (Netherlands)

    Dreger, P; Brand, R; Milligan, D; Corradini, P; Finke, J; Deliliers, GL; Martino, R; Russell, N; van Biezen, A; Michallet, M; Niederwieser, D

    2005-01-01

    To elucidate whether reduced-intensity conditioning (RIC) decreases treatment-related mortality (TRM) after allogeneic stem cell transplantation (allo-SCT) for chronic lymphocytic leukemia (CLL), we retrospectively compared 73 RIC cases from a recent EBMT survey with 82 patients from the EBMT databa

  8. Prediction of mortality and years of life lost due to leukemia cancer in residents in Xiamen%厦门市居民白血病死亡与减寿趋势预测

    Institute of Scientific and Technical Information of China (English)

    林艺兰; 陈敏; 张琼花; 池家煌

    2016-01-01

    Objective To explore the trend of mortality and years of life lost due to leukemia cancer in residents in Xia-men, so as to provide the basis data on preventing leukemia cancer in Xiamen. Methods The data of residents in Xiamen dying of leukemia cancer from 2010 to 2014 was collected and cleared up to calculate the evaluation indexes including the mortality rate, the average potential life lost (AYLL), and the average percentage change (APC) of mortality rate. GM(1,1) model was used to predict the future mortality and AYLL. Results From 2010 to 2014, the average mortality rate of leukemia cancer in res-idents in Xiamen was 3. 45 per 100,000 persons and the rate for male was 1. 51 times of that for female. The AYLL, which was 24. 63 years, had a decline trend from 2010 to 2014. All mortality rates and AYLLs could fit out the GM(1,1) model except the mortality rate in female. The mean absolute percentage errors between observed values and fitted values were 0. 54%-6. 97%. The mortality rate and AYLL of leukemia cancer in residents in Xiamen would decrease slightly from 2015 to 2017. Conclusion GM(1,1) model could be used to forecast the trend of mortality and years of life lost due to leukemia cancer in residents in Xia-men. Leukemia cancer is still an important cause of premature death among residents in Xiamen City. We should not relax the prevention and control of leukemia.%目的:探讨厦门市居民白血病死亡和减寿的变化趋势,为厦门市白血病综合防治工作提供依据。方法收集整理2010—2014年厦门市居民白血病死亡资料计算死亡率、平均减寿年数( AYLL)、死亡率年均变化百分比等评价指标,用GM(1,1)模型对死亡率和AYLL进行预测。结果2010—2014年,厦门市居民白血病死亡率3.45/10万,男性死亡率是女性的1.51倍;AYLL为24.63年,存在下降趋势。除女性死亡率外,其余男性死亡率、合计死亡率及所有AYLL均能拟合出GM(1,1)模型,预测值

  9. Chronic myelogenous leukemia (CML)

    Science.gov (United States)

    CML; Chronic myeloid leukemia; Chronic granulocytic leukemia; Leukemia - chronic granulocytic ... Chronic myelogenous leukemia is grouped into phases: Chronic Accelerated Blast crisis The chronic phase can last for ...

  10. Childhood Leukemia

    Science.gov (United States)

    ... fast growing type while chronic leukemia grows slowly. Children with leukemia usually have one of the acute types. Symptoms include Infections Fever Loss of appetite Tiredness Easy bruising or bleeding Swollen lymph nodes ...

  11. Allogeneic Transplantation for Patients With Acute Leukemia or Chronic Myelogenous Leukemia (CML)

    Science.gov (United States)

    2016-06-14

    Leukemia, Lymphocytic, Acute; Leukemia; Leukemia Acute Promyelocytic Leukemia (APL); Leukemia Acute Lymphoid Leukemia (ALL); Leukemia Chronic Myelogenous Leukemia (CML); Leukemia Acute Myeloid Leukemia (AML); Leukemia Chronic Lymphocytic Leukemia (CLL)

  12. Leukemia cutis

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    Varuna Mallya

    2015-01-01

    Full Text Available Patients with leukemia may show involvement of the skin. This skin involvement can be due to infiltration of skin by leukemic cells or it may be a part of nonspecific cutaneous manifestations. Leukemia cutis is the infiltration of neoplastic leucocytes or their precursors into the skin resulting in extensive clinical manifestations. Described mostly in acute myeloid leukemia and acute myelocytic monocytic leukemia, it is rare in chronic myeloid leukemia and is seen mostly during the blast crises. Its presence signals poor prognosis.

  13. Cdc42-mediated tubulogenesis controls cell specification

    DEFF Research Database (Denmark)

    Kesavan, Gokul; Sand, Fredrik Wolfhagen; Greiner, Thomas Uwe

    2009-01-01

    Understanding how cells polarize and coordinate tubulogenesis during organ formation is a central question in biology. Tubulogenesis often coincides with cell-lineage specification during organ development. Hence, an elementary question is whether these two processes are independently controlled......, or whether proper cell specification depends on formation of tubes. To address these fundamental questions, we have studied the functional role of Cdc42 in pancreatic tubulogenesis. We present evidence that Cdc42 is essential for tube formation, specifically for initiating microlumen formation and later...... for maintaining apical cell polarity. Finally, we show that Cdc42 controls cell specification non-cell-autonomously by providing the correct microenvironment for proper control of cell-fate choices of multipotent progenitors. For a video summary of this article, see the PaperFlick file with the Supplemental Data...

  14. Leukemia cutis

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    Angoori G Rao

    2012-01-01

    Full Text Available Leukemia cutis is the infiltration of neoplastic leukocytes or their precursors into the epidermis, the dermis, or the subcutis, resulting in clinically identifiable cutaneous lesions. Leukemia cutis may follow, precede or occur concomitantly with the diagnosis of systemic leukemia. A 50-year-old woman presented with asymptomatic multiple cutaneous nodules all over the body of 4 months duration. Cutaneous examination showed multiple hyperpigmented nodules and plaques involving face, trunk, and extremities. Peripheral smear showed abnormally elevated leucocyte count (TLC-70,000 with abnormal cells: myeloblasts 40%, promyelocytes 8% and myelocytes 39%. Auer rods were present in few myeloblasts. Bone marrow aspiration showed increased cellularity, erythroid hyperplasia with megaloblastic change, increased myeloblasts with maturation arrest. Immunohistochemistry showed strongly positive myeloperoxidase infiltrating cells and negative for CD20 and CD3 consistent with the diagnosis of AML-M 2 with leukemia cutis. This case is reported for its rarity.

  15. Understanding Leukemia

    Science.gov (United States)

    ... material presented in this publication Jane Liesveld, MD Professor, Department of Medicine, Hematology/Oncology Clinical Director, Blood ... of leukemia cell. The marrow has two main jobs. The first job is to form myeloid cells. ...

  16. Mortal assets

    Energy Technology Data Exchange (ETDEWEB)

    Howe, Geoffrey R.; Zablotska, Lydia B.; Fix, John J.; Egel, John N.; Buchanan, Jeffrey A.

    2005-11-01

    Workers employed in 15 utilities that generate nuclear power in the United States have been followed for up to 18 years between 1979 and 1997. Their cumulative dose from whole-body ionizing radiation has been determined from the dose records maintained by the facilities themselves and the REIRS and REMS systems maintained by the Nuclear Regulatory Commission and the Department of Energy, respectively. Mortality in the cohort from a number of causes has been analyzed with respect to individual radiation doses. The cohort displays a very substantial healthy worker effect, i.e. considerably lower cancer and noncancer mortality than the general population. Based on 26 and 368 deaths, respectively, positive though statistically nonsignificant associations were seen for mortality from leukemia (excluding chronic lymphocytic leukemia) and all solid cancers combined, with excess relative risks per sievert of 5.67 (95% confidence interval (CI) -2.56, 30.4) and 0.596 (95% CI -2.01, 4.64), respectively. These estimates are very similar to those from the atomic bomb survivors study, though the wide confidence intervals are also consistent with lower or higher risk estimates. A strong positive and statistically significant association between radiation dose and deaths from arteriosclerotic heart disease including coronary heart disease was also observed in the cohort, with an ERR of 8.78 (95% CI 2.10, 20.0). Whle associations with heart disease have been reported in some other occupational studies, the magnitude of the present association is not consistent with them and therefore needs cautious interpretation and merits further attention. At present, the relatively small number of deaths and the young age of the cohort (mean age at end of follow-up is 45 years) limit the power of the study, but further follow-up is 45 years) limit the power of the study, but further follow-up and the inclusion of the present data in an ongoing IARC combined analysis of nuclear workers from 15

  17. Germ cell specification and regeneration in planarians.

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    Newmark, P A; Wang, Y; Chong, T

    2008-01-01

    In metazoans, two apparently distinct mechanisms specify germ cell fate: Determinate specification (observed in animals including Drosophila, Caenorhabditis elegans, zebra fish, and Xenopus) uses cytoplasmic factors localized to specific regions of the egg, whereas epigenetic specification (observed in many basal metazoans, urodeles, and mammals) involves inductive interactions between cells. Much of our understanding of germ cell specification has emerged from studies of model organisms displaying determinate specification. In contrast, our understanding of epigenetic/inductive specification is less advanced and would benefit from studies of additional organisms. Freshwater planarians--widely known for their remarkable powers of regeneration--are well suited for studying the mechanisms by which germ cells can be induced. Classic experiments showed that planarians can regenerate germ cells from body fragments entirely lacking reproductive structures, suggesting that planarian germ cells could be specified by inductive signals. Furthermore, the availability of the genome sequence of the planarian Schmidtea mediterranea, coupled with the animal's susceptibility to systemic RNA interference (RNAi), facilitates functional genomic analyses of germ cell development and regeneration. Here, we describe recent progress in studies of planarian germ cells and frame some of the critical unresolved questions for future work.

  18. What Is Chronic Myeloid Leukemia?

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    ... Chronic Myeloid Leukemia (CML) About Chronic Myeloid Leukemia What Is Chronic Myeloid Leukemia? Cancer starts when cells ... their treatment is the same as for adults. What is leukemia? Leukemia is a cancer that starts ...

  19. What Is Chronic Lymphocytic Leukemia?

    Science.gov (United States)

    ... Chronic Lymphocytic Leukemia (CLL) About Chronic Lymphocytic Leukemia What Is Chronic Lymphocytic Leukemia? Cancer starts when cells ... body, including the lymph nodes, liver, and spleen. What is leukemia? Leukemia is a cancer that starts ...

  20. Leukemia revisited

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    Cronkite, E P

    1980-01-01

    Selected features of the historical development of our knowledge of leukemia are discussed. The use of different methodologies for study of the nature of leukemic cell proliferation are analyzed. The differences between older cell kinetic data using tritiated thymidine and autoradiography and the newer cell culture methods are more apparent than real. It is suggested that tritiated thymidine and extracorporeal irradiation of the blood may be useful for therapeutic agents that have not been given an adequate trial. Radiation leukemogenesis presents an opportunity for study of the nature of leukemogenesis that has not been exploited adequately.

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

    Science.gov (United States)

    2013-01-22

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

  2. Kelainan Hemostasis pada Leukemia

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    Zelly Dia Rofinda

    2012-09-01

    Full Text Available AbstrakLatar belakang: Leukemia adalah penyakit keganasan pada jaringan hematopoietik yang ditandai denganpenggantian elemen sumsum tulang normal oleh sel darah abnormal atau sel leukemik. Salah satu manifestasi klinisdari leukemia adalah perdarahan yang disebabkan oleh berbagai kelainan hemostasis.Kelainan hemostasis yang dapat terjadi pada leukemia berupa trombositopenia, disfungsi trombosit,koagulasi intravaskuler diseminata, defek protein koagulasi, fibrinolisis primer dan trombosis. Patogenesis danpatofosiologi kelainan hemostasis pada leukemia tersebut terjadi dengan berbagai mekanisme.Kata kunci: leukemia, kelainan hemostasisAbstractBackground: AbstractLeukemia is a malignancy of hematopoietic tissue which is characterized bysubstituted of bone marrow element with abnormal blood cell or leukemic cell. One of clinical manifestation ofleukemia is bleeding that is caused by several hemostasis disorders.Hemostasis disorders in leukemia such asthrombocytopenia, platelet dysfunction, disseminated intravascular coagulation, coagulation protein defect, primaryfibrinolysis and thrombosis. Pathogenesis and pathophysiology of thus hemostasis disorders in leukemia occur withdifferent mechanism.Keywords: leukemia, hemostasis disorder

  3. Oral health in children with leukemia

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    Vijay Prakash Mathur

    2015-04-01

    Full Text Available Leukemia is one of the most common malignancies affecting children in India. These children usually suffer from various oral complications, which may be due to the leukemia or due to the chemotherapeutic agents and/or radiotherapy. The complications may include some of the opportunistic infections like candidiasis, herpes simplex; hemorrhage, mucositis, taste alterations and increased incidence of dental caries etc. These complications can cause significant morbidity and mortality in the patients. The aim of this review is to summarize the various oral complications in these children and the methods of prevention and management.

  4. Pharm GKB: Leukemia, Nonlymphocytic, Acute [PharmGKB

    Lifescience Database Archive (English)

    Full Text Available Overview Alternate Names: Synonym ANLL; Acute Nonlymphoblastic Leukemia; Acute Nonl...ymphoblastic Leukemias; Acute Nonlymphocytic Leukemia; Acute Nonlymphocytic Leukemias; Leukemia, Acute Nonly...mphoblastic; Leukemia, Acute Nonlymphocytic; Leukemia, Nonlymphoblastic, Acute; Leukemias, Acute Nonlymphoblastic; Leukemias, Acute... Nonlymphocytic; Nonlymphoblastic Leukemia, Acute; Nonlymphoblastic Leukemias, Acut...e; Nonlymphocytic Leukemia, Acute; Nonlymphocytic Leukemias, Acute PharmGKB Accessi

  5. Chronic Lymphocytic Leukemia

    Science.gov (United States)

    Leukemia is cancer of the white blood cells. White blood cells help your body fight infection. Your blood cells form in your bone marrow. In leukemia, the bone marrow produces abnormal white blood cells. ...

  6. Acute Myeloid Leukemia

    Science.gov (United States)

    Leukemia is cancer of the white blood cells. White blood cells help your body fight infection. Your blood cells form in your bone marrow. In leukemia, however, the bone marrow produces abnormal white blood ...

  7. Chronic Myeloid Leukemia

    Science.gov (United States)

    Leukemia is cancer of the white blood cells. White blood cells help your body fight infection. Your blood cells form in your bone marrow. In leukemia, the bone marrow produces abnormal white blood cells. ...

  8. Acute Lymphocytic Leukemia

    Science.gov (United States)

    Leukemia is cancer of the white blood cells. White blood cells help your body fight infection. Your blood cells form in your bone marrow. In leukemia, however, the bone marrow produces abnormal white blood ...

  9. Lymphoblastic leukemia in pregnancy

    OpenAIRE

    Rojas Castrillo, Yaoska; Guevara González, José Guillermo

    2015-01-01

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

  10. Leukemia in pregnancy.

    Science.gov (United States)

    Firas, Al Sabty; Demeckova, E; Mistrik, M

    2008-01-01

    Pregnancy complicated with leukemia is rare. Validated data, out of which conclusions may be drawn regarding the management of pregnancy with leukemia are sparse. We report 5 cases of leukemia diagnosed during pregnancy with an overview of published literature (Ref. 19). Full Text (Free, PDF) www.bmj.sk.

  11. Occupational mortality

    DEFF Research Database (Denmark)

    Lynge, Elsebeth

    2011-01-01

    INTRODUCTION: This paper aims to present the methods and main results from the Danish occupational mortality studies, and to set the Danish studies into the international context of occupational mortality studies. RESEARCH TOPICS: The first Danish occupational mortality study from 1970...

  12. Mixed phenotype acute leukemia

    Institute of Scientific and Technical Information of China (English)

    Ye Zixing; Wang Shujie

    2014-01-01

    Objective To highlight the current understanding of mixed phenotype acute leukemia (MPAL).Data sources We collected the relevant articles in PubMed (from 1985 to present),using the terms "mixed phenotype acute leukemia","hybrid acute leukemia","biphenotypic acute leukemia",and "mixed lineage leukemia".We also collected the relevant studies in WanFang Data base (from 2000 to present),using the terms "mixed phenotype acute leukemia" and "hybrid acute leukemia".Study selection We included all relevant studies concerning mixed phenotype acute leukemia in English and Chinese version,with no limitation of research design.The duplicated articles are excluded.Results MPAL is a rare subgroup of acute leukemia which expresses the myeloid and lymphoid markers simultaneously.The clinical manifestations of MPAL are similar to other acute leukemias.The World Health Organization classification and the European Group for Immunological classification of Leukaemias 1998 cdteria are most widely used.MPAL does not have a standard therapy regimen.Its treatment depends mostly on the patient's unique immunophenotypic and cytogenetic features,and also the experience of individual physician.The lack of effective treatment contributes to an undesirable prognosis.Conclusion Our understanding about MPAL is still limited.The diagnostic criteria have not been unified.The treatment of MPAL remains to be investigated.The prognostic factor is largely unclear yet.A better diagnostic cdteria and targeted therapeutics will improve the therapy effect and a subsequently better prognosis.

  13. Congenital acute megakaryocytic leukemia

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    N B Mathur

    2011-01-01

    Full Text Available Congenital leukemia (CL is an extremely rare disorder in the newborn, significant proportion of which is of myeloid origin, primarily of M4 or M5 morphology. As compared to pediatric leukemia, CL is a more aggressive disease. Acute myeloid leukemia (AML-M7 or acute megakaryocytic leukemia is a rare type of AML with an incidence of 0.5 per million per year. Median age of presentation is 6 years, and children may present with a broad variety of symptoms including low-grade fever, diarrhea, easy bruising, failure to gain weight and life-threatening conditions.

  14. Mortality among rubber workers: V. processing workers.

    Science.gov (United States)

    Delzell, E; Monson, R R

    1982-07-01

    Cause-specific mortality was evaluated among 2,666 men employed in the processing division of a rubber manufacturing plant. The division was divided into two sections: front processing (compounding, mixing and milling operations) and back processing (extrusion, calendering, cement mixing and rubberized fabrics operations). Mortality rates for all processing workers combined and for men in each section were compared with rates for U.S. White males or for workers employed in other divisions of the same plant. Compared with either referent group, men in the processing division had increased mortality from leukemia, emphysema, and cancers of the stomach, large intestine, and biliary passages and liver. An excess number of deaths from stomach and larger intestine cancer was found predominantly among men in the front processing section (33 observed vs. 17.7 expected deaths, based on rates in nonprocessing workers). Increased mortality from leukemia (14 observed vs. 7.3 expected) and from emphysema (22 observed vs. 11.0 expected) was present among men employed in the back processing section. Examination of mortality from these causes according to age and the year starting work, duration of employment, and years since starting work in the relevant sections of the processing division suggested that observed excesses of stomach cancer, large intestine cancer, leukemia, and emphysema among processing workers are related to occupational exposures. These results are consistent with the findings of studies of other groups of rubber workers.

  15. [Acute plasma cell leukemia].

    Science.gov (United States)

    Monsalbe, V; Domíngues, C; Roa, I; Busel, D; González, S

    1989-01-01

    Plasma Cell Leukemia is a very rare form of plasmocytic dyscrasia, whose clinical and pathological characteristics warrant its recognition as a distinct subentity. We report the case of a 60 years old man who presented a rapidly fatal acute plasma cell leukemia, with multiple osteolytic lesions, hipercalcemia, renal and cardiac failure.

  16. Fludarabine Phosphate and Total-Body Irradiation Before Donor Peripheral Blood Stem Cell Transplant in Treating Patients With Chronic Lymphocytic Leukemia or Small Lymphocytic Leukemia

    Science.gov (United States)

    2016-07-18

    B-Cell Prolymphocytic Leukemia; Chronic Lymphocytic Leukemia; Prolymphocytic Leukemia; Recurrent Chronic Lymphocytic Leukemia; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; T-Cell Prolymphocytic Leukemia

  17. Acute Promyelocytic Leukemia in Four Year Old Female Child - A Case Report

    Directory of Open Access Journals (Sweden)

    Anirudha V. Kushtagi

    2014-07-01

    Full Text Available Leukemia is the most common malignancy of childhood representing about 30 % of oncohematological diseases diagnosed in children less than 15 years of age. We report the case of a 4 year old girl with acute promyelocytic leukemia whose blasts showed the morphology characteristic of acute promyelocytic leukemia variant. The case is reported because in the paediatric population the acute promyelocytic leukemia is a rare occurrence moreover, it represent a true oncohematology emergency, in this case the laboratory has a significant role since the timing of diagnosis must be very short. It helps in therapeutic protocols compared to conventional therapeutic protocols in Acute Myeloid Leukemia (AML, the introduction of retinoid All-Trans-Retinoic Acid (ATRA, both in children and adults with Acute Promyelocytic Leukemia (APL, has significantly reduced the early mortality.

  18. Invasive fungal infections in acute leukemia.

    Science.gov (United States)

    Bhatt, Vijaya R; Viola, George M; Ferrajoli, Alessandra

    2011-08-01

    Invasive fungal infection (IFI) is among the leading causes for morbidity, mortality, and economic burden for patients with acute leukemia. In the past few decades, the incidence of IFI has increased dramatically. The certainty of diagnosis of IFI is based on host factors, clinical evidence, and microbiological examination. Advancement in molecular diagnostic modalities (e.g. non-culture-based serum biomarkers such as β-glucan or galactomannan assays) and high-resolution radiological imaging has improved our diagnostic approach. The early use of these diagnostic tests assists in the early initiation of preemptive therapy. Nonetheless, the complexity of IFI in patients with leukemia and the limitations of these diagnostic tools still mandate astute clinical acumen. Its management has been further complicated by the increasing frequency of infection by non-Aspergillus molds (e.g. zygomycosis) and the emergence of drug-resistant fungal pathogens. In addition, even though the antifungal armamentarium has expanded rapidly in the past few decades, the associated mortality remains high. The decision to initiate antifungal treatment and the choice of anti-fungal therapy requires careful consideration of several factors (e.g. risk stratification, local fungal epidemiologic patterns, concomitant comorbidities, drug-drug interactions, prior history of antifungal use, overall cost, and the pharmacologic profile of the antifungal agents). In order to optimize our diagnostic and therapeutic management of IFI in patients with acute leukemia, further basic research and clinical trials are desperately needed.

  19. Pharm GKB: Leukemia, Myelomonocytic, Acute [PharmGKB

    Lifescience Database Archive (English)

    Full Text Available Overview Alternate Names: Synonym Acute Myelomonocytic Leukemia; Acute Myelomonocytic Leukemias; Acute... myelomonocytic leukaemia (clinical); Acute myelomonocytic leukemia (clinical); Acute mye...lomonocytic leukemia, FAB M4; Leukemia, Acute Myelomonocytic; Leukemia, Myeloid, Acute, M4; Leukemia, Myeloi...d, Naegeli-Type; Leukemia, Naegeli-Type Myeloid; Leukemias, Acute Myelomonocytic; Myeloid Leukemia, Acute..., M4; Myeloid Leukemia, Naegeli Type; Myeloid Leukemia, Naegeli-Type; Myelomonocytic Leukemia, Acute

  20. Pharm GKB: Leukemia, Monocytic, Acute [PharmGKB

    Lifescience Database Archive (English)

    Full Text Available Overview Alternate Names: Synonym Acute Monoblastic Leukemia; Acute Monoblastic Leukemias; Acute... Monocytic Leukemia; Acute Monocytic Leukemias; Acute monoblastic leukaemia; Acute monoblastic leukemia; Acute... monocytic leukaemia; Acute monocytic leukemia, morphology; Acute monocytoid leukemia; Leukemia, Acute... Monoblastic; Leukemia, Acute Monocytic; Leukemia, Monoblastic, Acute; Leukemia, Myeloid, Acute... Schilling-Type Myeloid; Leukemias, Acute Monoblastic; Leukemias, Acute Monocytic; M5a - Acute monoblastic leukaemia; M5a - Acute

  1. Cell-specific pattern recognition receptor signaling in antibacterial defense

    NARCIS (Netherlands)

    van Lieshout, M.H.P.

    2015-01-01

    Sepsis, the syndrome that describes infection complicated by acute organ failure, is most frequently caused by bacterial pneumonia and infection originating from the abdominal cavity and is a major cause of morbidity and mortality globally. A brisk and firm initial host response is needed for cleara

  2. Acute Lymphocytic Leukemia

    Science.gov (United States)

    ... for information in your local library and on the Internet. Good sources include the National Cancer Institute, the ... mayoclinic.org/diseases-conditions/acute-lymphocytic-leukemia/basics/definition/CON-20042915 . Mayo Clinic Footer Legal Conditions and ...

  3. Acute Myelogenous Leukemia (AML)

    Science.gov (United States)

    ... for information in your local library and on the Internet. Good sources include the National Cancer Institute, the ... mayoclinic.org/diseases-conditions/acute-myelogenous-leukemia/basics/definition/CON-20043431 . Mayo Clinic Footer Legal Conditions and ...

  4. Mortality investigation

    Science.gov (United States)

    Work, Thierry M.; Franson, J. Christian; Friend, Milton; Gibbs, Samantha E.J.; Wild, Margaret A.

    2015-01-01

    Wildlife mortality events usually occur unannounced and may find management agencies unaware. These events can become highly visible and politically charged affairs, depending upon the scale or species involved. The public, media, and (or) politicians may pressure managers, field investigators, and diagnosticians to quickly identify the cause or to comment on potential causes, the significance of the event, what is being done about it, and a resolution. It may be common during such events for speculation to rage, and for conflicting theories to be advanced to explain either the environmental conditions that led to the mortality or the actual cause of death.

  5. Occupation and leukemia in Nordic countries

    DEFF Research Database (Denmark)

    Talibov, Madar; Kautiainen, Susanna; Martinsen, Jan Ivar

    2012-01-01

    We studied occupational variation of the risk of acute myeloid leukemia, chronic lymphocytic leukemia, and other leukemia in Nordic countries.......We studied occupational variation of the risk of acute myeloid leukemia, chronic lymphocytic leukemia, and other leukemia in Nordic countries....

  6. BMS-214662 in Treating Patients With Acute Leukemia, Myelodysplastic Syndrome, or Chronic Myeloid Leukemia

    Science.gov (United States)

    2013-01-22

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

  7. Mortality Implications of Mortality Plateaus

    DEFF Research Database (Denmark)

    Missov, T. I.; Vaupel, J. W.

    2015-01-01

    This article aims to describe in a unified framework all plateau-generating random effects models in terms of (i) plausible distributions for the hazard (baseline mortality) and the random effect (unobserved heterogeneity, frailty) as well as (ii) the impact of frailty on the baseline hazard. Mor...

  8. Acute myeloid leukemia (AML) - children

    Science.gov (United States)

    Acute myeloid leukemia is a cancer of the blood and bone marrow. Bone marrow is the soft tissue inside ... develops quickly. Both adults and children can get acute myeloid leukemia ( AML ). This article is about AML in children.

  9. Cell-specific modulation of surfactant proteins by ambroxol treatment.

    Science.gov (United States)

    Seifart, Carola; Clostermann, Ursula; Seifart, Ulf; Müller, Bernd; Vogelmeier, Claus; von Wichert, Peter; Fehrenbach, Heinz

    2005-02-15

    Ambroxol [trans-4-(2-amino-3,5-dibromobenzylamino)-cyclohexanole hydrochloride], a mucolytic agent, was postulated to provide surfactant stimulatory properties and was previously used to prevent surfactant deficiency. Currently, the underlying mechanisms are not exactly clear. Because surfactant homeostasis is regulated by surfactant-specific proteins (SP), we analyzed protein amount and mRNA expression in whole lung tissue, isolated type II pneumocytes and bronchoalveolar lavage of Sprague-Dawley rats treated with ambroxol i.p. (75 mg/kg body weight, twice a day [every 12 h]). The methods used included competitive polymerase chain reaction (RT-PCR), Northern blotting, Western immunoblotting, and immunohistochemistry. In isolated type II pneumocytes of ambroxol-treated animals, SP-C protein and mRNA content were increased, whereas SP-A, -B and -D protein, mRNA, and immunoreactivity remained unaffected. However, ambroxol treatment resulted in a significant increase of SP-B and in a decrease of SP-D in whole lung tissue with enhanced immunostaining for SP-B in Clara Cells. SP-A and SP-D were significantly decreased in BAL fluid of ambroxol-treated animals. The data suggest that surfactant protein expression is modulated in a cell-specific manner by ambroxol, as type II pneumocytes exhibited an increase in SP-C, whereas Clara cells exhibited an increase in the immunoreactivity for SP-B accounting for the increased SP-B content of whole lung tissue. The results indicate that ambroxol may exert its positive effects, observed in the treatment of diseases related to surfactant deficiency, via modulation of surfactant protein expression.

  10. Advances in Stem Cell Therapy for Leukemia.

    Science.gov (United States)

    Tian, Hong; Qu, Qi; Liu, Liming; Wu, Depei

    2016-01-01

    Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the most effective post remission treatment for leukemia, resulting in lower relapse rates than alternative therapies. However, it is limited by the lack of suitable human leukocyte antigen (HLA) matched donors and high rates of transplant-related morbidity and mortality. Cord blood transplantation (CBT) and haploidentical SCT (haplo-SCT) expand the potential donor pool but are also associated with major complications. Co-infusion of third-party donor stem cells with a CBT/haplo-SCT, which is called "dual transplantation," has been reported to improve the outcome of HSCT by accelerating hematopoietic reconstitution and reducing the incidence of graft-versus-host disease (GVHD). In addition, infusion of HLA-mismatched donor granulocyte colony-stimulating factor-mobilized donor peripheral blood stem cells after chemotherapy, the so called "microtransplantation", has been shown to promote the graft-versus-leukemia effect and hasten hematopoietic recovery without amplifying GVHD. Herein, we review recent advances in stem cell therapy for leukemia with a specific focus on dual transplantation and microtransplantation.

  11. Pharm GKB: Leukemia, Biphenotypic, Acute [PharmGKB

    Lifescience Database Archive (English)

    Full Text Available Overview Alternate Names: Synonym Acute bilineal leukaemia; Acute bilineal leukemia; Acute... biphenotypic leukaemia; Acute biphenotypic leukemia; Acute mixed lineage leukaemia; Acute mixed line...age leukemia; B and T Cell Acute Lymphoblastic Leukemia; B and T Cell Leukemia, Acute; B- and T-Cell Acute L...ymphoblastic Leukemia; B- and T-Cell Leukemia, Acute; Leukemia, Lymphocytic, Acute..., Mixed Cell; Leukemia, Lymphocytic, Acute, Mixed-Cell; Leukemia, Mixed Cell; Leukemia, Mixed, B and T Cell

  12. Identification of Differentially Expressed Genes Associated with Prognosis of B Acute Lymphoblastic Leukemia

    OpenAIRE

    Idalia Garza-Veloz; Margarita L. Martinez-Fierro; Jose Carlos Jaime-Perez; Karol Carrillo-Sanchez; Maria Guadalupe Ramos-Del Hoyo; Angel Lugo-Trampe; Augusto Rojas-Martinez; Cesar Homero Gutierrez-Aguirre; Oscar Gonzalez-Llano; Rosario Salazar-Riojas; Alfredo Hidalgo-Miranda; David Gomez-Almaguer; Rocio Ortiz-Lopez

    2015-01-01

    Background. Acute lymphoblastic leukemia type B (B-ALL) is a neoplastic disorder with high mortality rates. The aim of this study was to validate the expression profile of 45 genes associated with signaling pathways involved in leukemia and to evaluate their association with the prognosis of B-ALL. Methods. 219 samples of peripheral blood mononuclear cells obtained from 73 B-ALL patients were studied at diagnosis, four, and eight weeks after starting treatment. Gene expression was analyzed by...

  13. Childhood Acute Lymphoblastic Leukemia

    DEFF Research Database (Denmark)

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

    2015-01-01

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

  14. Pharm GKB: Leukemia, Myeloid, Acute [PharmGKB

    Lifescience Database Archive (English)

    Full Text Available Amino Acid Translations are all sourced from dbSNP 144 Overview Alternate Names: Synonym AML - Acute... myeloblastic leukaemia; Acute Myeloblastic Leukemia; Acute Myeloblastic Leukemias; Acute... Myelocytic Leukemia; Acute Myelocytic Leukemias; Acute Myelogenous Leukemia; Acute Myelogenous Leukemias; Acute... granulocytic leukaemia; Acute myeloblastic leukemia; Acute myeloid leukaemia; Acute myeloid leukaemia - category; Acute... myeloid leukaemia, disease; Acute myeloid leukemia; Acute myelo

  15. Treating Chronic Myeloid Leukemia by Phase

    Science.gov (United States)

    ... Myeloid Leukemia (CML) Treating Chronic Myeloid Leukemia Treating Chronic Myeloid Leukemia by Phase Treatment options for people ... a stem cell donor with matching tissue type. Chronic phase The standard treatment for chronic phase CML ...

  16. Treatment Options for Childhood Acute Lymphoblastic Leukemia

    Science.gov (United States)

    ... Childhood AML Treatment Research Childhood Acute Lymphoblastic Leukemia Treatment (PDQ®)–Patient Version General Information About Childhood Acute ... Myelogenous Leukemia Treatment Hairy Cell Leukemia Treatment Past treatment for cancer and certain genetic conditions affect the ...

  17. Gemtuzumab Ozogamicin in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia or Acute Promyelocytic Leukemia

    Science.gov (United States)

    2016-07-26

    Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Promyelocytic Leukemia (M3); Childhood Acute Promyelocytic Leukemia (M3); Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Myeloid Leukemia

  18. Allogeneic stem cell transplantation in acute myeloid leukemia

    Directory of Open Access Journals (Sweden)

    Natasha Ali

    2012-11-01

    Full Text Available We report a case series of 12 patients with acute myeloid leukemia who underwent allogeneic stem cell transplant with a matched related donor. Male to female ratio was 1:1. The main complication post-transplant was graft-versus-host disease (n=7 patients. Transplant-related mortality involved one patient; cause of death was multi-organ failure. After a median follow up of 36.0±11.3 months, overall survival was 16%.

  19. Pharm GKB: Leukemia, Eosinophilic, Acute [PharmGKB

    Lifescience Database Archive (English)

    Full Text Available Overview Alternate Names: Synonym Acute Eosinophilic Leukemia; Acute Eosinophilic Leukemias; Acute... eosinophilic leukemia; Eosinophilic Leukemia, Acute; Eosinophilic Leukemias, Acute; Leukemia, Acute... Eosinophilic; Leukemias, Acute Eosinophilic PharmGKB Accession Id: PA446179 External Vocabularies Me...SH: Leukemia, Eosinophilic, Acute (D015472) SnoMedCT: Acute eosinophilic leukemia... (277604002) UMLS: C0023439 (C0023439) NDFRT: Leukemia, Eosinophilic, Acute [Disease/Finding] (N0000003269)

  20. B cell-specific deficiencies in mTOR limit humoral immune responses.

    Science.gov (United States)

    Zhang, Shuling; Pruitt, Margaret; Tran, Dena; Du Bois, Wendy; Zhang, Ke; Patel, Rushi; Hoover, Shelley; Simpson, R Mark; Simmons, John; Gary, Joy; Snapper, Clifford M; Casellas, Rafael; Mock, Beverly A

    2013-08-15

    Generation of high-affinity Abs in response to Ags/infectious agents is essential for developing long-lasting immune responses. B cell maturation and Ab responses to Ag stimulation require Ig somatic hypermutation (SHM) and class-switch recombination (CSR) for high-affinity responses. Upon immunization with either the model Ag 4-hydroxy-3-nitrophenylacetyl hapten (NP) conjugated to chicken γ globulin lysine (NP-CGG) or heat-killed Streptococcus pneumoniae capsular type 14 protein (Pn14), knock-in (KI) mice hypomorphic for mTOR function had a decreased ability to form germinal centers, develop high-affinity anti-NP-specific or anti-Pn14-specific Abs, and perform SHM/CSR. Hypomorphic mTOR mice also had a high mortality (40%) compared with wild-type (WT) (0%) littermates and had lower pneumococcal surface protein A-specific Ab titers when immunized and challenged with live S. pneumoniae infection. Mice with mTOR deleted in their B cell lineage (knockout [KO]) also produced fewer splenic germinal centers and decreased high-affinity Ab responses to NP-CGG than did their WT littermates. CSR rates were lower in mTOR KI and KO mice, and pharmacologic inhibition of mTOR in WT B cells resulted in decreased rates of ex vivo CSR. RNA and protein levels of activation-induced cytidine deaminase (AID), a protein essential for SHM and CSR, were lower in B cells from both KI and B cell-specific KO mice, concomitant with increases in phosphorylated AKT and FOXO1. Rescue experiments increasing AID expression in KI B cells restored CSR levels to those in WT B cells. Thus, mTOR plays an important immunoregulatory role in the germinal center, at least partially through AID signaling, in generating high-affinity Abs.

  1. Phase I Dose-Escalation Trial of Clofarabine Followed by Escalating Doses of Fractionated Cyclophosphamide in Children With Relapsed or Refractory Acute Leukemias

    Science.gov (United States)

    2010-09-21

    Myelodysplastic Syndrome; Acute Myeloid Leukemia; Myeloproliferative Disorders; Acute Lymphocytic Leukemia; Acute Promyelocytic Leukemia; Acute Leukemia; Chronic Myelogenous Leukemia; Myelofibrosis; Chronic Myelomonocytic Leukemia; Juvenile Myelomonocytic Leukemia

  2. Psychiatric aspects of adult leukemia.

    Science.gov (United States)

    Levenson, J A; Lesko, L M

    1990-02-01

    This report has discussed the normal psychological responses associated with diagnosis and treatment of leukemia, specific psychological disorders that are encountered in the context of treatment, and psychological issues that develop after definitive treatment as patients become survivors from leukemia. Psychopharmacologic and psychotherapeutic strategies to treat the specific disorders of anxiety, depression, and delirium have been outlined. Similarly, survival issues have been considered as an ever-growing number of patients are cured of leukemia.

  3. Down syndrome preleukemia and leukemia.

    Science.gov (United States)

    Maloney, Kelly W; Taub, Jeffrey W; Ravindranath, Yaddanapudi; Roberts, Irene; Vyas, Paresh

    2015-02-01

    Children with Down syndrome (DS) and acute leukemias acute have unique biological, cytogenetic, and intrinsic factors that affect their treatment and outcome. Myeloid leukemia of Down syndrome (ML-DS) is associated with high event-free survival (EFS) rates and frequently preceded by a preleukemia condition, the transient abnormal hematopoiesis (TAM) present at birth. For acute lymphoblastic leukemia (ALL), their EFS and overall survival are poorer than non-DS ALL, it is important to enroll them on therapeutic trials, including relapse trials; investigate new agents that could potentially improve their leukemia-free survival; and strive to maximize the supportive care these patients need.

  4. Decitabine, Cytarabine, and Daunorubicin Hydrochloride in Treating Patients With Acute Myeloid Leukemia

    Science.gov (United States)

    2016-07-20

    Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Monoblastic Leukemia; Adult Acute Monocytic Leukemia; Adult Acute Myeloid Leukemia With Maturation; Adult Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-MLL; Adult Acute Myeloid Leukemia Without Maturation; Adult Acute Myelomonocytic Leukemia; Alkylating Agent-Related Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  5. Epigenetic mechanisms in leukemia.

    Science.gov (United States)

    Zaidi, Sayyed K; Trombly, Daniel J; Dowdy, Christopher R; Lian, Jane B; Stein, Janet L; van Wijnen, Andre J; Stein, Gary S

    2012-09-01

    Focal organization of regulatory machinery within the interphase nucleus is linked to biological responsiveness and perturbed in cancer. Lineage determinant Runx proteins organize and assemble multi-protein complexes at sites of transcription within the nucleus and regulate both RNA polymerase II- and I-mediated gene expression. In addition, Runx proteins epigenetically control lineage determining transcriptional programs including: 1) architectural organization of macromolecular complexes in interphase, 2) regulation of gene expression through bookmarking during mitosis, and 3) microRNA-mediated translational control in the interphase nucleus. These mechanisms are compromised with the onset and progression of cancer. For example, the oncogenic AML1-ETO protein, which results from a chromosomal translocation between chromosomes 8 and 21, is expressed in nearly 25% of all acute myelogenous leukemias, disrupts Runx1 subnuclear localization during interphase and compromises transcriptional regulation. Epigenetically, the leukemic protein redirects the Runx1 DNA binding domain to leukemia-specific nuclear microenvironments, modifies regulatory protein accessibility to Runx1 target genes by imprinting repressive chromatin marks, and deregulates the microRNA (miR) profile of diseased myeloid cells. Consequently, the entire Runx1-dependent transcriptional program of myeloid cells is deregulated leading to onset and progression of acute myeloid leukemia and maintenance of leukemic phenotype. We discuss the potential of modified epigenetic landscape of leukemic cells as a viable therapeutic target.

  6. SB-715992 in Treating Patients With Acute Leukemia, Chronic Myelogenous Leukemia, or Advanced Myelodysplastic Syndromes

    Science.gov (United States)

    2013-01-10

    Acute Undifferentiated Leukemia; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Acute Promyelocytic Leukemia (M3); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Blastic Phase Chronic Myelogenous Leukemia; de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Excess Blasts in Transformation; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Untreated Adult Acute Myeloid Leukemia

  7. Obinutuzumab in chronic lymphocytic leukemia.

    Science.gov (United States)

    Dupuis, Jehan

    2015-09-01

    Obinutuzumab is the second next-generation monoclonal anti-CD20 antibody (after ofatumumab) to enter clinical practice in chronic lymphocytic leukemia. Its superiority in association with chlorambucil as compared with chlorambucil alone has led to its approval as a first-line treatment for chronic lymphocytic leukemia, for patients who are not candidates for a more intensive treatment.

  8. KEGG PATHWAY / Acute myeloid leukemia [KEGG

    Lifescience Database Archive (English)

    Full Text Available PATHWAY: map05221 Entry map05221Pathway Name Acute myeloid leukemia Description Acute...Class Human Diseases; Cancers Pathwaymap map05221Acute myeloid leukemia Disease H00003Acute myeloid leukemia...inkDB DBGET integrated database retrieval system KEGG PATHWAY / Acute myeloid leukemia ...

  9. Bendamustine Plus Alemtuzumab for Refractory Chronic Lymphocytic Leukemia (CLL)

    Science.gov (United States)

    2013-08-20

    Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Stage III Chronic Lymphocytic Leukemia; Stage III Small Lymphocytic Lymphoma; Stage IV Chronic Lymphocytic Leukemia; Stage IV Small Lymphocytic Lymphoma

  10. Obesity in patients with acute lymphoblastic leukemia in childhood

    Directory of Open Access Journals (Sweden)

    Iughetti Lorenzo

    2012-01-01

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

  11. Vorinostat in Treating Patients With Acute Myeloid Leukemia

    Science.gov (United States)

    2014-04-30

    Adult Acute Erythroid Leukemia (M6); Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Acute Promyelocytic Leukemia (M3); Recurrent Adult Acute Myeloid Leukemia; Refractory Cytopenia With Multilineage Dysplasia; Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  12. Cell-specific modulation of drug resistance in acute myeloid leukemic blasts by diphtheria fusion toxin, DT388-GMCSF.

    Science.gov (United States)

    Frankel, A E; Hall, P D; McLain, C; Safa, A R; Tagge, E P; Kreitman, R J

    1998-01-01

    Radiochemotherapy-resistant blasts commonly cause treatment failure in acute myeloid leukemia (AML), and their resistance is due, in part, to overexpression of multidrug resistance (mdr) proteins. We reasoned that targeted delivery of protein synthesis inactivating toxins to leukemic blasts would reduce the cellular concentrations of relatively short half-life resistance proteins and sensitize the cells to cytotoxic drugs. To test this hypothesis, we employed human granulocyte-macrophage colony-stimulating factor fused to truncated diphtheria toxin (DT388-GMCSF). The human AML cell line HL60 and its vincristine-resistant sublines, HL60Vinc and HL60VCR, were incubated in vitro for 24 h with varying concentrations of toxin. Doxorubicin was added for an additional 24 h, and cell cytotoxicity was assayed by thymidine incorporation and colony formation in semisolid medium. DT388-GMCSF sensitized HL60Vinc and HL60VCR but not HL60 to doxorubicin. Combination indices for three log cell kill varied from 0.2 to 0.3. In contrast, pretreatment with doxorubicin followed by toxins failed to show synergy. At least in the case of the vincristine-resistant cell lines, modulation of drug resistance correlated with reduction in membrane P-glycoprotein concentrations based on immunoblots with C219 antibody, flow cytometry with MRK16 antibody, and cell uptake of doxorubicin. These observations suggest clinical trials of combination therapy may be warranted in patients with refractory AML. Further, targeted toxins may represent a novel class of cell-specific modulators of drug resistance for a number of malignancies.

  13. Childhood Leukemia Survivors and Their Return to School: A Literature Review, Case Study, and Recommendations

    Science.gov (United States)

    Herrmann, D. Scott; Thurber, Jill R.; Miles, Kenneth; Gilbert, Gloria

    2011-01-01

    Leukemias (blood cell cancers) and central nervous system tumors are the most frequently occurring types of cancer in children. Mortality rates from all childhood cancers have decreased over the past 2 decades. As a result, many childhood cancer survivors are now returning to their schools after having been successfully treated. Although most of…

  14. Loss of the histone methyltransferase EZH2 induces resistance to multiple drugs in acute myeloid leukemia

    DEFF Research Database (Denmark)

    Göllner, Stefanie; Oellerich, Thomas; Agrawal-Singh, Shuchi

    2017-01-01

    In acute myeloid leukemia (AML), therapy resistance frequently occurs, leading to high mortality among patients. However, the mechanisms that render leukemic cells drug resistant remain largely undefined. Here, we identified loss of the histone methyltransferase EZH2 and subsequent reduction of h...

  15. Hyperglycemia during induction therapy is associated with increased infectious complications in childhood acute lymphocytic leukemia

    Science.gov (United States)

    Children with acute lymphocytic leukemia (ALL) are at high risk for developing hyperglycemia. Hyperglycemic adult ALL patients have shorter remissions, more infections, and increased mortality. No corresponding data are available in children. We hypothesized that children with ALL who become hypergl...

  16. Gemtuzumab Ozogamicin in Treating Patients With Acute Myeloid Leukemia

    Science.gov (United States)

    2013-09-23

    Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Promyelocytic Leukemia (M3); Recurrent Adult Acute Myeloid Leukemia

  17. Pharm GKB: Leukemia, Erythroblastic, Acute [PharmGKB

    Lifescience Database Archive (English)

    Full Text Available Overview Alternate Names: Synonym AML M6; Acute Erythroblastic Leukemia; Acute Erythroblastic Leukemias; Acu...te erythraemic myelosis [obs]; Acute erythremia [obs]; Acute erythremic myelosis [obs]; Acute... erythroid leukaemia; Acute erythroid leukemia; Acute myeloid leukaemia, M6 type; Acute myeloid le...Erythroblastic Leukemia, Acute; Erythroblastic Leukemias, Acute; Erythroleukaemia...; Erythroleukemia; Erythroleukemias; FAB M6; Leukemia, Acute Erythroblastic; Leukemia, Myeloid, Acute, M6; Leukemias, Acute

  18. Decitabine and Bortezomib in Treating Patients With Acute Myeloid Leukemia

    Science.gov (United States)

    2014-11-06

    Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  19. Childhood Leukemia and Electromagnetic Fields

    Directory of Open Access Journals (Sweden)

    Alpaslan Türkkan

    2009-12-01

    Full Text Available In this review, the relationship between very low frequency electromagnetic fields, originating from high voltage powerlines, and childhood leukemia was evaluated. Electromagnetic fields have biological effects. Whole populations are effected by different levels of electromagnetic fields but children are more sensible. In urban areas high voltage powerlines are the main sources of electromagnetic fields. The relation of electromagnetic fields due to high voltage powerlines and leukemia with consideration of dose-response and distance is investigated in several studies. There are different opinions on the effects of electromagnetic fields on general health. The relation between electromagnetic fields and childhood leukemia must be considered separately. Although there is no limit value, it is generally accepted that exposure to 0.4 µT and over doubles the risk of leukemia in children 15 years and younger. (Journal of Current Pediatrics 2009; 7: 137-41

  20. Plasma cell leukemia

    DEFF Research Database (Denmark)

    Fernández de Larrea, C; Kyle, R A; Durie, B G M

    2013-01-01

    Plasma cell leukemia (PCL) is a rare and aggressive variant of myeloma characterized by the presence of circulating plasma cells. It is classified as either primary PCL occurring at diagnosis or as secondary PCL in patients with relapsed/refractory myeloma. Primary PCL is a distinct clinic......-pathological entity with different cytogenetic and molecular findings. The clinical course is aggressive with short remissions and survival duration. The diagnosis is based upon the percentage (≥ 20%) and absolute number (≥ 2 × 10(9)/l) of plasma cells in the peripheral blood. It is proposed that the thresholds...... regimens and bortezomib-based regimens are recommended followed by high-dose therapy with autologous stem cell transplantation if feasible. Allogeneic transplantation can be considered in younger patients. Prospective multicenter studies are required to provide revised definitions and better understanding...

  1. Mast cell leukemia.

    Science.gov (United States)

    Georgin-Lavialle, Sophie; Lhermitte, Ludovic; Dubreuil, Patrice; Chandesris, Marie-Olivia; Hermine, Olivier; Damaj, Gandhi

    2013-02-21

    Mast cell leukemia (MCL) is a very rare form of aggressive systemic mastocytosis accounting for mast cell activation-involvement of the liver, spleen, peritoneum, bones, and marrow-are frequent. Diagnosis is based on the presence of ≥ 20% atypical mast cells in the marrow or ≥ 10% in the blood; however, an aleukemic variant is frequently encountered in which the number of circulating mast cells is < 10%. The common phenotypic features of pathologic mast cells encountered in most forms of mastocytosis are unreliable in MCL. Unexpectedly, non-KIT D816V mutations are frequent and therefore, complete gene sequencing is necessary. Therapy usually fails and the median survival time is < 6 months. The role of combination therapies and bone marrow transplantation needs further investigation.

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

    Science.gov (United States)

    2016-10-24

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

  3. Mortality table construction

    Science.gov (United States)

    Sutawanir

    2015-12-01

    Mortality tables play important role in actuarial studies such as life annuities, premium determination, premium reserve, valuation pension plan, pension funding. Some known mortality tables are CSO mortality table, Indonesian Mortality Table, Bowers mortality table, Japan Mortality table. For actuary applications some tables are constructed with different environment such as single decrement, double decrement, and multiple decrement. There exist two approaches in mortality table construction : mathematics approach and statistical approach. Distribution model and estimation theory are the statistical concepts that are used in mortality table construction. This article aims to discuss the statistical approach in mortality table construction. The distributional assumptions are uniform death distribution (UDD) and constant force (exponential). Moment estimation and maximum likelihood are used to estimate the mortality parameter. Moment estimation methods are easier to manipulate compared to maximum likelihood estimation (mle). However, the complete mortality data are not used in moment estimation method. Maximum likelihood exploited all available information in mortality estimation. Some mle equations are complicated and solved using numerical methods. The article focus on single decrement estimation using moment and maximum likelihood estimation. Some extension to double decrement will introduced. Simple dataset will be used to illustrated the mortality estimation, and mortality table.

  4. Molecular diagnosis of lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    Kalal Iravathy Goud

    2013-01-01

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

  5. Recent advances in orally administered cell-specific nanotherapeutics for inflammatory bowel disease

    Science.gov (United States)

    Si, Xiao-Ying; Merlin, Didier; Xiao, Bo

    2016-01-01

    Inflammatory bowel disease (IBD) is a chronic relapsing disease in gastrointestinal tract. Conventional medications lack the efficacy to offer complete remission in IBD therapy, and usually associate with serious side effects. Recent studies indicated that nanoparticle-based nanotherapeutics may offer precise and safe alternative to conventional medications via enhanced targeting, sustained drug release, and decreased adverse effects. Here, we reviewed orally cell-specific nanotherapeutics developed in recent years. In addition, the various obstacles for oral drug delivery are also reviewed in this manuscript. Orally administrated cell-specific nanotherapeutics is expected to become a novel therapeutic approach for IBD treatment. PMID:27678353

  6. On the global dynamics of a chronic myelogenous leukemia model

    Science.gov (United States)

    Krishchenko, Alexander P.; Starkov, Konstantin E.

    2016-04-01

    In this paper we analyze some features of global dynamics of a three-dimensional chronic myelogenous leukemia (CML) model with the help of the stability analysis and the localization method of compact invariant sets. The behavior of CML model is defined by concentrations of three cellpopulations circulating in the blood: naive T cells, effector T cells specific to CML and CML cancer cells. We prove that the dynamics of the CML system around the tumor-free equilibrium point is unstable. Further, we compute ultimate upper bounds for all three cell populations and provide the existence conditions of the positively invariant polytope. One ultimate lower bound is obtained as well. Moreover, we describe the iterative localization procedure for refining localization bounds; this procedure is based on cyclic using of localizing functions. Applying this procedure we obtain conditions under which the internal tumor equilibrium point is globally asymptotically stable. Our theoretical analyses are supplied by results of the numerical simulation.

  7. High Throughput Drug Sensitivity Assay and Genomics- Guided Treatment of Patients With Relapsed or Refractory Acute Leukemia

    Science.gov (United States)

    2016-11-14

    Acute Leukemia of Ambiguous Lineage; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Refractory Adult Acute Lymphoblastic Leukemia; Refractory Childhood Acute Lymphoblastic Leukemia

  8. Telomere Length and Mortality

    DEFF Research Database (Denmark)

    Kimura, Masayuki; Hjelmborg, Jacob V B; Gardner, Jeffrey P

    2008-01-01

    Leukocyte telomere length, representing the mean length of all telomeres in leukocytes, is ostensibly a bioindicator of human aging. The authors hypothesized that shorter telomeres might forecast imminent mortality in elderly people better than leukocyte telomere length. They performed mortality...

  9. Chronic meningitis by histoplasmosis: report of a child with acute myeloid leukemia

    Directory of Open Access Journals (Sweden)

    G.H. Pereira

    2008-12-01

    Full Text Available Meningitis is a common evolution in progressive disseminated histoplasmosis in children, and is asymptomatic in many cases. In leukemia, the impaired of the T cells function can predispose to the disseminated form. The attributed mortality rate in this case is 20%-40% and the relapse rate is as high as 50%; therefore, prolonged treatment may be emphasized. We have described a child with acute myeloid leukemia (AML, that developed skin lesions and asymptomatic chronic meningitis, with a good evolution after prolonged treatment with amphotericin B deoxycholate followed by fluconazole.

  10. Testicular involvement in acute lymphoblastic leukemia. Consequences of radiotherapy and chemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Brauner, R.; Czernichow, P.; Rappaport, R.; Schaison, G.

    1986-06-05

    Acute lymphoblastic leukemia has a higher mortality rate in boys as a result of possible testicular involvement; indeed, the testicle is the site of initial relapse in 6% of cases and is involved in 15% of all cases. Clinical diagnosis of testicular involvement is usually readily established. Treatment is delivery of 24 grays to both testicles and intensification of chemotherapy. In children who recover from their leukemia, this irradiation produces not only destruction of germ cells but also endocrine impairment which should be looked for and treated; replacement therapy with slow-action testosterone will be combined with the other hormonal treatments which pituitary deficiencies secondary to cranial irradiation may require.

  11. Acute myocardial infarction as a finding of acute promyelocytic leukemia-related coagulation disorder.

    Science.gov (United States)

    Özkurt, Zübeyde N; Aypar, Eda; Sarifakiogullari, Serpil; Taçoy, Gülten; Özdag, Murat; Kahraman, Seda; Çengel, Atiye

    2015-12-01

    Acute promyelocytic leukemia (APL) has one of the most favorable prognoses among other leukemia subtypes. However, the major cause of mortality in APL is disseminated intravascular coagulation at the presentation. We present a case of acute myocardial infarction (MI) at the time of APL diagnosis before treatment. The patient suffered from chest pain, sweating and giddiness. He was hypoxic, hypotensive and bradycardic. ECG showed inferior MI. Unfractioned heparin infusion (850 U/h) was started and 5 min after the previous ECG showed total ST resolution. We suggest that in this case, MI was not related to atherosclerotic plaque rupture but related to DIC manifestation.

  12. Excess mortality in hyperthyroidism

    DEFF Research Database (Denmark)

    Hjelm Brandt Kristensen, Frans; Pedersen, Dorthe Almind; Christensen, Kaare

    2012-01-01

    Hyperthyroidism is associated with severe comorbidity, such as stroke, and seems to confer increased mortality. However, it is unknown whether this increased mortality is explained by hyperthyroidism per se, comorbidity, and/or genetic confounding.......Hyperthyroidism is associated with severe comorbidity, such as stroke, and seems to confer increased mortality. However, it is unknown whether this increased mortality is explained by hyperthyroidism per se, comorbidity, and/or genetic confounding....

  13. Hairy Cell Leukemia Treatment Option Overview

    Science.gov (United States)

    ... Childhood ALL Treatment Childhood AML Treatment Research Hairy Cell Leukemia Treatment (PDQ®)–Patient Version General Information About Hairy Cell Leukemia Go to Health Professional Version Key Points ...

  14. Juvenile Myelomonocytic Leukemia (JMML) (For Parents)

    Science.gov (United States)

    ... Center Chronic Myelogenous Leukemia (CML) Coping With Your Child's Cancer: Liz Scott's Story Side Effects of Chemotherapy and ... Stem Cell Transplants Caring for a Seriously Ill Child Acute Myeloid Leukemia (AML) Cancer Center Chemotherapy Some Kinds of Cancer Kids Get ...

  15. Platelet enzyme abnormalities in leukemias

    Directory of Open Access Journals (Sweden)

    S Sharma

    2011-01-01

    Full Text Available Aim of the Study: The aim of this study was to evaluate platelet enzyme activity in cases of leukemia. Materials and Methods: Platelet enzymes glucose-6-phosphate dehydrogenase (G6PD, pyruvate kinase (PK and hexokinase (HK were studied in 47 patients of acute and chronic leukemia patients, 16 patients with acute myeloid leukemia (AML(13 relapse, three in remission, 12 patients with acute lymphocytic leukemia (ALL (five in relapse, seven in remission, 19 patients with chronic myeloid leukemia (CML. Results: The platelet G6PD activity was significantly low in cases of AML, ALL and also in CML. G6PD activity was normalized during AML remission. G6PD activity, although persistently low during ALL remission, increased significantly to near-normal during remission (P < 0.05 as compared with relapse (P < 0.01. Platelet PK activity was high during AML relapse (P < 0.05, which was normalized during remission. Platelet HK however was found to be decreased during all remission (P < 0.05. There was a significant positive correlation between G6PD and PK in cases of AML (P < 0.001 but not in ALL and CML. G6PD activity did not correlate with HK activity in any of the leukemic groups. A significant positive correlation was however seen between PK and HK activity in cases of ALL remission (P < 0.01 and CML (P < 0.05. Conclusions: Both red cell and platelet enzymes were studied in 36 leukemic patients and there was no statistically significant correlation between red cell and platelet enzymes. Platelet enzyme defect in leukemias suggests the inherent abnormality in megakaryopoiesis and would explain the functional platelet defects in leukemias.

  16. Ecthyma gangrenosum in a patient with acute leukemia.

    Science.gov (United States)

    Kryeziu, Emrush; Kryeziu, K; Bajraktari, Gjani; Abazi, M; Zylfiu, B; Rudhani, I; Sadiku, Sh; Ukimeri, A; Brovina, A; Dreshaj, Sh; Telaku, S

    2010-01-01

    Ecthymagangrenosum (EG)is a rare condition with characteristic clinical appearance of red maculae that progresses to a central area of necrosis surrounded by an erythematous halo. The most frequently it is caused by Pseudomonas bacteriaemia in neutropenic patient. The authors presents a patient with acute myloblastic leukemia M4 type in whom in relapse EG caused by Pseudomonas aeruginosa was found. The patient was treated with antibiotics and surgical debridement. The author wants to point out on clinical significance this condition with high mortality rate.

  17. Identification of benzodiazepine Ro5-3335 as an inhibitor of CBF leukemia through quantitative high throughput screen against RUNX1-CBFβ interaction.

    Science.gov (United States)

    Cunningham, Lea; Finckbeiner, Steven; Hyde, R Katherine; Southall, Noel; Marugan, Juan; Yedavalli, Venkat R K; Dehdashti, Seameen Jean; Reinhold, William C; Alemu, Lemlem; Zhao, Ling; Yeh, Jing-Ruey Joanna; Sood, Raman; Pommier, Yves; Austin, Christopher P; Jeang, Kuan-Teh; Zheng, Wei; Liu, Paul

    2012-09-04

    Core binding factor (CBF) leukemias, those with translocations or inversions that affect transcription factor genes RUNX1 or CBFB, account for ~24% of adult acute myeloid leukemia (AML) and 25% of pediatric acute lymphocytic leukemia (ALL). Current treatments for CBF leukemias are associated with significant morbidity and mortality, with a 5-y survival rate of ~50%. We hypothesize that the interaction between RUNX1 and CBFβ is critical for CBF leukemia and can be targeted for drug development. We developed high-throughput AlphaScreen and time-resolved fluorescence resonance energy transfer (TR-FRET) methods to quantify the RUNX1-CBFβ interaction and screen a library collection of 243,398 compounds. Ro5-3335, a benzodiazepine identified from the screen, was able to interact with RUNX1 and CBFβ directly, repress RUNX1/CBFB-dependent transactivation in reporter assays, and repress runx1-dependent hematopoiesis in zebrafish embryos. Ro5-3335 preferentially killed human CBF leukemia cell lines, rescued preleukemic phenotype in a RUNX1-ETO transgenic zebrafish, and reduced leukemia burden in a mouse CBFB-MYH11 leukemia model. Our data thus confirmed that RUNX1-CBFβ interaction can be targeted for leukemia treatment and we have identified a promising lead compound for this purpose.

  18. Cell-specific targeting of lipid-based carriers for ODN and DNA

    NARCIS (Netherlands)

    Bartsch, M; Weeke-Klimp, AH; Meijer, DKF; Scherphof, GL; Kamps, JAAM

    2005-01-01

    It is well recognized that there is an urgent need for non-toxic systemically applicable vectors for biologically active nucleotides to fully exploit the current potential of molecular medicine in gene therapy. Cell-specific targeting of non-viral lipid-based carriers for ODN and DNA is a prerequisi

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

    Science.gov (United States)

    2013-01-22

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

  20. Monoclonal antibodies reactive with hairy cell leukemia

    NARCIS (Netherlands)

    Visser, L; Shaw, A; Slupsky, J; Vos, H; Poppema, S

    1989-01-01

    Monoclonal antibodies reactive with hairy cell leukemia were developed to aid in the diagnosis of this subtype of B cell chronic lymphocytic leukemia and to gain better insight into the origin of hairy cells. Three antibodies were found to be of value in the diagnosis of hairy cell leukemia. Antibod

  1. A Case of Plasmacytoid Dendritic Cell Leukemia

    Directory of Open Access Journals (Sweden)

    Köpeczi Judit Beáta

    2013-04-01

    Full Text Available Introduction: Plasmacytoid dendritic cell leukemia is a rare subtype of acute leukemia, which has recently been established as a distinct pathologic entity that typically follows a highly aggressive clinical course in adults. The aim of this report is to present a case of plasmacytoid dendritic cell leukemia due to its rarity and difficulty to recognize and diagnose it.

  2. Treosulfan, Fludarabine Phosphate, and Total-Body Irradiation Before Donor Stem Cell Transplant in Treating Patients With High-Risk Acute Myeloid Leukemia, Myelodysplastic Syndrome, Acute Lymphoblastic Leukemia

    Science.gov (United States)

    2013-10-29

    Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Blastic Phase Chronic Myelogenous Leukemia; Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Acute Myeloid Leukemia in Remission; Childhood Chronic Myelogenous Leukemia; Childhood Myelodysplastic Syndromes; Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Childhood Acute Lymphoblastic Leukemia

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

    Science.gov (United States)

    2015-10-29

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

  4. PLASMA CELL LEUKEMIA

    Science.gov (United States)

    de Larrea, Carlos Fernandez; Kyle, Robert A.; Durie, Brian GM; Ludwig, Heinz; Usmani, Saad; Vesole, David H.; Hajek, Roman; Miguel, Jésus San; Sezer, Orhan; Sonneveld, Pieter; Kumar, Shaji K.; Mahindra, Anuj; Comenzo, Ray; Palumbo, Antonio; Mazumber, Amitabha; Anderson, Kenneth C.; Richardson, Paul G.; Badros, Ashraf Z.; Caers, Jo; Cavo, Michele; LeLeu, Xavier; Dimopoulos, Meletios A.; Chim, CS; Schots, Rik; Noeul, Amara; Fantl, Dorotea; Mellqvist, Ulf-Henrik; Landgren, Ola; Chanan-Khan, Asher; Moreau, Philippe; Fonseca, Rafael; Merlini, Giampaolo; Lahuerta, JJ; Bladé, Joan; Orlowski, Robert Z.; Shah, Jatin J.

    2014-01-01

    Plasma cell leukemia (PCL) is a rare and aggressive variant of myeloma characterized by the presence of circulating plasma cells. It is classified as either primary PCL occurring at diagnosis or as secondary PCL in patients with relapsed/refractory myeloma. Primary PCL is a distinct clinic-pathologic entity with different cytogenetic and molecular findings. The clinical course is aggressive with short remissions and survival duration. The diagnosis is based upon the percentage (≥ 20%) and absolute number (≥ 2 × 10 9/L) of plasma cells in the peripheral blood. It is proposed that the thresholds for diagnosis be reexamined and consensus recommendations are made for diagnosis, as well as, response and progression criteria. Induction therapy needs to begin promptly and have high clinical activity leading to rapid disease control in an effort to minimize the risk of early death. Intensive chemotherapy regimens and bortezomib-based regimens are recommended followed by high-dose therapy with autologous stem-cell transplantation (HDT/ASCT) if feasible. Allogeneic transplantation can be considered in younger patients. Prospective multicenter studies are required to provide revised definitions and better understanding of the pathogenesis of PCL. PMID:23288300

  5. Phenomenological theory of mortality

    Science.gov (United States)

    Azbel, Mark Ya.

    1997-09-01

    Extensive demographic studies relate aging to the increase in mortality, terminated by the species-specific lifespan limit. Meanwhile, recent experiments demonstrate that medfly mortality decreases at older ages, and challenge a limited lifespan paradigm. This paper proves that there exists a genetically programmed probability to die at any given age, and presents its phenomenological theory. The implications of the universal mortality law crucially depend on the cohort heterogeneity. For relatively high heterogeneity the law predicts unitarily vanishing old age mortality; this is verified with medfly data. For relatively low heterogeneity it predicts a precipitous drop in mortality fluctuations in old age. This is verified with demographic data. If comprehensive studies verify a species-specific characteristic age, then that age may be genetically manipulated. If the studies verify a unitary law of mortality, the results may be generalized to all species. A phenomenological model of mortality is presented.

  6. Decitabine With or Without Bortezomib in Treating Older Patients With Acute Myeloid Leukemia

    Science.gov (United States)

    2016-03-14

    Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Adult Acute Megakaryoblastic Leukemia; Adult Acute Monoblastic Leukemia; Adult Acute Monocytic Leukemia; Adult Acute Myeloid Leukemia With Minimal Differentiation; Adult Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-MLL; Adult Acute Myeloid Leukemia Without Maturation; Adult Erythroleukemia; Adult Pure Erythroid Leukemia; Alkylating Agent-Related Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  7. Acute leukemia in early childhood

    Directory of Open Access Journals (Sweden)

    M. Emerenciano

    2007-06-01

    Full Text Available Acute leukemia in early childhood is biologically and clinically distinct. The particular characteristics of this malignancy diagnosed during the first months of life have provided remarkable insights into the etiology of the disease. The pro-B, CD10 negative immunophenotype is typically found in infant acute leukemia, and the most common genetic alterations are the rearrangements of the MLL gene. In addition, the TEL/AML1 fusion gene is most frequently found in children older than 24 months. A molecular study on a Brazilian cohort (age range 0-23 months has detected TEL/AML1+ve (N = 9, E2A/PBX1+ve (N = 4, PML/RARA+ve (N = 4, and AML1/ETO+ve (N = 2 cases. Undoubtedly, the great majority of genetic events occurring in these patients arise prenatally. The environmental exposure to damaging agents that give rise to genetic changes prenatally may be accurately determined in infants since the window of exposure is limited and known. Several studies have shown maternal exposures that may give rise to leukemogenic changes. The Brazilian Collaborative Study Group of Infant Acute Leukemia has found that mothers exposed to dipyrone, pesticides and hormones had an increased chance to give birth to babies with infant acute leukemia [OR = 1.48 (95%CI = 1.05-2.07, OR = 2.27 (95%CI = 1.56-3.31 and OR = 9.08 (95%CI = 2.95-27.96], respectively. This review aims to summarize recent clues that have facilitated the elucidation of the biology of early childhood leukemias, with emphasis on infant acute leukemia in the Brazilian population.

  8. Bullous leukemia cutis mimicking facial cellulitis*

    Science.gov (United States)

    Caldato, Luciana de Sales; Britto, Juliana de Sousa; Niero-Melo, Ligia; Miot, Hélio Amante

    2016-01-01

    Bullous leukemia cutis is an uncommon clinical manifestation of cutaneous infiltration by leukemic cells, from B-cell chronic lymphocytic leukemia. We present the case of a 67-year-old, female, chronic lymphocytic leukemia patient. She was taking chlorambucil and developed facial edema with erythema and warmth, misjudged as facial cellulitis. Two days later, she developed bullous lesions in the arms, legs, neck and face. The histopathology of facial and bullous lesions confirmed leukemia cutis. All lesions disappeared following the administration of rituximab combined with cycles of fludarabine and cyclophosphamide. Although soft tissue infections are common complications in patients undergoing chemotherapy, leukemia cutis can also resemble cellulitis. PMID:27192532

  9. Therapeutic activity of two xanthones in a xenograft murine model of human chronic lymphocytic leukemia

    Directory of Open Access Journals (Sweden)

    Berthou Christian

    2010-12-01

    Full Text Available Abstract Background We previously reported that allanxanthone C and macluraxanthone, two xanthones purified from Guttiferae trees, display in vitro antiproliferative and proapoptotic activities in leukemic cells from chronic lymphocytic leukemia (CLL and leukemia B cell lines. Results Here, we investigated the in vivo therapeutic effects of the two xanthones in a xenograft murine model of human CLL, developed by engrafting CD5-transfected chronic leukemia B cells into SCID mice. Treatment of the animals with five daily injections of either allanxanthone C or macluraxanthone resulted in a significant prolongation of their survival as compared to control animals injected with the solvent alone (p = 0.0006 and p = 0.0141, respectively. The same treatment of mice which were not xenografted induced no mortality. Conclusion These data show for the first time the in vivo antileukemic activities of two plant-derived xanthones, and confirm their potential interest for CLL therapy.

  10. Outcome and medical costs of patients with invasive aspergillosis and acute myelogenous leukemia-myelodysplastic syndrome treated with intensive chemotherapy: An observational study

    OpenAIRE

    Slobbe, Lennert; Polinder, Suzanne; Doorduijn, Jeanette; Lugtenburg, Pieternella; Barzouhi, Abdelilah; Steyerberg, Ewout; Rijnders, Bart

    2008-01-01

    textabstractBackground. Invasive aspergillosis (IA) is a leading cause of mortality in patients with acute leukemia. Management of IA is expensive, which makes prevention desirable. Because hospital resources are limited, prevention costs have to be compared with treatment costs and outcome. Methods. In 269 patients treated for acute myelogenous leukemia-myelodysplastic syndrome (AML-MDS) during 2002-2007, evidence of IA was collected using high-resolution computed tomography and galactomanna...

  11. Cancer Incidence and Mortality in China, 2007

    Institute of Scientific and Technical Information of China (English)

    Wan-qing Chen; Hong-mei Zeng; Rong-shou Zheng; Si-wei Zhang; Jie He

    2012-01-01

    Objective:Cancer incidence and mortality data collected from population-based cancer registries were analyzed to present the overall cancer statistics in Chinese registration areas by age,sex and geographic area in 2007.Methods:In 2010,48 cancer registries reported cancer incidence and mortality data of 2007 to National Central Cancer Registry of China.Of them,38 registries' data met the national criteria.Incidence and mortality were calculated by cancer sites,age,gender,and area.Age-standardized rates were described by China and World population.Results:The crude incidence rate for all cancers was 276.16/100,000 (305.22/100,000 for male and 246.46/100,000 for female; 284.71/100,000 in urban and 251.07/100,000 in rural).Age-standardized incidence rates by China and World population were 145.39/100,000 and 189.46/100,000 respectively.The crude mortality rate for all cancers was 177.09/100,000 (219.15/100,000 for male and 134.10/100,000 for female; 173.55/100,000 in urban and 187.49/100,000 in rural).Age-standardized mortality rates by China and World population were 86.06/100,000 and 116.46/100,000,respectively.The top 10 most frequently common cancer sites were the lung,stomach,colon and rectum,liver,breast,esophagus,pancreas,bladder,brain and lymphoma,accounting for 76.12% of the total cancer cases.The top 10 causes of cancer death were cancers of the lung,liver,stomach,esophagus,colon and rectum,pancreas,breast,leukemia,brain and lymphoma,accounting for 84.37% of the total cancer deaths.Conclusion:Cancer remains a major disease threatening people's health in China.Prevention and control should be enhanced,especially for the main cancers.

  12. Applying molecular epidemiology in pediatric leukemia.

    Science.gov (United States)

    Schiffman, Joshua D

    2016-02-01

    Molecular epidemiology is the study of genetic and environmental risk for disease, with much effort centered on cancer. Childhood leukemia occurs in nearly a third of all patients newly diagnosed with pediatric cancer. only a small percentage of these new cases of childhood leukemia are associated with high penetrant hereditary cancer syndromes. Childhood leukemia, especially acute lymphoblastic leukemia, has been associated with a dysregulated immune system due to delayed infectious exposure at a young age. Identical twins with childhood leukemia suggest that acute lymphoblastic leukemia begins in utero and that the concordant presentation is due to a shared preleukemia subclone via placental transfer. Investigation of single nucleotide polymorphisms within candidate genes find that leukemia risk may be attributed to population-based polymorphisms affecting folate metabolism, xenobiotic metabolism, DNA repair, immunity, and B-cell development. More recently, genome-wide association studies for leukemia risk has led investigators to genes associated with B-cell development. When describing leukemia predisposition due to hereditary cancer syndromes, the following 6 categories become apparent on the basis of biology and clinical presentation: (1) genetic instability/DNA repair syndromes, (2) cell cycle/differentiation syndromes, (3) bone marrow failure syndromes, (4) telomere maintenance syndromes, (5) immunodeficiency syndromes, and (6) transcription factor syndromes and pure familial leukemia. understanding the molecular epidemiology of childhood leukemia can affect the treatment and tumor surveillance strategies for these high risk patients and their family members.

  13. Cell-specific biomarkers and targeted biopharmaceuticals for breast cancer treatment.

    Science.gov (United States)

    Liu, Mei; Li, Zhiyang; Yang, Jingjing; Jiang, Yanyun; Chen, Zhongsi; Ali, Zeeshan; He, Nongyue; Wang, Zhifei

    2016-08-01

    Breast cancer is the second leading cause of cancer death among women, and its related treatment has been attracting significant attention over the past decades. Among the various treatments, targeted therapy has shown great promise as a precision treatment, by binding to cancer cell-specific biomarkers. So far, great achievements have been made in targeted therapy of breast cancer. In this review, we first discuss cell-specific biomarkers, which are not only useful for classification of breast cancer subtyping but also can be utilized as goals for targeted therapy. Then, the innovative and generic-targeted biopharmaceuticals for breast cancer, including monoclonal antibodies, non-antibody proteins and small molecule drugs, are reviewed. Finally, we provide our outlook on future developments of biopharmaceuticals, and provide solutions to problems in this field.

  14. Cell-specific information processing in segregating populations of Eph receptor ephrin-expressing cells

    DEFF Research Database (Denmark)

    Jørgensen, Claus; Sherman, Andrew; Chen, Ginny I;

    2009-01-01

    Cells have self-organizing properties that control their behavior in complex tissues. Contact between cells expressing either B-type Eph receptors or their transmembrane ephrin ligands initiates bidirectional signals that regulate cell positioning. However, simultaneously investigating how...... information is processed in two interacting cell types remains a challenge. We implemented a proteomic strategy to systematically determine cell-specific signaling networks underlying EphB2- and ephrin-B1-controlled cell sorting. Quantitative mass spectrometric analysis of mixed populations of EphB2......- and ephrin-B1-expressing cells that were labeled with different isotopes revealed cell-specific tyrosine phosphorylation events. Functional associations between these phosphotyrosine signaling networks and cell sorting were established with small interfering RNA screening. Data-driven network modeling...

  15. Long-Term Mortality Trends Infographic

    Science.gov (United States)

    This infographic shows the National Cancer Institute 10-year Mortality Trends. The graphs show the Average Annual Percent of Change (AAPC) 2002-2011. For Men, Liver & IBD: 2.6*, Soft Tissue inc. Heart: 0.8*, Pancreas: 0.3*, Melanoma: 0.3*, Bladder: 0, Brain & ONS: -0.4, Oral Cavity: -0.5, Esophagus: -0.5*, Kidney: -0.8*, Leukemia: -0.9*, Myeloma: -1.1*, All Sites: -1.8*, Non Hodgkin Lymphoma: -2.3*, Larynx: -2.5*, Lung and Bronchus: -2.6*, Colon and Rectum: -3.9*, Stomach: -3.1*, and Prostate: -3.3*. For Women, Liver & IBD: 1.9*, Corpus & Uterus: 1.0*, Pancreas: 0.4*, Bladder: -0.4*, Kidney: -0.9*, Brain & ONS: -0.9*, Leukemia: -1.1*, Gallbladder: -1.2*, Lung & Bronchus: -1.2*, Cervix: -1.3*, All Sites: -1.4*, Esophagus: -1.5*, Myeloma: -1.6*, Breast: -1.9*, Oral Cavity: -2.0*, Ovary: -2.0*, Stomach: -2.7*, Colon & Rectum: -2.9*, and Non-Hodgkin Lymphoma: -3.1*. * AAPC is significantly different from zero (p<.05). www.cancer.gov Source: Special section of the Annual Report to the Nation on the Status of Cancer, 1975-2011

  16. Pharm GKB: Leukemia, B-Cell, Acute [PharmGKB

    Lifescience Database Archive (English)

    Full Text Available UTR Alleles, Functions, and Amino Acid Translations are all sourced from dbSNP 144 Overview Alternate Names: Synonym Acute... B-Cell Leukemia; Acute B-Cell Leukemias; Acute B-Lymphocytic Leukemia; Acute... B-Lymphocytic Leukemias; Acute lymphoblastic leukaemia, Burkitt's type; Acute lymphoblastic leuka...emia, mature B-cell type; Acute lymphoblastic leukemia, Burkitt's type; Acute lymphoblastic leukemia, mature... B-cell type; B Cell Leukemia, Acute; B Lymphocytic Leukemia, Acute; B-ALL; B-Cell Leukemia, Acute

  17. Cell-specific STORM super-resolution imaging reveals nanoscale organization of cannabinoid signaling

    OpenAIRE

    2014-01-01

    A major challenge in neuroscience is to determine the nanoscale position and quantity of signaling molecules in a cell-type-, and subcellular compartment-specific manner. We therefore developed a novel approach combining cell-specific physiological and anatomical characterization with superresolution imaging, and studied the molecular and structural parameters shaping the physiological properties of synaptic endocannabinoid signaling in the mouse hippocampus. We found that axon terminals of p...

  18. Environmental temperature and mortality

    OpenAIRE

    Näyhä, Simo

    2005-01-01

    In Finland, mortality increases steeply in autumn, reaches a peak during the Christhmas holidays and declines slowly towards a trough in August. The relative excess in daily mortality (peak vs. trough) is 30% for coronary heart disease, 40% for cerebral vascular accidents and 90% for diseases of the respiratory organs. There is a secondary peak in Midsummer, especially in coronary deaths of working aged men. Mortality is lowest at mean daily temperature of +14 degrees C, and it increases slow...

  19. Transplant Outcomes for Children with Hypodiploid Acute Lymphoblastic Leukemia

    Science.gov (United States)

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

    2015-01-01

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

  20. Elevated cell-specific microparticles are a biological marker for cerebral dysfunctions in human severe malaria.

    Directory of Open Access Journals (Sweden)

    Joël Bertrand Pankoui Mfonkeu

    Full Text Available Cerebral malaria (CM and severe anemia (SA are the most severe complications of Plasmodium falciparum infections. Although increased release of endothelial microparticles (MP correlates with malaria severity, the full extent of vascular cell vesiculation remains unknown. Here, we characterize the pattern of cell-specific MP in patients with severe malaria. We tested the hypothesis that systemic vascular activation contributes to CM by examining origins and levels of plasma MP in relation to clinical syndromes, disease severity and outcome. Patients recruited in Douala, Cameroon, were assigned to clinical groups following WHO criteria. MP quantitation and phenotyping were carried out using cell-specific markers by flow cytometry using antibodies recognizing cell-specific surface markers. Platelet, erythrocytic, endothelial and leukocytic MP levels were elevated in patients with cerebral dysfunctions and returned to normal by discharge. In CM patients, platelet MP were the most abundant and their levels significantly correlated with coma depth and thrombocytopenia. This study shows for the first time a widespread enhancement of vesiculation in the vascular compartment appears to be a feature of CM but not of SA. Our data underpin the role of MP as a biomarker of neurological involvement in severe malaria. Therefore, intervention to block MP production in severe malaria may provide a new therapeutic pathway.

  1. Cell-Specific Cre Strains For Genetic Manipulation in Salivary Glands.

    Directory of Open Access Journals (Sweden)

    Eri O Maruyama

    Full Text Available The secretory acinar cells of the salivary gland are essential for saliva secretion, but are also the cell type preferentially lost following radiation treatment for head and neck cancer. The source of replacement acinar cells is currently a matter of debate. There is evidence for the presence of adult stem cells located within specific ductal regions of the salivary glands, but our laboratory recently demonstrated that differentiated acinar cells are maintained without significant stem cell contribution. To enable further investigation of salivary gland cell lineages and their origins, we generated three cell-specific Cre driver mouse strains. For genetic manipulation in acinar cells, an inducible Cre recombinase (Cre-ER was targeted to the prolactin-induced protein (Pip gene locus. Targeting of the Dcpp1 gene, encoding demilune cell and parotid protein, labels intercalated duct cells, a putative site of salivary gland stem cells, and serous demilune cells of the sublingual gland. Duct cell-specific Cre expression was attempted by targeting the inducible Cre to the Tcfcp2l1 gene locus. Using the R26Tomato Red reporter mouse, we demonstrate that these strains direct inducible, cell-specific expression. Genetic tracing of acinar cells using PipGCE supports the recent finding that differentiated acinar cells clonally expand. Moreover, tracing of intercalated duct cells expressing DcppGCE confirms evidence of duct cell proliferation, but further analysis is required to establish that renewal of secretory acinar cells is dependent on stem cells within these ducts.

  2. Cell-Specific Cre Strains For Genetic Manipulation in Salivary Glands.

    Science.gov (United States)

    Maruyama, Eri O; Aure, Marit H; Xie, Xiaoling; Myal, Yvonne; Gan, Lin; Ovitt, Catherine E

    2016-01-01

    The secretory acinar cells of the salivary gland are essential for saliva secretion, but are also the cell type preferentially lost following radiation treatment for head and neck cancer. The source of replacement acinar cells is currently a matter of debate. There is evidence for the presence of adult stem cells located within specific ductal regions of the salivary glands, but our laboratory recently demonstrated that differentiated acinar cells are maintained without significant stem cell contribution. To enable further investigation of salivary gland cell lineages and their origins, we generated three cell-specific Cre driver mouse strains. For genetic manipulation in acinar cells, an inducible Cre recombinase (Cre-ER) was targeted to the prolactin-induced protein (Pip) gene locus. Targeting of the Dcpp1 gene, encoding demilune cell and parotid protein, labels intercalated duct cells, a putative site of salivary gland stem cells, and serous demilune cells of the sublingual gland. Duct cell-specific Cre expression was attempted by targeting the inducible Cre to the Tcfcp2l1 gene locus. Using the R26Tomato Red reporter mouse, we demonstrate that these strains direct inducible, cell-specific expression. Genetic tracing of acinar cells using PipGCE supports the recent finding that differentiated acinar cells clonally expand. Moreover, tracing of intercalated duct cells expressing DcppGCE confirms evidence of duct cell proliferation, but further analysis is required to establish that renewal of secretory acinar cells is dependent on stem cells within these ducts.

  3. Very late recurrences of leukemia: why does leukemia awake after many years of dormancy?

    Science.gov (United States)

    Norkin, Maxim; Uberti, Joseph P; Schiffer, Charles A

    2011-02-01

    We report a heterogeneous group of very late recurrences of leukemia occurring more than 10 years after initial treatment including 2 cases of childhood acute lymphoblastic leukemia (ALL) which recurred after more than 20 years of remission, 2 cases of donor cell leukemia which developed more than 10 years after allograft for acute myeloid leukemia (AML) and high risk myelodysplastic syndrome (MDS) and 2 cases of chronic myeloid leukemia (CML) relapsing 13 and 17 years after allograft. Case descriptions are followed by a discussion regarding possible mechanisms leading to leukemia recurrence and a review of the literature.

  4. Mortality and GH deficiency

    DEFF Research Database (Denmark)

    Stochholm, Kirstine; Gravholt, Claus Højbjerg; Laursen, Torben;

    2007-01-01

    OBJECTIVE: To estimate the mortality in Denmark in patients suffering from GH deficiency (GHD). DESIGN: Mortality was analyzed in 1794 GHD patients and 8014 controls matched on age and gender. All records in GHD patients were studied and additional morbidity noted. Patients were divided into chil......OBJECTIVE: To estimate the mortality in Denmark in patients suffering from GH deficiency (GHD). DESIGN: Mortality was analyzed in 1794 GHD patients and 8014 controls matched on age and gender. All records in GHD patients were studied and additional morbidity noted. Patients were divided...

  5. Maternal mortality from hemorrhage.

    Science.gov (United States)

    Haeri, Sina; Dildy, Gary A

    2012-02-01

    Hemorrhage remains as one of the top 3 obstetrics related causes of maternal mortality, with most deaths occurring within 24-48 hours of delivery. Although hemorrhage related maternal mortality has declined globally, it continues to be a vexing problem. More specifically, the developing world continue to shoulder a disproportionate share of hemorrhage related deaths (99%) compared with industrialized nations (1%). Given the often preventable nature of death from hemorrhage, the cornerstone of effective mortality reduction involves risk factor identification, quick diagnosis, and timely management. In this monograph we will review the epidemiology, etiology, and preventative measures related to maternal mortality from hemorrhage.

  6. Integrated genome-wide genotyping and gene expression profiling reveals BCL11B as a putative oncogene in acute myeloid leukemia with 14q32 aberrations.

    Science.gov (United States)

    Abbas, Saman; Sanders, Mathijs A; Zeilemaker, Annelieke; Geertsma-Kleinekoort, Wendy M C; Koenders, Jasper E; Kavelaars, Francois G; Abbas, Zabiollah G; Mahamoud, Souad; Chu, Isabel W T; Hoogenboezem, Remco; Peeters, Justine K; van Drunen, Ellen; van Galen, Janneke; Beverloo, H Berna; Löwenberg, Bob; Valk, Peter J M

    2014-05-01

    Acute myeloid leukemia is a neoplasm characterized by recurrent molecular aberrations traditionally demonstrated by cytogenetic analyses. We used high density genome-wide genotyping and gene expression profiling to reveal acquired cryptic abnormalities in acute myeloid leukemia. By genome-wide genotyping of 137 cases of primary acute myeloid leukemia, we disclosed a recurrent focal amplification on chromosome 14q32, which included the genes BCL11B, CCNK, C14orf177 and SETD3, in two cases. In the affected cases, the BCL11B gene showed consistently high mRNA expression, whereas the expression of the other genes was unperturbed. Fluorescence in situ hybridization on 40 cases of acute myeloid leukemia with high BCL11B mRNA expression [2.5-fold above median; 40 out of 530 cases (7.5%)] revealed 14q32 abnormalities in two additional cases. In the four BCL11B-rearranged cases the 14q32 locus was fused to different partner chromosomes. In fact, in two cases, we demonstrated that the focal 14q32 amplifications were integrated into transcriptionally active loci. The translocations involving BCL11B result in increased expression of full-length BCL11B protein. The BCL11B-rearranged acute myeloid leukemias expressed both myeloid and T-cell markers. These biphenotypic acute leukemias all carried FLT3 internal tandem duplications, a characteristic marker of acute myeloid leukemia. BCL11B mRNA expression in acute myeloid leukemia appeared to be strongly associated with expression of other T-cell-specific genes. Myeloid 32D(GCSF-R) cells ectopically expressing Bcl11b showed decreased proliferation rate and less maturation. In conclusion, by an integrated approach involving high-throughput genome-wide genotyping and gene expression profiling we identified BCL11B as a candidate oncogene in acute myeloid leukemia.

  7. Treatment of chronic lymphocytic leukemia.

    Science.gov (United States)

    Ferrajoli, Alessandra; O'Brien, Susan M

    2004-04-01

    Treatment options for patients with chronic lymphocytic leukemia have changed over the past two decades. This article reviews the experience accumulated with the use of alkylating agents alone and in combination; purine analogues alone and in combination and monoclonal antibodies such as rituximab, and alemtuzumab alone and in combination. The results obtained with different treatment strategies are summarized, compared, and reviewed.

  8. How Is Childhood Leukemia Classified?

    Science.gov (United States)

    ... tissues and organs beyond the bone marrow. These children often have fever, poor appetite, and weight loss. At this point the CML acts much like an aggressive acute leukemia (AML or, less often, ALL). Not ... questions about what phase your child’s CML is in, be sure to have the ...

  9. Acute leukemia and pregnancy: a review of management and outcome, 1972-1982.

    Science.gov (United States)

    Catanzarite, V A; Ferguson, J E

    1984-11-01

    Acute leukemia is a rare complication of pregnancy. Previous reviews that covered cases reported before the introduction of effective combination chemotherapy found fewer than 300 reported pregnancies, with a 36-69 per cent perinatal mortality and median maternal survival, from diagnosis, of less than 6 months. Advances in the fields of hematology-oncology, maternal-fetal medicine, and neonatology have resulted in a marked improvement in both perinatal survival statistics, and median maternal survival. Since 1972, there have been 14 pregnancies reported in patients cured of acute lymphocytic leukemia, with 1 early spontaneous abortion and 13 term infants. All mothers survived. There have been 47 reports of pregnancy in association with acute leukemia. In 40 pregnancies in which acute leukemia was treated, there were 5 abortions, 3 perinatal demises, 1 infant "liveborn in grave condition," and 31 surviving infants. Median maternal survival was at least 6, and possibly more than 12 months from delivery. In seven cases in which leukemia was untreated, there were one abortion, two perinatal demises, and four living infants; only one of six mothers survived beyond 6 months. Here, a case of pregnancy complicated by acute promyelocytic leukemia is presented. The mother was aggressively treated with combination chemotherapy. The fetus was closely monitored and delivered following a course of betamethasone at 34 weeks' gestation, and had no neonatal problems. The mother expired 13 months status-post bone marrow transplantation, 16 months after delivery. Cases of pregnancy complicated by acute leukemia reported in the period 1972-1982 are reviewed, and management is discussed in detail. Aggressive hematologic and obstetric management is advocated, and should result in further improvements in fetal and maternal outcome.

  10. Chronic myeloid leukemia in pregnancy: an absolute contraindication to neuraxial anesthesia?

    Science.gov (United States)

    Owsiak, J N; Bullough, A S

    2016-02-01

    Chronic myeloid leukemia is rare in pregnancy with an estimated incidence of 1:75000. It is a genetic myeloproliferative disorder marked by increased and unregulated growth of myeloid cells in the bone marrow. The terminal phase of chronic myeloid leukemia may develop into a blast crisis, defined as >30% myeloblasts in the circulation. A blast crisis resembles an acute leukemia and is associated with rapid clinical deterioration and short survival. Targeted gene therapy with tyrosine kinase inhibitors is effective in treatment but when these agents are discontinued, as in pregnancy, the patient may relapse and blast cells may enter the circulation. Theoretically, a central nervous system blast crisis may be induced by inadvertent intrathecal seeding of circulating blast cells, and is associated with a high mortality rate and a median life expectancy of three months. We describe the anesthetic management of a patient with chronic myeloid leukemia and blast cells in the circulation who required cesarean delivery. After considering the potential anesthetic risks and benefits, general anesthesia was chosen. Although an iatrogenic central nervous system blast crisis is extremely rare, the high morbidity and mortality associated with such an event should be considered when formulating an anesthetic plan.

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

    Science.gov (United States)

    2014-03-20

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

  12. Treatment of acute promyelocytic leukemia during pregnancy.

    Science.gov (United States)

    Yang, Daisy; Hladnik, Lindsay

    2009-06-01

    Management of the pregnant patient with acute promyelocytic leukemia (APL) is a challenge. Immediate treatment of APL is critical, as it is an oncologic emergency, with a high risk of morbidity and mortality associated with disseminated intravascular coagulation. However, administration of chemotherapy and differentiating agents in pregnancy is controversial because of potential teratogenic effects. In addition, complications associated with APL, including retinoic acid syndrome, add to the complexity of management. To better understand how to manage this complex patient care situation, we searched the PubMed database (January 1972-May 2008) for English-language articles about maternal and fetal outcomes resulting from APL treatment during pregnancy. A total of 42 cases from 35 articles were identified: 12 first-trimester, 21 second-trimester, and 9 third-trimester cases. The most commonly administered agents were all-trans-retinoic acid (ATRA), anthracyclines, and antimetabolites. Complete remission was reported in 35 (83%) of 42 patients. Administration of ATRA or chemotherapy in the first trimester was associated with an increased risk of fetal malformations and spontaneous abortion, whereas administration in the second and third trimesters was associated with relatively favorable fetal outcomes. The overall treatment of the pregnant patient with APL should include a discussion about pregnancy termination, especially if APL is diagnosed in the first trimester. If the pregnancy is to continue, then the appropriate chemotherapy regimen needs to be determined. Frequent fetal monitoring, along with aggressive management of potential APL-related complications, is necessary to allow for optimal maternal and fetal outcomes.

  13. INFECTIOUS COMPLICATIONS IN CHRONIC LYMPHOCYTIC LEUKEMIA

    Directory of Open Access Journals (Sweden)

    AnnaMaria Nosari

    2012-11-01

    Full Text Available Infectious complications have been known to be a major cause of morbidity and mortality in CLL patients who are predisposed to infections because of both the humoral immunodepression inherent to hematologic disease, which is related to stage and duration of CLL, and to further immunosuppression related to therapy. The majority of infections in CLL patients treated with alkilating agents is of bacterial origin. The immunodeficiency and natural infectious history of alkylator-resistant, corticosteroid-treated patients appears to have changed with the administration of purine analogs, which has been complicated by very severe and unusual infections and also more viral infections due to sustained reduction of CD4-positive T lymphocytes. The following introduction of monoclonal antibody therapies, in particular alemtuzumab, further increased the immunodepression, increasing also infections which appeared more often in patients with recurrent neutropenia due to chemotherapy cycles. Epidemiological data regarding fungal infections in lymphoproliferative disorders are scarce. Italian SEIFEM group in a retrospective multicentre study regarding CLL patients reported an incidence of mycoses 0.5%; however, chronic lymphoproliferative disorders emerged as second haematological underlying disease after acute leukemia in a French study on aspergillosis; in particular CLL with aspergillosis accounted for a third of these chronic lymphoproliferative diseases presenting mould infection.

  14. INFECTIOUS COMPLICATIONS IN CHRONIC LYMPHOCYTIC LEUKEMIA

    Directory of Open Access Journals (Sweden)

    AnnaMaria Nosari

    2012-01-01

    Full Text Available

    Infectious complications have been known to be a major cause of morbidity and mortality in CLL patients who are predisposed to infections because of both the humoral immunodepression inherent to hematologic disease, which is related to stage and duration of CLL, and to further immunosuppression related to therapy. The majority of infections in CLL patients treated with alkilating agents is of bacterial origin. The immunodeficiency and natural infectious history of alkylator-resistant, corticosteroid-treated patients appears to have changed with the administration of purine analogs, which has been complicated by very severe and unusual infections and also more viral infections due to sustained reduction of CD4-positive T lymphocytes. The following introduction of monoclonal antibody therapies, in particular alemtuzumab, further increased the immunodepression, increasing also infections which appeared more often in patients with recurrent neutropenia due to chemotherapy cycles.

    Epidemiological data regarding fungal infections in lymphoproliferative disorders are scarce. Italian SEIFEM group in a retrospective multicentre study regarding CLL patients reported an incidence of mycoses 0.5%; however, chronic lymphoproliferative disorders emerged as second haematological underlying disease after acute leukemia in a French study on aspergillosis; in particular CLL with aspergillosis accounted for a third of these chronic lymphoproliferative diseases presenting mould infection.

  15. Cell-Specific Promoters Enable Lipid-Based Nanoparticles to Deliver Genes to Specific Cells of the Retina In Vivo.

    Science.gov (United States)

    Wang, Yuhong; Rajala, Ammaji; Cao, Binrui; Ranjo-Bishop, Michelle; Agbaga, Martin-Paul; Mao, Chuanbin; Rajala, Raju V S

    2016-01-01

    Non-viral vectors, such as lipid-based nanoparticles (liposome-protamine-DNA complex [LPD]), could be used to deliver a functional gene to the retina to correct visual function and treat blindness. However, one of the limitations of LPD is the lack of cell specificity, as the retina is composed of seven types of cells. If the same gene is expressed in multiple cell types or is absent from one desired cell type, LPD-mediated gene delivery to every cell may have off-target effects. To circumvent this problem, we have tested LPD-mediated gene delivery using various generalized, modified, and retinal cell-specific promoters. We achieved retinal pigment epithelium cell specificity with vitelliform macular dystrophy (VMD2), rod cell specificity with mouse rhodopsin, cone cell specificity with red/green opsin, and ganglion cell specificity with thymocyte antigen promoters. Here we show for the first time that cell-specific promoters enable lipid-based nanoparticles to deliver genes to specific cells of the retina in vivo. This work will inspire investigators in the field of lipid nanotechnology to couple cell-specific promoters to drive expression in a cell- and tissue-specific manner.

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

    Science.gov (United States)

    2016-08-25

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

  17. Mortality in ankylosing spondylitis

    DEFF Research Database (Denmark)

    Exarchou, Sofia; Lie, Elisabeth; Lindström, Ulf;

    2016-01-01

    OBJECTIVES: Information on mortality in ankylosing spondylitis (AS) is scarce. Our study therefore aimed to assess: (1) mortality in AS versus the general population, and (2) predictors of death in the AS population. METHODS: Nationwide cohorts of patients with AS diagnosed at rheumatology...

  18. Mortality associated with phaeochromocytoma

    NARCIS (Netherlands)

    Prejbisz, A.; Lenders, J.W.M.; Eisenhofer, G.; Januszewicz, A.

    2013-01-01

    Two major categories of mortality are distinguished in patients with phaeochromocytoma. First, the effects of excessive circulating catecholamines may result in lethal complications if the disease is not diagnosed and/or treated timely. The second category of mortality is related to development of m

  19. Chronic B-Cell Leukemias and Agent Orange

    Science.gov (United States)

    ... Enter ZIP code here Enter ZIP code here Chronic B-cell Leukemias and Agent Orange Veterans who ... receive VA health care and disability compensation. About chronic B-cell leukemias Leukemia is a cancer of ...

  20. Sorafenib in Treating Patients With Refractory or Relapsed Acute Leukemia, Myelodysplastic Syndromes, or Blastic Phase Chronic Myelogenous Leukemia

    Science.gov (United States)

    2015-04-27

    Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Megakaryoblastic Leukemia; Adult Acute Monoblastic Leukemia; Adult Acute Monocytic Leukemia; Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With Maturation; Adult Acute Myeloid Leukemia With Minimal Differentiation; Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); RUNX1-RUNX1T1; Adult Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-MLL; Adult Acute Myeloid Leukemia Without Maturation; Adult Acute Myelomonocytic Leukemia; Adult Acute Promyelocytic Leukemia With t(15;17)(q22;q12); PML-RARA; Adult Erythroleukemia; Adult Pure Erythroid Leukemia; Alkylating Agent-Related Acute Myeloid Leukemia; Blastic Phase; de Novo Myelodysplastic Syndrome; Previously Treated Myelodysplastic Syndrome; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndrome

  1. Pharm GKB: Leukemia, Promyelocytic, Acute [PharmGKB

    Lifescience Database Archive (English)

    Full Text Available Overview Alternate Names: Synonym APL - Acute promyelocytic leukaemia; APL - Acute ...promyelocytic leukemia; APML - Acute promyelocytic leukaemia; APML - Acute promyelocytic leukemia; Acute Promyelocytic Leukemia; Acut...e Promyelocytic Leukemias; Acute myeloid leukaemia, PML/RAR-alpha; Acute myeloid le...ukemia, PML/RAR-alpha; Acute myeloid leukemia, t(15;17)(q22;q11-12); Acute promye...locytic leukaemia (clinical); Acute promyelocytic leukaemia, FAB M3; Acute promyelocytic leukaemia, PML/RAR-alpha; Acute

  2. Beta-cell specific deletion of Dicer1 leads to defective insulin secretion and diabetes mellitus.

    Directory of Open Access Journals (Sweden)

    Martins Kalis

    Full Text Available Mature microRNAs (miRNAs, derived through cleavage of pre-miRNAs by the Dicer1 enzyme, regulate protein expression in many cell-types including cells in the pancreatic islets of Langerhans. To investigate the importance of miRNAs in mouse insulin secreting β-cells, we have generated mice with a β-cells specific disruption of the Dicer1 gene using the Cre-lox system controlled by the rat insulin promoter (RIP. In contrast to their normoglycaemic control littermates (RIP-Cre(+/- Dicer1(Δ/wt, RIP-Cre(+/-Dicer1(flox/flox mice (RIP-Cre Dicer1(Δ/Δ developed progressive hyperglycaemia and full-blown diabetes mellitus in adulthood that recapitulated the natural history of the spontaneous disease in mice. Reduced insulin gene expression and concomitant reduced insulin secretion preceded the hyperglycaemic state and diabetes development. Immunohistochemical, flow cytometric and ultrastructural analyses revealed altered islet morphology, marked decreased β-cell mass, reduced numbers of granules within the β-cells and reduced granule docking in adult RIP-Cre Dicer1(Δ/Δ mice. β-cell specific Dicer1 deletion did not appear to disrupt fetal and neonatal β-cell development as 2-week old RIP-Cre Dicer1(Δ/Δ mice showed ultrastructurally normal β-cells and intact insulin secretion. In conclusion, we have demonstrated that a β-cell specific disruption of the miRNAs network, although allowing for apparently normal β-cell development, leads to progressive impairment of insulin secretion, glucose homeostasis and diabetes development.

  3. Azacitidine With or Without Entinostat in Treating Patients With Myelodysplastic Syndromes, Chronic Myelomonocytic Leukemia, or Acute Myeloid Leukemia

    Science.gov (United States)

    2016-03-16

    Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); RUNX1-RUNX1T1; Adult Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-MLL; Adult Acute Promyelocytic Leukemia With t(15;17)(q22;q12); PML-RARA; Alkylating Agent-Related Acute Myeloid Leukemia; Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndrome; Previously Treated Myelodysplastic Syndrome; Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndrome; Untreated Adult Acute Myeloid Leukemia

  4. Designs of precoding for LTE TDD using cell specific reference signals

    DEFF Research Database (Denmark)

    Sun, Fan; Lu, Lu; Sørensen, Troels Bundgaard

    2010-01-01

    We design non-codebook-based Multiple-Input Multiple-Output (MIMO) precoding schemes using multiple cell-specific reference signals patterns for the time division duplex (TDD) mode of LTE, where channel reciprocity can be exploited. Previously proposed non-codebookbased precoding schemes typically......, and to simplify UE implementation, a precoder-estimation scheme and a codebook-assisted scheme are designed. The codebook-assisted scheme has the novelty of using a codebook in equalization. Link throughput simulations indicate that the codebook-assisted scheme is preferable compared to the precoder...

  5. Acute lymphoblastic leukemia presenting with gross hematuria

    OpenAIRE

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

    2007-01-01

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

  6. Epidemiology and Clinical Characteristics of Mucormycosis in Patients with Leukemia; A 21-year Experience from Southern Iran

    Directory of Open Access Journals (Sweden)

    Amene S. Sarvestani

    2014-01-01

    Full Text Available Objectives: To determine the epidemiological aspect of mucormycosis, the nature of malignancies complicated by mucormycosis, the initial site of involvement and the subsequent outcome. Methods: This was a cross-sectional study which was performed by reviewing the medical records of 95 patients with leukemia complicated with biopsy-proven mucormycosis admitted to the educational hospitals affiliated with Shiraz University of Medical Sciences over a 21-year period. We recorded demographic information including age and sex and disease characteristics such as type of leukemia, site of involvement, paraclinical findings at the time of admission and the outcome of the patients. The incidence of mucormycosis in leukemia was determined by identifying the number of leukemia patients diagnosed within the last 17 years. Results: The male to female ratio was 2.39:1 in of 95 patients studied. The overall incidence rate of mucormycosis was 4.27 per 100 leukemic patients in last 17 years which showed a decreasing trend from 2001 to 2011. The most frequent type of leukemia was acute myelogenous leukemia (AML which was found in 58 patients (61.5%. The most common site of initial tumor involvement was sinonasal (90.16%. The mortality rate was about 54%, compared to the mortality rate of about 43.24% in patients with best prognosis of AML. Conclusion: The incidence of mucormycosis in leukemia showed a decreasing trend in our country and its recent incidence is comparable to that of other regions. The best preventive method against this lethal infection is to modify and control the environment which reduces the risk of exposure to air-born fungal spores.

  7. The Sequence of Cyclophosphamide and Myeloablative Total Body Irradiation in Hematopoietic Cell Transplantation for Patients with Acute Leukemia.

    Science.gov (United States)

    Holter-Chakrabarty, Jennifer L; Pierson, Namali; Zhang, Mei-Jie; Zhu, Xiaochun; Akpek, Görgün; Aljurf, Mahmoud D; Artz, Andrew S; Baron, Frédéric; Bredeson, Christopher N; Dvorak, Christopher C; Epstein, Robert B; Lazarus, Hillard M; Olsson, Richard F; Selby, George B; Williams, Kirsten M; Cooke, Kenneth R; Pasquini, Marcelo C; McCarthy, Philip L

    2015-07-01

    Limited clinical data are available to assess whether the sequencing of cyclophosphamide (Cy) and total body irradiation (TBI) changes outcomes. We evaluated the sequence in 1769 (CyTBI, n = 948; TBICy, n = 821) recipients of related or unrelated hematopoietic cell transplantation who received TBI (1200 to 1500 cGY) for acute leukemia from 2003 to 2010. The 2 cohorts were comparable for median age, performance score, type of leukemia, first complete remission, Philadelphia chromosome-positive acute lymphoblastic leukemia, HLA-matched siblings, stem cell source, antithymocyte globulin use, TBI dose, and type of graft-versus-host disease (GVHD) prophylaxis. The sequence of TBI did not significantly affect transplantation-related mortality (24% versus 23% at 3 years, P = .67; relative risk, 1.01; P = .91), leukemia relapse (27% versus 29% at 3 years, P = .34; relative risk, .89, P = .18), leukemia-free survival (49% versus 48% at 3 years, P = .27; relative risk, .93; P = .29), chronic GVHD (45% versus 47% at 1 year, P = .39; relative risk, .9; P = .11), or overall survival (53% versus 52% at 3 years, P = .62; relative risk, .96; P = .57) for CyTBI and TBICy, respectively. Corresponding cumulative incidences of sinusoidal obstruction syndrome were 4% and 6% at 100 days (P = .08), respectively. This study demonstrates that the sequence of Cy and TBI does not impact transplantation outcomes and complications in patients with acute leukemia undergoing hematopoietic cell transplantation with myeloablative conditioning.

  8. Mortality after shoulder arthroplasty

    DEFF Research Database (Denmark)

    Amundsen, Alexander; Rasmussen, Jeppe Vejlgaard; Olsen, Bo Sanderhoff

    2016-01-01

    BACKGROUND: The primary aim was to quantify the 30-day, 90-day, and 1-year mortality rates after primary shoulder replacement. The secondary aims were to assess the association between mortality and diagnoses and to compare the mortality rate with that of the general population. METHODS: The study...... included 5853 primary operations reported to the Danish Shoulder Arthroplasty Registry between 2006 and 2012. Information about deaths was obtained from the Danish Cause of Death Register and the Danish Civil Registration System. Age- and sex-adjusted control groups were retrieved from Statistics Denmark...

  9. Mortality in Asia.

    Science.gov (United States)

    1981-01-01

    Although the general trend in mortality between 1950 and 1975 in South and East Asia has been downward, there is considerable country-to-country variation in the rate of decline. In countries where combined economic, social, and political circumstances resulted in controlling the disease spectrum (e.g., China, Malaysia, Sri Lanka), mortality levels declined to those seen in low-mortality countries. In most of the large countries of the region however, mortality declined at a slower rate, even slowing down considerably in the 1970's while the death rates remained high (e.g., India, Bangladesh, Thailand, Philippines); this slowing down of mortality level is attributed essentially to the poverty-stricken masses of society which were not able to take advantage of social, technological, and health-promoting behavioral changes conducive to mortality decline. Infant mortality levels, although declining since 1950, followed the same dismal pattern of the general mortality level. The rate varies from less than 10/1000 live births (Japan) to more than 140/1000 (Bangladesh, Laos, Nepal). Generally, rural areas exhibited higher infant mortality than urban areas. The level of child mortality declines with increases in the mother's educational level in Bangladesh, India, Indonesia, Sri Lanka, and Thailand. The largest decline in child mortality occurs when at least 1 parent has secondary education. The premature retardation of mortality decline is caused by several factors: economic development, nutrition and food supply, provision and adequacy of health services, and demographic trends. The outlook for the year 2000 for most of Asia's countries will depend heavily on significant population increases. In most countries, particularly in South Asia, population is expected to increase by 75%, much of it in rural areas and among poorer socioeconomic groups. In view of this, Asia's health planners and policymakers will have to develop health policies which will strike a balance

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

    Science.gov (United States)

    2017-03-27

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

  11. Infection and childhood leukemia: review of evidence

    Directory of Open Access Journals (Sweden)

    Raquel da Rocha Paiva Maia

    2013-12-01

    Full Text Available OBJECTIVE : To analyze studies that evaluated the role of infections as well as indirect measures of exposure to infection in the risk of childhood leukemia, particularly acute lymphoblastic leukemia. METHODS : A search in Medline, Lilacs, and SciELO scientific publication databases initially using the descriptors “childhood leukemia” and “infection” and later searching for the words “childhood leukemia” and “maternal infection or disease” or “breastfeeding” or “daycare attendance” or “vaccination” resulted in 62 publications that met the following inclusion criteria: subject aged ≤ 15 years; specific analysis of cases diagnosed with acute lymphoblastic leukemia or total leukemia; exposure assessment of mothers’ or infants’ to infections (or proxy of infection, and risk of leukemia. RESULTS : Overall, 23 studies that assessed infections in children support the hypothesis that occurrence of infection during early childhood reduces the risk of leukemia, but there are disagreements within and between studies. The evaluation of exposure to infection by indirect measures showed evidence of reduced risk of leukemia associated mainly with daycare attendance. More than 50.0% of the 16 studies that assessed maternal exposure to infection observed increased risk of leukemia associated with episodes of influenza, pneumonia, chickenpox, herpes zoster, lower genital tract infection, skin disease, sexually transmitted diseases, Epstein-Barr virus, and Helicobacter pylori . CONCLUSIONS : Although no specific infectious agent has been identified, scientific evidence suggests that exposure to infections has some effect on childhood leukemia etiology.

  12. Integrative characterization of germ cell-specific genes from mouse spermatocyte UniGene library

    Directory of Open Access Journals (Sweden)

    Eddy Edward M

    2007-07-01

    Full Text Available Abstract Background The primary regulator of spermatogenesis, a highly ordered and tightly regulated developmental process, is an intrinsic genetic program involving male germ cell-specific genes. Results We analyzed the mouse spermatocyte UniGene library containing 2155 gene-oriented transcript clusters. We predict that 11% of these genes are testis-specific and systematically identified 24 authentic genes specifically and abundantly expressed in the testis via in silico and in vitro approaches. Northern blot analysis disclosed various transcript characteristics, such as expression level, size and the presence of isoform. Expression analysis revealed developmentally regulated and stage-specific expression patterns in all of the genes. We further analyzed the genes at the protein and cellular levels. Transfection assays performed using GC-2 cells provided information on the cellular characteristics of the gene products. In addition, antibodies were generated against proteins encoded by some of the genes to facilitate their identification and characterization in spermatogenic cells and sperm. Our data suggest that a number of the gene products are implicated in transcriptional regulation, nuclear integrity, sperm structure and motility, and fertilization. In particular, we found for the first time that Mm.333010, predicted to contain a trypsin-like serine protease domain, is a sperm acrosomal protein. Conclusion We identify 24 authentic genes with spermatogenic cell-specific expression, and provide comprehensive information about the genes. Our findings establish a new basis for future investigation into molecular mechanisms underlying male reproduction.

  13. Non-overlapping progesterone receptor cistromes contribute to cell-specific transcriptional outcomes.

    Directory of Open Access Journals (Sweden)

    Christine L Clarke

    Full Text Available The transcriptional effects of the ovarian hormone progesterone are pleiotropic, and binding to DNA of the nuclear progesterone receptor (PR, a ligand-activated transcription factor, results in diverse outcomes in a range of target tissues. To determine whether distinct patterns of genomic interaction of PR contribute to the cell specificity of the PR transcriptome, we have compared the genomic binding sites for PR in breast cancer cells and immortalized normal breast cells. PR binding was correlated with transcriptional outcome in both cell lines, with 60% of progestin-regulated genes associated with one or more PR binding regions. There was a remarkably low overlap between the PR cistromes of the two cell lines, and a similarly low overlap in transcriptional targets. A conserved PR binding element was identified in PR binding regions from both cell lines, but there were distinct patterns of enrichment of known cofactor binding motifs, with FOXA1 sites over-represented in breast cancer cell binding regions and NF1 and AP-1 motifs uniquely enriched in the immortalized normal line. Downstream analyses suggested that differential cofactor availability may generate these distinct PR cistromes, indicating that cofactor levels may modulate PR specificity. Taken together these data suggest that cell-specificity of PR binding is determined by the coordinated effects of key binding cofactors.

  14. Erythroid cell-specific alpha-globin gene regulation by the CP2 transcription factor family.

    Science.gov (United States)

    Kang, Ho Chul; Chae, Ji Hyung; Lee, Yeon Ho; Park, Mi-Ae; Shin, June Ho; Kim, Sung-Hyun; Ye, Sang-Kyu; Cho, Yoon Shin; Fiering, Steven; Kim, Chul Geun

    2005-07-01

    We previously demonstrated that ubiquitously expressed CP2c exerts potent erythroid-specific transactivation of alpha-globin through an unknown mechanism. This mechanism is reported here to involve specific CP2 splice variants and protein inhibitor of activated STAT1 (PIAS1). We identify a novel murine splice isoform of CP2, CP2b, which is identical to CP2a except that it has an additional 36 amino acids encoded by an extra exon. CP2b has an erythroid cell-specific transcriptional activation domain, which requires the extra exon and can form heteromeric complexes with other CP2 isoforms, but lacks the DNA binding activity found in CP2a and CP2c. Transcriptional activation of alpha-globin occurred following dimerization between CP2b and CP2c in erythroid K562 and MEL cells, but this dimerization did not activate the alpha-globin promoter in nonerythroid 293T cells, indicating that an additional erythroid factor is missing in 293T cells. PIAS1 was confirmed as a CP2 binding protein by the yeast two-hybrid screen, and expression of CP2b, CP2c, and PIAS1 in 293T cell induced alpha-globin promoter activation. These results show that ubiquitously expressed CP2b exerts potent erythroid cell-specific alpha-globin gene expression by complexing with CP2c and PIAS1.

  15. Laser capture microdissection in Ectocarpus siliculosus: the pathway to cell-specific transcriptomics in brown algae

    Directory of Open Access Journals (Sweden)

    Denis eSaint-Marcoux

    2015-02-01

    Full Text Available Laser capture microdissection (LCM facilitates the isolation of individual cells from tissue sections, and when combined with RNA amplification techniques, it is an extremely powerful tool for examining genome-wide expression profiles in specific cell-types. LCM has been widely used to address various biological questions in both animal and plant systems, however, no attempt has been made so far to transfer LCM technology to macroalgae. Macroalgae are a collection of widespread eukaryotes living in fresh and marine water. In line with the collective effort to promote molecular investigations of macroalgal biology, here we demonstrate the feasibility of using LCM and cell-specific transcriptomics to study development of the brown alga, Ectocarpus siliculosus. We describe a workflow comprising cultivation and fixation of algae on glass slides, laser microdissection, and RNA amplification. To illustrate the effectiveness of the procedure, we show qPCR data and metrics obtained from cell-specific transcriptomes generated from both upright and prostrate filaments of Ectocarpus.

  16. Cancer cell specific cytotoxic gene expression mediated by ARF tumor suppressor promoter constructs

    Energy Technology Data Exchange (ETDEWEB)

    Kurayoshi, Kenta [Department of Bioscience, School of Science and Technology, Kwansei Gakuin University, 2-1 Gakuen, Sanda, Hyogo 669-1337 (Japan); Ozono, Eiko [Centre for Molecular Oncology, Barts Cancer Institute, Queen Mary, University of London, John Vane Science Centre, Charterhouse Square, London EC1M 6BQ (United Kingdom); Iwanaga, Ritsuko; Bradford, Andrew P. [Department of Obstetrics and Gynecology, University of Colorado School of Medicine, Anschutz Medical Campus, 12800 East 19th Avenue, Aurora, CO 80045 (United States); Komori, Hideyuki [Center for Stem Cell Biology, Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109 (United States); Ohtani, Kiyoshi, E-mail: btm88939@kwansei.ac.jp [Department of Bioscience, School of Science and Technology, Kwansei Gakuin University, 2-1 Gakuen, Sanda, Hyogo 669-1337 (Japan)

    2014-07-18

    Highlights: • ARF promoter showed higher responsiveness to deregulated E2F activity than the E2F1 promoter. • ARF promoter showed higher cancer cell-specificity than E2F1 promoter to drive gene expression. • HSV-TK driven by ARF promoter showed higher cancer cell-specific cytotoxicity than that driven by E2F1 promoter. - Abstract: In current cancer treatment protocols, such as radiation and chemotherapy, side effects on normal cells are major obstacles to radical therapy. To avoid these side effects, a cancer cell-specific approach is needed. One way to specifically target cancer cells is to utilize a cancer specific promoter to express a cytotoxic gene (suicide gene therapy) or a viral gene required for viral replication (oncolytic virotherapy). For this purpose, the selected promoter should have minimal activity in normal cells to avoid side effects, and high activity in a wide variety of cancers to obtain optimal therapeutic efficacy. In contrast to the AFP, CEA and PSA promoters, which have high activity only in a limited spectrum of tumors, the E2F1 promoter exhibits high activity in wide variety of cancers. This is based on the mechanism of carcinogenesis. Defects in the RB pathway and activation of the transcription factor E2F, the main target of the RB pathway, are observed in almost all cancers. Consequently, the E2F1 promoter, which is mainly regulated by E2F, has high activity in wide variety of cancers. However, E2F is also activated by growth stimulation in normal growing cells, suggesting that the E2F1 promoter may also be highly active in normal growing cells. In contrast, we found that the tumor suppressor ARF promoter is activated by deregulated E2F activity, induced by forced inactivation of pRB, but does not respond to physiological E2F activity induced by growth stimulation. We also found that the deregulated E2F activity, which activates the ARF promoter, is detected only in cancer cell lines. These observations suggest that ARF promoter

  17. Mortality in spondylarthritis.

    Science.gov (United States)

    Prati, Clément; Claudepierre, Pascal; Pham, Thao; Wendling, Daniel

    2011-10-01

    Ankylosing spondylitis (AS) is a chronic inflammatory joint disease that can lead to chronic pain in axial and peripheral joints and to functional impairments after several years. Excess mortality has been reported in patients with AS. We reviewed recent studies of patients with AS who were treated and monitored according to the improved methods developed in the past few years, without radiation therapy. Our results do not support excess mortality in these patients. Long-term follow-up data from patients enrolled in biologics registries will provide additional information. Cardiovascular disease is the leading cause of death in patients with AS, as in the general population. However, the cardiovascular mortality rate may be slightly increased in patients with AS, probably as a result of dyslipidemia and early endothelial dysfunction. Similarly, and as expected, there is excess mortality related to the spinal disease itself and to renal and gastrointestinal disease. More surprisingly, alcohol abuse and injury or suicide cause excess mortality compared to the general population. In the absence of radiation or radium-224 therapy, and regardless of the other treatments used, the evidence does not support an increased rate of lymphoma or other malignancies compared to the general population. In this review, we discuss the causes and rates of mortality in patients with AS.

  18. Maternal acute lymphoctic leukemia with rearrangement of the mixed lineage leukemia gene occurring during pregnancy.

    Science.gov (United States)

    Aljurf, Mahmoud; Nassar, Amr; Saleh, Abu J; Almhareb, Fahed; Alzahrani, Hazzaa; Walter, Claudia; Bakr, Mohammad; Ahmed, Syed Osman; Chaudhri, Naeem

    2009-01-01

    Acute lymphoblastic leukemia (ALL) is a relatively rare disease during pregnancy, accounting for about 15% of all cases of pregnancy-associated leukemia. Although mixed lineage leukemia gene (MLL) rearrangement is the dominant genetic aberration in infantile acute leukemia, the occurrence of MLL gene rearrangement in maternal ALL occurring during pregnancy has not been reported. Out of 31 cases of maternal leukemia diagnosed during pregnancy at our institution, 5 were ALL cases. Three of the 5 patients had MLL gene rearrangement. The data for these 5 patients are presented in this report. We believe that the association of MLL gene rearrangement with maternal leukemia is biologically plausible and this observation needs to be validated in a larger cohort of pregnancy-associated maternal leukemia cases.

  19. Cancer incidence, hospital morbidity, and mortality in young adults in Brazil.

    Science.gov (United States)

    Santos, Sabrina da Silva; Melo, Leticia Rodrigues; Koifman, Rosalina Jorge; Koifman, Sergio

    2013-05-01

    There are still relatively few studies in the world on cancer incidence and mortality in young adults. The current study aimed to explore cancer distribution in young adults in Brazil. A descriptive study was conducted on cancer incidence (selected State capitals), hospital morbidity, and mortality (Brazil and selected capitals) in the 20-24-year age strata in 2000-2002, and trends in cancer mortality rates in Brazil in 1980-2008 in the same population. Testicular cancer was the principal anatomical site in young adult males; in young adult women, the main sites were thyroid, uterine cervix, and Hodgkin disease. Brain cancer was the principal cause of death from cancer in both sexes, and time trends in mortality showed an increase in mortality from brain cancer in men and from lymphocytic leukemia in both sexes. As a whole, the results show an epidemiological pattern of cancer in young adults with regional distribution characteristics.

  20. Conventional chemotherapy for acute myeloid leukemia: a Brazilian experience

    Directory of Open Access Journals (Sweden)

    Kátia Borgia Barbosa Pagnano

    2000-11-01

    Full Text Available CONTEXT: Young patients affected by acute myeloid leukemia (AML achieve complete remission (CR using conventional chemotherapy in about 55-85%. However, 30% of patients fail to achieve CR and the remission duration is often only about 12 months. More intensive treatment after CR seems to be necessary in order to maintain CR and obtain a definitive cure. In Brazil, few reports have been published on this important subject. OBJECTIVE: The aim of this study was to describe a Brazilian experience in the treatment of "de novo" acute myeloid leukemia (AML in younger adult patients (age < 60 years. DESIGN: Retrospective analysis. SETTING: University Hospital, Hematology and Hemotherapy Center, State University of Campinas, Brazil. PARTICIPANTS: Newly diagnosed cases of "de novo" AML in the period from January 1994 to December 1998 were evaluated retrospectively, in relation to response to treatment, overall survival (OS and disease free survival (DFS. Cases with acute promyelocytic leukemia (APL were also included in this analysis. RESULTS: On the basis of an intention to treat, 78 cases of AML, including 17 cases of APL, were evaluated. The overall median follow-up was 272 days. The complete remission (CR rate was 63.6% in the AML group (excluding APL and 78% in the APL group. The 5-year estimated disease-free survival (DFS was 80% for the APL group and 34% for the AML group (P = 0.02. The 5-year estimated overall survival (OS was 52% for the APL group and 20.5% for the AML group, respectively (P = NS. Relapse was observed in 12/39 (30.7% patients with AML and 1/11 (9% with APL. CONCLUSIONS: These results are similar to those reported in the literature. However, relapse and mortality rates remain high, and a search for more aggressive strategies in order to prevent relapse is recommended.

  1. The discovery and early understanding of leukemia

    NARCIS (Netherlands)

    Kampen, Kim R.

    2012-01-01

    The early history of leukemia reaches back 200 years. In 1811, Peter Cullen defined a case of splenitis acutus with unexplainable milky blood. Alfred Velpeau defined the leukemia associated symptoms, and observed pus in the blood vessels (1825). Alfred Donne detected a maturation arrest of the white

  2. SnapShot: chronic lymphocytic leukemia.

    Science.gov (United States)

    Ciccone, Maria; Ferrajoli, Alessandra; Keating, Michael J; Calin, George A

    2014-11-10

    Chronic lymphocytic leukemia (CLL) is the most common leukemia among adults in western countries. This SnapShot depicts the origins and evolution of this B cell malignancy, describes prognostic factors and CLL animal models, and illustrates therapies in preclinical and clinical development against CLL.

  3. Successful pregnancy in acute promyelocytic leukemia.

    Science.gov (United States)

    Alegre, A; Chunchurreta, R; Rodriguez-Alarcon, J; Cruz, E; Prada, M

    1982-01-01

    A successful pregnancy with a normal baby in a woman with acute promyelocytic leukemia treated with daunorubicin from the ninth week of gestation is reported. Daunorubicin is an effective agent against this leukemia during pregnancy. That daunorubicin may be safely used, when required during the early gestation, is suggested.

  4. Treatment of Aggressive NK-Cell Leukemia

    DEFF Research Database (Denmark)

    Boysen, Anders Kindberg; Jensen, Paw; Johansen, Preben;

    2011-01-01

    Aggressive NK-cell leukemia is a rare malignancy with neoplastic proliferation of natural killer cells. It often presents with constitutional symptoms, a rapid declining clinical course, and a poor prognosis with a median survival of a few months. The disease is usually resistant to cytotoxic...... literature concerning treatment of aggressive NK-cell leukemia....

  5. Fungal natural products targeting chronic lymphocytic leukemia

    DEFF Research Database (Denmark)

    Bladt, Tanja Thorskov; Kildgaard, Sara; Knudsen, Peter Boldsen

    2012-01-01

    Chronic lymphocytic leukemia (CLL) is the most common leukemia in adults from the western world. No curative treatments of CLL are presently known so the treatment strategy today is primarily to prolong patient survival,1 why we have initiated new activities towards discovery of novel compounds w...

  6. Proximity to mining industry and cancer mortality.

    Science.gov (United States)

    Fernández-Navarro, Pablo; García-Pérez, Javier; Ramis, Rebeca; Boldo, Elena; López-Abente, Gonzalo

    2012-10-01

    Mining installations are releasing toxic substances into the environment which could pose a health problem to populations in their vicinity. We sought to investigate whether there might be excess cancer-related mortality in populations residing in towns lying in the vicinity of Spanish mining industries governed by the Integrated Pollution Prevention and Control Directive, and the European Pollutant Release and Transfer Register Regulation, according to the type of extraction method used. An ecologic study was designed to examine municipal mortality due to 32 types of cancer, across the period 1997 through 2006. Population exposure to pollution was estimated on the basis of distance from town of residence to pollution source. Poisson regression models, using the Bayesian conditional autoregressive model proposed by Besag, York and Molliè and Integrated Nested Laplace Approximations for Bayesian inference, were used: to analyze risk of dying from cancer in a 5-kilometer zone around mining installations; effect of type of industrial activity; and to conduct individual analyses within a 50-kilometer radius of each installation. Excess mortality (relative risk, 95% credible interval) of colorectal cancer (1.097, 1.041-1.157), lung cancer (1.066, 1.009-1.126) specifically related with proximity to opencast coal mining, bladder cancer (1.106, 1.016-1.203) and leukemia (1.093, 1.003-1.191) related with other opencast mining installations, was detected among the overall population in the vicinity of mining installations. Other tumors also associated in the stratified analysis by type of mine, were: thyroid, gallbladder and liver cancers (underground coal installations); brain cancer (opencast coal mining); stomach cancer (coal and other opencast mining installations); and myeloma (underground mining installations). The results suggested an association between risk of dying due to digestive, respiratory, hematologic and thyroid cancers and proximity to Spanish mining

  7. Oogenesis requires germ cell-specific transcriptional regulators Sohlh1 and Lhx8

    Science.gov (United States)

    Pangas, Stephanie A.; Choi, Youngsok; Ballow, Daniel J.; Zhao, Yangu; Westphal, Heiner; Matzuk, Martin M.; Rajkovic, Aleksandar

    2006-01-01

    Mammalian oogenesis requires oocyte-specific transcriptional regulators. The full complement of oocyte-specific transcription factors is unknown. Here, we describe the finding that Sohlh1, a spermatogenesis and oogenesis basic helix–loop–helix transcription factor in females, is preferentially expressed in oocytes and required for oogenesis. Sohlh1 disruption perturbs follicular formation in part by causing down-regulation of two genes that are known to disrupt folliculogenesis: newborn ovary homeobox gene (Nobox) and factor in the germ-line alpha (Figla). In addition, we show that Lhx8 is downstream of Sohlh1 and critical in fertility. Thus, Sohlh1 and Lhx8 are two germ cell-specific, critical regulators of oogenesis. PMID:16690745

  8. Identification of cell-specific targets of sumoylation during mouse spermatogenesis.

    Science.gov (United States)

    Xiao, Yuxuan; Pollack, Daniel; Andrusier, Miriam; Levy, Avi; Callaway, Myrasol; Nieves, Edward; Reddi, Prabhakara; Vigodner, Margarita

    2016-02-01

    Recent findings suggest diverse and potentially multiple roles of small ubiquitin-like modifier (SUMO) in testicular function and spermatogenesis. However, SUMO targets remain uncharacterized in the testis due to the complex multicellular nature of testicular tissue, the inability to maintain and manipulate spermatogenesis in vitro, and the technical challenges involved in identifying low-abundance endogenous SUMO targets. In this study, we performed cell-specific identification of sumoylated proteins using concentrated cell lysates prepared with de-sumoylation inhibitors from freshly purified spermatocytes and spermatids. One-hundred and twenty proteins were uniquely identified in the spermatocyte and/or spermatid fractions. The identified proteins are involved in the regulation of transcription, stress response, microRNA biogenesis, regulation of major enzymatic pathways, nuclear-cytoplasmic transport, cell-cycle control, acrosome biogenesis, and other processes. Several proteins with important roles during spermatogenesis were chosen for further characterization by co-immunoprecipitation, co-localization, and in vitro sumoylation studies. GPS-SUMO Software was used to identify consensus and non-consensus sumoylation sites within the amino acid sequences of the proteins. The analyses confirmed the cell-specific sumoylation and/or SUMO interaction of several novel, previously uncharacterized SUMO targets such as CDK1, RNAP II, CDC5, MILI, DDX4, TDP-43, and STK31. Furthermore, several proteins that were previously identified as SUMO targets in somatic cells (KAP1 and MDC1) were identified as SUMO targets in germ cells. Many of these proteins have a unique role in spermatogenesis and during meiotic progression. This research opens a novel avenue for further studies of SUMO at the level of individual targets.

  9. Foxi3 deficiency compromises hair follicle stem cell specification and activation

    Science.gov (United States)

    Shirokova, Vera; Biggs, Leah C.; Jussila, Maria; Ohyama, Takahiro; Groves, Andrew K.; Mikkola, Marja L.

    2017-01-01

    The hair follicle is an ideal system to study stem cell specification and homeostasis due to its well characterized morphogenesis and stereotypic cycles of stem cell activation upon each hair cycle to produce a new hair shaft. The adult hair follicle stem cell niche consists of two distinct populations, the bulge and the more activation-prone secondary hair germ. Hair follicle stem cells are set aside during early stages of morphogenesis. This process is known to depend on the Sox9 transcription factor, but otherwise the establishment of the hair follicle stem cell niche is poorly understood. Here we show that that mutation of Foxi3, a Forkhead family transcription factor mutated in several hairless dog breeds, compromises stem cell specification. Further, loss of Foxi3 impedes hair follicle downgrowth and progression of the hair cycle. Genome-wide profiling revealed a number of downstream effectors of Foxi3 including transcription factors with a recognized function in hair follicle stem cells such as Lhx2, Runx1, and Nfatc1, suggesting that the Foxi3 mutant phenotype results from simultaneous downregulation of several stem cell signature genes. We show that Foxi3 displays a highly dynamic expression pattern during hair morphogenesis and cycling, and identify Foxi3 as a novel secondary hair germ marker. Absence of Foxi3 results in poor hair regeneration upon hair plucking, and a sparse fur phenotype in unperturbed mice that exacerbates with age, caused by impaired secondary hair germ activation leading to progressive depletion of stem cells. Thus, Foxi3 regulates multiple aspects of hair follicle development and homeostasis. PMID:26992132

  10. Identification of cell-specific targets of sumoylation during mouse spermatogenesis

    Science.gov (United States)

    Xiao, Yuxuan; Pollack, Daniel; Andrusier, Miriam; Levy, Avi; Callaway, Myrasol; Nieves, Edward; Reddi, Prabhakara; Vigodner, Margarita

    2015-01-01

    Recent findings suggest diverse and potentially multiple roles of SUMO in testicular function and spermatogenesis. However, SUMO targets remain uncharacterized in the testis due to the complex multicellular nature of testicular tissue, the inability to maintain and manipulate spermatogenesis in vitro, and the technical challenges involved in identifying low-abundance endogenous SUMO targets. In this study, we performed cell-specific identification of sumoylated proteins using concentrated cell lysates prepared with de-sumoylation inhibitors from freshly purified spermatocytes and spermatids. One-hundred and twenty proteins were uniquely identified in the spermatocyte and/or spermatid fractions. The identified proteins are involved in the regulation of transcription, stress response, microRNA biogenesis, regulation of major enzymatic pathways, nuclear-cytoplasmic transport, cell cycle control, acrosome biogenesis, and other processes. Several proteins with important roles during spermatogenesis were chosen for further characterization by co-immunoprecipitation, co-localization and in-vitro sumoylation studies. GPS-SUMO software was used to identify consensus and non-consensus sumoylation sites within the amino acid sequences of the proteins. The analyses confirmed the cell-specific sumoylation and/or SUMO interaction of several novel, previously uncharacterized SUMO targets such as CDK1, RNAP II, CDC5, MILI, DDX4, TDP-43 and STK31. Furthermore, several proteins that were previously identified as SUMO targets in somatic cells (e.g., KAP1, MDC1) were identified as SUMO targets in germ cells. Many of these proteins have a unique role in spermatogenesis and during meiotic progression. This research opens a novel avenue for further studies of SUMO at the level of individual targets. PMID:26701181

  11. Combinatorial synthesis and screening of cancer cell-specific nanomedicines targeted via phage fusion proteins

    Directory of Open Access Journals (Sweden)

    James W. Gillespie

    2015-06-01

    Full Text Available Active tumor targeting of nanomedicines has recently shown significant improvements in the therapeutic activity of currently existing drug delivery systems, such as liposomal doxorubicin (Doxil/Caelyx/Lipodox. Previously, we have shown that isolated pVIII major coat proteins of the fd tet filamentous phage vector, containing cancer cell-specific peptide fusions at their N terminus, can be used as active targeting ligands in a liposomal doxorubicin delivery system in vitro and in vivo. Here, we show a novel major coat protein isolation procedure in 2-propanol that allows spontaneous incorporation of the hydrophobic protein core into preformed liposomal doxorubicin with minimal damage or drug loss while still retaining the targeting ligand exposed for cell-specific targeting. Using a panel of 12 structurally unique ligands with specificity towards breast, lung, and/or pancreatic cancer, we showed the feasibility of pVIII major coat proteins to significantly increase the throughput of targeting ligand screening in a common nanomedicine core. Phage protein-modified Lipodox samples showed an average doxorubicin recovery of 82.8% across all samples with 100% of protein incorporation in the correct orientation (N-terminus exposed. Following cytotoxicity screening in a doxorubicin-sensitive breast cancer line (MCF-7, three major groups of ligands were identified. Ligands showing the most improved cytotoxicity included: DMPGTVLP, ANGRPSMT, VNGRAEAP, and ANDVYLD showing a 25-fold improvement (p < 0.05 in toxicity. Similarly DGQYLGSQ, ETYNQPYL, and GSSEQLYL ligands with specificity towards a doxorubicin-insensitive pancreatic cancer line (PANC-1 showed significant increases in toxicity (2-fold; p < 0.05. Thus, we demonstrated proof-of-concept that pVIII major coat proteins can be screened in significantly higher throughput to identify novel ligands displaying improved therapeutic activity in a desired cancer phenotype.

  12. Racial-Sex Disparities--A Challenging Battle Against Cancer Mortality in the USA.

    Science.gov (United States)

    Fu, Wenjiang J

    2015-06-01

    Decline in US cancer mortality has recently been reported, based on either pooled mortality of all cancer sites or age-adjusted mortality rates of specific sites. While the former could be dominated by a few cancer sites and would not reflect that of other sites, the latter used the US 2000 Population as reference for age-standardization, which was lack of justification. This study aimed to examine US cancer mortality trend and disparities in sites, races, and sex. We studied cancer incidence-based mortality by race and sex from 1974 to 2008 of cervix, prostate, colon and rectum, lung, leukemia, liver, pancreas, and stomach in the Surveillance, Epidemiology, and End Results database. We developed a model-based mortality rate and examined rate ratio of each calendar period to the first period within each race-sex group. Cancer mortality of cervix, colon and rectum, leukemia, and stomach declined in all groups. Prostate cancer increased first in all racial groups and decreased thereafter at different pace. Lung cancer declined among males of all races but increased among females. Liver cancer increased steadily fast among white and black females, doubled in whites and black males, and climbed slowly in other races. Pancreas cancer declined among black males and females, and changed little among others. Cancer mortality trend presents heterogeneity across sites, races, and sex. Recently observed mortality decline may not reflect every cancer site or group. More effort needs to focus on specific race-sex groups that had increasing lung and liver cancer mortality.

  13. Cancer mortality patterns among hairdressers and barbers in 24 US states, 1984 to 1995.

    Science.gov (United States)

    Lamba, A B; Ward, M H; Weeks, J L; Dosemeci, M

    2001-03-01

    We evaluated cancer mortality patterns among hairdressers and barbers, according to occupation, coded on 7.2 million death certificates in 24 states from 1984 to 1995. Of the 38,721 deaths among white and black hairdressers and barbers of both sexes, 9495 were from all malignant neoplasms. Mortality odds ratios were significantly elevated for all malignant neoplasms, lung cancer, and all lymphatic and hemopoietic cancers among black and white female hairdressers. White female hairdressers had significant excess mortality from cancers of the stomach, colon, pancreas, breast, and bladder and from non-Hodgkin's lymphoma and lymphoid leukemia; mortality from these cancers was also elevated among black female hairdressers. White male hairdressers had significantly elevated mortality from non-melanoma skin cancer and non-Hodgkin's lymphoma. Mortality from all malignant neoplasms, although significantly elevated among both white and black female hairdressers, was significantly below the null for white male hairdressers. Black and white male barbers had significantly elevated mortality from stomach and pharyngeal cancer, respectively. A significant deficit in mortality from all neoplasms and cancers of the pancreas, lung, and prostate was noted for white male barbers. This large study of cancer mortality among hairdressers and barbers showed some differences in mortality patterns by gender and race. Further studies are required to determine if specific occupational exposures may explain some of the elevated cancer rates.

  14. The expression and clinical significance of survivin gene in leukemia

    Institute of Scientific and Technical Information of China (English)

    王艳

    2006-01-01

    Objective To investigate the expression of survivin in leukemia and the prognostic significance in acute leukemia(AL). Methods The expression of survivin mRNA was measured in 105 AL and 21 chronic myelogenous leukemia (CML) patients with semi-quantity reverse transcription (RT)-PCR.15 adults were tested as normal

  15. 42 CFR 81.24 - Guidelines for leukemia.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 1 2010-10-01 2010-10-01 false Guidelines for leukemia. 81.24 Section 81.24 Public... Causation § 81.24 Guidelines for leukemia. (a) For claims involving leukemia, DOL will calculate one or more probability of causation estimates from up to three of the four alternate leukemia risk models included...

  16. Veliparib and Temozolomide in Treating Patients With Acute Leukemia

    Science.gov (United States)

    2016-12-19

    Accelerated Phase of Disease; Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(8;21); (q22; q22.1); RUNX1-RUNX1T1; Adult Acute Myeloid Leukemia With t(9;11)(p22.3;q23.3); MLLT3-KMT2A; Adult Acute Promyelocytic Leukemia With PML-RARA; Adult B Acute Lymphoblastic Leukemia; Adult B Acute Lymphoblastic Leukemia With t(9;22)(q34.1;q11.2); BCR-ABL1; Adult T Acute Lymphoblastic Leukemia; Alkylating Agent-Related Acute Myeloid Leukemia; Blastic Phase; Chronic Myelomonocytic Leukemia; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Disease; Secondary Acute Myeloid Leukemia; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Myeloid Leukemia

  17. Molecular Therapeutic Approaches for Pediatric Acute Myeloid Leukemia

    Directory of Open Access Journals (Sweden)

    Sarah K Tasian

    2014-03-01

    Full Text Available Approximately two thirds of children with acute myeloid leukemia (AML are cured with intensive multi-agent chemotherapy. However, primary chemorefractory and relapsed AML remains a significant source of childhood cancer mortality, highlighting the need for new therapies. Further therapy intensification with traditional cytotoxic agents is not feasible given the potential for significant toxicity to normal tissues with conventional chemotherapy and the risk for long-term end-organ dysfunction. Significant emphasis has been placed upon the development of molecularly targeted therapeutic approaches for adults and children with high-risk subtypes of AML with the goal of improving remission induction and minimizing relapse. Several promising agents are currently in clinical testing or late preclinical development for AML, including monoclonal antibodies against leukemia cell surface proteins, kinase inhibitors, proteasome inhibitors, epigenetic agents, and chimeric antigen receptor engineered T cell immunotherapies. Many of these therapies have been specifically tested in children with relapsed/refractory AML via phase 1 and 2 trials with a smaller number of new agents under phase 3 evaluation for children with de novo AML. Although successful identification and implementation of new drugs for children with AML remains a formidable challenge, enthusiasm for novel molecular therapeutic approaches is great given the potential for significant clinical benefit for children who will otherwise fail standard therapy.

  18. Chemotherapy for acute leukemia during pregnancy. Five case reports.

    Science.gov (United States)

    Fassas, A; Kartalis, G; Klearchou, N; Tsatalas, K; Sinacos, Z; Mantalenakis, S

    1984-01-01

    We summarize the cases of four women with acute myeloid leukemia (AML) and of one with acute lymphoid leukemia (ALL) presenting in the first, second and third trimester of pregnancy. Remission of AML was induced by doxorubicin, vincristine, and cytosine arabinoside. The ALL case was treated with vincristine and prednisone initially, and subsequently with vindesine for maintenance. Four patients entered a complete (3 AML and the ALL case), and one (AML) a partial remission. This patient was delivered of a normal, 3140 g, male infant by Caesarian section in the 38th gestational week and 1 month later she died of her disease. One patient (AML, promyelocytic type) who presented in the 10th week of pregnancy underwent elective abortion while in remission after induction treatment. The patient with ALL gave birth to a normal, full-term, male infant by Caesarian section. The two other patients (AML) had spontaneous deliveries of normal male infants in the 37th and 38th weeks of pregnancy. Growth and development of three of the children are normal at 12, 36, and 37 months of life while the fourth child was lost to follow-up evaluation. The disease relapsed in all mothers but they are still alive at 15 (ALL), 37, and 42 months after diagnosis. We feel that current chemotherapy could improve the high post-partum maternal mortality rate and the chance of producing live babies without excessive risk to the fetus or the mother, even if administered relatively early in the course of pregnancy.

  19. IDH mutations in acute myeloid leukemia.

    Science.gov (United States)

    Rakheja, Dinesh; Konoplev, Sergej; Medeiros, L Jeffrey; Chen, Weina

    2012-10-01

    Acute myeloid leukemia is a heterogeneous group of diseases. Mutations of the isocitrate dehydrogenase (IDH) genes represent a novel class of point mutations in acute myeloid leukemia. These mutations prevent oxidative decarboxylation of isocitrate to α-ketoglutarate and confer novel enzymatic activity, facilitating the reduction of α-ketoglutarate to d-2-hydroxyglutarate, a putative oncometabolite. IDH1/IDH2 mutations are heterozygous, and their combined frequency is approximately 17% in unselected acute myeloid leukemia cases, 27% in cytogenetically normal acute myeloid leukemia cases, and up to 67% in acute myeloid leukemia cases with cuplike nuclei. These mutations are largely mutually exclusive. Despite many similarities of IDH1 and IDH2 mutations, it is possible that they represent distinct molecular or clinical subgroups of acute myeloid leukemia. All known mutations involve arginine (R), in codon 132 of IDH1 or codon 140 or 172 of IDH2. IDH1(R132) and IDH2(R140) mutations are frequently accompanied by normal cytogenetics and NPM1 mutation, whereas IDH2(R172) is frequently the only mutation detected in acute myeloid leukemia. There is increasing evidence that the prognostic impact of IDH1/2 mutations varies according to the specific mutation and also depends on the context of concurrent mutations of other genes. IDH1(R132) mutation may predict poor outcome in a subset of patients with molecular low-risk acute myeloid leukemia, whereas IDH2(R172) mutations confer a poor prognosis in patients with acute myeloid leukemia. Expression of IDH1/2 mutants induces an increase in global DNA hypermethylation and inhibits TET2-induced cytosine 5-hydroxymethylation, DNA demethylation. These data suggest that IDH1/2 mutations constitute a distinct mutational class in acute myeloid leukemia, which affects the epigenetic state, an important consideration for the development of therapeutic agents.

  20. The mortality of companies

    Science.gov (United States)

    Daepp, Madeleine I. G.; Hamilton, Marcus J.; West, Geoffrey B.; Bettencourt, Luís M. A.

    2015-01-01

    The firm is a fundamental economic unit of contemporary human societies. Studies on the general quantitative and statistical character of firms have produced mixed results regarding their lifespans and mortality. We examine a comprehensive database of more than 25 000 publicly traded North American companies, from 1950 to 2009, to derive the statistics of firm lifespans. Based on detailed survival analysis, we show that the mortality of publicly traded companies manifests an approximately constant hazard rate over long periods of observation. This regularity indicates that mortality rates are independent of a company's age. We show that the typical half-life of a publicly traded company is about a decade, regardless of business sector. Our results shed new light on the dynamics of births and deaths of publicly traded companies and identify some of the necessary ingredients of a general theory of firms. PMID:25833247

  1. Ipilimumab and Decitabine in Treating Patients With Relapsed or Refractory Myelodysplastic Syndrome or Acute Myeloid Leukemia

    Science.gov (United States)

    2016-09-12

    Chimerism; Hematopoietic Cell Transplantation Recipient; Previously Treated Myelodysplastic Syndrome; RAEB-1; RAEB-2; Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  2. Relapsed childhood acute lymphoblastic leukemia in the Nordic countries

    DEFF Research Database (Denmark)

    Oskarsson, Trausti; Söderhäll, Stefan; Arvidson, Johan;

    2016-01-01

    .001) if relapse occurred in the period 1992-2001. Factors independently predicting mortality after relapse included short duration of first remission, bone marrow involvement, age ten years or over, unfavorable cytogenetics, and Down syndrome. T-cell immunophenotype was not an independent prognostic factor unless......Relapse is the main reason for treatment failure in childhood acute lymphoblastic leukemia. Despite improvements in the up-front therapy, survival after relapse is still relatively poor, especially for high-risk relapses. The aims of this study were to assess outcomes following acute lymphoblastic...... included in the study. There were no statistically significant differences in outcome between the up-front protocols or between the relapse protocols used, but an improvement over time was observed. The 5-year overall survival for patients relapsing in the period 2002-2011 was 57.5±3.4%, but 44.7±3.2% (P

  3. [Results of the treatment of nonlymphoblastic acute leukemia in a pediatric population].

    Science.gov (United States)

    Rivera Luna, R; Ajuria Gottwald, E; Silva Sosa, M; González Chirinos, P

    1977-01-01

    On a prospective fashion during approximately two years, 22 pediatric patients with acute non lymphocytic leukemia were evaluated. Of this population the majority had acute mielocytic leukemia, followed by acute myelomonocytic leukemia. Absolutely all patients at the time of diagnosis and subsequently every 4 to 6 weeks had a bone marrow aspiration test. When the patients were first seen, 54% of them presented fever; lymph node enlargement was not a common finding. Only few of this patients presented splenomegaly and/or hepatomegaly. In regards to complete blood counts the most outstanding of its was the presence of leukocyte count above 20000/mm.3 in 8 of this patients. From the 22 patients studied only 21 are evaluable. All 21 patients were treated with a 4 drug combination (modified COAP). Sixteen patients (76%) achieved bone marrow remission, of which only 15 patients (71%) achieved complete remission. The median duration remission was of 9.2 months with a range of 2 to 26 months. At the present time only 7 patients (33%) are alive and on remission. Two more patients are alive but in full relapse. The mortality rate of this study is of 59%. The review of recent chemotherapy reports is presented and the need for further trials is emphasized especially in view of recent papers published in which it appears that better results are being obtained at last in children's acute non lymphocitic leukemia.

  4. Autologous stem cell transplantation versus alternative allogeneic donor transplants in adult acute leukemias.

    Science.gov (United States)

    Claude Gorin, Norbert

    2016-04-01

    The availability of alternative sources of stem cells including most recently T-replete haploidentical marrow or peripheral blood, and the increasing use of reduced-intensity conditioning (RIC), renders feasible an allogeneic transplant to almost all patients with acute leukemia up to 70 years of age. Autologous stem cell transplantation (ASCT) for consolidation of complete remission (CR), however, offers in some circumstances an alternative option. Although associated with a higher relapse rate, autologous transplant benefits from a lower non-relapse mortality, the absence of graft-versus-host disease (GVHD), and a better quality of life for long-term survivors. The recent use of intravenous busulfan (IVBU) with high-dose melphalan, better monitoring of minimal residual disease (MRD), and maintenance therapy post autografting bring new interest. Few retrospective studies compared the outcome following alternative donor versus autologous transplants for remission consolidation. Genoidentical and phenoidentical allogeneic stem cell transplantations are undisputed gold standards, but there are no data showing the superiority of alternative allogeneic donor over autologous transplantation, at the time of undetectable MRD, in patients with good- and intermediate-1 risk acute myelocytic leukemia (AML) in first complete remission (CR1), acute promyelocytic leukemia in second complete remission (CR2), and Philadelphia chromosome-positive (Ph(+)) acute lymphocytic leukemia (ALL).

  5. Acute myelogenous leukemia in pregnancy.

    Science.gov (United States)

    D'Emilio, A; Dragone, P; De Negri, G; Montaldi, A; Stella, M; Battista, R

    1989-01-01

    We report on a patient with acute promyelocytic leukemia diagnosed at the 22nd week of pregnancy. She received chemotherapeutic treatment and reached a complete remission. At the 28th week of gestation the patient delivered, by cesarean section, a normal male infant. At present the mother is still disease-free 27 months after diagnosis. The child, too, is in good health. We point out the possibility of producing live babies with current chemotherapy regimens without exposing either the mother or the fetus to excessive risks.

  6. Causes and prognostic factors of remission induction failure in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and idarubicin

    NARCIS (Netherlands)

    J. de Serna (Javier); P. Montesinos (Pau); E. Vellenga (Edo); C. Rayón (Chelo); R. Parody (Ricardo); A. León (Angel); J. Esteve (Jordi); J.M. Bergua (Juan Miguel); G. Milone (Gustavo); G. Debén (Guillermo); C. Rivas (Concha); M. González (Marcos); M. Tormo (Mar); J. Díaz-Mediavilla (Joaquín); J.D. González (Jose); S. Negri (Silvia); E. Amutio (Elena); S. Brunet (Salut); B. Löwenberg (Bob); M.A. Sanz (Miguel Angel)

    2008-01-01

    textabstractAn understanding of the prognostic factors associated with the various forms of induction mortality in patients with acute promyelocytic leukemia (APL) has remained remarkably limited. This study reports the incidence, time of occurrence, and prognostic factors of the major categories of

  7. Causes and prognostic factors of remission induction failure in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and idarubicin

    NARCIS (Netherlands)

    de la Serna, Javier; Montesinos, Pau; Vellenga, Edo; Rayon, Chelo; Parody, Ricardo; Leon, Angel; Esteve, Jordi; Bergua, Juan M.; Milone, Gustavo; Deben, Guillermo; Rivas, Concha; Gonzalez, Marcos; Tormo, Mar; Diaz-Mediavilla, Joaquin; Gonzalez, Jose D.; Negri, Silvia; Amutio, Elena; Brunet, Salut; Lowenberg, Bob; Sanz, Miguel A.

    2008-01-01

    An understanding of the prognostic factors associated with the various forms of induction mortality in patients with acute promyelocytic leukemia (APL) has remained remarkably limited. This study reports the incidence, time of occurrence, and prognostic factors of the major categories of induction f

  8. Value of routine bone marrow examination in pediatric acute myeloid leukemia (AML) : A study of the Dutch Childhood Oncology Group (DCOG)

    NARCIS (Netherlands)

    Hageman, Ilse M. G.; Peek, Annemarie M. L.; de Haas, Valerie; Damen-Korbijn, Carin M.; Kaspers, Gertjan J. L.

    2012-01-01

    Background The outcome of the treatment of pediatric acute myeloid leukemia (AML) is still disappointing, due to relatively high treatment-related mortality and relapse rates (3040%). Past treatment protocols have called for routine screening via bone marrow aspiration (BMA) after achievement of fir

  9. Outcome and medical costs of patients with invasive aspergillosis and acute myelogenous leukemia-myelodysplastic syndrome treated with intensive chemotherapy: An observational study

    NARCIS (Netherlands)

    L. Slobbe (Lennert); S. Polinder (Suzanne); J.K. Doorduijn (Jeanette); P.J. Lugtenburg (Pieternella); A. el Barzouhi (Abdelilah); E.W. Steyerberg (Ewout); B.J.A. Rijnders (Bart)

    2008-01-01

    textabstractBackground. Invasive aspergillosis (IA) is a leading cause of mortality in patients with acute leukemia. Management of IA is expensive, which makes prevention desirable. Because hospital resources are limited, prevention costs have to be compared with treatment costs and outcome. Methods

  10. CMV reactivation after allogeneic HCT and relapse risk: evidence for early protection in acute myeloid leukemia.

    Science.gov (United States)

    Green, Margaret L; Leisenring, Wendy M; Xie, Hu; Walter, Roland B; Mielcarek, Marco; Sandmaier, Brenda M; Riddell, Stanley R; Boeckh, Michael

    2013-08-15

    The association between cytomegalovirus (CMV) reactivation and relapse was evaluated in a large cohort of patients with acute myeloid leukemia (AML) (n = 761), acute lymphoblastic leukemia (ALL) (n = 322), chronic myeloid leukemia (CML) (n = 646), lymphoma (n = 254), and myelodysplastic syndrome (MDS) (n = 371) who underwent allogeneic hematopoietic cell transplantation (HCT) between 1995 and 2005. In multivariable models, CMV pp65 antigenemia was associated with a decreased risk of relapse by day 100 among patients with AML (hazard ratio [HR] = 0.56; 95% confidence interval [CI], 0.3-0.9) but not in patients with ALL, lymphoma, CML, or MDS. The effect appeared to be independent of CMV viral load, acute graft-versus-host disease, or ganciclovir-associated neutropenia. At 1 year after HCT, early CMV reactivation was associated with reduced risk of relapse in all patients, but this did not reach significance for any disease subgroup. Furthermore, CMV reactivation was associated with increased nonrelapse mortality (HR = 1.31; 95% CI, 1.1-1.6) and no difference in overall mortality (HR = 1.05; 95% CI, 0.9-1.3). This report demonstrates a modest reduction in early relapse risk after HCT associated with CMV reactivation in a large cohort of patients without a benefit in overall survival.

  11. [Mortality in metropolitan regions].

    Science.gov (United States)

    Simoes Ccds

    1980-01-01

    Data from the 1970 census and a 1974-1975 survey carried out in Brazil by the Fundacao Instituto Brasileiro de Geografia e Estatistica are used to examine recent mortality trends in urban areas. Specifically, life expectancy in nine metropolitan areas is analyzed in relation to income, diet, and sanitary facilities in the home.

  12. Affine stochastic mortality

    NARCIS (Netherlands)

    D.F. Schrager

    2006-01-01

    We propose a new model for stochastic mortality. The model is based on the literature on affine term structure models. It satisfies three important requirements for application in practice: analytical tractibility, clear interpretation of the factors and compatibility with financial option pricing m

  13. 7-Hydroxystaurosporine and Perifosine in Treating Patients With Relapsed or Refractory Acute Leukemia, Chronic Myelogenous Leukemia or High Risk Myelodysplastic Syndromes

    Science.gov (United States)

    2013-09-27

    Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Acute Promyelocytic Leukemia (M3); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Blastic Phase Chronic Myelogenous Leukemia; Myelodysplastic/Myeloproliferative Neoplasms; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; T-cell Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Myeloid Leukemia

  14. An innovative pre-targeting strategy for tumor cell specific imaging and therapy

    Science.gov (United States)

    Qin, Si-Yong; Peng, Meng-Yun; Rong, Lei; Jia, Hui-Zhen; Chen, Si; Cheng, Si-Xue; Feng, Jun; Zhang, Xian-Zheng

    2015-08-01

    A programmed pre-targeting system for tumor cell imaging and targeting therapy was established based on the ``biotin-avidin'' interaction. In this programmed functional system, transferrin-biotin can be actively captured by tumor cells with the overexpression of transferrin receptors, thus achieving the pre-targeting modality. Depending upon avidin-biotin recognition, the attachment of multivalent FITC-avidin to biotinylated tumor cells not only offered the rapid fluorescence labelling, but also endowed the pre-targeted cells with targeting sites for the specifically designed biotinylated peptide nano-drug. Owing to the successful pre-targeting, tumorous HepG2 and HeLa cells were effectively distinguished from the normal 3T3 cells via fluorescence imaging. In addition, the self-assembled peptide nano-drug resulted in enhanced cell apoptosis in the observed HepG2 cells. The tumor cell specific pre-targeting strategy is applicable for a variety of different imaging and therapeutic agents for tumor treatments.A programmed pre-targeting system for tumor cell imaging and targeting therapy was established based on the ``biotin-avidin'' interaction. In this programmed functional system, transferrin-biotin can be actively captured by tumor cells with the overexpression of transferrin receptors, thus achieving the pre-targeting modality. Depending upon avidin-biotin recognition, the attachment of multivalent FITC-avidin to biotinylated tumor cells not only offered the rapid fluorescence labelling, but also endowed the pre-targeted cells with targeting sites for the specifically designed biotinylated peptide nano-drug. Owing to the successful pre-targeting, tumorous HepG2 and HeLa cells were effectively distinguished from the normal 3T3 cells via fluorescence imaging. In addition, the self-assembled peptide nano-drug resulted in enhanced cell apoptosis in the observed HepG2 cells. The tumor cell specific pre-targeting strategy is applicable for a variety of different imaging

  15. Leukemia and ionizing radiation revisited

    Energy Technology Data Exchange (ETDEWEB)

    Cuttler, J.M. [Cuttler & Associates Inc., Vaughan, Ontario (Canada); Welsh, J.S. [Loyola University-Chicago, Dept. or Radiation Oncology, Stritch School of Medicine, Maywood, Illinois (United States)

    2016-03-15

    A world-wide radiation health scare was created in the late 19508 to stop the testing of atomic bombs and block the development of nuclear energy. In spite of the large amount of evidence that contradicts the cancer predictions, this fear continues. It impairs the use of low radiation doses in medical diagnostic imaging and radiation therapy. This brief article revisits the second of two key studies, which revolutionized radiation protection, and identifies a serious error that was missed. This error in analyzing the leukemia incidence among the 195,000 survivors, in the combined exposed populations of Hiroshima and Nagasaki, invalidates use of the LNT model for assessing the risk of cancer from ionizing radiation. The threshold acute dose for radiation-induced leukemia, based on about 96,800 humans, is identified to be about 50 rem, or 0.5 Sv. It is reasonable to expect that the thresholds for other cancer types are higher than this level. No predictions or hints of excess cancer risk (or any other health risk) should be made for an acute exposure below this value until there is scientific evidence to support the LNT hypothesis. (author)

  16. Chronic lymphocytic leukemia: present status.

    Science.gov (United States)

    Montserrat, E; Rozman, C

    1995-03-01

    Chronic lymphocytic leukemia (CLL) is the form of leukemia which occurs most frequently in Western countries. Its etiology is unknown, and no relationship with viruses or genes has been demonstrated. Epidemiological data suggest that genetic and ambiental factors might be of some significance. Clinical features of CLL are due to the accumulation of leukemic cells in bone marrow and lymphoid organs as well as the immune disturbances that accompany the disease. The prognosis of patients with CLL varies. Treatment is usually indicated by the risk of the individual patient, which is clearly reflected by the stage of the disease. In the early stage (Binet A, Rai O) it is reasonable to defer therapy until disease progression is observed. By contrast, because their median survival is less than five years, patients with more advanced stages require therapy. For almost 50 years, no major advances in the management of CLL, which has revolved around the use of alkylating agents, have been made. In recent years, the therapeutic approach in patients with CLL has changed as a result of the introduction of combination chemotherapy regimens and, in particular, purine analogues. The latter are already the treatment of choice for patients not responding to standard therapies, and their role as front-line therapy is being investigated. Bone marrow transplants are also being increasingly used. It is to be hoped that in years to come the outcome of patients with CLL will be improved by these advances.

  17. Retrospective cohort mortality study of workers exposed to formaldehyde in the garment industry

    Energy Technology Data Exchange (ETDEWEB)

    Stayner, L.T.; Elliott, L.; Blade, L.; Keenlyside, R.; Halperin, W.

    1988-01-01

    In order to assess the possible human carcinogenicity of formaldehyde we conducted a retrospective cohort mortality study of workers exposed for at least three months to formaldehyde in three garment facilities which produced permanent press garments. A total of 11,030 workers contributing 188,025 person-years were included in the study. Vital status was successfully ascertained through 1982 for over 96% of the cohort. The average (TWA) formaldehyde exposure at the three plants monitored in 1981 and 1984 by NIOSH was 0.15 ppm but past exposures may have been substantially higher. In general, mortality from nonmalignant causes was less than expected. A statistically significant excess in mortality from cancers of the buccal cavity (SMR = 343) and connective tissue (SMR = 364) was observed. Statistically nonsignificant excesses in mortality were observed for cancers of the trachea, bronchus and lung (SMR = 114), pharynx (SMR = 112), bladder (SMR = 145), leukemia and aleukemia (SMR = 113), and other lymphopoietic neoplasms (SMR = 170). Mortality from cancers of the trachea, bronchus and lung was inversely related to duration of exposure and latency. In contrast, mortality from cancers of the buccal cavity, leukemias, and other lymphopoietic neoplasms increased with duration of formaldehyde exposure and/or latency. These neoplasms also were found to be highest among workers first exposed during a time period of high potential formaldehyde exposures in this industry (1955-1962). However, it should be recognized that these findings are based on relatively small numbers and that confounding by other factors may still exist. The results from this investigation, although far from conclusive, do provide evidence of a possible relationship between formaldehyde exposure and the development of upper respiratory cancers (buccal), leukemias, and other lymphopoietic neoplasms in humans.

  18. A retrospective cohort mortality study of workers exposed to formaldehyde in the garment industry.

    Science.gov (United States)

    Stayner, L T; Elliott, L; Blade, L; Keenlyside, R; Halperin, W

    1988-01-01

    In order to assess the possible human carcinogenicity of formaldehyde we conducted a retrospective cohort mortality study of workers exposed for at least three months to formaldehyde in three garment facilities which produced permanent press garments. A total of 11,030 workers contributing 188,025 person-years were included in the study. Vital status was successfully ascertained through 1982 for over 96% of the cohort. The average (TWA) formaldehyde exposure at the three plants monitored in 1981 and 1984 by NIOSH was 0.15 ppm but past exposures may have been substantially higher. In general, mortality from nonmalignant causes was less than expected. A statistically significant excess in mortality from cancers of the buccal cavity (SMR = 343) and connective tissue (SMR = 364) was observed. Statistically nonsignificant excesses in mortality were observed for cancers of the trachea, bronchus and lung (SMR = 114), pharynx (SMR = 112), bladder (SMR = 145), leukemia and aleukemia (SMR = 113), and other lymphopoietic neoplasms (SMR = 170). Mortality from cancers of the trachea, bronchus and lung was inversely related to duration of exposure and latency. In contrast, mortality from cancers of the buccal cavity, leukemias, and other lymphopoietic neoplasms increased with duration of formaldehyde exposure and/or latency. These neoplasms also were found to be highest among workers first exposed during a time period of high potential formaldehyde exposures in this industry (1955-1962). However, it should be recognized that these findings are based on relatively small numbers and that confounding by other factors may still exist. The results from this investigation, although far from conclusive, do provide evidence of a possible relationship between formaldehyde exposure and the development of upper respiratory cancers (buccal), leukemias, and other lymphopoietic neoplasms in humans.

  19. Ginsenoside Rh2 Mitigates Pediatric Leukemia Through Suppression of Bcl-2 in Leukemia Cells

    Directory of Open Access Journals (Sweden)

    Xiaoru Wang

    2015-09-01

    Full Text Available Background/Aims: Acute myeloid leukemia (AML is a severe malignant cancer worldwide, in both adult and pediatric patients. Since bone marrow cell transplantation is seriously limited by the availability of the immune-paired donor sources, the therapy for pediatric leukemia remains challenging. Ginsenoside Rh2 (GRh2 is a well-characterized component in red ginseng, and has established therapeutic effects for different diseases, although whether GRh2 may have a therapeutic effect on pediatric leukemia has not been investigated. Methods: We examined the effects of GRh2 on the survival of mice in an acute leukemia model. We analyzed the effects of GRh2 on the cell viability of leukemia cell lines in vitro, using a CCK-8 assay and an MTT assay. We analyzed the effects of GRh2 on the apoptosis of leukemia cell lines in vitro, by flow cytometry. We analyzed the levels of Bcl-2 and microRNA-21 (miR-21 in GRh2-treated leukemia cells. Prediction of binding between miR-21 and 3'-UTR of Bcl-2 mRNA was performed by a bioinformatics algorithm and confirmed by a dual luciferase reporter assay. Results: GRh2 significantly prolonged the survival of mice with pediatric leukemia. GRh2 significantly decreased the viability of leukemia cells in vitro, through induction of apoptosis. GRh2 significantly decreased the levels of an anti-apoptotic protein Bcl-2 in leukemia cells, possibly through induction of miR-21, which suppressed the translation of Bcl-2 mRNA via 3'-UTR binding. Conclusion: GRh2 may be an effective treatment for pediatric leukemia, and GRh2 may induce apoptosis of leukemia cells through miR-21-modulated suppression of Bcl-2.

  20. Yttrium Y 90 Anti-CD45 Monoclonal Antibody BC8 Followed by Donor Stem Cell Transplant in Treating Patients With High-Risk Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, or Myelodysplastic Syndrome

    Science.gov (United States)

    2016-09-29

    Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Chronic Myelomonocytic Leukemia; Previously Treated Myelodysplastic Syndrome; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts; Secondary Acute Myeloid Leukemia

  1. Molecular Cloning and Functional Analysis of ESGP, an Embryonic Stem Cell and Germ Cell Specific Protein

    Institute of Scientific and Technical Information of China (English)

    Yan-Mei CHEN; Zhong-Wei DU; Zhen YAO

    2005-01-01

    Several putative Oct-4 downstream genes from mouse embryonic stem (ES) cells have been identified using the suppression-subtractive hybridization method. In this study, one of the novel genes encoding an ES cell and germ cell specific protein (ESGP) was cloned by rapid amplification of cDNA ends.ESGP contains 801 bp encoding an 84 amino acid small protein and has no significant homology to any known genes. There is a signal peptide at the N-terminal of ESGP protein as predicted by SeqWeb (GCG)(SeqWeb version 2.0.2, http://gcg.biosino.org:8080/). The result of immunofluorescence assay suggested that ESGP might encode a secretory protein. The expression pattern of ESGP is consistent with the expression of Oct-4 during embryonic development. ESGP protein was detected in fertilized oocyte, from 3.5 day postcoital (dpc) blastocyst to 17.5 dpc embryo, and was only detected in testis and ovary tissues in adult. In vitro, ESGP was only expressed in pluripotent cell lines, such as embryonic stem cells, embryonic carcinoma cells and embryonic germ cells, but not in their differentiated progenies. Despite its specific expression,forced expression of ESGP is not indispensable for the effect of Oct-4 on ES cell self-renewal, and does not affect the differentiation to three germ layers.

  2. Cell-specific STORM super-resolution imaging reveals nanoscale organization of cannabinoid signaling.

    Science.gov (United States)

    Dudok, Barna; Barna, László; Ledri, Marco; Szabó, Szilárd I; Szabadits, Eszter; Pintér, Balázs; Woodhams, Stephen G; Henstridge, Christopher M; Balla, Gyula Y; Nyilas, Rita; Varga, Csaba; Lee, Sang-Hun; Matolcsi, Máté; Cervenak, Judit; Kacskovics, Imre; Watanabe, Masahiko; Sagheddu, Claudia; Melis, Miriam; Pistis, Marco; Soltesz, Ivan; Katona, István

    2015-01-01

    A major challenge in neuroscience is to determine the nanoscale position and quantity of signaling molecules in a cell type- and subcellular compartment-specific manner. We developed a new approach to this problem by combining cell-specific physiological and anatomical characterization with super-resolution imaging and studied the molecular and structural parameters shaping the physiological properties of synaptic endocannabinoid signaling in the mouse hippocampus. We found that axon terminals of perisomatically projecting GABAergic interneurons possessed increased CB1 receptor number, active-zone complexity and receptor/effector ratio compared with dendritically projecting interneurons, consistent with higher efficiency of cannabinoid signaling at somatic versus dendritic synapses. Furthermore, chronic Δ(9)-tetrahydrocannabinol administration, which reduces cannabinoid efficacy on GABA release, evoked marked CB1 downregulation in a dose-dependent manner. Full receptor recovery required several weeks after the cessation of Δ(9)-tetrahydrocannabinol treatment. These findings indicate that cell type-specific nanoscale analysis of endogenous protein distribution is possible in brain circuits and identify previously unknown molecular properties controlling endocannabinoid signaling and cannabis-induced cognitive dysfunction.

  3. Selection of apoptotic cell specific human antibodies from adult bone marrow.

    Directory of Open Access Journals (Sweden)

    Caroline Grönwall

    Full Text Available Autoreactive antibodies that recognize neo-determinants on apoptotic cells in mice have been proposed to have protective, homeostatic and immunoregulatory properties, although our knowledge about the equivalent antibodies in humans has been much more limited. In the current study, human monoclonal antibodies with binding specificity for apoptotic cells were isolated from the bone marrow of healthy adults using phage display technology. These antibodies were shown to recognize phosphorylcholine (PC-associated neo-determinants. Interestingly, three of the four identified apoptotic cell-specific antibody clones were encoded by VH3 region rearrangements with germline or nearly germline configuration without evidence of somatic hypermutation. Importantly, the different identified antibody clones had diverse heavy chain CDR3 and deduced binding surfaces as suggested by structure modeling. This may suggest a potentially great heterogeneity in human antibodies recognizing PC-related epitopes on apoptotic cells. To re-construct the postulated structural format of the parental anti-PC antibody, the dominant clone was also expressed as a recombinant human polymeric IgM, which revealed a substantially increased binding reactivity, with dose-dependent and antigen-inhibitable binding of apoptotic cells. Our findings may have implication for improved prognostic testing and therapeutic interventions in human inflammatory disease.

  4. Enhanced cell-specific ablation in zebrafish using a triple mutant of Escherichia coli nitroreductase.

    Science.gov (United States)

    Mathias, Jonathan R; Zhang, Zhanying; Saxena, Meera T; Mumm, Jeff S

    2014-04-01

    Transgenic expression of bacterial nitroreductase (NTR) facilitates chemically-inducible targeted cell ablation. In zebrafish, the NTR system enables studies of cell function and cellular regeneration. Metronidazole (MTZ) has become the most commonly used prodrug substrate for eliciting cell loss in NTR-expressing transgenic zebrafish due to the cell-specific nature of its cytotoxic derivatives. Unfortunately, MTZ treatments required for effective cell ablation border toxic effects, and, thus, likely incur undesirable nonspecific effects. Here, we tested whether a triple mutant variant of NTR, previously shown to display improved activity in bacterial assays, can solve this issue by promoting cell ablation in zebrafish using reduced prodrug treatment regimens. We generated several complementary transgenic zebrafish lines expressing either wild-type or mutant NTR (mutNTR) in specific neural cell types, and assayed prodrug-induced cell ablation kinetics using confocal time series imaging and plate reader-based quantification of fluorescent reporters expressed in targeted cell types. The results show that cell ablation can be achieved in mutNTR expressing transgenic lines with markedly shortened prodrug exposure times and/or at lower prodrug concentrations. The mutNTR variant characterized here can circumvent problematic nonspecific/toxic effects arising from low prodrug conversion efficiency, thus increasing the effectiveness and versatility of this selective cell ablation methodology.

  5. Intercalated cell-specific Rh B glycoprotein deletion diminishes renal ammonia excretion response to hypokalemia.

    Science.gov (United States)

    Bishop, Jesse M; Lee, Hyun-Wook; Handlogten, Mary E; Han, Ki-Hwan; Verlander, Jill W; Weiner, I David

    2013-02-15

    The ammonia transporter family member, Rh B Glycoprotein (Rhbg), is an ammonia-specific transporter heavily expressed in the kidney and is necessary for the normal increase in ammonia excretion in response to metabolic acidosis. Hypokalemia is a common clinical condition in which there is increased renal ammonia excretion despite the absence of metabolic acidosis. The purpose of this study was to examine Rhbg's role in this response through the use of mice with intercalated cell-specific Rhbg deletion (IC-Rhbg-KO). Hypokalemia induced by feeding a K(+)-free diet increased urinary ammonia excretion significantly. In mice with intact Rhbg expression, hypokalemia increased Rhbg protein expression in intercalated cells in the cortical collecting duct (CCD) and in the outer medullary collecting duct (OMCD). Deletion of Rhbg from intercalated cells inhibited hypokalemia-induced changes in urinary total ammonia excretion significantly and completely prevented hypokalemia-induced increases in urinary ammonia concentration, but did not alter urinary pH. We conclude that hypokalemia increases Rhbg expression in intercalated cells in the cortex and outer medulla and that intercalated cell Rhbg expression is necessary for the normal increase in renal ammonia excretion in response to hypokalemia.

  6. TOPAZ1, a novel germ cell-specific expressed gene conserved during evolution across vertebrates.

    Directory of Open Access Journals (Sweden)

    Adrienne Baillet

    Full Text Available BACKGROUND: We had previously reported that the Suppression Subtractive Hybridization (SSH approach was relevant for the isolation of new mammalian genes involved in oogenesis and early follicle development. Some of these transcripts might be potential new oocyte and granulosa cell markers. We have now characterized one of them, named TOPAZ1 for the Testis and Ovary-specific PAZ domain gene. PRINCIPAL FINDINGS: Sheep and mouse TOPAZ1 mRNA have 4,803 bp and 4,962 bp open reading frames (20 exons, respectively, and encode putative TOPAZ1 proteins containing 1,600 and 1653 amino acids. They possess PAZ and CCCH domains. In sheep, TOPAZ1 mRNA is preferentially expressed in females during fetal life with a peak during prophase I of meiosis, and in males during adulthood. In the mouse, Topaz1 is a germ cell-specific gene. TOPAZ1 protein is highly conserved in vertebrates and specifically expressed in mouse and sheep gonads. It is localized in the cytoplasm of germ cells from the sheep fetal ovary and mouse adult testis. CONCLUSIONS: We have identified a novel PAZ-domain protein that is abundantly expressed in the gonads during germ cell meiosis. The expression pattern of TOPAZ1, and its high degree of conservation, suggests that it may play an important role in germ cell development. Further characterization of TOPAZ1 may elucidate the mechanisms involved in gametogenesis, and particularly in the RNA silencing process in the germ line.

  7. Whole-brain circuit dissection in free-moving animals reveals cell-specific mesocorticolimbic networks

    Science.gov (United States)

    Michaelides, Michael; Anderson, Sarah Ann R.; Ananth, Mala; Smirnov, Denis; Thanos, Panayotis K.; Neumaier, John F.; Wang, Gene-Jack; Volkow, Nora D.; Hurd, Yasmin L.

    2013-01-01

    The ability to map the functional connectivity of discrete cell types in the intact mammalian brain during behavior is crucial for advancing our understanding of brain function in normal and disease states. We combined designer receptor exclusively activated by designer drug (DREADD) technology and behavioral imaging with μPET and [18F]fluorodeoxyglucose (FDG) to generate whole-brain metabolic maps of cell-specific functional circuits during the awake, freely moving state. We have termed this approach DREADD-assisted metabolic mapping (DREAMM) and documented its ability in rats to map whole-brain functional anatomy. We applied this strategy to evaluating changes in the brain associated with inhibition of prodynorphin-expressing (Pdyn-expressing) and of proenkephalin-expressing (Penk-expressing) medium spiny neurons (MSNs) of the nucleus accumbens shell (NAcSh), which have been implicated in neuropsychiatric disorders. DREAMM revealed discrete behavioral manifestations and concurrent engagement of distinct corticolimbic networks associated with dysregulation of Pdyn and Penk in MSNs of the NAcSh. Furthermore, distinct neuronal networks were recruited in awake versus anesthetized conditions. These data demonstrate that DREAMM is a highly sensitive, molecular, high-resolution quantitative imaging approach. PMID:24231358

  8. Quasispecies of Hepatitis C Virus Participate in Cell-Specific Infectivity.

    Science.gov (United States)

    Fukuhara, Takasuke; Yamamoto, Satomi; Ono, Chikako; Nakamura, Shota; Motooka, Daisuke; Mori, Hiroyuki; Kurihara, Takeshi; Sato, Asuka; Tamura, Tomokazu; Motomura, Takashi; Okamoto, Toru; Imamura, Michio; Ikegami, Toru; Yoshizumi, Tomoharu; Soejima, Yuji; Maehara, Yoshihiko; Chayama, Kazuaki; Matsuura, Yoshiharu

    2017-03-22

    It is well documented that a variety of viral quasispecies are found in the patients with chronic infection of hepatitis C virus (HCV). However, the significance of quasispecies in the specific infectivity to individual cell types remains unknown. In the present study, we analyzed the role of quasispecies of the genotype 2a clone, JFH1 (HCVcc), in specific infectivity to the hepatic cell lines, Huh7.5.1 and Hep3B. HCV RNA was electroporated into Huh7.5.1 cells and Hep3B/miR-122 cells expressing miR-122 at a high level. Then, we adapted the viruses to Huh7 and Hep3B/miR-122 cells by serial passages and termed the resulting viruses HCVcc/Huh7 and HCVcc/Hep3B, respectively. Interestingly, a higher viral load was obtained in the homologous combination of HCVcc/Huh7 in Huh7.5.1 cells or HCVcc/Hep3B in Hep3B/miR-122 cells compared with the heterologous combination. By using a reverse genetics system and deep sequence analysis, we identified several adaptive mutations involved in the high affinity for each cell line, suggesting that quasispecies of HCV participate in cell-specific infectivity.

  9. Optogenetics in the cerebellum: Purkinje cell-specific approaches for understanding local cerebellar functions.

    Science.gov (United States)

    Tsubota, Tadashi; Ohashi, Yohei; Tamura, Keita

    2013-10-15

    The cerebellum consists of the cerebellar cortex and the cerebellar nuclei. Although the basic neuronal circuitry of the cerebellar cortex is uniform everywhere, anatomical data demonstrate that the input and output relationships of the cortex are spatially segregated between different cortical areas, which suggests that there are functional distinctions between these different areas. Perturbation of cerebellar cortical functions in a spatially restricted fashion is thus essential for investigating the distinctions among different cortical areas. In the cerebellar cortex, Purkinje cells are the sole output neurons that send information to downstream cerebellar and vestibular nuclei. Therefore, selective manipulation of Purkinje cell activities, without disturbing other neuronal types and passing fibers within the cortex, is a direct approach to spatially restrict the effects of perturbations. Although this type of approach has for many years been technically difficult, recent advances in optogenetics now enable selective activation or inhibition of Purkinje cell activities, with high temporal resolution. Here we discuss the effectiveness of using Purkinje cell-specific optogenetic approaches to elucidate the functions of local cerebellar cortex regions. We also discuss what improvements to current methods are necessary for future investigations of cerebellar functions to provide further advances.

  10. Spermatogenic Cell-Specific Gene Mutation in Mice via CRISPR-Cas9.

    Science.gov (United States)

    Bai, Meizhu; Liang, Dan; Wang, Yinghua; Li, Qing; Wu, Yuxuan; Li, Jinsong

    2016-05-20

    Tissue-specific knockout technology enables the analysis of the gene function in specific tissues in adult mammals. However, conventional strategy for producing tissue-specific knockout mice is a time- and labor-consuming process, restricting rapid study of the gene function in vivo. CRISPR-Cas9 system from bacteria is a simple and efficient gene-editing technique, which has enabled rapid generation of gene knockout lines in mouse by direct injection of CRISPR-Cas9 into zygotes. Here, we demonstrate CRISPR-Cas9-mediated spermatogenic cell-specific disruption of Scp3 gene in testes in one step. We first generated transgenic mice by pronuclear injection of a plasmid containing Hspa2 promoter driving Cas9 expression and showed Cas9 specific expression in spermatogenic cells. We then produced transgenic mice carrying Hspa2 promoter driven Cas9 and constitutive expressed sgRNA targeting Scp3 gene. Male founders were infertile due to developmental arrest of spermatogenic cells while female founders could produce progeny normally. Consistently, male progeny from female founders were infertile and females could transmit the transgenes to the next generation. Our study establishes a CRISPR-Cas9-based one-step strategy to analyze the gene function in adult tissues by a temporal-spatial pattern.

  11. Selumetinib in Treating Patients With Recurrent or Refractory Acute Myeloid Leukemia

    Science.gov (United States)

    2015-07-06

    Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Promyelocytic Leukemia (M3); Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasms; Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia

  12. Allogeneic stem cell transplantation for patients harboring T315I BCR-ABL mutated leukemias

    DEFF Research Database (Denmark)

    Nicolini, Franck Emmanuel; Basak, Grzegorz W; Soverini, Simona;

    2011-01-01

    T315I(+) Philadelphia chromosome-positive leukemias are inherently resistant to all licensed tyrosine kinase inhibitors, and therapeutic options remain limited. We report the outcome of allogeneic stem cell transplantation in 64 patients with documented BCR-ABL(T315I) mutations. Median follow...... myeloid leukemia. The occurrence of chronic GVHD had a positive impact on overall survival (P = .047). Transplant-related mortality rates were low. Multivariate analysis identified only blast phase at transplantation (hazard ratio 3.68, P = .0011) and unrelated stem cell donor (hazard ratio 2.98, P = .011......) as unfavorable factors. We conclude that allogeneic stem cell transplantation represents a valuable therapeutic tool for eligible patients with BCR-ABL(T315I) mutation, a tool that may or may not be replaced by third-generation tyrosine kinase inhibitors....

  13. Combination Chemotherapy in Treating Young Patients With Down Syndrome and Acute Myeloid Leukemia or Myelodysplastic Syndromes

    Science.gov (United States)

    2017-02-07

    Childhood Acute Basophilic Leukemia; Childhood Acute Eosinophilic Leukemia; Childhood Acute Erythroleukemia (M6); Childhood Acute Megakaryocytic Leukemia (M7); Childhood Acute Minimally Differentiated Myeloid Leukemia (M0); Childhood Acute Monoblastic Leukemia (M5a); Childhood Acute Monocytic Leukemia (M5b); Childhood Acute Myeloblastic Leukemia With Maturation (M2); Childhood Acute Myeloblastic Leukemia Without Maturation (M1); Childhood Acute Myelomonocytic Leukemia (M4); Childhood Myelodysplastic Syndromes; de Novo Myelodysplastic Syndromes; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies

  14. Bortezomib in Treating Patients With High-Risk Acute Myeloid Leukemia in Remission

    Science.gov (United States)

    2014-10-30

    Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome; Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Promyelocytic Leukemia (M3); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Secondary Acute Myeloid Leukemia

  15. HIV and maternal mortality.

    Science.gov (United States)

    Lathrop, Eva; Jamieson, Denise J; Danel, Isabella

    2014-11-01

    The majority of the 17 million women globally that are estimated to be infected with HIV live in Sub-Saharan Africa. Worldwide, HIV-related causes contributed to 19 000-56 000 maternal deaths in 2011 (6%-20% of maternal deaths). HIV-infected pregnant women have two to 10 times the risk of dying during pregnancy and the postpartum period compared with uninfected pregnant women. Many of these deaths can be prevented with the implementation of high-quality obstetric care, prevention and treatment of common co-infections, and treatment of HIV with ART. The paper summarizes what is known about HIV disease progression in pregnancy, specific causes of HIV-related maternal deaths, and the potential impact of treatment with antiretroviral therapy on maternal mortality. Recommendations are proposed for improving maternal health and decreasing maternal mortality among HIV-infected women based on existing evidence.

  16. [AIDS mortality in France].

    Science.gov (United States)

    Hatton, F; Maguin, P; Nicaud, V; Renaud, G

    1986-01-01

    A study about mortality by AIDS had been undertaken since July 1st 1983, in the Service of Information on Medical causes of Death (INSERM SC8), which is in charge of developing mortality statistics in France. From July 1st 1983 to September 30th 1985, 243 deaths due to AIDS were recorded. Only the cases where this diagnosis was clearly mentioned were selected; more than 90% were notified by hospitals and mainly by highly specialized services. The number of deaths, which was low and varied rather irregularly at the beginning, then increased by successive stages. The first year, during which a tenth of deaths was recorded every three months, was followed by a great increase, doubling, then tripling the initial numbers. Lastly, a second and sudden rise occurred during the third trimester of 1985, the trimestrial number of deaths due to AIDS reaching 80.

  17. Cancer Mortality Projections in Korea up to 2032.

    Science.gov (United States)

    Son, Mia; Yun, Jae-Won

    2016-06-01

    Predicting cancer mortality is important to estimate the needs of cancer-related services and to prevent cancer. Despite its significance, a long-term future projection of cancer mortality has not been conducted; therefore, our objective was to estimate future cancer mortality in Korea by cancer site through 2032. The specially designed Nordpred software was used to estimate cancer mortality. The cancer death data from 1983 to 2012 and the population projection data from 1983 to 2032 were obtained from the Korean National Statistics Office. Based on our analysis, age-standardized rates with the world standard population of all cancer deaths were estimated to decline from 2008-2012 to 2028-2032 (men: -39.8%, women: -33.1%). However, the crude rates are predicted to rise (men: 29.8%, women: 24.4%), and the overall number of the cancer deaths is also estimated to increase (men: 35.5%, women: 32.3%). Several cancer deaths are projected to increase (lung, liver and gallbladder, colon and rectum, pancreas and leukemia in both sexes; prostate cancer in men; and breast and ovarian cancer in women), whereas other cancer deaths are expected to decrease (stomach, esophagus and larynx in both sexes and cervical cancer in women). The largest contribution to increasing cancer deaths is due to the aging of the Korean population. In conclusion, a strategy for primary prevention, early detection, and early treatment to cope with the rapidly increasing death of cancer due to population aging is urgently required.

  18. Temporal trend of mortality from major cancers in Xuanwei, China.

    Science.gov (United States)

    Lin, Hualiang; Ning, Bofu; Li, Jihua; Zhao, Guangqiang; Huang, Yunchao; Tian, Linwei

    2015-12-01

    Although a number of studies have examined the etiology of lung cancer in Xuanwei County, China, other types of cancer in this county have not been reported systematically. This study aimed to investigate the temporal trend of eight major cancers in Xuanwei County using data from three mortality surveys (1973-1975, 1990-1992, and 2004-2005). The Chinese population in 1990 was used as a standard population to calculate agestandardized mortality rates. Cancers of lung, liver, breast, brain, esophagus, leukemia, rectum, and stomach were identified as the leading cancers in this county in terms of mortality rate. During the three time periods, lung cancer remained as the most common type of cancer. The mortality rates for all other types of cancer were lower than those of the national average, but an increasing trend was observed for all the cancers, particularly from 1990-1992 to 2004-2005. The temporal trend could be partly explained by changes in risk factors, but it also may be due to the improvement in cancer diagnosis and screening. Further epidemiological studies are warranted to systematically examine the underlying reasons for the temporal trend of the major cancers in Xuanwei County.

  19. Pelvic fractures and mortality.

    OpenAIRE

    K.H. Chong; DeCoster, T.; Osler, T.; Robinson, B.

    1997-01-01

    A retrospective study of all patients (N = 343) with pelvic fractures admitted to our trauma service was conducted to evaluate the impact of pelvic fractures on mortality. All patients sustained additional injuries with an average Injury Severity Score (ISS) of twenty. Thirty-six patients died. This group had more severe pelvic fractures as graded by the Tile classification as well as a greater number and severity of associated injuries. Six patients died as a direct result of pelvic hemorrha...

  20. Deciphering infant mortality

    Science.gov (United States)

    Berrut, Sylvie; Pouillard, Violette; Richmond, Peter; Roehner, Bertrand M.

    2016-12-01

    This paper is about infant mortality. In line with reliability theory, "infant" refers to the time interval following birth during which the mortality (or failure) rate decreases. This definition provides a systems science perspective in which birth constitutes a sudden transition falling within the field of application of the Transient Shock (TS) conjecture put forward in Richmond and Roehner (2016c). This conjecture provides predictions about the timing and shape of the death rate peak. It says that there will be a death rate spike whenever external conditions change abruptly and drastically and also predicts that after a steep rise there will be a much longer hyperbolic relaxation process. These predictions can be tested by considering living organisms for which the transient shock occurs several days after birth. Thus, for fish there are three stages: egg, yolk-sac and young adult phases. The TS conjecture predicts a mortality spike at the end of the yolk-sac phase and this timing is indeed confirmed by observation. Secondly, the hyperbolic nature of the relaxation process can be tested using very accurate Swiss statistics for postnatal death rates spanning the period from one hour immediately after birth through to age 10 years. It turns out that since the 19th century despite a significant and large reduction in infant mortality, the shape of the age-specific death rate has remained basically unchanged. Moreover the hyperbolic pattern observed for humans is also found for small primates as recorded in the archives of zoological gardens. Our overall objective is to identify a series of cases which start from simple systems and move step by step to more complex organisms. The cases discussed here we believe represent initial landmarks in this quest.

  1. Clofarabine, Cytarabine, and G-CSF in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

    Science.gov (United States)

    2015-05-05

    Acute Myeloid Leukemia; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Promyelocytic Leukemia (M3); Recurrent Adult Acute Myeloid Leukemia

  2. Romidepsin in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

    Science.gov (United States)

    2015-12-03

    Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Promyelocytic Leukemia (M3); Recurrent Adult Acute Myeloid Leukemia

  3. Supportive Care for Chronic Lymphocytic Leukemia

    Science.gov (United States)

    ... low red blood cell counts, it is called autoimmune hemolytic anemia (AIHA). This also can be treated with drugs ... Leukemia Causes, Risk Factors, and Prevention Early Detection, Diagnosis, and Staging Treatment After Treatment Back To Top ...

  4. Monoclonal antibodies in chronic lymphocytic leukemia.

    Science.gov (United States)

    Ferrajoli, Alessandra; Faderl, Stefan; Keating, Michael J

    2006-09-01

    Multiple options are now available for the treatment of chronic lymphocytic leukemia. Over the last 10 years, monoclonal antibodies have become an integral part of the management of this disease. Alemtuzumab has received approval for use in patients with fludarabine-refractory chronic lymphocytic leukemia. Rituximab has been investigated extensively in chronic lymphocytic leukemia both as a single agent and in combination with chemotherapy and other monoclonal antibodies. Epratuzumab and lumiliximab are newer monoclonal antibodies in the early phase of clinical development. This article will review the monoclonal antibodies more commonly used to treat chronic lymphocytic leukemia, the results obtained with monoclonal antibodies as single agents and in combination with chemotherapy, and other biological agents and newer compounds undergoing clinical trials.

  5. Acute Lymphoblastic Leukemia (ALL) (For Parents)

    Science.gov (United States)

    ... kidney function panels, and blood chemistries can give important information about the number of normal blood cells in ... for examination in a lab. Cancerous WBCs can collect in this area. ... important because treatment varies among different types of leukemia. ...

  6. Viewpoints on the proinflammation state of leukemia

    Institute of Scientific and Technical Information of China (English)

    WU Kefu; MA Xiaotong

    2003-01-01

    Proinflammation represents a pathophysiological state on the early stage of a number of diseases, especially the infectious and immunological ones. In recent years, proinflammation has attracted much attention, and the term "proinflammation factors" appears frequently in the literature. While investigating leukemia and leukemic cells from the angle of "proinflammation state", we got some intriguing findings, e.g. we detected the significantly elevated expression of proinflammation factor IL-18 in patients with acute myeloid leukemia (AML), which could up-regulate matrix metalloproteinases (MMP) and specific tissue inhibitors (TIMPs). The increased MMP may play a role in the aggressiveness of myeloid leukemic cells, and be associated with a poor prognosis. This phenomenon reflects an ignored aspect of leukemia. Investigations from the angle of "proinflammation state" have broaden the fields of tumor and leukemia study.

  7. The Danish National Acute Leukemia Registry

    DEFF Research Database (Denmark)

    Østgård, Lene Sofie Granfeldt; Nørgaard, Jan Maxwell; Raaschou-Jensen, Klas Kræsten;

    2016-01-01

    AIM OF DATABASE: The main aim of the Danish National Acute Leukemia Registry (DNLR) was to obtain information about the epidemiology of the hematologic cancers acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), and myelodysplastic syndrome (MDS). STUDY POPULATION: The registry...... patients is currently 90%. MAIN VARIABLES AND DESCRIPTIVE DATA: Approximately, 250 AML patients, 25 ALL patients, and 230 MDS patients are registered in the DNLR every year. In January 2015, the registry included detailed patient characteristics, disease characteristics, treatment characteristics...... years. To ensure this high coverage, completeness, and quality of data, linkage to the Danish Civil Registration System and the Danish National Registry of Patients, and several programmed data entry checks are used. CONCLUSION: The completeness and positive predictive values of the leukemia data have...

  8. What Is Acute Lymphocytic Leukemia (ALL)?

    Science.gov (United States)

    ... Lymphoid tissue is found in lymph nodes, the thymus, the spleen, the tonsils and adenoids, and is ... destroy some germs by surrounding and digesting them. Development of leukemia Any type of early blood-forming ...

  9. Treatment Option Overview (Adult Acute Myeloid Leukemia)

    Science.gov (United States)

    ... Childhood AML Treatment Research Adult Acute Myeloid Leukemia Treatment (PDQ®)–Patient Version General Information About Adult Acute ... bleeding and forming blood clots. Smoking, previous chemotherapy treatment, and exposure to radiation may affect the risk ...

  10. Increased leukemia risk in Chernobyl cleanup workers

    Science.gov (United States)

    A new study found a significantly elevated risk for chronic lymphocytic leukemia among workers who were engaged in recovery and clean-up activities following the Chernobyl power plant accident in 1986.

  11. Acute myeloid leukemia presenting as galactorrhea

    Science.gov (United States)

    Nambiar, K. Rakul; Devi, R. Nandini

    2016-01-01

    Acute myeloid leukemia (AML) presents with symptoms related to pancytopenia (weakness, infections, bleeding diathesis) and organ infiltration with leukemic cells. Galactorrhea is an uncommon manifestation of AML. We report a case of AML presenting with galactorrhea. PMID:27695173

  12. Acute myeloid leukemia presenting as galactorrhea

    OpenAIRE

    Nambiar, K. Rakul; Nair, Sreejith G.; Devi, R. Nandini

    2016-01-01

    Acute myeloid leukemia (AML) presents with symptoms related to pancytopenia (weakness, infections, bleeding diathesis) and organ infiltration with leukemic cells. Galactorrhea is an uncommon manifestation of AML. We report a case of AML presenting with galactorrhea.

  13. Granulocyte Colony-stimulating Factor-primed Bone Marrow: An Excellent Stem-cell Source for Transplantation in Acute Myelocytic Leukemia and Chronic Myelocytic Leukemia

    Directory of Open Access Journals (Sweden)

    Yuhang Li

    2015-01-01

    Full Text Available Background: Steady-state bone marrow (SS-BM and granulocyte colony-stimulating growth factor-primed BM/peripheral blood stem-cell (G-BM/G-PBSC are the main stem-cell sources used in allogeneic hematopoietic stem-cell transplantation. Here, we evaluated the treatment effects of SS-BM and G-BM/G-PBSC in human leucocyte antigen (HLA-identical sibling transplantation. Methods: A total of 226 patients (acute myelogenous leukemia-complete remission 1, chronic myelogenous leukemia-chronic phase 1 received SS-BM, G-BM, or G-PBSC from an HLA-identical sibling. Clinical outcomes (graft-versus-host disease [GVHD], overall survival, transplant-related mortality [TRM], and leukemia-free survival [LFS] were analyzed. Results: When compared to SS-BM, G-BM gave faster recovery time to neutrophil or platelet (P 0.05. Conclusions: G-CSF-primed bone marrow shared the advantages of G-PBSC and SS-BM. We conclude that G-BM is an excellent stem-cell source that may be preferable to G-PBSC or SS-BM in patients receiving HLA-identical sibling hematopoietic stem-cell transplantation.

  14. Cancer mortality and morbidity among rubber workers.

    Science.gov (United States)

    Monson, R R; Fine, L J

    1978-10-01

    Mortality and morbidity from cancer among a cohort of 13,570 white male rubber workers were examined. Each man worked for at least 5 years at the Akron, Ohio, plant of the B. F. Goodrich Company. The potential period of follow-up was from January 1, 1940 to June 30, 1976. Departmental work histories were based primarily on records maintained by Local no. 5, United Rubber Workers. The occurrence of cancer was measured by death certificates and by a survey of Akron-area hospital tumor registries from 1964 to 1974. Two types of analyses were made: 1) an external comparison of mortality rates of rubber workers versus rates of U.S. white males, and 2) an internal comparison of cancer morbidity rates among persons who were employed in various work areas of the plant. Excess cases of specific cancers (observed/expected numbers) among workers in specific work areas included: stomach and intestine: rubber making (30/14.4); lung: tire curing (31/14.1), fuel cells and/or deicers (46/29.1); bladder: chemical plant (6/2.4), and tire building (16/10.7); skin cancer: tire assembly (12/1.9); brain cancer: tire assembly (8/2.0); lymphatic cancer: tire building (8/3.2); and leukemia: calendering (8/2.2), tire curing (8/2.6), tire building (12/7.5), elevators (4/1.4), tubes (4/1.6), and rubber fabrics (4/1.1). Agents that may be responsible for these excesses were considered.

  15. Autonomous growth potential of leukemia blast cells is associated with poor prognosis in human acute leukemias

    Directory of Open Access Journals (Sweden)

    Jakubowski Ann A

    2009-12-01

    Full Text Available Abstract We have described a severe combined immunodeficiency (SCID mouse model that permits the subcutaneous growth of primary human acute leukemia blast cells into a measurable subcutaneous nodule which may be followed by the development of disseminated disease. Utilizing the SCID mouse model, we examined the growth potential of leukemic blasts from 133 patients with acute leukemia, (67 acute lymphoblastic leukemia (ALL and 66 acute myeloid leukemia (AML in the animals after subcutaneous inoculation without conditioning treatment. The blasts displayed three distinct growth patterns: "aggressive", "indolent", or "no tumor growth". Out of 133 leukemias, 45 (33.8% displayed an aggressive growth pattern, 14 (10.5% displayed an indolent growth pattern and 74 (55.6% did not grow in SCID mice. The growth probability of leukemias from relapsed and/or refractory disease was nearly 3 fold higher than that from patients with newly diagnosed disease. Serial observations found that leukemic blasts from the same individual, which did not initiate tumor growth at initial presentation and/or at early relapse, may engraft and grow in the later stages of disease, suggesting that the ability of leukemia cells for engraftment and proliferation was gradually acquired following the process of leukemia progression. Nine autonomous growing leukemia cell lines were established in vitro. These displayed an aggressive proliferation pattern, suggesting a possible correlation between the capacity of human leukemia cells for autonomous proliferation in vitro and an aggressive growth potential in SCID mice. In addition, we demonstrated that patients whose leukemic blasts displayed an aggressive growth and dissemination pattern in SClD mice had a poor clinical outcome in patients with ALL as well as AML. Patients whose leukemic blasts grew indolently or whose leukemia cells failed to induce growth had a significantly longer DFS and more favorable clinical course.

  16. Lenalidomide and Chronic Lymphocytic Leukemia

    Directory of Open Access Journals (Sweden)

    Ana Pilar González-Rodríguez

    2013-01-01

    Full Text Available Lenalidomide is an oral immunomodulatory drug used in multiple myeloma and myelodysplastic syndrome and most recently it has shown to be effective in the treatment of various lymphoproliferative disorders such as chronic lymphocytic leukemia (CLL and non-Hodgkin lymphoma. The mechanism of action of lenalidomide varies depending on the pathology, and in the case of CLL, it appears to primarily act by restoring the damaged mechanisms of tumour immunosurveillance. This review discusses the potential mechanism of action and efficacy of lenalidomide, alone or in combination, in treatment of CLL and its toxic effects such as tumor lysis syndrome (TLS and tumor flare reaction (TFR, that make its management different from other hematologic malignancies.

  17. High frequency of T cells specific for cryptic epitopes in melanoma patients

    Science.gov (United States)

    Andersen, Rikke Sick; Andersen, Sofie Ramskov; Hjortsø, Mads Duus; Lyngaa, Rikke; Idorn, Manja; Køllgård, Tania Maria; Met, Özcan; thor Straten, Per; Hadrup, Sine Reker

    2013-01-01

    A number of cytotoxic T-cell epitopes are cryptic epitopes generated from non-conventional sources. These include epitopes that are encoded by alternative open reading frames or in generally non-coding genomic regions, such as introns. We have previously observed a frequent recognition of cryptic epitopes by tumor infiltrating lymphocytes isolated from melanoma patients. Here, we show that such cryptic epitopes are more frequently recognized than antigens of the same class encoded by canonical reading frames. Furthermore, we report the presence of T cells specific for three cryptic epitopes encoded in intronic sequences, as a result of incomplete splicing, in the circulation of melanoma patients. One of these epitopes derives from antigen isolated from immunoselected melanoma 2 (AIM2), while the two others are encoded in an alternative open reading frame of an incompletely spliced form of N-acetylglucosaminyl-transferase V (GNT-V) known as NA17-A. We have detected frequent T-cell responses against AIM2 and NA17-A epitopes in the blood of melanoma patients, both prior and after one round of in vitro peptide stimulation, but not in the circulation of healthy individuals and patients with breast or renal carcinoma. In summary, our findings indicate that the T-cell reactivity against AIM2 and NA17-A in the blood of melanoma patients is extensive, suggesting that—similar to melan A (also known as MART1)—these antigens might be used for immunomonitoring or as model antigens in several clinical and preclinical settings. PMID:24073381

  18. The cell specificity of gene expression in the response to heat stress in corals.

    Science.gov (United States)

    Traylor-Knowles, N; Rose, N H; Palumbi, S R

    2017-03-02

    Previous transcriptional studies in heat stressed corals have shown that many genes are responsive to generalized heat stress whereas the expression patterns of specific gene networks after heat stress show strong correlations with variation in bleaching outcomes. However, where these specific genes are expressed is unknown. Here we employed in situ hybridization to identify patterns of spatial gene expression of genes previously predicted to be involved in general stress response and bleaching. We found that Tumor Necrosis Factor Receptors (TNFRs), known to be strong responders to heat stress, were not expressed in gastrodermal symbiont-containing cells but were widely expressed in specific cells of the epidermal layer. The transcription factors AP-1 and FosB implicated as early signals of heat stress and were widely expressed throughout the oral gastrodermis and epidermis. By contrast, a G-protein coupled receptor gene (GPCR), and a fructose bisphosphate aldolase C gene (Aldolase), previously implicated in bleaching, was expressed in symbiont containing gastrodermal cells, and in epidermal tissue. Finally, Chordin-like/Kielin (Chordin-like) a gene highly correlated to bleaching was expressed solely in the oral gastrodermis. From this study we confirm that heat responsive genes occur widely in coral tissues outside of symbiont containing cells, and that gene expression in response to heat stress that causes bleaching does not signal by itself that a gene is expressed in the symbiotic cells where bleaching occurs. Joint information about expression patterns in response to heat and cell specificity will allow greater dissection of the regulatory pathways and specific cell reactions that lead to coral bleaching.

  19. Immunoprofiling reveals unique cell-specific patterns of wall epitopes in the expanding Arabidopsis stem.

    Science.gov (United States)

    Hall, Hardy C; Cheung, Jingling; Ellis, Brian E

    2013-04-01

    The Arabidopsis inflorescence stem undergoes rapid directional growth, requiring massive axial cell-wall extension in all its tissues, but, at maturity, these tissues are composed of cell types that exhibit markedly different cell-wall structures. It is not clear whether the cell-wall compositions of these cell types diverge rapidly following axial growth cessation, or whether compositional divergence occurs at earlier stages in differentiation, despite the common requirement for cell-wall extensibility. To examine this question, seven cell types were assayed for the abundance and distribution of 18 major cell-wall glycan classes at three developmental stages along the developing inflorescence stem, using a high-throughput immunolabelling strategy. These stages represent a phase of juvenile growth, a phase displaying the maximum rate of stem extension, and a phase in which extension growth is ceasing. The immunolabelling patterns detected demonstrate that the cell-wall composition of most stem tissues undergoes pronounced changes both during and after rapid extension growth. Hierarchical clustering of the immunolabelling signals identified cell-specific binding patterns for some antibodies, including a sub-group of arabinogalactan side chain-directed antibodies whose epitope targets are specifically associated with the inter-fascicular fibre region during the rapid cell expansion phase. The data reveal dynamic, cell type-specific changes in cell-wall chemistry across diverse cell types during cell-wall expansion and maturation in the Arabidopsis inflorescence stem, and highlight the paradox between this structural diversity and the uniform anisotropic cell expansion taking place across all tissues during stem growth.

  20. Excess Early Mortality in Schizophrenia

    DEFF Research Database (Denmark)

    Laursen, Thomas Munk; Nordentoft, Merete; Mortensen, Preben Bo

    2014-01-01

    Schizophrenia is often referred to as one of the most severe mental disorders, primarily because of the very high mortality rates of those with the disorder. This article reviews the literature on excess early mortality in persons with schizophrenia and suggests reasons for the high mortality as ...

  1. A comparison between allogeneic stem cell transplantation from unmanipulated haploidentical and unrelated donors in acute leukemia

    Directory of Open Access Journals (Sweden)

    Simona Piemontese

    2017-01-01

    Full Text Available Abstract Background In the absence of a HLA-matched related or matched unrelated donor, allogeneic stem cell transplantation (allo-SCT from mismatched unrelated donors or haploidentical donors are potential alternatives for patients with acute leukemia with an indication to allo-SCT. The objective of this study was to compare the outcome of allo-SCT from T cell-replete haploidentical (Haplo versus matched (MUD 10/10 or mismatched unrelated donor at a single HLA-locus (MMUD 9/10 for patients with acute leukemia in remission. Methods Two hundred sixty-five adult patients with de novo acute leukemia in first or second remission that received a Haplo-SCT between January 2007 and December 2013 were compared with 2490 patients receiving a MUD 10/10 and 813 receiving a MMUD 9/10. Propensity score weighted analysis was conducted in order to control for disease risk imbalances between the groups. Results The weighted 3-year non-relapse mortality and relapse incidence were 29 and 30% for Haplo, 21 and 29% for MUD 10/10, and 29 and 25% for MMUD 9/10, respectively. The weighted 3-year leukemia-free survival (LFS and overall survival (OS were 41 and 46% for Haplo, 50 and 56% for MUD 10/10, and 46 and 48% for MMUD 9/10, respectively. Using weighted Cox model, both LFS and OS were significantly higher in transplants from MUD 10/10 compared from those in Haplo but not different between transplants from MMUD 9/10 and Haplo. The type of donor was not significantly associated with neither acute nor chronic graft-versus-host disease. Conclusions Patients with acute leukemia in remission have better outcomes if transplanted from a MUD 10/10. We did not find any significant difference in outcome between transplants from MMUD 9/10 and Haplo, suggesting that both can be equally used in the absence of a 10/10 MUD. Key point 1 Better outcomes using fully (10/10 matched unrelated donor for allo-SCT in acute leukemia in remission. Key point 2 Similar outcomes after allo

  2. Delineation of glutamate pathways and secretory responses in pancreatic islets with β-cell-specific abrogation of the glutamate dehydrogenase

    DEFF Research Database (Denmark)

    Vetterli, Laurène; Carobbio, Stefania; Pournourmohammadi, Shirin;

    2012-01-01

    In pancreatic β-cells, glutamate dehydrogenase (GDH) modulates insulin secretion, although its function regarding specific secretagogues is unclear. This study investigated the role of GDH using a β-cell-specific GDH knockout mouse model, called βGlud1(-/-). The absence of GDH in islets isolated ...

  3. Granulocyte Colony-stimulating Factor-primed Bone Marrow: An Excellent Stem-cell Source for Transplantation in Acute Myelocytic Leukemia and Chronic Myelocytic Leukemia

    Institute of Scientific and Technical Information of China (English)

    Yuhang Li; Min Jiang; Chen Xu; Jianlin Chen; Botao Li; Jun Wang; Jiangwei Hu

    2015-01-01

    Background:Steady-state bone marrow (SS-BM) and granulocyte colony-stimulating growth factor-primed BM/peripheral blood stem-cell (G-BM/G-PBSC) are the main stem-cell sources used in allogeneic hematopoietic stem-cell transplantation.Here,we evaluated the treatment effects of SS-BM and G-BM/G-PBSC in human leucocyte antigen (HLA)-identical sibling transplantation.Methods:A total of 226 patients (acute myelogenous leukemia-complete remission 1,chronic myelogenous leukemia-chronic phase 1) received SS-BM,G-BM,or G-PBSC from an HLA-identical sibling.Clinical outcomes (graft-versus-host disease [GVHD],overall survival,transplant-related mortality [TRM],and leukemia-free survival [LFS]) were analyzed.Results:When compared to SS-BM,G-BM gave faster recovery time to neutrophil or platelet (P < 0.05).Incidence of grade Ⅲ-Ⅳ acute GVHD and extensive chronic GVHD (cGVHD) was lower than seen with SS-BM (P < 0.05) and similar to G-PBSC.Although the incidence of cGVHD in the G-BM group was similar to SS-BM,both were lower than G-PBSC (P < 0.05).G-BM and G-PBSC exhibited similar survival,LFS,and TRM,but were significantly different from SS-BM (P < 0.05).There were no significant differences in leukemia relapse rates among the groups (P > 0.05).Conclusions:G-CSF-primed bone marrow shared the advantages of G-PBSC and SS-BM.We conclude that G-BM is an excellent stem-cell source that may be preferable to G-PBSC or SS-BM in patients receiving HLA-identical sibling hematopoietic stem-cell transplantation.

  4. Overexpression of Rac1 in leukemia patients and its role in leukemia cell migration and growth

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Jiying [State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 288 Nanjing Road, Tianjin 300020 (China); Rao, Qing, E-mail: raoqing@gmail.com [State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 288 Nanjing Road, Tianjin 300020 (China); Wang, Min; Wei, Hui; Xing, Haiyan; Liu, Hang; Wang, Yanzhong; Tang, Kejing; Peng, Leiwen; Tian, Zheng; Wang, Jianxiang [State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 288 Nanjing Road, Tianjin 300020 (China)

    2009-09-04

    Rac1 belongs to the Rho family that act as critical mediators of signaling pathways controlling cell migration and proliferation and contributes to the interactions of hematopoietic stem cells with their microenvironment. Alteration of Rac1 might result in unbalanced interactions and ultimately lead to leukemogenesis. In this study, we analyze the expression of Rac1 protein in leukemia patients and determine its role in the abnormal behaviours of leukemic cells. Rac1 protein is overexpressed in primary acute myeloid leukemia cells as compared to normal bone marrow mononuclear cells. siRNA-mediated silencing of Rac1 in leukemia cell lines induced inhibition of cell migration, proliferation, and colony formation. Additionally, blocking Rac1 activity by an inhibitor of Rac1-GTPase, NSC23766, suppressed cell migration and growth. We conclude that overexpression of Rac1 contributes to the accelerated migration and high proliferation potential of leukemia cells, which could be implicated in leukemia development and progression.

  5. Stillbirth and Infant Mortality

    DEFF Research Database (Denmark)

    Nøhr, Ellen Aagaard

    2012-01-01

    mechanisms behind these associations remain largely unknown. Although maternal obesity is associated with a wide range of complications in the mother and neonate that may impair fetal and infant survival, the increased risk of stillbirth and infant mortality is virtually unchanged when accounting...... indicating that some of the excess risk may have a placental origin. To further understand the associations between maternal obesity and late fetal and infant death, we need better and more detailed clinical data, which is difficult to obtain on a population level given the rarity of the outcomes. The best...

  6. Decitabine and Valproic Acid in Treating Patients With Refractory or Relapsed Acute Myeloid Leukemia or Previously Treated Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

    Science.gov (United States)

    2013-09-27

    Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Recurrent Adult Acute Myeloid Leukemia; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Untreated Adult Acute Myeloid Leukemia

  7. Acute lymphoblastic leukemia with pregnancy: a rare case

    Directory of Open Access Journals (Sweden)

    Surbhi Bhargava

    2015-06-01

    Full Text Available Pregnancy complicated with leukemia is rare. Validated data out of which conclusions may be drawn regarding management of pregnancy with leukemia are sparse. [Int J Reprod Contracept Obstet Gynecol 2015; 4(3.000: 887-888

  8. Acute lymphoblastic leukemia with pregnancy: a rare case

    OpenAIRE

    2015-01-01

    Pregnancy complicated with leukemia is rare. Validated data out of which conclusions may be drawn regarding management of pregnancy with leukemia are sparse. [Int J Reprod Contracept Obstet Gynecol 2015; 4(3.000): 887-888

  9. AR-42 and Decitabine in Treating Patients With Acute Myeloid Leukemia

    Science.gov (United States)

    2016-04-21

    Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  10. Leukemia in donor cells after allogeneic hematopoietic stem cell transplant

    OpenAIRE

    2002-01-01

    The development of leukemia in donor cells after allogeneic hematopoietic stem cell transplant is an extremely rare event. We report here the case of a patient who developed myelodysplastic syndrome/acute myeloid leukemia, in cells of donor origin 3.5 years after related donor HSCT for refractory chronic lymphocytic leukemia and therapy-induced myelodysplastic syndrome. The origin of the leukemia was determined by analysis of minisatillite polymorphism tested on CD34(+) cells.

  11. Cord blood transplantation for the treatment of acute leukemia

    Institute of Scientific and Technical Information of China (English)

    Meerim Park; Young-ho Lee

    2013-01-01

    Objective This review discussed the available data on treatment outcomes of cord blood transplantation (CBT) for acute leukemia.Data sources The data cited in this review were obtained from articles listed in Medline and Pubmed.Study selection We reviewed the articles of clinical results from various registries and institutions,as well as our experiences with CBT in children,adolescents and adults.Results This research has clearly shown that cord blood (CB) has several unique characteristics resulting in distinct advantage and disadvantages when compared to transplantation with unrelated donor bone marrow or peripheral blood stem cells.The field of CBT has advanced from investigating its safety and feasibility to addressing more specific issues such as accelerating engraftment,extending access,and examining outcomes in specific subgroups of patients.Many approaches have been investigated in the attempt to improve engraftment and survival.Variable factors have been identified,such as factors related to donor choice (human leukocyte antigen (HLA) compatibility,cell dose,and others) and transplantation (conditioning and graft-versus-host disease prophylaxis regimen).Data support that CB should be considered a reasonable option in those that do not have HLA matched sibling donor and for those in whom the time to transplant is critical.Conclusions CB is a reasonable alternative to unrelated donor bone marrow or peripheral blood progenitor cells for transplantation.Recently developed strategies aimed at improving hematopoietic recovery and reducing early transplantation-related mortality could further improve treatment outcomes of CBT for patients with acute leukemia.

  12. KRAS (G12D Cooperates with AML1/ETO to Initiate a Mouse Model Mimicking Human Acute Myeloid Leukemia

    Directory of Open Access Journals (Sweden)

    Shanmin Zhao

    2014-01-01

    Full Text Available Background/Aims: It has been demonstrated that KRAS mutations represent about 90% of cancer-associated mutations, and that KRAS mutations play an essential role in neoplastic transformation. Cancer-associated RAS mutations occur frequently in acute myeloid leukemia (AML, suggesting a functional role for Ras in leukemogenesis. Methods: We successfully established a mouse model of human leukemia by transplanting bone marrow cells co-transfected with the K-ras (G12D mutation and AML1/ETO fusion protein. Results: Mice transplanted with AML/ETO+KRAS co-transduced cells had the highest mortality rate than mice transplanted with AML/ETO- or KRAS-transduced cells (115d vs. 150d. Upon reaching a terminal disease stage, EGFP-positive cells dominated their spleen, lymph nodes, peripheral blood and central nervous system tissue. Immunophenotyping, cytologic analyses revealed that AML/ETO+KRAS leukemias predominantly contained immature myeloid precursors (EGFP+/c-Kit+/Mac-1-/Gr-1-. Histologic analyses revealed that massive leukemic infiltrations were closely packed in dense sheets that effaced the normal architecture of spleen and thymus in mice transplanted with AML1/ETO + KRAS co-transduced cells. K-ras mRNA and protein expression were upregulated in bone marrow cells of the K-ras group and AML1/ETO + Kras group. The phosphorylation of MEK/ERK was significantly enhanced in the AML1/ETO + Kras group. The similar results of the AML1/ETO + Nras group were consistent with those reported previously. Conclusion: Co-transduction of KrasG12D and AML1/ETO induces acute monoblastic leukemia. Since expression of mutant K-ras alone was insufficient to induce leukemia, this model may be useful for investigating the multi-step leukemogenesis model of human leukemia.

  13. In vitro radiosensitivity of human leukemia cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Weichselbaum, R.R.; Greenberger, J.S.; Schmidt, A.; Karpas, A.; Moloney, W.C.; Little, J.B.

    1981-05-01

    The in vitro radiobiologic survival values (anti n, D/sub 0/) of four tumor lines derived from human hematopoietic tumors were studied. These cell lines were HL60 promyelocytic leukemia; K562 erythroleukemia; 45 acute lymphocytic leukemia; and 176 acute monomyelogenous leukemia. More cell lines must be examined before the exact relationship between in vitro radiosensitivity and clinical radiocurability is firmly established.

  14. Acute Myeloid Leukemia - Genetics Home Reference [Genetics Home Reference (Conditions)

    Lifescience Database Archive (English)

    Full Text Available Conditions Genes Chromosomes Handbook Glossary Resources Conditions > Acute Myeloid...te myeloid leukemia with mutated CEBPA Fanconi anemia You may also search Genetics Home Reference for Acut...e Myeloid Leukemia for additional information. Published : October 27, 2014 Acute Myeloid Leukemia - Genetics Home Reference ...

  15. The MLL recombinome of acute leukemias in 2013

    DEFF Research Database (Denmark)

    Meyer, C; Hofmann, Julian; Burmeister, T;

    2013-01-01

    Chromosomal rearrangements of the human MLL (mixed lineage leukemia) gene are associated with high-risk infant, pediatric, adult and therapy-induced acute leukemias. We used long-distance inverse-polymerase chain reaction to characterize the chromosomal rearrangement of individual acute leukemia ...

  16. Arsenic Trioxide in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

    Science.gov (United States)

    2016-10-04

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Recurrent Adult Acute Myeloid Leukemia

  17. How I treat leukemia during pregnancy.

    Science.gov (United States)

    Milojkovic, Dragana; Apperley, Jane F

    2014-02-13

    Leukemia in pregnancy remains a challenging therapeutic prospect. The prevalence is low at ∼1 in 10 000 pregnancies, and as a result data are limited to small retrospective series and case reports, rendering evidence-based recommendations for management strategies difficult. The management of the leukemias in pregnancy requires close collaboration with obstetric and neonatology colleagues as both the maternal and fetal outcomes must be taken into consideration. The decision to introduce or delay chemotherapy must be balanced against the impact on maternal and fetal survival and morbidity. Invariably, acute leukemia diagnosed in the first trimester necessitates intensive chemotherapy that is likely to induce fetal malformations. As delaying treatment in this situation is usually inappropriate, counseling with regard to termination of pregnancy is often essential. For chronic disease and acute leukemia diagnosed after the second trimester, therapeutic termination of the pregnancy is not inevitable and often, standard management approaches similar to those in nongravid patients can be used. Here, the management of the acute and chronic leukemias will be addressed.

  18. Analysis of the mortality among Cogema workers monitored for external radiation exposure

    Energy Technology Data Exchange (ETDEWEB)

    Metz-Flamant, C.; Hitz, M.; Samson, E.; Rogel, A.; Telle-Lamberton, M.; Tirmarche, M. [Institut de Radioprotection et de Surete Nucleaire (IRSN), 92 - Fontenay-aux-Roses (France); Caer, S.; Quesne, B. [Cogema, Coordination Medicale, 78 - Velizy-Villacoublay (France)

    2006-07-01

    The present study follows 9287 Cogema workers exposed to low level of ionizing radiation from the beginning of employment to the end of 1994. This paper presents analyses of the mortality of Cogema workers monitored for external radiation exposure and the relation between their mortality and their cumulative external radiation dose. Workers were followed up for an average of 13 years. The percentage of subjects lost to follow up was less than 1%. during the follow-up period, 441 deaths occurred. The mean cumulative dose among the whole cohort was 19.4 mSv. As expected, the mortality of the cohort was lower than that of the French national population. The healthy worker effect is often observed in other nuclear workers studies. Part of the healthy worker effect is explained by a proportion of unemployed persons in general population, with a higher mortality rate. All causes S.M.R. increased with calendar period and duration of employment. this increase was not significant for all cancers S.M.R. by duration of employment. This could illustrate the decrease of the initial selection at employment with time. A significant increase in risk was observed for all cancers excluding leukemia mortality with increase of radiation dose in the 15-country study. Significant excess of leukemia by cumulative radiation exposure was observed in the 3-country study and was borderline significant in the 15-country study and in the UK National register for radiation workers study. A positive trend, not statistically significant, by level of external doses was observed in our study for all cancers and leukemia excluding chronic lymphatic leukemia mortality, but the analyses lack of statistical power. A significant trend was observed only for non-Hodgkin lymphoma death, but considering the large number of statistic tests computed, this result must be carefully interpreted. A borderline significant trend was observed for lung cancer death, a significant increase risk of lung cancer death

  19. Acute promyelocytic leukemia and pregnancy.

    Science.gov (United States)

    Giagounidis, A A; Beckmann, M W; Giagounidis, A S; Aivado, M; Emde, T; Germing, U; Riehs, T; Heyll, A; Aul, C

    2000-04-01

    In acute promyelocytic leukemia (APL), the use of all-trans-retinoic acid (ATRA) as a differentiating agent induces complete remission in a high percentage of patients. In pregnancy, however, this drug bears the risk of severe teratogenicity to the child. We report the case of a 23-yr-old woman at 21 weeks' gestation suffering from APL. She was treated with ATRA (45 mg/m2) for 40 d and two courses of standard chemotherapy. The mother achieved complete remission within 22 d of treatment. Fetal development was normal, and a healthy premature girl was born in the 35th week of pregnancy. In a review of the literature we have identified 14 cases of APL in pregnancy treated with ATRA alone or in combination with chemotherapy. ATRA has been used as early as in the 3rd week of gestation and in no case have malformations or other teratogenic effects occurred. Side-effects, however, ranged from fetal cardiac arrhythmias to induction of labour. Although known to exhibit severe teratogenic effects during the first trimester of pregnancy, ATRA seems to be reasonably safe during the second and third trimesters in the treatment of APL. However, careful obstetric follow-up is mandatory regarding fetal cardiac complications.

  20. Obinutuzumab for chronic lymphocytic leukemia.

    Science.gov (United States)

    Rioufol, Catherine; Salles, Gilles

    2014-10-01

    Chronic lymphocytic leukemia (CLL) is a frequent hematological malignancy that is incurable using standard approaches. Two anti-CD20 monoclonal antibodies (mAb), rituximab and ofatumumab, have been approved for CLL treatment. A new glycoengineered type II humanized anti-CD20 mAb, obinutuzumab (GA101), has been developed and demonstrates increased activity against B-cell malignancies by inducing direct cell death and better antibody-dependent cellular cytotoxicity. In a recent randomized Phase III study in patients with newly diagnosed CLL and coexisting conditions, obinutuzumab plus chlorambucil demonstrated significant improvement in progression-free survival and several other outcome parameters, in contrast to rituximab plus chlorambucil. Grade 3-4 infusion-related reactions and neutropenia occurred more frequently in patients who received obinutuzumab compared with those who received rituximab; however, the rate of serious infections was similar. Obinutuzumab represents a promising new option for patients with CLL and must be investigated with other chemotherapy regimens or with new targeted agents.

  1. Temporal gene expression profile of human precursor B leukemia cells induced by adhesion receptor: identification of pathways regulating B-cell survival.

    Science.gov (United States)

    Astier, Anne Laurence; Xu, Ronghui; Svoboda, Marek; Hinds, Esther; Munoz, Olivier; de Beaumont, Rosalie; Crean, Colin Daniel; Gabig, Theodore; Freedman, Arnold Stephen

    2003-02-01

    The physical interactions between B cells and stromal cells from the lymphoid tissue microenvironment are critical to the survival of normal and malignant B cells. They are principally mediated by integrins expressed on B cells and counterreceptors on stromal cells. Specifically, alpha4beta1 integrin engagement rescues B cells from physiological or drug-induced apoptosis. Therefore, in order to understand the mechanisms by which integrins prevent apoptosis in leukemia B cells, we compared the temporal gene expression profiles induced by beta1-integrin ligation with fibronectin (Fn) or adhesion by poly-L-Lysine in serum-starved precursor B leukemia cells. Among the 38 selected differentially expressed genes, 6 genes involved in adhesion (VAV2, EPB41L1, CORO1A), proliferation (FRAP1, CCT4), and intercellular communication (GJB3) were validated by real-time quantitative polymerase chain reaction (RT-Q-PCR). Gene expression modulation could also be validated at the protein level for 5 other genes. We show that integrin stimulation up-regulated FBI-1 expression but inhibited CD79a, Requiem, c-Fos, and caspase 7 induction when the cells underwent apoptosis. We further demonstrate that Fn stimulation also inhibits caspase 3 activation but increases XIAP and survivin expression. Moreover, integrin stimulation also prevents caspase activation induced by doxorubicin. Therefore, we identified genes modulated by adhesion of human precursor B leukemia cells that regulate proliferation and apoptosis, highlighting new pathways that might provide insights into future therapy aiming at targeting apoptosis of leukemia cells.

  2. Bacillus cereus bacteremia and multiple brain abscesses during acute lymphoblastic leukemia induction therapy.

    Science.gov (United States)

    Hansford, Jordan R; Phillips, Marianne; Cole, Catherine; Francis, Joshua; Blyth, Christopher C; Gottardo, Nicholas G

    2014-04-01

    Bacillus cereus can cause serious infections in immunosuppressed patients. This population may be susceptible to B. cereus pneumonia, bacteremia, cellulitis, and rarely cerebral abscess. Here we report an 8-year-old boy undergoing induction therapy for acute lymphoblastic leukemia who developed multifocal B. cereus cerebral abscesses, highlighting the propensity for B. cereus to develop cerebral abscesses. A review of the literature over the past 25 years identified another 11 cases (3 children and 8 adults) of B. cereus cerebral abscess in patients undergoing cancer therapy. B. cereus cerebral abscesses were associated with a high mortality rate (42%) and significant morbidity. Notably, B. cereus bacteremia with concomitant cerebral abscess was associated with induction chemotherapy for acute leukemia in both children and adults (10 of 12 case reports). Our case report and review of the literature highlights the propensity for B. cereus to develop cerebral abscess(es). Therefore, early consideration for neuroimaging should be given for any neutropenic cancer patient identified with B. cereus bacteremia, in particular those with acute leukemia during induction therapy.

  3. Allogeneic stem cell transplantation for advanced acute promyelocytic leukemia in the ATRA and ATO era.

    Science.gov (United States)

    Ramadan, Safaa M; Di Veroli, Ambra; Camboni, Agnese; Breccia, Massimo; Iori, Anna Paola; Aversa, Franco; Cupelli, Luca; Papayannidis, Cristina; Bacigalupo, Andrea; Arcese, William; Lo-Coco, Francesco

    2012-11-01

    The role of allogeneic stem cell transplant in advanced acute promyelocytic leukemia patients who received standard first- and second-line therapy is still unknown. We report the outcome of 31 acute promyelocytic leukemia patients (median age 39 years) who underwent allogeneic transplant in second remission (n=15) or beyond (n=16). Sixteen patients were real-time polymerase chain reaction positive and 15 negative for PML/RARA pre-transplant. The 4-year overall survival was 62% and 31% for patients transplanted in second remission and beyond, respectively (P=0.05), and 64% and 27% for patients with pre-transplant negative and positive real-time polymerase chain reaction, respectively (P=0.03). The 4-year cumulative incidence of relapse was 32% and 44% for patients transplanted in second remission and beyond, respectively (P=0.37), and 30% and 47% for patients transplanted with negative and positive real-time polymerase chain reaction, respectively (P=0.30). Transplant-related mortality was 19.6%. In conclusion, allogeneic transplant is effective in advanced acute promyelocytic leukemia in the all-trans-retinoic acid and arsenic trioxide era, and should be considered once relapse is diagnosed.

  4. Maternal mortality due to trauma.

    Science.gov (United States)

    Romero, Vivian Carolina; Pearlman, Mark

    2012-02-01

    Maternal mortality is an important indicator of adequacy of health care in our society. Improvements in the obstetric care system as well as advances in technology have contributed to reduction in maternal mortality rates. Trauma complicates up to 7% of all pregnancies and has emerged as the leading cause of maternal mortality, becoming a significant concern for the public health system. Maternal mortality secondary to trauma can often be prevented by coordinated medical care, but it is essential that caregivers recognize the unique situation of providing simultaneous care to 2 patients who have a complex physiologic relationship. Optimal management of the pregnant trauma victim requires a multidisciplinary team, where the obstetrician plays a central role. This review focuses on the incidence of maternal mortality due to trauma, the mechanisms involved in traumatic injury, the important anatomic and physiologic changes that may predispose to mortality due to trauma, and finally, preventive strategies that may decrease the incidence of traumatic maternal death.

  5. Solar radiation and the incidence and mortality of leading invasive cancers in the United States

    Science.gov (United States)

    Fleischer, Alan B.; Fleischer, Sarah E.

    2016-01-01

    ABSTRACT Invasive cancer risk is inversely related to ultraviolet light exposure. This study explores relationships between cancer and the satellite-derived sunlight energy. We obtained the North America Land Data Assimilation System (NLDAS) daily average sunlight for the continental United States from 1999–2011. US Cancer Statistics age-adjusted-incidence and mortality was also obtained from the Centers for Disease Control and Prevention (CDC). We found that cancer incidence for all invasive cancers and for 11 of 22 leading cancers significantly decreased with increased solar radiation. Cancer mortality for all invasive cancers was not significantly associated with solar radiation, but for 7 of 22 leading cancers, including cancers of the uterus, leukemias, lung, ovary, and urinary bladder, increased solar radiation predicted decreased mortality. With increasing solar radiation, increased incidence and cancer mortality was observed for liver cancer and increased incidence but not mortality was observed for cervical cancer. The current study confirms studies relating UV radiation to the incidence and mortality of a variety of cancer types. We find associations between solar radiation energy and the incidence and mortality of a number of types of cancers. PMID:27195056

  6. Solar radiation and the incidence and mortality of leading invasive cancers in the United States.

    Science.gov (United States)

    Fleischer, Alan B; Fleischer, Sarah E

    2016-01-01

    Invasive cancer risk is inversely related to ultraviolet light exposure. This study explores relationships between cancer and the satellite-derived sunlight energy. We obtained the North America Land Data Assimilation System (NLDAS) daily average sunlight for the continental United States from 1999-2011. US Cancer Statistics age-adjusted-incidence and mortality was also obtained from the Centers for Disease Control and Prevention (CDC). We found that cancer incidence for all invasive cancers and for 11 of 22 leading cancers significantly decreased with increased solar radiation. Cancer mortality for all invasive cancers was not significantly associated with solar radiation, but for 7 of 22 leading cancers, including cancers of the uterus, leukemias, lung, ovary, and urinary bladder, increased solar radiation predicted decreased mortality. With increasing solar radiation, increased incidence and cancer mortality was observed for liver cancer and increased incidence but not mortality was observed for cervical cancer. The current study confirms studies relating UV radiation to the incidence and mortality of a variety of cancer types. We find associations between solar radiation energy and the incidence and mortality of a number of types of cancers.

  7. Cell-specific detection of microRNA expression during cardiomyogenesis by combined in situ hybridization and immunohistochemistry

    DEFF Research Database (Denmark)

    Schneider, Mikael; Andersen, Ditte Caroline; Silahtaroglu, Asli

    2011-01-01

    . However, although several miRNAs have been identified as differentially regulated during cardiac development and disease, their distinct cell-specific localization remains largely undetermined, likely owing to a lack of adequate methods. We therefore report the development of a markedly improved approach...... combining fluorescence-based miRNA-in situ hybridization (miRNA-ISH) with immunohistochemistry (IHC). We have applied this protocol to differentiating embryoid bodies (EBs) as well as embryonic and adult mouse hearts, to detect miRNAs that were upregulated during EB cardiomyogenesis, as determined by array...... present highlight the importance of determining exact cell-specific localization of miRNAs by sequential miRNA-ISH and IHC in studies aiming at understanding the role of miRNAs and their targets. This approach will hopefully aid in identifying relevant miRNA targets of both the heart and other organs....

  8. Management of acute myeloid leukemia during pregnancy.

    Science.gov (United States)

    Avivi, Irit; Brenner, Benjamin

    2014-06-01

    Diagnosis of acute leukemia during pregnancy presents significant medical challenges. Pancytopenia, caused by bone marrow substitution with leukemic cells, impairs maternal and fetal health. Chemotherapeutic agents required to be immediately used to save the mother's life are likely to adversely affect fetal development and outcome, especially if administered at an early gestational stage. Patients diagnosed with acute leukemia during the first trimester are, therefore, recommended to undergo pregnancy termination. At later gestational stages, antileukemic therapy can be administered, although in this case, fetal outcome is still associated with increased incidence of growth restriction and loss. Special attention to the issue of future reproduction, adopting a personalized fertility preservation approach, is required. This article addresses these subjects, presenting women diagnosed with acute myeloid and acute promyelocytic leukemia in pregnancy. The rarity of this event, resulting in insufficient data, emphasizes the need for collaborative efforts to optimize management of this complicated clinical condition.

  9. Acute myeloid leukemia in the pregnant patient.

    Science.gov (United States)

    Thomas, Xavier

    2015-08-01

    Although acute myeloid leukemia (AML) mostly occurs in older patients, it could be seen in women of childbearing age. It is therefore not surprising that in some patients, the management of AML will be complicated by a coexistent pregnancy. However, the association of leukemia and pregnancy is uncommon. Its incidence is estimated to be 1 in 75,000-100,000 pregnancies. During pregnancy, most leukemias are acute: two-thirds are myeloid and one-third are lymphoblastic. There is no standard approach for this clinical dilemma, in part because of variables such as the type of AML, the seriousness of the symptoms, and the patient's personal beliefs. In many cases, the diagnostic workup has to be altered because of the pregnancy, and often available treatments have varying risks to the fetus. While chemotherapy is reported to have some risks during the first trimester, it is admitted that it can be administered safely during the second and the third trimesters.

  10. Gender difference in child mortality.

    Science.gov (United States)

    Ahmed, F A

    1990-12-01

    1976 census data and data on births to 8788 ever married women from the 1980 Egyptian Fertility Survey were analyzed to determine if son preference was responsible for higher mortality among girls than among boys and what factors were associated with this higher mortality. During 0-3 years, boys were more likely to die than females. For example, the overall male-female sex ratio for the 1st year was 118:100. At ages 5, 10, 15, and 2 0, however, girls were more likely to die. The sex rations for these years were 98, 95, 93, and 91. In fact, the excess mortality among illiterate mothers accounted for most of the overall excess mortality. As mother's educational level rose, the excess mortality of girls fell, so that by university level boys experienced excess mortality (130, 111, 112, 105). Less educated mothers breast fed sons longer and waited more months after birth of a son to have another child indicating son preference, but these factors did not necessarily contribute to excess mortality. The major cause of female excess mortality in Egypt was that boys received favored treatment of digestive and respiratory illnesses as indicated by accessibility to a pharmacy (p.01). Norms/traditions and religion played a significant role in excess mortality. The effect of norms/traditions was greater than religion, however. Mother's current and past employment strongly contributed to reducing girls' mortality levels (p.01). These results indicated that Egypt should strive to increase the educational level of females and work opportunities for women to reduce female child mortality. Further, it should work to improve women's status which in turn will reduce norms/traditions that encourage son preference and higher mortality level for girls.

  11. Determination and comparison of incidence rate and trend ofmorbidity of leukemia and lymphoma in Mazandaran province (1376-1382

    Directory of Open Access Journals (Sweden)

    B. Tahmasebi

    2006-01-01

    Full Text Available Background and purpose: Malignancies are the second most important cause of mortality in many countries. Leukemia and lymphoma happen with significantly high incidence rates throughout the world particularly in Iran where it causes remarkable mortality as well as high diagnosis and treatment expenditures for both families and health system. Leukemia and lymphoma totally include about 11 percent of cancers in Mazandaran province. The purpose of this study was a general and specific description of leukemia and lymphoma in Mazandaran province.Materials and Methods: In this study, the medical records of all patients with certain diagnosis of leukemia and lymphoma along with valid laboratory or pathology reports were reviewed from 1376-1382. Data collection was undertaken by Babol health research center affiliated to Tehran University Medical Sciences. This research consists of cross-sectional, descriptive and analytic studies and examines variables including: age, sex, city of inhabitation, year of incidence and type of malignancy. The incidence rates in 100,000 persons of related population have been calculated and analyzed.Results: In Mazandaran province, 1146 cases of leukemia (lymphoidic and myeloidic and lymphoma (Hodgkin's and non Hodgkin's were diagnosed from 1376-1382. an average of 5.9 leukemia and lymphoma cases per 100,000 occure annually. The highest incidence rates were obtained at age of 70 or above (26.4 and the least at age of 0-9 (2.26.The incidence rates in males and females were 7.05 and 4.76 respectively and the male to female incidence rate was 1.48. The highest incidence rate was observed in Babol (7.29 and the least was equally calculated in Neka and Tonekabon (1.47. The highest and lowest incidence were obtained in 1380 (7.75 and 1377 (3.15 respectively. Regarding the type of malignancy, non Hodgkin lymphoma, 2.53 in 100000 persons, was the most prevalent and myeloidic leukemia, 1.07 in 100000 persons, the least prevalent

  12. Boswellia sacra essential oil induces tumor cell-specific apoptosis and suppresses tumor aggressiveness in cultured human breast cancer cells

    OpenAIRE

    Suhail Mahmoud M; Wu Weijuan; Cao Amy; Mondalek Fadee G; Fung Kar-Ming; Shih Pin-Tsen; Fang Yu-Ting; Woolley Cole; Young Gary; Lin Hsueh-Kung

    2011-01-01

    Abstract Background Gum resins obtained from trees of the Burseraceae family (Boswellia sp.) are important ingredients in incense and perfumes. Extracts prepared from Boswellia sp. gum resins have been shown to possess anti-inflammatory and anti-neoplastic effects. Essential oil prepared by distillation of the gum resin traditionally used for aromatic therapy has also been shown to have tumor cell-specific anti-proliferative and pro-apoptotic activities. The objective of this study was to opt...

  13. Caspofungin Acetate or Fluconazole in Preventing Invasive Fungal Infections in Patients With Acute Myeloid Leukemia Who Are Undergoing Chemotherapy

    Science.gov (United States)

    2017-01-31

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Childhood Acute Erythroleukemia (M6); Childhood Acute Megakaryocytic Leukemia (M7); Childhood Acute Minimally Differentiated Myeloid Leukemia (M0); Childhood Acute Monoblastic Leukemia (M5a); Childhood Acute Monocytic Leukemia (M5b); Childhood Acute Myeloblastic Leukemia With Maturation (M2); Childhood Acute Myeloblastic Leukemia Without Maturation (M1); Childhood Acute Myeloid Leukemia in Remission; Childhood Acute Myelomonocytic Leukemia (M4); Fungal Infection; Neutropenia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia; Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies

  14. Adult mortality in preindustrial Quebec

    Directory of Open Access Journals (Sweden)

    Claudine Lacroix - - - Bertrand Desjardins

    2012-01-01

    Full Text Available This paper presents the main results of a detailed study on adult mortality in French Canadians born before 1750 and having married inthe colony of New France. Using data from parish registers, mortality is studied using abridged life tables, with staggered entries according to age at first marriage. Survival tables and log-Rank tests are used to support the results. Three features were selected for the study of differential mortality: gender, type of residence area (urban or rural, and cohort. The mortality of French Canadians is compared to that of their French contemporaries.

  15. Classification differences and maternal mortality

    DEFF Research Database (Denmark)

    Salanave, B; Bouvier-Colle, M H; Varnoux, N;

    1999-01-01

    of experts into obstetric or non-obstetric causes. An ICD-9 code (International Classification of Diseases) was attributed to each case. These were compared to the codes given in each country. Correction indices were calculated, giving new estimates of maternal mortality rates. SUBJECTS: There were....... This change was substantial in three countries (P maternal mortality rate for participating countries was 7.7 per...... and consequently affect maternal mortality rates. Differences in classification of death must be taken into account when comparing maternal mortality rates, as well as differences in obstetric care, underreporting of maternal deaths and other factors such as the age distribution of mothers....

  16. Synthesis of fluorescent dye-doped silica nanoparticles for target-cell-specific delivery and intracellular microRNA imaging.

    Science.gov (United States)

    Li, Henan; Mu, Yawen; Qian, Shanshan; Lu, Jusheng; Wan, Yakun; Fu, Guodong; Liu, Songqin

    2015-01-21

    MicroRNA (miRNA) is found to be up-regulated in many kinds of cancer and therefore is classified as an oncomiR. Herein, we design a multifunctional fluorescent nanoprobe (FSiNP-AS/MB) with the AS1411 aptamer and a molecular beacon (MB) co-immobilized on the surface of the fluorescent dye-doped silica nanoparticles (FSiNPs) for target-cell-specific delivery and intracellular miRNA imaging. The FSiNPs were prepared by a facile reverse microemulsion method from tetraethoxysilane and silane derivatized coumarin that was previously synthesized by click chemistry. The as-prepared FSiNPs possess uniform size distribution, good optical stability and biocompatibility. In addition, there is a remarkable affinity interaction between the AS1411 aptamer and the nucleolin protein on the cancer cell surface. Thus, a target-cell-specific delivery system by the FSiNP-AS/MB is proposed for effectively transferring a MB into the cancer cells to recognize the target miRNA. Using miRNA-21 in MCF-7 cells (a human breast cancer cell line) as a model, the proposed multifunctional nanosystems not only allow target-cell-specific delivery with the binding affinity of AS1411, but also can track simultaneously the transfected cells and detect intracellular miRNA in situ. The proposed multifunctional nanosystems are a promising platform for a highly sensitive luminescent nonviral vector in biomedical and clinical research.

  17. The Impact of Lipoprotein-Associated Oxidative Stress on Cell-Specific Microvesicle Release in Patients with Familial Hypercholesterolemia

    Directory of Open Access Journals (Sweden)

    M. H. Nielsen

    2016-01-01

    Full Text Available Objective. Microvesicles (MVs are small cell-derived particles shed upon activation. Familial hypercholesterolemia (FH particularly when associated with Achilles tendon xanthomas (ATX predisposes to atherosclerosis, possibly through oxLDL-C interaction with the CD36 receptor. To investigate the hypothesis that MVs derived from cells involved in atherosclerosis are increased in FH and that CD36 expressing MVs (CD36+ MVs may be markers of oxLDL-C-induced cell activation, cell-specific MVs were measured in FH patients with and without ATX and their association with atherogenic lipid profile was studied. Approach and Results. Thirty FH patients with and without ATX and twenty-three controls were included. Plasma concentrations of MVs and CD36+ MVs derived from platelets (PMVs, erythrocytes (ErytMVs, monocytes (MMVs, and endothelial cells (EMVs, as well as tissue factor-positive cells (TF+ MVs, were measured by flow cytometry. Total MVs, MMVs, EMVs, ErytMVs, and TF+ MVs were significantly increased in FH patients, compared to controls. CD36+ MVs derived from endothelial cells and monocytes were significantly higher in FH patients and oxLDL-C predicted all the investigated cell-specific CD36+ MVs in FH patients with ATX. Conclusions. MVs derived from cells involved in atherosclerosis were increased in FH and may contribute to elevated atherothrombosis risk. The increased cell-specific CD36+ MVs observed in FH may represent markers of oxLDL-C-induced cell activation.

  18. Psychological Risk Factors in Acute Leukemia

    Directory of Open Access Journals (Sweden)

    Gouva M.

    2009-04-01

    Full Text Available Several theoretical models have been occasionally proposed to account for the involvement of psychological factors in cancer genesis. Family environment and relations as well as certain personality traits were correlated to cancer onset. However, little is known in the case of acute leukemia. The present study examined family environment, state-trait anxiety, hostility and the direction of hostility as well as alexithymia in 41 acute leukemia patients and their first degree relatives (70. In accordance with previous findings, the present results showed that family cohesion, conflict and organization as well as guilt, state anxiety and alexithymia were significant risk factors for the development of the disease.

  19. Allogeneic stem-cell transplantation in patients with refractory acute leukemia: a long-term follow-up.

    Science.gov (United States)

    Oyekunle, A A; Kröger, N; Zabelina, T; Ayuk, F; Schieder, H; Renges, H; Fehse, N; Waschke, O; Fehse, B; Kabisch, H; Zander, A R

    2006-01-01

    We examined retrospectively 44 patients with refractory acute leukemia (acute myeloid leukemia (AML)/acute lymphoblastic leukemia=25/19) who underwent allogeneic transplantation at our center between 11/1990 and 04/2004. The median leukemic blasts was 25% and age 28 years (range, 3-56). Twenty-one patients had untreated relapse, 13 failed reinduction, eight in partial remission and two aplastic. Conditioning was myeloablative using cyclophosphamide, busulfan, total-body irradiation and etoposide (Bu/Cy/VP, n=22; TBI/Cy/VP, n=17; others, n=5) followed by marrow or peripheral blood transplant (n=23/21) from unrelated or related donors (n=28/16). All patients had graft-versus-host disease (GVHD) prophylaxis with cyclosporin and methotrexate. One patient experienced late graft failure. Severe acute-GVHD and chronic-GVHD appeared in eight and 14 patients, respectively. Thirteen patients (30%) remain alive after a median of 25.3 months (range, 2.4-134.1); with 31 deaths, mostly from relapse (n=15) and infections (n=12). Overall survival (OS) and progression-free survival (PFS) at 5 years was 28 and 26%, respectively. OS and PFS were significantly better with blasts < or =20% and time to transplant < or =1 year while transplant-related mortality was less with the use of TBI. We conclude that patients with refractory leukemia can benefit from allogeneic BMT, especially with < or =20% marrow blast.

  20. Prevalence of Gene Rearrangements in Mexican Children with Acute Lymphoblastic Leukemia: A Population Study—Report from the Mexican Interinstitutional Group for the Identification of the Causes of Childhood Leukemia

    Directory of Open Access Journals (Sweden)

    Vilma Carolina Bekker-Méndez

    2014-01-01

    Full Text Available Mexico has one of the highest incidences of childhood leukemia worldwide and significantly higher mortality rates for this disease compared with other countries. One possible cause is the high prevalence of gene rearrangements associated with the etiology or with a poor prognosis of childhood acute lymphoblastic leukemia (ALL. The aims of this multicenter study were to determine the prevalence of the four most common gene rearrangements [ETV6-RUNX1, TCF3-PBX1, BCR-ABL1, and MLL rearrangements] and to explore their relationship with mortality rates during the first year of treatment in ALL children from Mexico City. Patients were recruited from eight public hospitals during 2010–2012. A total of 282 bone marrow samples were obtained at each child’s diagnosis for screening by conventional and multiplex reverse transcription polymerase chain reaction to determine the gene rearrangements. Gene rearrangements were detected in 50 (17.7% patients. ETV6-RUNX1 was detected in 21 (7.4% patients, TCF3-PBX1 in 20 (7.1% patients, BCR-ABL1 in 5 (1.8% patients, and MLL rearrangements in 4 (1.4% patients. The earliest deaths occurred at months 1, 2, and 3 after diagnosis in patients with MLL, ETV6-RUNX1, and BCR-ABL1 gene rearrangements, respectively. Gene rearrangements could be related to the aggressiveness of leukemia observed in Mexican children.

  1. Prevalence of Gene Rearrangements in Mexican Children with Acute Lymphoblastic Leukemia: A Population Study—Report from the Mexican Interinstitutional Group for the Identification of the Causes of Childhood Leukemia

    Science.gov (United States)

    Bekker-Méndez, Vilma Carolina; Miranda-Peralta, Enrique; Núñez-Enríquez, Juan Carlos; Olarte-Carrillo, Irma; Guerra-Castillo, Francisco Xavier; Pompa-Mera, Ericka Nelly; Ocaña-Mondragón, Alicia; Bernáldez-Ríos, Roberto; Medina-Sanson, Aurora; Jiménez-Hernández, Elva; Amador-Sánchez, Raquel; Peñaloza-González, José Gabriel; de Diego Flores-Chapa, José; Fajardo-Gutiérrez, Arturo; Flores-Lujano, Janet; Rodríguez-Zepeda, María del Carmen; Dorantes-Acosta, Elisa María; Bolea-Murga, Victoria; Núñez-Villegas, Nancy; Velázquez-Aviña, Martha Margarita; Torres-Nava, José Refugio; Reyes-Zepeda, Nancy Carolina; González-Bonilla, Cesar; Mejía-Aranguré, Juan Manuel

    2014-01-01

    Mexico has one of the highest incidences of childhood leukemia worldwide and significantly higher mortality rates for this disease compared with other countries. One possible cause is the high prevalence of gene rearrangements associated with the etiology or with a poor prognosis of childhood acute lymphoblastic leukemia (ALL). The aims of this multicenter study were to determine the prevalence of the four most common gene rearrangements [ETV6-RUNX1, TCF3-PBX1, BCR-ABL1, and MLL rearrangements] and to explore their relationship with mortality rates during the first year of treatment in ALL children from Mexico City. Patients were recruited from eight public hospitals during 2010–2012. A total of 282 bone marrow samples were obtained at each child's diagnosis for screening by conventional and multiplex reverse transcription polymerase chain reaction to determine the gene rearrangements. Gene rearrangements were detected in 50 (17.7%) patients. ETV6-RUNX1 was detected in 21 (7.4%) patients, TCF3-PBX1 in 20 (7.1%) patients, BCR-ABL1 in 5 (1.8%) patients, and MLL rearrangements in 4 (1.4%) patients. The earliest deaths occurred at months 1, 2, and 3 after diagnosis in patients with MLL, ETV6-RUNX1, and BCR-ABL1 gene rearrangements, respectively. Gene rearrangements could be related to the aggressiveness of leukemia observed in Mexican children. PMID:25692130

  2. Indonesia lowers infant mortality.

    Science.gov (United States)

    Bain, S

    1991-11-01

    Indonesia's success in reaching World Health Organization (WHO) universal immunization coverage standards is described as the result of a strong national program with timely, targeted donor support. USAID/Indonesia's Expanded Program for Immunization (EPI) and other USAID bilateral cooperation helped the government of Indonesia in its goal to immunize children against diphtheria, pertussis, tetanus, polio, tuberculosis, and measles by age 1. The initial project was to identify target areas and deliver vaccines against the diseases, strengthen the national immunization organization and infrastructure, and develop the Ministry of Health's capacity to conduct studies and development activities. This EPI project spanned the period 1979-90, and set the stage for continued expansion of Indonesia's immunization program to comply with the full international schedule and range of immunizations of 3 DPT, 3 polio, 1 BCG, and 1 measles inoculation. The number of immunization sites has increased from 55 to include over 5,000 health centers in all provinces, with additional services provided by visiting vaccinators and nurses in most of the 215,000 community-supported integrated health posts. While other contributory factors were at play, program success is at least partially responsible for the 1990 infant mortality rate of 58/1,000 live births compared to 72/1,000 in 1985. Strong national leadership, dedicated health workers and volunteers, and cooperation and funding from UNICEF, the World Bank, Rotary International, and WHO also played crucially positive roles in improving immunization practice in Indonesia.

  3. Cholecalciferol in Treating Patients With Acute Myeloid Leukemia Undergoing Intensive Induction Chemotherapy

    Science.gov (United States)

    2015-06-18

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Untreated Adult Acute Myeloid Leukemia

  4. Decitabine in Treating Patients With Myelodysplastic Syndromes or Acute Myeloid Leukemia

    Science.gov (United States)

    2013-09-27

    Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative; de Novo Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Untreated Adult Acute Myeloid Leukemia

  5. Ets motifs are necessary for endothelial cell-specific expression of a 723-bp Tie-2 promoter/enhancer in Hprt targeted transgenic mice

    NARCIS (Netherlands)

    Minami, Takashi; Kuivenhoven, Jan Albert; Evans, Valerie; Kodama, Tatsuhiko; Rosenberg, Robert D; Aird, William C

    2003-01-01

    OBJECTIVE: Tie-2 is an endothelial cell-specific receptor tyrosine kinase that is involved in the remodeling of blood vessels and angiogenesis. Our goal was to characterize Tie-2 promoter function as a means of providing insight into the mechanisms of endothelial cell-specific gene regulation. METHO

  6. Mucormycosis of the paranasal sinuses in a patient with acute myeloid leukemia

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    Čolović Nataša

    2016-01-01

    Full Text Available Introduction. Invasive fungal infection is among the leading causes of morbidity, mortality, and economic burden for patients with acute leukemia after induction of chemotherapy. In the past few decades, the incidence of invasive fungal infection has increased dramatically. Its management has been further complicated by the increasing frequency of infection by non-Aspergillus molds (e.g. Mucorales. Neutropenic patients are at a high risk of developing an invasive mucormycosis with fulminant course and high mortality rate (35-100%. Case Outline. We are presenting the case of a 72-year-old male with an acute monoblastic leukemia. The patient was treated during five days with hydroxycarbamide 2 × 500 mg/day, followed by cytarabine 2 × 20 mg/sc over the next 10 days. He developed febrile neutropenia, headache, and edema of the right orbital region of the face. Computed tomography of the sinuses revealed shadow in sinuses with thickening of mucosa of the right paranasal sinuses. Lavage and aspirate from the sinuses revealed Rhizopus oryzae. Mucormycosis was successfully treated with amphotericin B (5 mg/kg/day followed by ketoconazole (400 mg/day. Two months later the patient died from primary disease. Conclusion. In patients with acute leukemia who developed aplasia, febrile neutropenia, and pain in paranasal sinuses, fungal infection should be taken into consideration. New and non-invasive methods for taking samples from sinuses should be standardized in order to establish an early and accurate diagnosis of mucormycosis with the source in paranasal sinuses, and to start early treatment by a proper antifungal drug. Clear communication between physician and mycologist is critical to ensure proper and timely sampling of lavage and aspirate from sinuses and correct specimen processing when mucormycosis is suspected clinically. [Projekat Ministartsva nauke Republike Srbije, br. OI 175034

  7. Chronic Myelogenous Leukemia (CML) (For Parents)

    Science.gov (United States)

    ... kidney function panels, and blood chemistries can give important information about the number of normal blood cells in ... for examination in a lab. Cancerous WBCs can collect around the brain and ... is important because treatment varies among different types of leukemia. ...

  8. 47,XYY karyotype in acute myeloid leukemia.

    Science.gov (United States)

    Palanduz, S; Aktan, M; Ozturk, S; Tutkan, G; Cefle, K; Pekcelen, Y

    1998-10-01

    A case of acute myelomonocytic leukemia (AMMoL; M4) with a 47,XYY karyotype is reported. This chromosome aneuploidy was found in both bone marrow cells and mitogen-stimulated lymphocytes. The contribution of XYY chromosomal constitution in the pathogenesis of AMMoL is controversial.

  9. TARGETED NANOPARTICLES FOR PEDIATRIC LEUKEMIA THERAPY

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    Riyaz eBasha

    2014-05-01

    Full Text Available The two major forms of leukemia, acute lymphoblastic leukemia (ALL and acute myeloid leukemia (AML account for about one third of the malignancies diagnosed in children. Despite the marked successes in ALL and AML treatment, concerns remain regarding the occurrence of resistant disease in subsets of patients the residual effects of therapy that often persist for decades beyond the cessation of treatment. Therefore, new approaches are needed to reduce or to avoid off target toxicities, associated with chemotherapy and their long term residual effects. Recently, nanotechnology has been employed to enhance cancer therapy, via improving the bioavailability and therapeutic efficacy of anti-cancer agents. While in the last several years, numerous review articles appeared detailing the size, composition, assembly and performance evaluation of different types of drug carrying nanoparticles, the description and evaluation of lipoprotein based drug carriers have been conspicuously absent from most of these major reviews. The current review focuses on such information regarding nanoparticles with an emphasis on high density lipoprotein (HDL-based drug delivery systems to examine their potential role(s in the enhanced treatment of children with leukemia.

  10. Differentiation Therapy of Acute Myeloid Leukemia

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    Elzbieta Gocek

    2011-05-01

    Full Text Available Acute Myeloid Leukemia (AML is a predominant acute leukemia among adults, characterized by accumulation of malignantly transformed immature myeloid precursors. A very attractive way to treat myeloid leukemia, which is now called ‘differentiation therapy’, was proposed as in vitro studies have shown that a variety of agents stimulate differentiation of the cell lines isolated from leukemic patients. One of the differentiation-inducing agents, all-trans retinoic acid (ATRA, which can induce granulocytic differentiation in myeloid leukemic cell lines, has been introduced into clinics to treat patients with acute promyelocytic leukemia (APL in which a PML-RARA fusion protein is generated by a t(15;17(q22;q12 chromosomal translocation. Because differentiation therapy using ATRA has significantly improved prognosis for patients with APL, many efforts have been made to find alternative differentiating agents. Since 1,25-dihydroxyvitamin D3 (1,25D is capable of inducing in vitro monocyte/macrophage differentiation of myeloid leukemic cells, clinical trials have been performed to estimate its potential to treat patients with AML or myelodysplastic syndrome (MDS. Unfortunately therapeutic concentrations of 1,25D can induce potentially fatal systemic hypercalcemia, thus limiting clinical utility of that compound. Attempts to overcome this problem have focused on the synthesis of 1,25D analogs (VDAs which retain differentiation inducing potential, but lack its hypercalcemic effects. This review aims to discuss current problems and potential solutions in differentiation therapy of AML.

  11. Differentiation Therapy of Acute Myeloid Leukemia

    Energy Technology Data Exchange (ETDEWEB)

    Gocek, Elzbieta; Marcinkowska, Ewa, E-mail: ema@cs.uni.wroc.pl [Department of Biotechnology, University of Wroclaw, ul Tamka 2, Wroclaw 50-137 (Poland)

    2011-05-16

    Acute Myeloid Leukemia (AML) is a predominant acute leukemia among adults, characterized by accumulation of malignantly transformed immature myeloid precursors. A very attractive way to treat myeloid leukemia, which is now called ‘differentiation therapy’, was proposed as in vitro studies have shown that a variety of agents stimulate differentiation of the cell lines isolated from leukemic patients. One of the differentiation-inducing agents, all-trans retinoic acid (ATRA), which can induce granulocytic differentiation in myeloid leukemic cell lines, has been introduced into clinics to treat patients with acute promyelocytic leukemia (APL) in which a PML-RARA fusion protein is generated by a t(15;17)(q22;q12) chromosomal translocation. Because differentiation therapy using ATRA has significantly improved prognosis for patients with APL, many efforts have been made to find alternative differentiating agents. Since 1,25-dihydroxyvitamin D{sub 3} (1,25D) is capable of inducing in vitro monocyte/macrophage differentiation of myeloid leukemic cells, clinical trials have been performed to estimate its potential to treat patients with AML or myelodysplastic syndrome (MDS). Unfortunately therapeutic concentrations of 1,25D can induce potentially fatal systemic hypercalcemia, thus limiting clinical utility of that compound. Attempts to overcome this problem have focused on the synthesis of 1,25D analogs (VDAs) which retain differentiation inducing potential, but lack its hypercalcemic effects. This review aims to discuss current problems and potential solutions in differentiation therapy of AML.

  12. Treatment strategies in acute myeloid leukemia

    NARCIS (Netherlands)

    Han Li-na, [No Value; Zhou Jin, [No Value; Schuringa, Jan Jacob; Vellenga, Edo

    2011-01-01

    Objective To summarize the risk stratification and current treatment strategies for acute myeloid leukemia (AML) and discuss the role of emerging novel agents that might be applied in future clinical trials. Data sources The data in this article were collected from PubMed database with relevant Engl

  13. Trisomy 8 in leukemia: A GCRI experience

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    Sonal R Bakshi

    2012-01-01

    Full Text Available Trisomy of chromosome 8 is frequently reported in myeloid lineage disorders and also detected in lymphoid neoplasms as well as solid tumors suggesting its role in neoplastic progression in general. It is likely to be a disease-modulating secondary event with underlying cryptic aberrations as it has been frequently reported in addition to known abnormalities contributing to clinical heterogeneity and modifying prognosis. Here, we share our findings of trisomy 8 in leukemia patients referred for diagnostic and prognostic cytogenetic assessment. Total 60 cases of trisomy 8, as a sole anomaly or in addition to other chromosomal aberrations, were reported (January 2005-September 2008. Unstimulated bone marrow or blood samples were cultured, followed by GTG banding and karyotyping as per the ISCN 2005. Patients with +8 were chronic myeloid leukemia (CML (36, acute myeloid leukemia (AML (17, and acute lymphoblastic leukemia (ALL (7. In 7 patients, trisomy 8 was the sole anomaly, whereas in 6 patients +8 was in addition to normal clone, in 47 patients, the +8 was in addition to t(9;22, t(15;17, and others, including 3 with tetrasomy 8. Only one patient showed constitutional +8. The present study will form the basis of further cumulative studies to correlate potential differential effects of various karyotypic anomalies on disease progression and survival following a therapeutic regime. To unravel the role of extra 8 chromosome, constitutional chromosomal analysis and uniparental disomy will be considered.

  14. Cytarabine dose for acute myeloid leukemia

    NARCIS (Netherlands)

    B. Löwenberg (Bob); T. Pabst (Thomas); E. Vellenga (Edo); W. van Putten; H.C. Schouten (Harry); C. Graux (Carlos); A. Ferrant (Augustin); P. Sonneveld (Pieter); B.J. Biemond (Bart); A. Gratwohl (Alois); G.E. de Greef (Georgine); L.F. Verdonck (Leo); M.R. Schaafsma (Martijn); M. Gregor (Michael); M. Theobald; U. Schanz (Urs); J. Maertens (Johan); G.J. Ossenkoppele (Gert)

    2011-01-01

    textabstractBACKGROUND: Cytarabine (ara-C) is an important drug in the treatment of acute myeloid leukemia (AML). High-dose cytarabine (2000 to 3000 mg per square meter of body-surface area) is toxic but results in higher rates of relapse-free survival than does the conventional dose of 100 to 400 m

  15. Cytarabine Dose for Acute Myeloid Leukemia

    NARCIS (Netherlands)

    Lowenberg, Bob; Pabst, Thomas; Vellenga, Edo; van Putten, Wim; Schouten, Harry C.; Graux, Carlos; Ferrant, Augustin; Sonneveld, Pieter; Biemond, Bart J.; Gratwohl, Alois; de Greef, Georgine E.; Verdonck, Leo F.; Schaafsma, Martijn R.; Gregor, Michael; Theobald, Matthias; Schanz, Urs; Maertens, Johan; Ossenkoppele, Gert J.

    2011-01-01

    BACKGROUND Cytarabine (ara-C) is an important drug in the treatment of acute myeloid leukemia (AML). High-dose cytarabine (2000 to 3000 mg per square meter of body-surface area) is toxic but results in higher rates of relapse-free survival than does the conventional dose of 100 to 400 mg per square

  16. Dental Treatment in Patients with Leukemia

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    Caroline Zimmermann

    2015-01-01

    Full Text Available Dental treatment of patients with leukemia should be planned on the basis of antineoplastic therapy which can be chemotherapy with or without radiotherapy and bone marrow transplantation. Many are the oral manifestations presented by these patients, arising from leukemia and/or treatment. In addition, performing dental procedures at different stages of treatment (before, during, or after must follow certain protocols in relation to the haematological indices of patients, aimed at maintaining health and contributing to the effectiveness of the results of antineoplastic therapy. Through a literature review, the purpose of this study was to report the hematological abnormalities present in patients with leukemia, trying to correlate them with the feasibility of dental treatment at different stages of the disease. It is concluded in this paper that dental treatment in relation to haematological indices presented by patients with leukemia must follow certain protocols, mainly related to neutrophil and platelet counts, and the presence of the dentist in a multidisciplinary team is required for the health care of this patient.

  17. Novel transforming genes in murine myeloid leukemia

    NARCIS (Netherlands)

    A.M.S. Joosten (Marieke)

    2002-01-01

    textabstractLeukemia is characterised by an accumulation in the bone marrow of non-functional blood cells arrested at a particular stage of differentiation. In the process of normal hematopoiesis, errors may occur as the result of mutations in the DNA of hematopoietic precursor cells. These genetic

  18. Molecular Insights in MLL Rearranged Acute Leukemia

    NARCIS (Netherlands)

    R.W. Stam (Ronald)

    2006-01-01

    textabstractAcute lymphoblastic leukemia (ALL) in infants (<1 year of age) is characterized by a high incidence (~80%) of rearrangements of the MLL gene, resistance to several important chemotherapeutic drugs, and a poor treatment outcome. With overall survival rates for infant ALL not exceeding 50%

  19. Midostaurin and Decitabine in Treating Older Patients With Newly Diagnosed Acute Myeloid Leukemia and FLT3 Mutation

    Science.gov (United States)

    2016-10-10

    Acute Myeloid Leukemia With FLT3/ITD Mutation; Acute Myeloid Leukemia With Gene Mutations; FLT3 Tyrosine Kinase Domain Point Mutation; Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  20. DIFFERENTIATION SYNDROME IN PROMYELOCYTIC LEUKEMIA : CLINICAL PRESENTATION, PATHOGENESIS AND TREATMENT

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    Eduardo Magalhães Rego

    2011-10-01

    Full Text Available Differentiation syndrome (DS represents a life-threatening complication in patients with acute promyelocytic leukemia (APL undergoing induction therapy with all-trans retinoic acid (ATRA or arsenic trioxide (ATO. It affects about 20-25% of all patients and there are no definitive diagnostic criteria. Clinically, DS is characterized by weight gain, fever not attributable to infection, respiratory distress, cardiac involvement, hypotension, and/or acute renal failure. At the histological point of view, there is an extensive interstitial and intra-alveolar pulmonary infiltration by maturing myeloid cells, endothelial cell damage, intra-alveolar edema, inter-alveolar hemorrhage, and fibrinous exsudates. DS pathogenesis is not completely understood, but it is believed that an excessive inflammatory response is the main phenomenon involved, which results in increased production of chemokines and expression of adhesion molecules on APL cells. Due to the high morbidity and mortality associated with DS, its recognition and the prompt initiation of the treatment is of utmost importance. Dexamethasone is considered the mainstay of treatment of DS, and the recommended dose is 10 mg twice daily by intravenous route until resolution of DS. In severe cases (respiratory or acute renal failure it is recommended the discontinuation of ATRA or ATO until recovery.

  1. Inhibition by streptovaricins of Rauscher leukemia virus splenomegaly.

    Science.gov (United States)

    Borden, E C; Carter, W A; Sensenbrenner, L L; Owens, A H; Lichtenstein, J; Gray, G D; Neil, G L; Nichol, F R; Li, L H

    1974-12-15

    Streptovaricins (Sv), ansa macrolide antibiotics, inhibited Rauscher leukemia virus (RLV) splenomegaly by 25-50%. All streptovaricins tested were effective when administered orally either by diet ad lib or by intubation from infection to time of killing. When delivered by intubation, Sv was measurable in plasma for up to 6 h. SvC, at 300 mg/kg/day, reduced mean spleen weight of infected mice from 478 plus or minus 51 (SE) mg to 300 plus or minus 55 (SE) mg. Rifampicin, at 250 mg/kg/day, had no similar activity. Decrease in caloric intake and in body-weight gain also resulted in an inhibition of RLV splenomegaly; although Sv-treated mice gained weight, the increase was usually slightly less than controls. However, mice treated with a Sv diet for a week prior to infection, after an initial period of weight loss, gained at a rate equivalent to control group, and when killed had a marked reduction in splenomegaly. The selectivity of streptovaricins and specificity for viral events was suggested by several observations: (1) Splenomegaly and mortality, induced by L1210 or a non-infective transplantable tumor of RLV origin, was not inhibited. (2) No inhibition of normal hematopoietic spleen colonies was observed. (3) Host immune responses, including cellular and humoral immunity and interferon production and action, were not inhibited. Thus, although the effect of slightly decreased weight and intake could not be unequivocally established, the findings were most compatible with a selective inhibition of RLV splenomegaly by Sv.

  2. Treatment and prognostic assessment of acute myeloid leukemia

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    Bannur Ramanna Nandeesh

    2016-06-01

    Full Text Available Acute myeloid leukemia (AML is a heterogeneous group of clonal malignant myeloid neoplasms. Malignant transformation of hematopoietic progenitor cell leads to clonal expansion and replacement of normal bone marrow cells with malignant cells leading to suppression of normal haematopoiesis. Advancements in our understanding of disease biology have allowed AML to be classified based on its gene expression profile, which includes previously identified cytogenetic subgroups, and distinct novel subgroups which have prognostic significance. Identification of mutations in DNMT3A and IDH 1 genes in cytogenetically normal AML (by gene sequencing helps to identify patients with poor prognosis. Redesigning the treatment regimen consisting of cytarabine and daunorubicin has improved the treatment outcomes without increase in the treatment-related mortality. Increasing the dose of daunorubicin to 90 mg/m2 improves complete remission rates without increasing treatment-related complications both in young and elderly patients. Cytarabine (200 mg/m2 in cycle I and 2 g/m2 in cycle 2 is shown to be as effective as high dose cytarabine (1000 mg/m2 twice daily in cycle 1and 2 g/m2 twice daily in cycle 2 and is associated with less treatment-related toxicities. [Int J Basic Clin Pharmacol 2016; 5(3.000: 579-586

  3. Immunophenotypes and Immune Markers Associated with Acute Promyelocytic Leukemia Prognosis

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    Fang Xu

    2014-01-01

    Full Text Available CD2+, CD34+, and CD56+ immunophenotypes are associated with poor prognoses of acute promyelocytic leukemia (APL. The present study aimed to explore the role of APL immunophenotypes and immune markers as prognostic predictors on clinical outcomes. A total of 132 patients with de novo APL were retrospectively analyzed. Immunophenotypes were determined by flow cytometry. Clinical features, complete remission (CR, relapse, and five-year overall survival (OS rate were assessed and subjected to multivariate analyses. The CD13+CD33+HLA-DR-CD34− immunophenotype was commonly observed in patients with APL. Positive rates for other APL immune markers including cMPO, CD117, CD64, and CD9 were 68.7%, 26%, 78.4%, and 96.6%, respectively. When compared with patients with CD2− APL, patients with CD2+ APL had a significantly higher incidence of early death (50% versus 15.7%; P=0.016, lower CR rate (50% versus 91.1%; P=0.042, and lower five-year OS rate (41.7% versus 74.2%; P=0.018. White blood cell (WBC count before treatment was found to be the only independent risk factor of early death, CR failure, and five-year mortality rate. Flow cytometric immunophenotype analysis can facilitate prompt APL diagnosis. Multivariate analysis has demonstrated that WBC count before treatment is the only known independent risk factor that predicts prognosis for APL in this study population.

  4. Immunotherapy with natural killer cells: a possible approach for the treatment of Acute Myeloid Leukemia also in Brazil

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    Lúcia Silla

    Full Text Available SUMMARY The allogeneic hematopoietic stem cell transplantation (HSCT can cure intermediate and high-risk acute myeloid leukemia. Even with the development of strategies to reduce HSCT toxicity, this is still a complex treatment with high morbidity and mortality. Knowledge of the graft versus leukemia effect of HSCT has prepared the way for the development of Adoptive Immunotherapy or in vitro expansion of activated lymphocytes without alloreactivity, with subsequent intravenous infusion. The infusion of genetically modified T lymphocytes and haploidentical natural killer cells has been tested as an alternative to HSCT with very interesting results worldwide and in Brazil, as we not only have the technology of in vitro expansion of clinical grade lymphocytes available, but also do it according to the Good Manufacturing Practices that have been determined internationally.

  5. Rapid lung MRI - paradigm shift in evaluation of febrile neutropenia in children with leukemia: a pilot study.

    Science.gov (United States)

    Sodhi, Kushaljit Singh; Khandelwal, Niranjan; Saxena, Akshay Kumar; Bhatia, Anmol; Bansal, Deepak; Trehan, Amita; Singh, Meenu; Agarwal, Ritesh

    2016-01-01

    Immunocompromised children with hematological malignancies are at increased risk of developing potentially fatal pulmonary infections. Early detection and prompt treatment is critical to combat morbidity and mortality in these children. Twenty-six children with leukemia (age range: 5-13years) presenting with fever and neutropenia were included in this prospective study, which was approved by the institutional ethics committee. All patients underwent HRCT and MRI of the chest on the same day. The findings of HRCT and MRI were compared, with HRCT as the standard of reference. There was perfect agreement between MRI and CT examinations findings by kappa test (κ = 1). No significant difference was observed between the two modalities by the McNemar test (p > 0.05). Rapid lung MRI is technically feasible; has a high correlation, sensitivity and specificity to CT scan; and can emerge as the first line modality for the detection of pulmonary nodules in children with leukemia and persistent febrile neutropenia.

  6. Methylation of Gene CHFR Promoter in Acute Leukemia Cells

    Institute of Scientific and Technical Information of China (English)

    GONG Hui; LIU Wengli; ZHOU Jianfeng; XU Huizhen

    2005-01-01

    Summary: In order to explore whether gene CHFR was inactivated by methylation in leukemia cells, the expression of CHFR was examined before and after treatment with demethylation agent in Molt-4, Jurkat and U937 leukemia cell lines by means of RT-PCR. The methylation of promoter in Molt-4, Jurkat and U937 cells as well as 41 acute leukemia patients was analyzed by MS-PCR. The results showed that methylation of CHFR promoter was inactivated and could be reversed by treatment with a demethylating agent in Molt-4, Jurkat and U937. CHFR promoter methylation was detected in 39 % of acute leukemia patients. There was no difference in incidence of CHFR promoter methylation between acute myelocytic leukemia and acute lymphocytic leukemia. In conclusion, CHFR is frequently inactivated in acute leukemia and is a good candidate for the leukemia supper gene. By affecting mitotic checkpoint function, CHFR inactivation likely plays a key role in tumorigenesis in acute leukemia. Moreover, the methylation of gene CHFR appears to be a good index with which to predict the sensitivity of acute leukemia to microtubule inhibitors.

  7. [Asthma mortality trends in Mexico].

    Science.gov (United States)

    Salas Ramírez, M; Segura Méndez, N H; Martínez-Cairo Cueto, S

    1994-04-01

    The objective of this cross-sectional study was to estimate mortality and morbidity from asthma in Mexico by federative entity (state) of residence, age, and sex during the period between 1960 and 1988. Statistics published by the National Institute of Statistics, Geography, and Information Science were reviewed, as were vital statistics and information from other sources. Data were selected on mortality, hospital admissions, and outpatient visits, as well as population by federative entity, age, and sex. Mortality and morbidity rates were adjusted for age using the direct method. From 1960 to 1987, mortality decreased for both sexes. The groups with the highest asthma mortality were those under 4 years of age and those over 50. From 1960 to the present, the state with the highest mortality was Tlaxcala. Hospitalizations increased from 10 to 140 per 100,000 population for the country as a whole. When both outpatient visits and hospitalizations were considered, the morbidity rates rose from 180 to 203.4 per 100,000 between 1960 and 1970. In 1970, hospital morbidity was higher among males than females. From 1960 up to the 1990s, the highest rates of hospitalization and outpatient visits were registered among those under 4 and those over 60. The states with the highest asthma hospitalization rates were Morelos, Baja California Sur, Nuevo León, Durango, and Tamaulipas. It is concluded that asthma mortality in Mexico is showing a downward trend, while morbidity is increasing considerably, especially among adolescents.

  8. Polycomb-Mediated Repression and Sonic Hedgehog Signaling Interact to Regulate Merkel Cell Specification during Skin Development.

    Directory of Open Access Journals (Sweden)

    Carolina N Perdigoto

    2016-07-01

    Full Text Available An increasing amount of evidence indicates that developmental programs are tightly regulated by the complex interplay between signaling pathways, as well as transcriptional and epigenetic processes. Here, we have uncovered coordination between transcriptional and morphogen cues to specify Merkel cells, poorly understood skin cells that mediate light touch sensations. In murine dorsal skin, Merkel cells are part of touch domes, which are skin structures consisting of specialized keratinocytes, Merkel cells, and afferent neurons, and are located exclusively around primary hair follicles. We show that the developing primary hair follicle functions as a niche required for Merkel cell specification. We find that intraepidermal Sonic hedgehog (Shh signaling, initiated by the production of Shh ligand in the developing hair follicles, is required for Merkel cell specification. The importance of Shh for Merkel cell formation is further reinforced by the fact that Shh overexpression in embryonic epidermal progenitors leads to ectopic Merkel cells. Interestingly, Shh signaling is common to primary, secondary, and tertiary hair follicles, raising the possibility that there are restrictive mechanisms that regulate Merkel cell specification exclusively around primary hair follicles. Indeed, we find that loss of Polycomb repressive complex 2 (PRC2 in the epidermis results in the formation of ectopic Merkel cells that are associated with all hair types. We show that PRC2 loss expands the field of epidermal cells competent to differentiate into Merkel cells through the upregulation of key Merkel-differentiation genes, which are known PRC2 targets. Importantly, PRC2-mediated repression of the Merkel cell differentiation program requires inductive Shh signaling to form mature Merkel cells. Our study exemplifies how the interplay between epigenetic and morphogen cues regulates the complex patterning and formation of the mammalian skin structures.

  9. Polycomb-Mediated Repression and Sonic Hedgehog Signaling Interact to Regulate Merkel Cell Specification during Skin Development

    Science.gov (United States)

    Bar, Carmit; Tsai, Pai-Chi; Valdes, Victor J.; Cohen, Idan; Santoriello, Francis J.; Zhao, Dejian; Hsu, Ya-Chieh; Ezhkova, Elena

    2016-01-01

    An increasing amount of evidence indicates that developmental programs are tightly regulated by the complex interplay between signaling pathways, as well as transcriptional and epigenetic processes. Here, we have uncovered coordination between transcriptional and morphogen cues to specify Merkel cells, poorly understood skin cells that mediate light touch sensations. In murine dorsal skin, Merkel cells are part of touch domes, which are skin structures consisting of specialized keratinocytes, Merkel cells, and afferent neurons, and are located exclusively around primary hair follicles. We show that the developing primary hair follicle functions as a niche required for Merkel cell specification. We find that intraepidermal Sonic hedgehog (Shh) signaling, initiated by the production of Shh ligand in the developing hair follicles, is required for Merkel cell specification. The importance of Shh for Merkel cell formation is further reinforced by the fact that Shh overexpression in embryonic epidermal progenitors leads to ectopic Merkel cells. Interestingly, Shh signaling is common to primary, secondary, and tertiary hair follicles, raising the possibility that there are restrictive mechanisms that regulate Merkel cell specification exclusively around primary hair follicles. Indeed, we find that loss of Polycomb repressive complex 2 (PRC2) in the epidermis results in the formation of ectopic Merkel cells that are associated with all hair types. We show that PRC2 loss expands the field of epidermal cells competent to differentiate into Merkel cells through the upregulation of key Merkel-differentiation genes, which are known PRC2 targets. Importantly, PRC2-mediated repression of the Merkel cell differentiation program requires inductive Shh signaling to form mature Merkel cells. Our study exemplifies how the interplay between epigenetic and morphogen cues regulates the complex patterning and formation of the mammalian skin structures. PMID:27414999

  10. Open Label, Phase II Study to Evaluate Efficacy and Safety of Oral Nilotinib in Philadelphia Positive (Ph+) Chronic Myelogenous Leukemia (CML) Pediatric Patients.

    Science.gov (United States)

    2016-10-07

    Leukemia; Leukemia,Pediatric; Leukemia, Myleiod; Leukemia, Mylegenous, Chronic; Leukemia, Mylegenous, Accelerated; BCR-ABL Positive; Myeloproliferative Disorder; Bone Marrow Disease; Hematologic Diseases; Neoplastic Processes; Imatinib; Dasatinib; Enzyme Inhibitor; Protein Kinase Inhibitor

  11. Tretinoin, Cytarabine, and Daunorubicin Hydrochloride With or Without Arsenic Trioxide Followed by Tretinoin With or Without Mercaptopurine and Methotrexate in Treating Patients With Acute Promyelocytic Leukemia

    Science.gov (United States)

    2013-06-04

    Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Promyelocytic Leukemia (M3); Childhood Acute Promyelocytic Leukemia (M3); Untreated Adult Acute Myeloid Leukemia; Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies

  12. Vorinostat and Decitabine in Treating Patients With Advanced Solid Tumors or Relapsed or Refractory Non-Hodgkin's Lymphoma, Acute Myeloid Leukemia, Acute Lymphocytic Leukemia, or Chronic Myelogenous Leukemia

    Science.gov (United States)

    2014-08-26

    Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Blastic Phase Chronic Myelogenous Leukemia; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Secondary Acute Myeloid Leukemia; Splenic Marginal Zone Lymphoma; Stage III Adult Burkitt Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Mixed Cell Lymphoma; Stage III Adult Diffuse Small Cleaved Cell Lymphoma; Stage III Adult Immunoblastic Large Cell Lymphoma; Stage III Adult Lymphoblastic Lymphoma; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage III Mantle Cell Lymphoma; Stage III Marginal Zone Lymphoma; Stage III Small Lymphocytic Lymphoma; Stage IV Adult Burkitt Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Mixed Cell Lymphoma; Stage IV Adult Diffuse Small Cleaved Cell Lymphoma; Stage IV Adult Immunoblastic Large Cell Lymphoma; Stage IV Adult Lymphoblastic Lymphoma; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Grade 3 Follicular Lymphoma; Stage IV Mantle Cell Lymphoma; Stage IV Marginal Zone Lymphoma

  13. Trends in child mortality in India.

    Science.gov (United States)

    Behl, A S

    2013-01-08

    To assess Indias recent trends in child mortality rates and disparities and identify ways to reduce child mortality and wealth-related health disparities, we analyzed three years of data from Indias National Family Health Survey related to child mortality. Nationally, declines in average child mortality were statistically significant, but declines in inequality were not. Urban areas had lower child mortality rates than rural areas but higher inequalities. Interstate differences in child mortality rates were significant, with rates in the highest-mortality states four to six times higher than in the lowest-mortality states. However, child mortality in most states declined.

  14. The law of mortality revisited: interspecies comparisons of mortality.

    Science.gov (United States)

    Olshansky, S J

    2010-01-01

    In 1825 the British actuary Benjamin Gompertz believed he had discovered a consistency in the timing of death in people that was so important that he labelled his observation a 'law of mortality'. To Gompertz, this 'law' was equivalent in importance to Newton's law of gravity because he believed it would be observed in all living things. Gompertz's quest for the 'law' eventually failed, as did similar efforts by other scientists in the 19th and most of the 20th century. However, the search for the law of mortality was successfully resolved in 1996 when my colleagues and I discovered that the only way to 'see' Gompertz's law expressed as common age patterns of death across species was to partition total mortality into its intrinsic and extrinsic components, and examine mortality schedules on a uniform time scale. Scientists had been unable to reveal the law of mortality in the past not only because they could not partition total mortality, but also because of the previous anthropocentric perspective that forced some scientists to view duration of life along a single time scale - one based on human measurements of chronological time. The law of mortality is relevant today not only because it links the epidemiology of disease, ageing and death across species, but because it creates a window into the future for those who study disease epidemiology in animals that now live long enough in protected environments to experience the biological consequences of ageing. In this paper I summarize the historical search for the law of mortality, explain why the solution could only be found by linking two seemingly unconnected scientific disciplines (evolution biology and actuarial/demographics), explain why age patterns of disease and death in humans may be used to understand and predict disease epidemiology in other species, and describe how a new scientific discipline has arisen in the modern era as a result of this research.

  15. Combination Chemotherapy With or Without PSC 833, Peripheral Stem Cell Transplantation, and/or Interleukin-2 in Treating Patients With Acute Myeloid Leukemia

    Science.gov (United States)

    2013-06-03

    Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Erythroid Leukemia (M6); Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monoblastic Leukemia and Acute Monocytic Leukemia (M5); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Childhood Acute Basophilic Leukemia; Childhood Acute Eosinophilic Leukemia; Childhood Acute Erythroleukemia (M6); Childhood Acute Megakaryocytic Leukemia (M7); Childhood Acute Minimally Differentiated Myeloid Leukemia (M0); Childhood Acute Monoblastic Leukemia (M5a); Childhood Acute Monoblastic Leukemia and Acute Monocytic Leukemia (M5); Childhood Acute Monocytic Leukemia (M5b); Childhood Acute Myeloblastic Leukemia With Maturation (M2); Childhood Acute Myeloblastic Leukemia Without Maturation (M1); Childhood Acute Myelomonocytic Leukemia (M4); Childhood Myelodysplastic Syndromes; de Novo Myelodysplastic Syndromes; Untreated Adult Acute Myeloid Leukemia; Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies

  16. Decitabine, Donor Natural Killer Cells, and Aldesleukin in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

    Science.gov (United States)

    2016-01-07

    Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia

  17. 76 FR 3075 - Availability of an Environmental Assessment for Field Testing Feline Leukemia Vaccine, Live...

    Science.gov (United States)

    2011-01-19

    ... Feline Leukemia Vaccine, Live Canarypox Vector AGENCY: Animal and Plant Health Inspection Service, USDA... testing, and then to field test, an unlicensed Feline Leukemia Vaccine, Live Canarypox Vector. The.... Product: Feline Leukemia Vaccine, Live Canarypox Vector. Field Test Locations: Alabama,...

  18. File list: Pol.Bld.20.AllAg.Leukemia,_Myeloid [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  19. File list: Pol.Bld.10.AllAg.Leukemia,_Myeloid [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  20. File list: Pol.Bld.50.AllAg.Leukemia,_Lymphoid [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  1. File list: Unc.Bld.50.AllAg.Leukemia,_Lymphoid [Chip-atlas[Archive

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  4. File list: Pol.Bld.05.AllAg.Leukemia,_Lymphoid [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  5. File list: Unc.Bld.05.AllAg.Leukemia,_Lymphoid [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  8. File list: Pol.Bld.10.AllAg.Leukemia,_Lymphoid [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  9. File list: Pol.Bld.20.AllAg.Leukemia,_Myeloid [Chip-atlas[Archive

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    Lifescience Database Archive (English)

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  12. File list: Pol.Bld.20.AllAg.Leukemia,_Lymphoid [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  13. File list: Pol.Bld.05.AllAg.Leukemia,_Myeloid [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  14. Stressful social relations and mortality

    DEFF Research Database (Denmark)

    Lund, Rikke; Christensen, Ulla; Nilsson, Charlotte Juul

    2014-01-01

    BACKGROUND: Few studies have examined the relationship between stressful social relations in private life and all-cause mortality. OBJECTIVE: To evaluate the association between stressful social relations (with partner, children, other family, friends and neighbours, respectively) and all......-cause mortality in a large population-based study of middle-aged men and women. Further, to investigate the possible modification of this association by labour force participation and gender. METHODS: We used baseline data (2000) from The Danish Longitudinal Study on Work, Unemployment and Health, including 9875...... men and women aged 36-52 years, linked to the Danish Cause of Death Registry for information on all-cause mortality until 31 December 2011. Associations between stressful social relations with partner, children, other family, friends and neighbours, respectively, and all-cause mortality were examined...

  15. CDC WONDER: Mortality - Infant Deaths

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Mortality - Infant Deaths (from Linked Birth / Infant Death Records) online databases on CDC WONDER provide counts and rates for deaths of children under 1 year...

  16. Azacitidine in combination with intensive induction chemotherapy in older patients with acute myeloid leukemia: The AML-AZA trial of the Study Alliance Leukemia.

    Science.gov (United States)

    Müller-Tidow, C; Tschanter, P; Röllig, C; Thiede, C; Koschmieder, A; Stelljes, M; Koschmieder, S; Dugas, M; Gerss, J; Butterfaß-Bahloul, T; Wagner, R; Eveslage, M; Thiem, U; Krause, S W; Kaiser, U; Kunzmann, V; Steffen, B; Noppeney, R; Herr, W; Baldus, C D; Schmitz, N; Götze, K; Reichle, A; Kaufmann, M; Neubauer, A; Schäfer-Eckart, K; Hänel, M; Peceny, R; Frickhofen, N; Kiehl, M; Giagounidis, A; Görner, M; Repp, R; Link, H; Kiani, A; Naumann, R; Brümmendorf, T H; Serve, H; Ehninger, G; Berdel, W E; Krug, U

    2016-03-01

    DNA methylation changes are a constant feature of acute myeloid leukemia. Hypomethylating drugs such as azacitidine are active in acute myeloid leukemia (AML) as monotherapy. Azacitidine monotherapy is not curative. The AML-AZA trial tested the hypothesis that DNA methyltransferase inhibitors such as azacitidine can improve chemotherapy outcome in AML. This randomized, controlled trial compared the efficacy of azacitidine applied before each cycle of intensive chemotherapy with chemotherapy alone in older patients with untreated AML. Event-free survival (EFS) was the primary end point. In total, 214 patients with a median age of 70 years were randomized to azacitidine/chemotherapy (arm-A) or chemotherapy (arm-B). More arm-A patients (39/105; 37%) than arm-B (25/109; 23%) showed adverse cytogenetics (P=0.057). Adverse events were more frequent in arm-A (15.44) versus 13.52 in arm-B, (P=0.26), but early death rates did not differ significantly (30-day mortality: 6% versus 5%, P=0.76). Median EFS was 6 months in both arms (P=0.96). Median overall survival was 15 months for patients in arm-A compared with 21 months in arm-B (P=0.35). Azacitidine added to standard chemotherapy increases toxicity in older patients with AML, but provides no additional benefit for unselected patients.

  17. Disturbed α-Cell Function in Mice with β-Cell Specific Overexpression of Human Islet Amyloid Polypeptide

    Directory of Open Access Journals (Sweden)

    Bo Ahrén

    2008-01-01

    Full Text Available Exogenous administration of islet amyloid polypeptide (IAPP has been shown to inhibit both insulin and glucagon secretion. This study examined α-cell function in mice with β-cell specific overexpression of human IAPP (hIAPP after an oral protein gavage (75 mg whey protein/mouse. Baseline glucagon levels were higher in transgenic mice (41±4.0 pg/mL, n=6 than in wildtype animals (19±5.1 pg/mL, n=5, P=.015. In contrast, the glucagon response to protein was impaired in transgenic animals (21±2.7 pg/mL in transgenic mice versus 38±5.7 pg/mL in wildtype mice at 15 minutes; P=.027. Baseline insulin levels did not differ between the groups, while the insulin response, as the glucagon response, was impaired after protein challenge (P=.018. Glucose levels were not different between the groups and did not change significantly after protein gavage. Acetaminophen was given through gavage to the animals (2 mg/mouse to estimate gastric emptying. The plasma acetaminophen profile was similar in the two groups of mice. We conclude that disturbances in glucagon secretion exist in mice with β-cell specific overexpression of human IAPP, which are not secondary to changes in gastric emptying. The reduced glucagon response to protein challenge may reflect a direct inhibitory influence of hIAPP on glucagon secretion.

  18. Biological evaluation of a novel Herceptin-platinum (II) conjugate for efficient and cancer cell specific delivery.

    Science.gov (United States)

    Huang, Rong; Sun, Yu; Zhang, Xiang-yang; Sun, Bai-wang; Wang, Qiu-cui; Zhu, Jin

    2015-07-01

    Platinum-based drugs have been widely used for the treatment of malignant tumors. However, their applications are limited by severe side effects for their lack of selectivity for cancer cells. The development of antibody drug conjugates (ADCs) have provided a platform to reduce drug toxicity and improve drug efficacy. Here we describe a nover conjugate comprising of Herceptin (an anti-HER2 antibody) and platinum drug via a cathepsin B cleavable dipetide for enhancing drug accumulation and HER2-positive cancer cell specific delivery. This conjugate is believed to be cleaved by cathepsin B, leading to a 1,6-elimination reaction and activation of drug release. Herceptin-Pt(II) is evaluated to have approximately loaded with 6.4 moles platinum drugs per mole of antibody. We demonstrate that Herceptin-Pt(II) retain high and selective binding affinity for HER2 protein and HER2-positive SK-BR-3 cancer cells. The in vitro cytotoxicity tests indicate that Herceptin-Pt(II) exhibits much higher cytotoxicity than oxaliplatin against SK-BR-3 cells. More importantly, Herceptin-Pt(II) shows no obvious inhibition against the growth of both MCF-7 and MDA-MB-231 cells, which express lower levels of HER2. Furthermore, compared with free oxaliplatin, Herceptin significantly improved the cellular uptake of platinum drugs in SK-BR-3 cells. In summary, Herceptin-platinum (II) conjugate is a remarkable and potent platform for efficient and cancer cell specific delivery.

  19. DOF-binding sites additively contribute to guard cell-specificity of AtMYB60 promoter

    Directory of Open Access Journals (Sweden)

    Cominelli Eleonora

    2011-11-01

    Full Text Available Abstract Background We previously demonstrated that the Arabidopsis thaliana AtMYB60 protein is an R2R3MYB transcription factor required for stomatal opening. AtMYB60 is specifically expressed in guard cells and down-regulated at the transcriptional levels by the phytohormone ABA. Results To investigate the molecular mechanisms governing AtMYB60 expression, its promoter was dissected through deletion and mutagenesis analyses. By studying different versions of AtMYB60 promoter::GUS reporter fusions in transgenic plants we were able to demonstrate a modular organization for the AtMYB60 promoter. Particularly we defined: a minimal promoter sufficient to confer guard cell-specific activity to the reporter gene; the distinct roles of different DOF-binding sites organised in a cluster in the minimal promoter in determining guard cell-specific expression; the promoter regions responsible for the enhancement of activity in guard cells; a promoter region responsible for the negative transcriptional regulation by ABA. Moreover from the analysis of single and multiple mutants we could rule out the involvement of a group of DOF proteins, known as CDFs, already characterised for their involvement in flowering time, in the regulation of AtMYB60 expression. Conclusions These findings shed light on the regulation of gene expression in guard cells and provide new promoter modules as useful tools for manipulating gene expression in guard cells, both for physiological studies and future biotechnological applications.

  20. Zebrafish embryos as in vivo test tubes to unravel cell-specific mechanisms of neurogenesis during neurodevelopment and in diseases.

    Science.gov (United States)

    Samarut, Éric

    2016-01-01

    Zebrafish has become a model of choice for developmental studies in particular for studying neural development and related mechanisms involved in diseases. Indeed, zebrafish provides a fast, handy and accurate model to perform functional genomics on a gene or network of genes of interest. Recently, we successfully purified neural stem cells (NSCs) by fluorescence-activated cell sorting (FACS) from whole embryos in order to analyze cell-specific transcriptomic effects by RNA sequencing. As a result, our work sheds light on signaling pathways that are more likely to be involved in our morpholino-induced neurogenesis phenotype. This cell purification strategy brings zebrafish to a higher level since it now allows one to investigate cell-specific effects of a genetic condition of interest (knockout, knock-down, gain-of-function etc.) at the genomic, transcriptomic and proteomic levels in a genuine in vivo context. With this new potential, there is no doubt that zebrafish will be of a major model with which to unravel complex underlying molecular mechanisms of neurological disorders such as epilepsy, autism spectrum disorders and schizophrenia.

  1. DGP1, a drought-induced guard cell-specific promoter and its function analysis in tobacco plants

    Institute of Scientific and Technical Information of China (English)

    LI; Jun; GONG; Ximing; LIN; Huiqiong; SONG; Quanbo; CHEN; J

    2005-01-01

    The genetic regulation of stomatal movement mainly depends on an efficient control system of gene expression, and guard cell-specific promoter is becoming the best choice. Here we combined the dehydration responsive element (DRE) with guard cell specific element (GCSE) to construct a novel promoter, DGP1. Histochemical assays in transgenic tobacco carryingβ-glucuronidase (gus) gene fused to DGP1 demonstrated that GUS activity was found to be highly inducible by drought treatment and specifically restricted to guard cells. No GUS activity was detected in roots, stems or flowers after treatment. Further quantitative analysis showed that GUS activity in the epidermal strips was apparently induced by dehydration and dramatically increased with the elongation of treatment. The GUS activity after 8 h treatment was 179 times that of those without treatment. Although GUS activity in roots, stems or mesophyll increased after treatment, no great changes were observed. These results suggested that DGP1 could drive target gene expressed in guard cells when plant is subjected to drought stress. And this gets us prepared to control opening and closing of stomata through plant gene engineering.

  2. A satellite cell-specific knockout of the androgen receptor reveals myostatin as a direct androgen target in skeletal muscle.

    Science.gov (United States)

    Dubois, Vanessa; Laurent, Michaël R; Sinnesael, Mieke; Cielen, Nele; Helsen, Christine; Clinckemalie, Liesbeth; Spans, Lien; Gayan-Ramirez, Ghislaine; Deldicque, Louise; Hespel, Peter; Carmeliet, Geert; Vanderschueren, Dirk; Claessens, Frank

    2014-07-01

    Androgens have well-established anabolic actions on skeletal muscle, although the direct effects of the androgen receptor (AR) in muscle remain unclear. We generated satellite cell-specific AR-knockout (satARKO) mice in which the AR is selectively ablated in satellite cells, the muscle precursor cells. Total-limb maximal grip strength is decreased by 7% in satARKO mice, with soleus muscles containing ∼10% more type I fibers and 10% less type IIa fibers than the corresponding control littermates. The weight of the perineal levator ani muscle is markedly reduced (-52%). Thus, muscle AR is involved in fiber-type distribution and force production of the limb muscles, while it is a major determinant of the perineal muscle mass. Surprisingly, myostatin (Mstn), a strong inhibitor of skeletal muscle growth, is one of the most androgen-responsive genes (6-fold reduction in satARKO) through direct transcription activation by the AR. Consequently, muscle hypertrophy in response to androgens is augmented in Mstn-knockout mice. Our finding that androgens induce Mstn signaling to restrain their own anabolic actions has implications for the treatment of muscle wasting disorders.-Dubois, V., Laurent, M. R., Sinnesael, M., Cielen, N., Helsen, C., Clinckemalie, L., Spans, L., Gayan-Ramirez, G., Deldicque, L., Hespel, P., Carmeliet, G., Vanderschueren, D., and Claessens, F. A satellite cell-specific knockout of the androgen receptor reveals myostatin as a direct androgen target in skeletal muscle.

  3. Cell-specific promoter in adenovirus vector for transgenic expression of SERCA1 ATPase in cardiac myocytes.

    Science.gov (United States)

    Inesi, G; Lewis, D; Sumbilla, C; Nandi, A; Strock, C; Huff, K W; Rogers, T B; Johns, D C; Kessler, P D; Ordahl, C P

    1998-03-01

    Adenovirus-mediated transfer of cDNA encoding the chicken skeletal muscle sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA1) yielded selective expression in cultured chick embryo cardiac myocytes under control of a segment (-268 base pair) of the cell-specific cardiac troponin T (cTnT) promoter or nonselective expression in myocytes and fibroblasts under control of a constitutive viral [cytomegalovirus (CMV)] promoter. Under optimal conditions nearly all cardiac myocytes in culture were shown to express transgenic SERCA1 ATPase. Expression was targeted to intracellular membranes and was recovered in subcellular fractions with a pattern identical to that of the endogenous SERCA2a ATPase. Relative to control myocytes, transgenic SERCA1 expression increased up to four times the rates of ATP-dependent (and thapsigargin-sensitive) Ca2+ transport activity of cell homogenates. Although the CMV promoter was more active than the cTnT promoter, an upper limit for transgenic expression of functional enzyme was reached under control of either promoter by adjustment of the adenovirus plaque-forming unit titer of infection media. Cytosolic Ca2+ concentration transients and tension development of whole myocytes were also influenced to a similar limit by transgenic expression of SERCA1 under control of either promoter. Our experiments demonstrate that a cell-specific protein promoter in recombinant adenovirus vectors yields highly efficient and selective transgene expression of a membrane-bound and functional enzyme in cardiac myocytes.

  4. Selective de-repression of germ cell-specific genes in mouse embryonic fibroblasts in a permissive epigenetic environment.

    Science.gov (United States)

    Sekinaka, Tamotsu; Hayashi, Yohei; Noce, Toshiaki; Niwa, Hitoshi; Matsui, Yasuhisa

    2016-09-09

    Epigenetic modifications play crucial roles on establishment of tissue-specific transcription profiles and cellular characteristics. Direct conversions of fibroblasts into differentiated tissue cells by over-expression of critical transcription factors have been reported, but the epigenetic mechanisms underlying these conversions are still not fully understood. In addition, conversion of somatic cells into germ cells has not yet been achieved. To understand epigenetic mechanisms that underlie germ cell characteristics, we attempted to use defined epigenetic factors to directly convert mouse embryonic fibroblasts (MEFs) into germ cells. Here, we successfully induced germ cell-specific genes by inhibiting repressive epigenetic modifications via RNAi or small-molecule compounds. Under these conditions, some tissue-specific genes and stimulus-inducible genes were also induced. Meanwhile, the treatments did not result in genome-wide transcriptional activation. These results suggested that a permissive epigenetic environment resulted in selective de-repression of stimulus- and differentiation-inducible genes including germ cell-specific genes in MEFs.

  5. Selective de-repression of germ cell-specific genes in mouse embryonic fibroblasts in a permissive epigenetic environment

    Science.gov (United States)

    Sekinaka, Tamotsu; Hayashi, Yohei; Noce, Toshiaki; Niwa, Hitoshi; Matsui, Yasuhisa

    2016-01-01

    Epigenetic modifications play crucial roles on establishment of tissue-specific transcription profiles and cellular characteristics. Direct conversions of fibroblasts into differentiated tissue cells by over-expression of critical transcription factors have been reported, but the epigenetic mechanisms underlying these conversions are still not fully understood. In addition, conversion of somatic cells into germ cells has not yet been achieved. To understand epigenetic mechanisms that underlie germ cell characteristics, we attempted to use defined epigenetic factors to directly convert mouse embryonic fibroblasts (MEFs) into germ cells. Here, we successfully induced germ cell-specific genes by inhibiting repressive epigenetic modifications via RNAi or small-molecule compounds. Under these conditions, some tissue-specific genes and stimulus-inducible genes were also induced. Meanwhile, the treatments did not result in genome-wide transcriptional activation. These results suggested that a permissive epigenetic environment resulted in selective de-repression of stimulus- and differentiation-inducible genes including germ cell-specific genes in MEFs. PMID:27608931

  6. Frank hematuria as the presentation feature of acute leukemia

    Directory of Open Access Journals (Sweden)

    Suriya Owais

    2010-01-01

    Full Text Available Muco-cutaneous bleeding is a common presenting feature of acute leukemias. Mucosal bleeding usually manifests as gum bleeding and/or epistaxis but may occur in any mucosal surface of the body. Hematuria as an isolated or main presenting feature of acute leukemia is rare. We describe two cases of acute leukemia, a 19 year old male with acute lymphoblastic leukemia and a 52 year old male with acute myeloid leukemia, both presenting with gross hematuria. There was no demonstrable leukemic infiltration of the urinary tract on imaging studies. Hematuria in these patients was likely to be due to occult leukemic infiltration of the urinary system, aggravated by thrombocytopenia, as it subsided after starting chemotherapy. Our cases highlight that hematuria should be remembered as a rare presenting feature of acute leukemia.

  7. Chronic lymphocytic leukemia is infrequent in Mexican mestizos.

    Science.gov (United States)

    Ruiz-Argüelles, G J; Velázquez, B M; Apreza-Molina, M G; Pérez-Romano, B; Ruiz-Reyes, G; Ruiz-Argüelles, A

    1999-06-01

    Chronic lymphocytic leukemia (CLL) is the most frequent leukemia in adults living in Western countries, and accounts for approximately 30% of adult leukemias. In a 15-year period in a single institution, we identified 19 patients with CLL in a group of 211 adults with leukemia (9% of adult leukemias). Of these 19 CLL patients, 8 had a Caucasian phenotype, 4 were born outside the country, and only 11 were Mexican mestizos. On the other hand, in a multicenter experience involving 1968 Mexican adults with leukemia, CLL represented 6.6% of the cases, a figure significantly lower than that reported in Caucasians (P mestizos, and this low prevalence may stem from the genetic origin of this racial group. The data also suggest a genetic predisposition of Caucasians to suffer from this disease.

  8. [Cytogenetic abnormalities and gene mutations in myeloid leukemia].

    Science.gov (United States)

    Kato, Naoko; Kitamura, Toshio

    2009-10-01

    Myeloid leukemia is a clinically and genetically heterogeneous disease. Cytogenetic studies have revealed specific chromosomal abnormalities, such as translocations, and inversions. Fusion proteins derived from these abnormalities were identified in various subtypes of leukemia. Because most of these fusion proteins were not sufficient to induce leukemia by themselves in mouse models, additional oncogenic events have been thought to be necessary for leukemogenesis. Recently, a hypothesis called "two-hit model" for leukemia has been proposed. Two broad classes of mutations that proliferative or survival advantage of hematopoietic progenitors and impaired differentiation are required for inducing leukemia. In this article, we summarize some typical chromosomal abnormalities or gene mutations associated with myeloid leukemia on the basis of this hypothesis.

  9. Endogenous murine leukemia virus-encoded proteins in radiation leukemias of BALB/c mice

    Energy Technology Data Exchange (ETDEWEB)

    Tress, E.; Pierotti, M.; DeLeo, A.B.; O' Donnell, P.V.; Fleissner, E.

    1982-02-01

    To explore the role of endogenous retroviruses in radiation-induced leukemogenesis in the mouse, we have examined virus-encoded proteins in nine BALB/c leukemias by pulsechase labeling procedures and serological typing with monospecific and monoclonal antibodies. The major gag precursor protein, Pr65/sup gag/, was observed in all cases, but only three leukemias expressed detectable amounts of the glycosylated gag species, gP95/sup gag/, or its precursor, Pr75/sup gag/. No evidence was found for synthesis of gag-host fusion proteins. None of the leukemias released infectious xenotropic or dualtropic virus, but all nine expressed at least one env protein with xenotropic properties. In two instances a monoclonal antibody, 35/56, which is specific for the NuLV G/sub IX/ antigen, displayed a distinctive reactivity with this class of env protein, although this antibody is unreactive with replicating xenotropic viruses. An ecotropic/xenotropic recombinant env protein with the same 35/56 phenotype was observed in a leukemia induced by a strongly leukemogenic virus isolated from a BALB/c radiation leukemia.

  10. Zoonotic Infections in Pediatric Patients With Acute Leukemia

    OpenAIRE

    2013-01-01

    Few studies have described the impact of zoonotic diseases in children with leukemia. This study aimed to describe the frequency of and associated demographic factors for zoonotic diseases in pediatric acute leukemia patients. Descriptive and comparative statistics relative to age, sex, and patient region were performed on an assembled 11-year retrospective cohort of acute leukemia patients. Of 10,197 patients, 88 patients (0.86%) were found to have a zoonotic infection. Gastrointestinal dise...

  11. Determination of the Prevalence of HGV Infection in Leukemia Patients

    Directory of Open Access Journals (Sweden)

    Ramin Yaghoubi

    2011-09-01

    Full Text Available Background: The potential of acute and chronic viral hepatitis infections in blood leukocytes is one of the possible risk factors of leukemia. Between hepatitis viruses, HGV is important for unknown mechanism of pathogenesis in affecting the outcome of leukemia. In this research the prevalence of HGV infection was studied for evaluation of the possible role of this viral infection in the pathophysiology of leukemia. Methods: In this study, 100 EDTA treated blood samples were collected for 2 and half a year from different types of leukemia and also healthy control group, respectively. The plasma of these blood samples were harvested and stored at -80°C till laboratory tests were performed. Serological and antigenic markers of HBV, HCV and HGV were analyzed by ELISA methods. The HGV viremia was also studied by an in-house nested-RT-PCR method in plasma samples of patients with leukemia and control population. Results: Anti-E2-Ab was detected in 1(1% of leukemia patients who has not the history of HBV and HCV infections. HGV-RNA was diagnosed in 4(4% of patients with leukemia and 1(1% of control group. Simultaneous infection of HGV-RNA and HBsAg was detected in one of patients with leukemia. Significant difference was seen between the prevalence of HBV infection in leukemia patients and control group (P=0.02. Also significant correlation was detected between sex and the prevalence of HBV infection in leukemia patients (P=0.02. None of studied risk factors of leukemia were not significantly correlated with HGV infection. Conclusion: In this study the low prevalence of active and persistent HGV infections in leukemia patients in comparing with control population was confirmed. Also detection of HGV and HBV co-infection in these patients, announced the need of completed studies in different populations with different hematological malignancies and/or abnormalities, for better therapeutic and laboratory management of these cancers.

  12. Pregnancy, Maternal Tobacco Smoking, and Early Age Leukemia in Brazil

    OpenAIRE

    2012-01-01

    Background: Cigarette smoking has been associated with acute myeloid leukemia but hypothesis on the association between maternal smoking during pregnancy and childhood leukemia is unclear. Objectives: To investigate the association between maternal exposure to tobacco smoking during pregnancy and early age (< 2 yr.) leukemia (EAL). Methods: A hospital-based multicenter case-control study aiming to explore EAL risk factors was carried out in Brazil during 1999-2007. Data were collected by ...

  13. A retrospective cohort study of cause-specific mortality and incidence of hematopoietic malignancies in Chinese benzene-exposed workers.

    Science.gov (United States)

    Linet, Martha S; Yin, Song-Nian; Gilbert, Ethel S; Dores, Graça M; Hayes, Richard B; Vermeulen, Roel; Tian, Hao-Yuan; Lan, Qing; Portengen, Lutzen; Ji, Bu-Tian; Li, Gui-Lan; Rothman, Nathaniel

    2015-11-01

    Benzene exposure has been causally linked with acute myeloid leukemia (AML), but inconsistently associated with other hematopoietic, lymphoproliferative and related disorders (HLD) or solid tumors in humans. Many neoplasms have been described in experimental animals exposed to benzene. We used Poisson regression to estimate adjusted relative risks (RR) and the likelihood ratio statistic to derive confidence intervals for cause-specific mortality and HLD incidence in 73,789 benzene-exposed compared with 34,504 unexposed workers in a retrospective cohort study in 12 cities in China. Follow-up and outcome assessment was based on factory, medical and other records. Benzene-exposed workers experienced increased risks for all-cause mortality (RR = 1.1, 95% CI = 1.1, 1.2) due to excesses of all neoplasms (RR = 1.3, 95% CI = 1.2, 1.4), respiratory diseases (RR = 1.7, 95% CI = 1.2, 2.3) and diseases of blood forming organs (RR = ∞, 95% CI = 3.4, ∞). Lung cancer mortality was significantly elevated (RR = 1.5, 95% CI = 1.2, 1.9) with similar RRs for males and females, based on three-fold more cases than in our previous follow-up. Significantly elevated incidence of all myeloid disorders reflected excesses of myelodysplastic syndrome/acute myeloid leukemia (RR = 2.7, 95% CI = 1.2, 6.6) and chronic myeloid leukemia (RR = 2.5, 95% CI = 0.8, 11), and increases of all lymphoid disorders included excesses of non-Hodgkin lymphoma (RR = 3.9, 95%CI = 1.5, 13) and all lymphoid leukemia (RR = 5.4, 95%CI = 1.0, 99). The 28-year follow-up of Chinese benzene-exposed workers demonstrated increased risks of a broad range of myeloid and lymphoid neoplasms, lung cancer, and respiratory diseases and suggested possible associations with other malignant and non-malignant disorders.

  14. [Acute myeloid leukemia originating from the same leukemia clone after the complete remission of acute lymphoid leukemia].

    Science.gov (United States)

    Matsuda, Isao; Nakamaki, Tsuyoshi; Amaya, Hiroshi; Kiyosaki, Masanobu; Kawakami, Keiichiro; Yamada, Kazunari; Yokoyama, Akihiro; Hino, Ken-ichiro; Tomoyasu, Shigeru

    2003-09-01

    A 22-year-old female was diagnosed as having acute lymphoid leukemia (ALL) in February 1995, from the findings of peroxidase negative, CD10+, CD19+, TdT+ and rearrangement of IgH and TCR beta. AdVP (doxorubicin, vincristine and prednisolone) therapy achieved a complete remission (CR). Bone marrow transplantation had to be abandoned because of the lack of an HLA-identical donor. Intensification therapy was thus carried out repeatedly. In June 1998, myeloblast with Auer rods, peroxidase positive, CD13+, CD33+ and HLA-DR+, appeared. The patient was diagnosed as having lineage switch acute myeloid leukemia (AML) from ALL. Though A-DMP (cytosine arabinoside, daunorubicin, 6-mercaptopurine) therapy was resistant, AdVP therapy led to a CR. The patient died of cardiotoxicity from anthracyclines in February 1999. From the results of the Ramasamy method using the clonal rearrangements of the Ig heavy chain gene locus, the origin of the pathological cells of ALL and AML was indicated to be the same leukemia clone.

  15. Decitabine, Vorinostat, and Cytarabine in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

    Science.gov (United States)

    2014-12-19

    Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); RUNX1-RUNX1T1; Adult Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-MLL; Adult Acute Promyelocytic Leukemia With t(15;17)(q22;q12); PML-RARA; Alkylating Agent-Related Acute Myeloid Leukemia; Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Daniel Willian Lustosa de Sousa

    2015-08-01

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

  18. Induction of T-cell immunity against leukemia by dendritic cells pulsed with total RNA isolated from leukemia cells

    Institute of Scientific and Technical Information of China (English)

    李牧; 尤胜国; 葛薇; 马双; 马楠; 赵春华

    2003-01-01

    Objectives To assess the feasibility and efficacy of eliciting leukemia-specific T-cell responses in syngeneic mice in vitro and in vivo using dendritic cells (DCs) pulsed with total RNA from leukemia cells.Methods DCs generated from bone marrow culture in vitro in the presence of combined cytokines were pulsed with cellular total RNA isolated from cultured L615 cells by cationic lipid 1,2-dioleoyloxy-3-(trimethylammonium) propane (DOTAP). T-cell responses were evaluated by in vitro proliferation, and cytotoxicity assay. And in vivo immune protection and proghosis of mice with leukemia were studied.Conclusions These data support the use of DCs/RNA vaccine as a feasible and effective route to elicit leukemia immunity against unidentified leukemia-associated antigens for treatment of leukemia-bearing animals.

  19. The biology and targeting of FLT3 in pediatric leukemia

    Directory of Open Access Journals (Sweden)

    Colleen eAnnesley

    2014-09-01

    Full Text Available Despite remarkable improvement in treatment outcomes in pediatric leukemia over the past several decades, the prognosis for high risk groups of acute myeloid leukemia (AML and acute lymphoblastic leukemia (ALL, as well as for relapsed leukemia, remains poor. Intensified chemotherapy regimens have somewhat improved success rates, but at the cost of drastically increased morbidity and long term adverse effects. With the success of imatinib in Philadelphia-chromosome positive leukemia and all-trans retinoic acid in acute promyelocytic leukemia, the quest to find additional molecularly targeted therapies has generated much excitement over the past 15 years. Another such possible target in pediatric acute leukemia is FMS-like tyrosine kinase 3 (FLT3. FLT3 aberrations are among the most frequently identified transforming events in AML, and have significant clinical implications in both high risk pediatric AML and in certain high risk groups of pediatric ALL. Therefore, the successful targeting of FLT3 has tremendous potential to improve outcomes in these subsets of patients. This article will give an overview of the molecular function and signaling of the FLT3 receptor, as well as its pathogenic role in leukemia. We review the discovery of targeting FLT3, discuss currently available FLT3 inhibitors in pediatric leukemia and results of clinical trials to date, and finally, consider the future promise and challenges of FLT3 inhibitor therapy.

  20. Acute myelogenous leukemia and acute leukemic appendicitis: A case report

    Institute of Scientific and Technical Information of China (English)

    Po-Jen Hsiao; Shih-Ming Kuo; Jia-Hong Chen; Hsuen-Fu Lin; Pau-Ling Chu; Shih-Hua Lin; Ching-Liang Ho

    2009-01-01

    Acute myelogenous leukemia (AML) can involve the gastrointestinal tract but rarely involves the appendix.We report a male patient who had 1 year partial remission from AML and who presented with apparent acute appendicitis as the initial manifestation of leukemia relapse. Pathological findings of the appendix revealed transmural infiltrates of myeloblasts, whichindicated a diagnosis of leukemia. Unfortunately, the patient died from progression of the disease on the 19th d after admission. Although leukemic cell infiltration of the appendix is uncommon, patients with leukemia relapse can present with symptoms mimicking acute appendicitis.

  1. Zoonotic infections in pediatric patients with acute leukemia.

    Science.gov (United States)

    Lothstein, Katherine; Fisher, Brian; Li, Yimei; Seif, Alix; Harris, Tracey; Torp, Kari; Kavcic, Marko; Huang, Yuan-Shung V; Rheingold, Susan R; Aplenc, Richard

    2013-12-01

    Few studies have described the impact of zoonotic diseases in children with leukemia. This study aimed to describe the frequency of and associated demographic factors for zoonotic diseases in pediatric acute leukemia patients. Descriptive and comparative statistics relative to age, sex, and patient region were performed on an assembled 11-year retrospective cohort of acute leukemia patients. Of 10,197 patients, 88 patients (0.86%) were found to have a zoonotic infection. Gastrointestinal diseases were the most commonly (86.4%) identified zoonotic illnesses. Although rare, zoonotic diseases do occur in children with leukemia and frequency varies by age, region, and gender.

  2. The human application of gene therapy to re-program T-cell specificity using chimeric antigen receptors

    Institute of Scientific and Technical Information of China (English)

    Alan DGuerrero; Judy SMoyes; Laurence JN Cooper

    2014-01-01

    The adoptive transfer of T cells is a promising approach to treat cancers. Primary human T cells can be modified using viral and non-viral vectors to promote the specific targeting of cancer cells via the introduction of exogenous T-cell receptors (TCRs) or chimeric antigen receptors (CARs). This gene transfer displays the potential to increase the specificity and potency of the anticancer response while decreasing the systemic adverse effects that arise from conventional treatments that target both cancerous and healthy cells. This review highlights the generation of clinical-grade T cells expressing CARs for immunotherapy, the use of these cels to target B-cellmalignancies and, particularly, the first clinical trials deploying the Sleeping Beauty gene transfer system, which engineers T cells to target CD19+ leukemia and non-Hodgkin’s lymphoma.

  3. Chronic lymphocytic leukemia in African Americans.

    Science.gov (United States)

    Coombs, Catherine C; Falchi, Lorenzo; Weinberg, J Brice; Ferrajoli, Alessandra; Lanasa, Mark C

    2012-11-01

    Chronic lymphocytic leukemia (CLL) is the most prevalent leukemia in the United States with almost 4390 attributable deaths per year. Epidemiologic data compiled by the Surveillance, Epidemiology and End Results (SEER) program identifies important differences in incidence and survival for African Americans with CLL. Although the incidence of CLL is lower among African Americans than among Caucasians (4.6 and 6.2 per 100 000 men, respectively), age-adjusted survival is inferior. African American patients with CLL are almost twice as likely to die from a CLL-related complication in the first 5 years after diagnosis as are Caucasian patients with CLL. The biologic basis for these observations is almost entirely unexplored, and a comprehensive clinical analysis of African American patients with CLL is lacking. This is the subject of the present review.

  4. The Genomic Landscape of Juvenile Myelomonocytic Leukemia

    Science.gov (United States)

    Chang, Tiffany Y.; Gelston, Laura C.; Wang, Yong-Dong; Mazor, Tali; Esquivel, Emilio; Yu, Ariel; Seepo, Sara; Olsen, Scott; Rosenberg, Mara; Archambeault, Sophie L.; Abusin, Ghada; Beckman, Kyle; Brown, Patrick A.; Briones, Michael; Carcamo, Benjamin; Cooper, Todd; Dahl, Gary V.; Emanuel, Peter D.; Fluchel, Mark N.; Goyal, Rakesh K.; Hayashi, Robert J.; Hitzler, Johann; Hugge, Christopher; Liu, Y. Lucy; Messinger, Yoav H.; Mahoney, Donald H.; Monteleone, Philip; Nemecek, Eneida R.; Roehrs, Philip A.; Schore, Reuven J.; Stine, Kimo C.; Takemoto, Clifford M.; Toretsky, Jeffrey A.; Costello, Joseph F.; Olshen, Adam B.; Stewart, Chip; Li, Yongjin; Ma, Jing; Gerbing, Robert B.; Alonzo, Todd A.; Getz, Gad; Gruber, Tanja; Golub, Todd; Stegmaier, Kimberly; Loh, Mignon L.

    2015-01-01

    Juvenile myelomonocytic leukemia (JMML) is a myeloproliferative neoplasm (MPN) of childhood with a poor prognosis. Mutations in NF1, NRAS, KRAS, PTPN11 and CBL occur in 85% of patients, yet there are currently no risk stratification algorithms capable of predicting which patients will be refractory to conventional treatment and therefore be candidates for experimental therapies. In addition, there have been few other molecular pathways identified aside from the Ras/MAPK pathway to serve as the basis for such novel therapeutic strategies. We therefore sought to genomically characterize serial samples from patients at diagnosis through relapse and transformation to acute myeloid leukemia in order to expand our knowledge of the mutational spectrum in JMML. We identified recurrent mutations in genes involved in signal transduction, gene splicing, the polycomb repressive complex 2 (PRC2) and transcription. Importantly, the number of somatic alterations present at diagnosis appears to be the major determinant of outcome. PMID:26457647

  5. The Danish National Chronic Lymphocytic Leukemia Registry

    DEFF Research Database (Denmark)

    da Cunha-Bang, Caspar; Geisler, Christian Hartmann; Enggaard, Lisbeth;

    2016-01-01

    , and for decision on treatment initiation as well as characteristics included in the CLL International Prognostic Index are collected. DESCRIPTIVE DATA: To ensure full coverage of Danish CLL patients in the registry, both continuous queries in case of missing data, and cross-referencing with the Danish National......, 3,082 patients have been registered. CONCLUSION: The Danish National CLL Registry is based within the Danish National Hematology Database. The registry covers a cohort of all patients diagnosed with CLL in Denmark since 2008. It forms the basis for quality assessment of CLL treatment in Denmark......AIM: In 2008, the Danish National Chronic Lymphocytic Leukemia Registry was founded within the Danish National Hematology Database. The primary aim of the registry is to assure quality of diagnosis and care of patients with chronic lymphocytic leukemia (CLL) in Denmark. Secondarily, to evaluate...

  6. Optimization of experimental human leukemia models (review

    Directory of Open Access Journals (Sweden)

    D. D. Pankov

    2012-01-01

    Full Text Available Actual problem of assessing immunotherapy prospects including antigenpecific cell therapy using animal models was covered in this review.Describe the various groups of currently existing animal models and methods of their creating – from different immunodeficient mice to severalvariants of tumor cells engraftment in them. The review addresses the possibility of tumor stem cells studying using mouse models for the leukemia treatment with adoptive cell therapy including WT1. Also issues of human leukemia cells migration and proliferation in a mice withdifferent immunodeficiency degree are discussed. To assess the potential immunotherapy efficacy comparison of immunodeficient mouse model with clinical situation in oncology patients after chemotherapy is proposed.

  7. Optimization of experimental human leukemia models (review

    Directory of Open Access Journals (Sweden)

    D. D. Pankov

    2014-07-01

    Full Text Available Actual problem of assessing immunotherapy prospects including antigenpecific cell therapy using animal models was covered in this review.Describe the various groups of currently existing animal models and methods of their creating – from different immunodeficient mice to severalvariants of tumor cells engraftment in them. The review addresses the possibility of tumor stem cells studying using mouse models for the leukemia treatment with adoptive cell therapy including WT1. Also issues of human leukemia cells migration and proliferation in a mice withdifferent immunodeficiency degree are discussed. To assess the potential immunotherapy efficacy comparison of immunodeficient mouse model with clinical situation in oncology patients after chemotherapy is proposed.

  8. Global characteristics of childhood acute promyelocytic leukemia.

    Science.gov (United States)

    Zhang, L; Samad, A; Pombo-de-Oliveira, M S; Scelo, G; Smith, M T; Feusner, J; Wiemels, J L; Metayer, C

    2015-03-01

    Acute promyelocytic leukemia (APL) comprises approximately 5-10% of childhood acute myeloid leukemia (AML) cases in the US. While variation in this percentage among other populations was noted previously, global patterns of childhood APL have not been thoroughly characterized. In this comprehensive review of childhood APL, we examined its geographic pattern and the potential contribution of environmental factors to observed variation. In 142 studies (spanning >60 countries) identified, variation was apparent-de novo APL represented from 2% (Switzerland) to >50% (Nicaragua) of childhood AML in different geographic regions. Because a limited number of previous studies addressed specific environmental exposures that potentially underlie childhood APL development, we gathered 28 childhood cases of therapy-related APL, which exemplified associations between prior exposures to chemotherapeutic drugs/radiation and APL diagnosis. Future population-based studies examining childhood APL patterns and the potential association with specific environmental exposures and other risk factors are needed.

  9. Cytogenetic patterns in acute nonlymphocytic leukemia

    Energy Technology Data Exchange (ETDEWEB)

    Testa, J.R.; Rowley, J.D.

    1978-01-01

    Analysis of chromosomal banding patterns in acute nonlymphocytic leukemia (ANLL) reveals that approximately 50% of patients have an abnormal karyotype. Although there is substantial variability, certain nonrandom abnormalities occur, e.g., +8, -7, and the 8;21 translocation (often accompanied by loss of an X or Y chromosome). The 15;17 translocation appears to be highly specific for acute promyelocytic leukemia. These abnormalities usually are not seen in remission, but reappear in relapse, sometimes exhibiting further clonal evolution; a +8 is the most frequently observed evolutionary change. Patients with ANLL following treatment of a malignant lymphoma tend to have hypodiploid modal numbers and frequently show loss of a chromosome No. 5 or No. 7.

  10. Histamine revisited: Role in acute myeloid leukemia

    Directory of Open Access Journals (Sweden)

    Prasan R Bhandari

    2013-01-01

    Full Text Available Histamine dihydrochloride (HDC is derived from biogenic amine histamine. It suppresses the production of reactive oxygen species which inhibits the stimulation of T cells and natural killer (NK cells. Co-administration of the cytokine interleukin (IL-2 and HDC assists the activation of T cells and NK cells by IL-2, causing in the destruction of cancer cells, including those of acute myeloid leukemia (AML. A significantly longer leukemia-free survival (LFS; primary endpoint was demonstrated in a phase III trial in adult patients with AML in first or subsequent remission, in those who received subcutaneous HDC and concomitant subcutaneous IL-2 as maintenance therapy compared to that of patients receiving no treatment. However, the difference in overall survival (OS between the two groups was not significant. Patients had acceptable levels of adverse effects. Thus, HDC in addition to IL-2 appears to be a useful maintenance therapy option for adult patients with AML in remission.

  11. Metabolism pathways in chronic lymphocytic leukemia.

    Science.gov (United States)

    Rozovski, Uri; Hazan-Halevy, Inbal; Barzilai, Merav; Keating, Michael J; Estrov, Zeev

    2016-01-01

    Alterations in chronic lymphocytic leukemia (CLL) cell metabolism have been studied by several investigators. Unlike normal B lymphocytes or other leukemia cells, CLL cells, like adipocytes, store lipids and utilize free fatty acids (FFA) to produce chemical energy. None of the recently identified mutations in CLL directly affects metabolic pathways, suggesting that genetic alterations do not directly contribute to CLL cells' metabolic reprogramming. Conversely, recent data suggest that activation of STAT3 or downregulation of microRNA-125 levels plays a crucial role in the utilization of FFA to meet the CLL cells' metabolic needs. STAT3, known to be constitutively activated in CLL, increases the levels of lipoprotein lipase (LPL) that mediates lipoprotein uptake and shifts the CLL cells' metabolism towards utilization of FFA. Herein, we review the evidence for altered lipid metabolism, increased mitochondrial activity and formation of reactive oxygen species (ROS) in CLL cells, and discuss the possible therapeutic strategies to inhibit lipid metabolism pathways in patient with CLL.

  12. The Application of Spectral Karyotyping in Leukemia

    Institute of Scientific and Technical Information of China (English)

    Bo Guo; Wanming Da; Xiaoping Han

    2006-01-01

    Spectral karyotyping (SKY) is a novel cytogenetic technique, which has been developed to unambiguously display and identify all 24 human chromosomes at one time without previous knowledge of any abnormalities involved. SKY can discern aberrations that fail to be easily detected by conventional banding techniques and by fluorescent in situ hybridization (FISH). Therefore SKY is highly accurate, highly sensitive, and highly prognostic. In this report the featurese and application of SKY in studies of leukemia are reviewed.

  13. Mast cell leukemia: an extremely rare disease.

    Science.gov (United States)

    Lu, Dai-Yin; Gau, Jyh-Pyng; Hong, Ying-Chung; Liu, Chun-Yu; Yu, Yuan-Bin; Hsiao, Liang-Tsai; Liu, Jin-Hwang; Chen, Po-Min; Chiou, Tzeon-Jye; Tzeng, Cheng-Hwai

    2014-08-01

    Systemic mastocytosis is characterized by pathologic proliferation and accumulation of mast cells in at least one extracutaneous organ such as liver, spleen, bone marrow, or lymph nodes. The clinical features are highly variable depending on impairment of the involved organ systems. It often raises diagnostic challenges. Here we report a case of a 78-year-old patient with mast cell leukemia. The literature is reviewed regarding the diagnosis and updated management of this rare disease.

  14. Philadelphia chromosome positive leukemia including acute lymphoblastic leukemia, acute myeloid leukemia and accelerate phase myeloid leukemia. | EU Clinical Trials Register [EU Clinical Trials Register

    Lifescience Database Archive (English)

    Full Text Available udio in aperto di fase II per determinare la tollerabilita` e l`efficacia antileucemica di STI571 in pazienti adulti con leucemia... Ph+ incluse la leucemia linfoblastica acuta, la leucemia mieloide acuta e la leucemia ...e phase myeloid leukemia. leucemia Ph+ incluse la leucemia linfoblastica acuta, la leucemia... mieloide acuta e la leucemia mieloide cronica in fase accelerata. E.1.1.2Therapeutic area Disease

  15. B cell acute lymphocytic leukemia in pregnancy.

    Science.gov (United States)

    Bottsford-Miller, Justin; Haeri, Sina; Baker, Arthur M; Boles, Jeremiah; Brown, Mark

    2011-08-01

    Acute lymphocytic leukemia (ALL) is a rare occurrence in pregnancy and can be rapidly fatal if left untreated. The need for immediate treatment of ALL, coupled with the maternal-fetal risks from the chemotherapy regimen render a therapeutic dilemma in pregnant women with ALL. We report a case of ALL diagnosed in the 24th week of pregnancy to outline our management strategy, to demonstrate the feasibility of treatment with multi-agent chemotherapy, and to provide a review of the literature.

  16. T-cell-specific deletion of Mof blocks their differentiation and results in genomic instability in mice.

    Science.gov (United States)

    Gupta, Arun; Hunt, Clayton R; Pandita, Raj K; Pae, Juhee; Komal, K; Singh, Mayank; Shay, Jerry W; Kumar, Rakesh; Ariizumi, Kiyoshi; Horikoshi, Nobuo; Hittelman, Walter N; Guha, Chandan; Ludwig, Thomas; Pandita, Tej K

    2013-05-01

    Ataxia telangiectasia patients develop lymphoid malignancies of both B- and T-cell origin. Similarly, ataxia telangiectasia mutated (Atm)-deficient mice exhibit severe defects in T-cell maturation and eventually develop thymomas. The function of ATM is known to be influenced by the mammalian orthologue of the Drosophila MOF (males absent on the first) gene. Here, we report the effect of T-cell-specific ablation of the mouse Mof (Mof) gene on leucocyte trafficking and survival. Conditional Mof(Flox/Flox) (Mof (F/F)) mice expressing Cre recombinase under control of the T-cell-specific Lck proximal promoter (Mof(F/F)/Lck-Cre(+)) display a marked reduction in thymus size compared with Mof(F/F)/Lck-Cre(-) mice. In contrast, the spleen size of Mof(F/F)/Lck-Cre(+) mice was increased compared with control Mof(F/F)/Lck-Cre(-) mice. The thymus of Mof(F/F)/Lck-Cre(+) mice contained significantly reduced T cells, whereas thymic B cells were elevated. Within the T-cell population, CD4(+)CD8(+) double-positive T-cell levels were reduced, whereas the immature CD4(-)CD8(-) double-negative (DN) population was elevated. Defective T-cell differentiation is also evident as an increased DN3 (CD44(-)CD25(+)) population, the cell stage during which T-cell receptor rearrangement takes place. The differentiation defect in T cells and reduced thymus size were not rescued in a p53-deficient background. Splenic B-cell distributions were similar between Mof(F/F)/Lck-Cre(+) and Mof(F/F)/Lck-Cre(-) mice except for an elevation of the κ light-chain population, suggestive of an abnormal clonal expansion. T cells from Mof(F/F)/Lck-Cre(+) mice did not respond to phytohaemagglutinin (PHA) stimulation, whereas LPS-stimulated B cells from Mof(F/F)/Lck-Cre(+) mice demonstrated spontaneous genomic instability. Mice with T-cell-specific loss of MOF had shorter lifespans and decreased survival following irradiation than did Mof(F/F)/Lck-Cre(-) mice. These observations suggest that Mof plays a critical

  17. An Immunocompetent Mouse Model for MLL/AF9 Leukemia Reveals the Potential of Spontaneous Cytotoxic T-Cell Response to an Antigen Expressed in Leukemia Cells.

    Directory of Open Access Journals (Sweden)

    Kana Hasegawa

    Full Text Available Leukemia differs substantially with respect to stromal milieu from tumors that progress locally as solid masses, and the physiological importance of immunosurveillance in leukemia remains unclear. However, currently available mouse leukemia models have critical limitations in the context of analyzing immunological regulation of leukemia development. In this study, we transferred mouse MLL/AF9 leukemia-initiating cells into immunocompetent recipient mice without any pre-conditioning such as irradiation, and then analyzed the spontaneous T cell response to an immunogenic antigen expressed in leukemia cells. When the minimum numbers of leukemia-initiating cells for engraftment were transferred, leukemia cells were eradicated by the adaptive immune response in most, if not all, wild-type mice, but not in Rag2-/- recipient mice, which lack adaptive immunity. By contrast, mice transplanted with larger numbers of leukemia cells always developed leukemia. In mice with advanced leukemia, antigen-specific CTLs were also expanded, but were unresponsive to antigen stimulation and expressed high levels of PD-1 and LAG-3. These results provide the first clear demonstration that the spontaneous CTL response to a tumor-cell antigen has the potential to eradicate leukemia, whereas antigen-specific CTLs are exhausted in animals with advanced leukemia. This immunocompetent mouse leukemia model provides a useful platform for developing effective immunotherapies against leukemia.

  18. Home pesticide exposures and risk of childhood leukemia: Findings from the childhood leukemia international consortium.

    Science.gov (United States)

    Bailey, Helen D; Infante-Rivard, Claire; Metayer, Catherine; Clavel, Jacqueline; Lightfoot, Tracy; Kaatsch, Peter; Roman, Eve; Magnani, Corrado; Spector, Logan G; Th Petridou, Eleni; Milne, Elizabeth; Dockerty, John D; Miligi, Lucia; Armstrong, Bruce K; Rudant, Jérémie; Fritschi, Lin; Simpson, Jill; Zhang, Luoping; Rondelli, Roberto; Baka, Margarita; Orsi, Laurent; Moschovi, Maria; Kang, Alice Y; Schüz, Joachim

    2015-12-01

    Some previous studies have suggested that home pesticide exposure before birth and during a child's early years may increase the risk of childhood leukemia. To further investigate this, we pooled individual level data from 12 case-control studies in the Childhood Leukemia International Consortium. Exposure data were harmonized into compatible formats. Pooled analyses were undertaken using multivariable unconditional logistic regression. The odds ratio (ORs) for acute lymphoblastic leukemia (ALL) associated with any pesticide exposure shortly before conception, during pregnancy and after birth were 1.39 (95% confidence interval [CI]: 1.25, 1.55) (using 2,785 cases and 3,635 controls), 1.43 (95% CI: 1.32, 1.54) (5,055 cases and 7,370 controls) and 1.36 (95% CI: 1.23, 1.51) (4,162 cases and 5,179 controls), respectively. Corresponding ORs for risk of acute myeloid leukemia (AML) were 1.49 (95% CI: 1.02, 2.16) (173 cases and 1,789 controls), 1.55 (95% CI: 1.21, 1.99) (344 cases and 4,666 controls) and 1.08 (95% CI: 0.76, 1.53) (198 cases and 2,655 controls), respectively. There was little difference by type of pesticide used. The relative similarity in ORs between leukemia types, time periods and pesticide types may be explained by similar exposure patterns and effects across the time periods in ALL and AML, participants' exposure to multiple pesticides, or recall bias. Although some recall bias is likely, until a better study design can be found to investigate the associations between home pesticide use and childhood leukemia in an equally large sample, it would appear prudent to limit the use of home pesticides before and during pregnancy, and during childhood.

  19. Leukemia Associated Antigens: Their Dual Role as Biomarkers and Immunotherapeutic Targets for Acute Myeloid Leukemia

    Directory of Open Access Journals (Sweden)

    Michael Schmitt

    2007-01-01

    Full Text Available Leukemia associated antigens (LAAs are being increasingly identified by methods such as cytotoxic T-lymphocyte (CTL cloning, serological analysis of recombinant cDNA expression libraries (SEREX and mass spectrometry (MS. In additional, large scale screening techniques such as microarray, single nucleotide polymorphisms (SNPs, serial analysis of gene expression (SAGE and 2-dimensional gel electrophoresis (2-DE have expanded our understanding of the role that tumor antigens play in the biological processes which are perturbed in acute myeloid leukemia (AML. It has become increasingly apparent that these antigens play a dual role, not only as targets for immunotherapy, but also as biomarkers of disease state, stage, response to treatment and survival. We need biomarkers to enable the identification of the patients who are most likely to benefit from specific treatments (conventional and/or novel and to help clinicians and scientists improve clinical end points and treatment design. Here we describe the LAAs identified in AML, to date, which have already been shown to play a dual role as biomarkers of AML disease.Abbreviations: AML: acute myeloid leukemia; APL: acute promyelocytic leukemia; ATRA: all-trans-retinoic acid; B-CLL: B-cell chronic lymphocytic leukemia; CT: cancer-testis; CTL: cytotoxic T-lymphocyte; FAB: French-American-British; HI: hypusination inhibitors; HSP: heat shock protein; ITD: internal tandem duplication; LAA: leukemia associated antigen; MDS: myelodysplastic syndrome; MGEA6: meningioma antigen 6; MPD: myeloproliferative disease; MS: mass spectrometry; NK: natural killer; PRAME: preferentially expressed antigen of melanoma; PRTN3: proteinase 3; RAGE-1: renal antigen 1; RHAMM: receptor for hyaluronic acid-mediated motility; RQ-PCR: real-time PCR; SAGE: serial analysis of gene expression; SCT: stem cell transplant; SEREX: serological analysis of recombinant cDNA expression libraries; SNPs: single nucleotide polymorphisms; UPD

  20. Leukemia Mediated Endothelial Cell Activation Modulates Leukemia Cell Susceptibility to Chemotherapy through a Positive Feedback Loop Mechanism.

    Directory of Open Access Journals (Sweden)

    Bahareh Pezeshkian

    Full Text Available In acute myeloid leukemia (AML, the chances of achieving disease-free survival are low. Studies have demonstrated a supportive role of endothelial cells (ECs in normal hematopoiesis. Here we show that similar intercellular relationships exist in leukemia. We demonstrate that leukemia cells themselves initiate these interactions by directly modulating the behavior of resting ECs through the induction of EC activation. In this inflammatory state, activated ECs induce the adhesion of a sub-set of leukemia cells through the cell adhesion molecule E-selectin. These adherent leukemia cells are sequestered in a quiescent state and are unaffected by chemotherapy. The ability of adherent cells to later detach and again become proliferative following exposure to chemotherapy suggests a role of this process in relapse. Interestingly, differing leukemia subtypes modulate this process to varying degrees, which may explain the varied response of AML patients to chemotherapy and relapse rates. Finally, because leukemia cells themselves induce EC activation, we postulate a positive-feedback loop in leukemia that exists to support the growth and relapse of the disease. Together, the data defines a new mechanism describing how ECs and leukemia cells interact during leukemogenesis, which could be used to develop novel treatments for those with AML.

  1. Maternal mortality in Bijapur district

    Directory of Open Access Journals (Sweden)

    Vidya A. Thobbi

    2015-04-01

    Full Text Available Objectives: The objectives of this study is to evaluate the incidence of maternal deaths, causes responsible for maternal mortality, direct and indirect factors, and various preventable methods to reduce maternal mortality rate. Background: 95% of maternal deaths occur in Asia and Africa. The need for undertaking this study is to know the maternal mortality rate, analyze the causes and preventable factors of death occurring in the district of Bijapur, Karnataka, India. Methodology: It is a study of 2years from the Records of District Health Office and Institutions on maternal mortality from June 2011 to May 2013 in Bijapur. Results: In two years there were fifty eight maternal deaths and seventy nine thousand five hundred and sixty six live births, hence maternal mortality ratio was seventy three per lakh live births. Eighty two percent of maternal deaths occurred in families who belonged to Below Poverty Line. Prevalence of anemia in pregnancy was 79.3%. Severe anemia (Hemoglobin <7g% seen in 5.1% was the most common indirect cause of death. Forty three percent of the deaths occurred at private setups. Hemorrhage, Septicemia and Preeclampsia & Eclampsia were responsible for 44.82%, 15.51% and 6.89% respectively. Conclusion: Majority of the maternal deaths are preventable if these four delays are avoided: a Delay in identifying the problem. b Delay in seeking care. c Delay in reaching the referral institute. d Delay in getting treatment on reaching the referral institute.

  2. Conserved functional antagonism of CELF and MBNL proteins controls stem cell-specific alternative splicing in planarians.

    Science.gov (United States)

    Solana, Jordi; Irimia, Manuel; Ayoub, Salah; Orejuela, Marta Rodriguez; Zywitza, Vera; Jens, Marvin; Tapial, Javier; Ray, Debashish; Morris, Quaid; Hughes, Timothy R; Blencowe, Benjamin J; Rajewsky, Nikolaus

    2016-08-09

    In contrast to transcriptional regulation, the function of alternative splicing (AS) in stem cells is poorly understood. In mammals, MBNL proteins negatively regulate an exon program specific of embryonic stem cells; however, little is known about the in vivo significance of this regulation. We studied AS in a powerful in vivo model for stem cell biology, the planarian Schmidtea mediterranea. We discover a conserved AS program comprising hundreds of alternative exons, microexons and introns that is differentially regulated in planarian stem cells, and comprehensively identify its regulators. We show that functional antagonism between CELF and MBNL factors directly controls stem cell-specific AS in planarians, placing the origin of this regulatory mechanism at the base of Bilaterians. Knockdown of CELF or MBNL factors lead to abnormal regenerative capacities by affecting self-renewal and differentiation sets of genes, respectively. These results highlight the importance of AS interactions in stem cell regulation across metazoans.

  3. The Impact of Lipoprotein-Associated Oxidative Stress on Cell-Specific Microvesicle Release in Patients with Familial Hypercholesterolemia

    DEFF Research Database (Denmark)

    Nielsen, M H; Irvine, H; Vedel, S;

    2016-01-01

    was studied. Approach and Results. Thirty FH patients with and without ATX and twenty-three controls were included. Plasma concentrations of MVs and CD36+ MVs derived from platelets (PMVs), erythrocytes (ErytMVs), monocytes (MMVs), and endothelial cells (EMVs), as well as tissue factor-positive cells (TF+ MVs......Objective. Microvesicles (MVs) are small cell-derived particles shed upon activation. Familial hypercholesterolemia (FH) particularly when associated with Achilles tendon xanthomas (ATX) predisposes to atherosclerosis, possibly through oxLDL-C interaction with the CD36 receptor. To investigate...... the hypothesis that MVs derived from cells involved in atherosclerosis are increased in FH and that CD36 expressing MVs (CD36+ MVs) may be markers of oxLDL-C-induced cell activation, cell-specific MVs were measured in FH patients with and without ATX and their association with atherogenic lipid profile...

  4. Chromatin programming by developmentally regulated transcription factors: lessons from the study of haematopoietic stem cell specification and differentiation.

    Science.gov (United States)

    Obier, Nadine; Bonifer, Constanze

    2016-11-01

    Although the body plan of individuals is encoded in their genomes, each cell type expresses a different gene expression programme and therefore has access to only a subset of this information. Alterations to gene expression programmes are the underlying basis for the differentiation of multiple cell types and are driven by tissue-specific transcription factors (TFs) that interact with the epigenetic regulatory machinery to programme the chromatin landscape into transcriptionally active and inactive states. The haematopoietic system has long served as a paradigm for studying the molecular principles that regulate gene expression in development. In this review article, we summarize the current knowledge on the mechanism of action of TFs regulating haematopoietic stem cell specification and differentiation, and place this information into the context of general principles governing development.

  5. Differentiation of Induced Pluripotent Stem Cells to Lentoid Bodies Expressing a Lens Cell-Specific Fluorescent Reporter.

    Directory of Open Access Journals (Sweden)

    Taruna Anand

    Full Text Available Curative approaches for eye cataracts and other eye abnormalities, such as myopia and hyperopia currently suffer from a lack of appropriate models. Here, we present a new approach for in vitro growth of lentoid bodies from induced pluripotent stem (iPS cells as a tool for ophthalmological research. We generated a transgenic mouse line with lens-specific expression of a fluorescent reporter driven by the alphaA crystallin promoter. Fetal fibroblasts were isolated from transgenic fetuses, reprogrammed to iPS cells, and differentiated to lentoid bodies exploiting the specific fluorescence of the lens cell-specific reporter. The employment of cell type-specific reporters for establishing and optimizing differentiation in vitro seems to be an efficient and generally applicable approach for developing differentiation protocols for desired cell populations.

  6. Comparison of cell-specific activity between free-living and attached bacteria using isolates and natural assemblages

    DEFF Research Database (Denmark)

    Grossart, H.P.; Tang, K.W.; Kiørboe, Thomas

    2007-01-01

    to model aggregates (agar spheres) had threefold higher BPP and two orders of magnitude higher protease activity than their free-living counterpart. These observations could be explained by preferential colonization of the agar spheres by bacteria with inherently higher metabolic activity and/or individual......Marine snow aggregates are microbial hotspots that support high bacterial abundance and activities. We conducted laboratory experiments to compare cell-specific bacterial protein production (BPP) and protease activity between free-living and attached bacteria. Natural bacterial assemblages attached...... bacteria increasing their metabolism upon attachment to surfaces. In subsequent experiments, we used four strains of marine snow bacteria isolates to test the hypothesis that bacteria could up- and down-regulate their metabolism while on and off an aggregate. The protease activity of attached bacteria...

  7. Expression of NR2B in cerebellar granule cells specifically facilitates effect of motor training on motor learning.

    Science.gov (United States)

    Jiao, Jianwei; Nakajima, Akira; Janssen, William G M; Bindokas, Vytautas P; Xiong, Xiaoli; Morrison, John H; Brorson, James R; Tang, Ya-Ping

    2008-02-27

    It is believed that gene/environment interaction (GEI) plays a pivotal role in the development of motor skills, which are acquired via practicing or motor training. However, the underlying molecular/neuronal mechanisms are still unclear. Here, we reported that the expression of NR2B, a subunit of NMDA receptors, in cerebellar granule cells specifically enhanced the effect of voluntary motor training on motor learning in the mouse. Moreover, this effect was characterized as motor learning-specific and developmental stage-dependent, because neither emotional/spatial memory was affected nor was the enhanced motor learning observed when the motor training was conducted starting at the age of 3 months old in these transgenic mice. These results indicate that changes in the expression of gene(s) that are involved in regulating synaptic plasticity in cerebellar granule cells may constitute a molecular basis for the cerebellum to be involved in the GEI by facilitating motor skill learning.

  8. Expression of NR2B in cerebellar granule cells specifically facilitates effect of motor training on motor learning.

    Directory of Open Access Journals (Sweden)

    Jianwei Jiao

    Full Text Available It is believed that gene/environment interaction (GEI plays a pivotal role in the development of motor skills, which are acquired via practicing or motor training. However, the underlying molecular/neuronal mechanisms are still unclear. Here, we reported that the expression of NR2B, a subunit of NMDA receptors, in cerebellar granule cells specifically enhanced the effect of voluntary motor training on motor learning in the mouse. Moreover, this effect was characterized as motor learning-specific and developmental stage-dependent, because neither emotional/spatial memory was affected nor was the enhanced motor learning observed when the motor training was conducted starting at the age of 3 months old in these transgenic mice. These results indicate that changes in the expression of gene(s that are involved in regulating synaptic plasticity in cerebellar granule cells may constitute a molecular basis for the cerebellum to be involved in the GEI by facilitating motor skill learning.

  9. Comparative cell-specific transcriptomics reveals differentiation of C4 photosynthesis pathways in switchgrass and other C4 lineages.

    Science.gov (United States)

    Rao, Xiaolan; Lu, Nan; Li, Guifen; Nakashima, Jin; Tang, Yuhong; Dixon, Richard A

    2016-03-01

    Almost all C4 plants require the co-ordination of the adjacent and fully differentiated cell types, mesophyll (M) and bundle sheath (BS). The C4 photosynthetic pathway operates through two distinct subtypes based on how malate is decarboxylated in BS cells; through NAD-malic enzyme (NAD-ME) or NADP-malic enzyme (NADP-ME). The diverse or unique cell-specific molecular features of M and BS cells from separate C4 subtypes of independent lineages remain to be determined. We here provide an M/BS cell type-specific transcriptome data set from the monocot NAD-ME subtype switchgrass (Panicum virgatum). A comparative transcriptomics approach was then applied to compare the M/BS mRNA profiles of switchgrass, monocot NADP-ME subtype C4 plants maize and Setaria viridis, and dicot NAD-ME subtype Cleome gynandra. We evaluated the convergence in the transcript abundance of core components in C4 photosynthesis and transcription factors to establish Kranz anatomy, as well as gene distribution of biological functions, in these four independent C4 lineages. We also estimated the divergence between NAD-ME and NADP-ME subtypes of C4 photosynthesis in the two cell types within C4 species, including differences in genes encoding decarboxylating enzymes, aminotransferases, and metabolite transporters, and differences in the cell-specific functional enrichment of RNA regulation and protein biogenesis/homeostasis. We suggest that C4 plants of independent lineages in both monocots and dicots underwent convergent evolution to establish C4 photosynthesis, while distinct C4 subtypes also underwent divergent processes for the optimization of M and BS cell co-ordination. The comprehensive data sets in our study provide a basis for further research on evolution of C4 species.

  10. Detection of tumor cell-specific mRNA and protein in exosome-like microvesicles from blood and saliva.

    Science.gov (United States)

    Yang, Jieping; Wei, Fang; Schafer, Christopher; Wong, David T W

    2014-01-01

    The discovery of disease-specific biomarkers in oral fluids has revealed a new dimension in molecular diagnostics. Recent studies have reported the mechanistic involvement of tumor cells derived mediators, such as exosomes, in the development of saliva-based mRNA biomarkers. To further our understanding of the origins of disease-induced salivary biomarkers, we here evaluated the hypothesis that tumor-shed secretory lipidic vesicles called exosome-like microvesicles (ELMs) that serve as protective carriers of tissue-specific information, mRNAs, and proteins, throughout the vasculature and bodily fluids. RNA content was analyzed in cell free-saliva and ELM-enriched fractions of saliva. Our data confirmed that the majority of extracellular RNAs (exRNAs) in saliva were encapsulated within ELMs. Nude mice implanted with human lung cancer H460 cells expressing hCD63-GFP were used to follow the circulation of tumor cell specific protein and mRNA in the form of ELMs in vivo. We were able to identify human GAPDH mRNA in ELMs of blood and saliva of tumor bearing mice using nested RT-qPCR. ELMs positive for hCD63-GFP were detected in the saliva and blood of tumor bearing mice as well as using electric field-induced release and measurement (EFIRM). Altogether, our results demonstrate that ELMs carry tumor cell-specific mRNA and protein from blood to saliva in a xenografted mouse model of human lung cancer. These results therefore strengthen the link between distal tumor progression and the biomarker discovery of saliva through the ELMs.

  11. Cell-specific activation and detoxification of benzene metabolites in mouse and human bone marrow: Identification of target cells and a potential role for modulation of apoptosis in benzene toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Ross, D.; Siegel, D.; Schattenberg, D.G. [Univ. of Colorado Health Sciences Center, Denver, CO (United States)] [and others

    1996-12-01

    The role of cell-specific metabolism in benzene toxicity was examined in both murine and human bone marrow. Hemopoietic progenitor cells and stromal cells are important control points for regulation of hemopoiesis. We show that the selective toxicity of hydroquinone at the level of the macrophage in murine bone marrow stroma may be explained by a high peroxidase/nicotanimicle adenine dinucleotide phosphate, reduced [NAD(P)H]:quinone oxidoreductase (NQO1) ratio. Peroxidases metabolize hydroquinone to the reactive 1,4-benzoquinone, whereas NQO1 reduces the quinones formed, resulting in detoxification. Peroxidase and NQO1 activity in human stromal cultures vary as a function of time in culture, with peroxidase activity decreasing and NQO1 activity increasing with time. Peroxidase activity and, more specifically, myeloperoxidase, which had previously been considered to be expressed at the promyelocyte level, was detected in murine lineage-negative and human CD34{sup +} progenitor cells. This provides a metabolic mechanism whereby phenolic metabolites of benzene can be bioactivated in progenitor cells, which are considered initial target cells for the development of leukemias. Consequences of a high peroxidase/NQO1 ratio in HL-60 cells were shown to include hydroquinone-induced apoptosis. Hydroquinone can also inhibit proteases known to play a role in induction of apoptosis, suggesting that it may be able to inhibit apoptosis induced by other stimuli. Modulation of apoptosis may lead to aberrant hemopoiesis and neoplastic progression. This enzyme-directed approach has identified target cells of the phenolic metabolites of benzene in bone marrow and provided a metabolic basis for benzene-induced toxicity at the level of the progenitor cell in both murine and human bone marrow. 60 refs., 8 figs.

  12. Decline in breast cancer mortality

    DEFF Research Database (Denmark)

    Njor, Sisse Helle; Schwartz, Walter; Blichert-Toft, Mogens

    2015-01-01

    OBJECTIVES: When estimating the decline in breast cancer mortality attributable to screening, the challenge is to provide valid comparison groups and to distinguish the screening effect from other effects. In Funen, Denmark, multidisciplinary breast cancer management teams started before screening...... was introduced; both activities came later in the rest of Denmark. Because Denmark had national protocols for breast cancer treatment, but hardly any opportunistic screening, Funen formed a "natural experiment", providing valid comparison groups and enabling the separation of the effect of screening from other...... factors. METHODS: Using Poisson regression we compared the observed breast cancer mortality rate in Funen after implementation of screening with the expected rate without screening. The latter was estimated from breast cancer mortality in the rest of Denmark controlled for historical differences between...

  13. Electrocardiographic Predictors of Cardiovascular Mortality

    Directory of Open Access Journals (Sweden)

    Ioana Mozos

    2015-01-01

    Full Text Available Cardiovascular diseases are the main causes of mortality. Sudden cardiac death may also appear in athletes, due to underlying congenital or inherited cardiac abnormalities. The electrocardiogram is used in clinical practice and clinical trials, as a valid, reliable, accessible, inexpensive method. The aim of the present paper was to review electrocardiographic (ECG signs associated with cardiovascular mortality and the mechanisms underlying those associations, providing a brief description of the main studies in this area, and consider their implication for clinical practice in the general population and athletes. The main ECG parameters associated with cardiovascular mortality in the present paper are the P wave (duration, interatrial block, and deep terminal negativity of the P wave in V1, prolonged QT and Tpeak-Tend intervals, QRS duration and fragmentation, bundle branch block, ST segment depression and elevation, T waves (inverted, T wave axes, spatial angles between QRS and T vectors, premature ventricular contractions, and ECG hypertrophy criteria.

  14. Mortality rates among wild chimpanzees.

    Science.gov (United States)

    Hill, K; Boesch, C; Goodall, J; Pusey, A; Williams, J; Wrangham, R

    2001-05-01

    In order to compare evolved human and chimpanzees' life histories we present a synthetic life table for free-living chimpanzees, derived from data collected in five study populations (Gombe, Taï, Kibale, Mahale, Bossou). The combined data from all populations represent 3711 chimpanzee years at risk and 278 deaths. Males show higher mortality than females and data suggest some inter-site variation in mortality. Despite this variation, however, wild chimpanzees generally have a life expectancy at birth of less than 15 years and mean adult lifespan (after sexual maturity) is only about 15 years. This is considerably lower survival than that reported for chimpanzees in zoos or captive breeding colonies, or that measured among modern human hunter-gatherers. The low mortality rate of human foragers relative to chimpanzees in the early adult years may partially explain why humans have evolved to senesce later than chimpanzees, and have a longer juvenile period.

  15. Targeted interventions and infant mortality.

    Science.gov (United States)

    Lovel, H

    1989-01-01

    The main causes of infant mortality in 71% of the cases are diarrhea, measles, acute respiratory infection, and neonatal tetanus. A UN child survival strategy includes growth monitoring, oral rehydration, breast feeding, immunization, fertility, food and female literacy (GOBI-FFF). Previous research has shown a correlation between low levels of infant mortality and high levels of female literacy. Educated women are more likely to delay marriage, and childbearing. Child mortality is much higher for those born to women under 20 years old and also much higher for those born within 1 or 2 after the previous birth. Maternal mortality is also higher for mothers under 20 and with closely spaced births of 3 or more children. The majority of adults in developing countries have knowledge of family planning but teen pregnancy is a concern. Better nutrition during pregnancy would decrease infant deaths. Growth monitoring is another way to reduce infant mortality and morbidity. The difficulties are in the reluctance to adapt programs to local traditional methods of growth monitoring and going to direct recording scales. Immunization is estimated to have prevented over 3 million deaths from measles, tetanus, whooping cough and polio in 1984 alone. In spite of progress, only 50% of children in developing countries are immunized against diphtheria, pertussis, polio, and tetanus by the age of 1 year. these activities must be integrated into primary health care and community development projects to make better contact with people needing this service. oral rehydration therapy not only reduces mortality from diarrhea but can reduce morbidity by reducing the duration of the illness and by increasing the weight gain. Breast feeding has been shown in many studies to reduce the risk of deaths of infants. The promotion of breast feeding includes the issues of maternity leave, job security, and child care at the work place.

  16. Mortality in adult congenital heart disease

    NARCIS (Netherlands)

    Verheugt, Carianne L.; Uiterwaal, Cuno S. P. M.; van der Velde, Enno T.; Meijboom, Folkert J.; Pieper, Petronella G.; van Dijk, Arie P. J.; Vliegen, Hubert W.; Grobbee, Diederick E.; Mulder, Barbara J. M.

    2010-01-01

    Mortality in adults with congenital heart disease is known to be increased, yet its extent and the major mortality risks are unclear. The Dutch CONCOR national registry for adult congenital heart disease was linked to the national mortality registry. Cox's regression was used to assess mortality pre

  17. Is cancer mortality increasing in France?

    OpenAIRE

    Hill, C.; Jan, P; Doyon, F

    2001-01-01

    Long-term trends in cancer mortality are reported by site. Overall, cancer mortality has been decreasing in France since 1987 in the male population and since 1968 in the female population. Improvement in treatments and diagnosis should lead to persistently declining mortality rates, unless the tobacco epidemic reverses the trend in female mortality. © 2001 Cancer Research Campaign http://www.bjcancer.com

  18. Cancer Mortality Among Techa Riverside Residents (Southern Urals). Chronically Exposed to Radiation During the Prenatal Period and in Childhood

    Energy Technology Data Exchange (ETDEWEB)

    Ostroumova, E. V.; Akleyev, A. V.

    2004-07-01

    Imperfect technology and lack of management and utilization facilities for reprocessing liquid waste released by the Mayak PA resulted in a protracted combined (external and internal) environmental radiation exposure of the population resident on the banks of the Techa River. The followup of 8.640 subjects exposed during the prenatal period and in childhood covered the period of 49 years (1.1.1950-31.12.1998), the total person-years under observation amounted to 222,686. From 1950 through 1998 1,231 death cases were registered in the catchment area (5 raions in Chelyabinsk OBlast through which the Techa flows). In 70 cases death was caused by solid cancers, and in 12 cases by leukemia. Analyses of solid cancer mortality yielded higher rates for men as compared to women (p<0.001). No significant differences in death rates were observed between different ethnic groups (Slavs vs Tartars and Bashkirs). A statistically significant increase in solid cancer mortality with attained age was shown (p<0.001). The age at first exposure was demonstrated to be a factor modifying the solid cancer mortality rate (p=0.049). The highest risk of death from solid cancers was manifested by persons whose exposure started in the prenatal period or at the age under 5 years. There were 4.6 excess cases in this group of 30 observed solid cancer cases, whereas in the group including subjects aged 5 years or older at first exposure only 1 excess case was registered among the 40 observed cancer cases. The obtained leukemia mortality ERR value (CLL excluded) was 7.76, p=0.09. The excess leukemia death was found to be 7.6 out of of 10 observed cases. The analysis performed should be regarded as a preliminary one, taking into account the need to further extend the followup of the cohort and a potential verification of dose estimates in the future. (Author) 11 refs.

  19. Acute leukemias in Piauí: comparison with features observed in other regions of Brazil

    Directory of Open Access Journals (Sweden)

    Rego M.F.N.

    2003-01-01

    Full Text Available Differences in age and sex distribution as well as FAB (French-American-British classification types have been reported for acute leukemias in several countries. We studied the demographics and response to treatment of patients with acute myeloid leukemia (AML and acute lymphoblastic leukemia (ALL between 1989 and 2000 in Teresina, Piauí, and compared these results with reports from Brazil and other countries. Complete data concerning 345 patients (230 ALL, 115 AML were reviewed. AML occurred predominantly in adults (77%, with a median age of 34 years, similar to that found in the southeast of Brazil but lower than the median age in the United States and Europe (52 years. FAB distribution was similar in children and adults and FAB-M2 was the most common type, as also found in Japan. The high frequency of FAB-M3 described in most Brazilian studies and for Hispanics in the United States was not observed. Overall survival for adults was 40%, similar to other studies in Brazil. A high mortality rate was observed during induction. No clinical or hematological parameter influenced survival in the Cox model. ALL presented the characteristic peak of incidence between 2-8 years. Most of the cases were CD10+ pre-B ALL. In 25%, abnormal expression of myeloid antigens was observed. Only 10% of the patients were older than 30 years. Overall survival was better for children. Age and leukocyte count were independent prognostic factors. These data demonstrate that, although there are regional peculiarities, the application of standardized treatments and good supportive care make it possible to achieve results observed in other countries for the same chemotherapy protocols.

  20. Epigenetic regulation of putative tumor suppressor TGFBI in human leukemias

    Institute of Scientific and Technical Information of China (English)

    Fang Hongbo; Liu Jing; Guo Dan; Liu Peixiang; Zhao Yongliang

    2014-01-01

    Background Both in vitro and in vivo data have demonstrated the TGFBI gene functions as a putative tumor suppressor and is frequently downregulated in human tumors of different histological types.The hypermethylation of the TGFBI promoter,as one of the main regulatory mechanisms,is associated with TGFBI silencing.In this study,we used a methylation-specific PCR (MSP) method to evaluate the methylation status of the TGFBI promoter in human leukemias.Methods Real-time RT-PCR and methylation-specific PCR approaches were performed to define the TGFBI expression and promoter methylation in human leukemia call lines and clinical samples.Genomic DNA was isolated from peripheral blood mononuclear cells from leukemia patients,bisulfite-converted,and analyzed by the MSP method.Results Hypermethylation of the TGFBI promoter occurred in leukemia cell lines and demethylation treatment reexpressed TGFBI at a substantially increased level in most of leukemia cell lines tested.Furthermore,a much higher level of CpG island methylation and a significantly lower TGFBI expression were also identified in clinical leukemia samples.Conclusion The results suggest an important role of promoter methylation in regulating TGFBI expression in leukemia,which provides a useful diagnostic marker for clinical management of human leukemias.

  1. MicroRNA miR-125b causes leukemia.

    Science.gov (United States)

    Bousquet, Marina; Harris, Marian H; Zhou, Beiyan; Lodish, Harvey F

    2010-12-14

    MicroRNA miR-125b has been implicated in several kinds of leukemia. The chromosomal translocation t(2;11)(p21;q23) found in patients with myelodysplasia and acute myeloid leukemia leads to an overexpression of miR-125b of up to 90-fold normal. Moreover, miR-125b is also up-regulated in patients with B-cell acute lymphoblastic leukemia carrying the t(11;14)(q24;q32) translocation. To decipher the presumed oncogenic mechanism of miR-125b, we used transplantation experiments in mice. All mice transplanted with fetal liver cells ectopically expressing miR-125b showed an increase in white blood cell count, in particular in neutrophils and monocytes, associated with a macrocytic anemia. Among these mice, half died of B-cell acute lymphoblastic leukemia, T-cell acute lymphoblastic leukemia, or a myeloproliferative neoplasm, suggesting an important role for miR-125b in early hematopoiesis. Furthermore, coexpression of miR-125b and the BCR-ABL fusion gene in transplanted cells accelerated the development of leukemia in mice, compared with control mice expressing only BCR-ABL, suggesting that miR-125b confers a proliferative advantage to the leukemic cells. Thus, we show that overexpression of miR-125b is sufficient both to shorten the latency of BCR-ABL-induced leukemia and to independently induce leukemia in a mouse model.

  2. Acute acalculous cholecystitis complicating chemotherapy for acute myeloblastic leukemia

    OpenAIRE

    Olfa Kassar; Feten Kallel; Manel Ghorbel; Hatem. Bellaaj; Zeineb Mnif; Moez Elloumi

    2015-01-01

    Acute acalculous cholecystitis is a rare complication in the treatment of acute myeloblastic leukemia. Diagnosis of acute acalculous cholecystitis remains difficult during neutropenic period. We present two acute myeloblastic leukemia patients that developed acute acalculous cholecystitis during chemotherapy-induced neutropenia. They suffered from fever, vomiting and acute pain in the epigastrium. Ultrasound demonstrated an acalculous gallbladder. Surgical management was required in one patie...

  3. Surviving childhood leukemia: career, family, and future expectations.

    Science.gov (United States)

    Brown, Chris; Pikler, Vanessa I; Lavish, Lea A; Keune, Kristen M; Hutto, C J

    2008-01-01

    The authors examine the impact of childhood leukemia on the career development of 11 young adult survivors, using consensual qualitative research. They discuss the results and implications of childhood leukemia on the survivor's career, family, and future expectations, and provide recommendations for addressing the critical coping and management challenges encountered by survivors, their families, and the helping professionals who treat them.

  4. Data quality in the Danish National Acute Leukemia Registry

    DEFF Research Database (Denmark)

    Ostgård, Lene Sofie Granfeldt; Nørgaard, Jan Maxwell; Severinsen, Marianne Tang;

    2013-01-01

    The Danish National Acute Leukemia Registry (DNLR) has documented coverage of above 98.5%. Less is known about the quality of the recorded data.......The Danish National Acute Leukemia Registry (DNLR) has documented coverage of above 98.5%. Less is known about the quality of the recorded data....

  5. Prolymphocytic leukemia: postmortem findings after long-term survival.

    Science.gov (United States)

    Pacheco, J; Hillman, N; Lin, J; Batata, A

    1983-07-01

    A patient had prolymphocytic leukemia and survived for 44 months. A partial remission for more than 11 months and a short complete remission were induced by agents commonly used for the treatment of acute myelocytic leukemia. However, surface markers identified the disease as of B-cell origin.

  6. Molecular mechanisms in differentiation-induction in acute promyelocytic leukemia

    NARCIS (Netherlands)

    Nigten, Jeannet

    2007-01-01

    Leukemia is a hematological malignancy that is characterized by the clonal expansion of immature hematopoietic cells, which have escaped from the tightly coordinated cell cycle regulation, differentiation and apoptosis controls. In general, leukemia is characterized by a variety of mutations in path

  7. miR-150 suppresses the proliferation and tumorigenicity of leukemia stem cells by targeting the Nanog signaling pathway

    Directory of Open Access Journals (Sweden)

    Dan-dan Xu

    2016-11-01

    Full Text Available Proliferation, a key feature of cancer cells, accounts for the majority of cancer-related diseases resulting in mortality. MicroRNAs (miRNAs plays important post-transcriptional modulation roles by acting on multiple signaling pathways, but the underlying mechanism in proliferation and tumorigenicity is unclear. Here, we identified the role of miR-150 in proliferation and tumorigenicity in leukemia stem cells (LSCs (CD34+CD38- cells. miR-150 expression was significantly down-regulated in LSCs from leukemia cell lines and clinical samples. Functional assays demonstrated that increased miR-150 expression inhibited proliferation and clonal and clonogenic growth, enhanced chemosensitivity, and attenuated tumorigenic activity of LSCs in vitro. Transplantation animal studies revealed that miR-150 overexpression progressively abrogates tumour growth. Immunohistochemistry assays demonstrated that miR-150 overexpression enhanced caspase-3 level and reduced Ki-67 level. Moreover, luciferase reporter assays indicated Nanog is a direct and functional target of miR-150. Nanog silencing using small interfering RNA recapitulated anti-proliferation and tumorigenicity inhibition effects. Furthermore, miR-150 directly down-regulated the expression of other cancer stem cell factors including Notch2 and CTNNB1. These results provide insights into the specific biological behaviour of miR-150 in regulating LSC proliferation and tumorigenicity. Targeting this miR-150/Nanog axis would be a helpful therapeutic strategy to treat acute myeloid leukemia.

  8. Activation of a promyelocytic leukemia-tumor protein 53 axis underlies acute promyelocytic leukemia cure.

    Science.gov (United States)

    Ablain, Julien; Rice, Kim; Soilihi, Hassane; de Reynies, Aurélien; Minucci, Saverio; de Thé, Hugues

    2014-02-01

    Acute promyelocytic leukemia (APL) is driven by the promyelocytic leukemia (PML)-retinoic acid receptor-α (PML-RARA) fusion protein, which interferes with nuclear receptor signaling and PML nuclear body (NB) assembly. APL is the only malignancy definitively cured by targeted therapies: retinoic acid (RA) and/or arsenic trioxide, which both trigger PML-RARA degradation through nonoverlapping pathways. Yet, the cellular and molecular determinants of treatment efficacy remain disputed. We demonstrate that a functional Pml-transformation-related protein 53 (Trp53) axis is required to eradicate leukemia-initiating cells in a mouse model of APL. Upon RA-induced PML-RARA degradation, normal Pml elicits NB reformation and induces a Trp53 response exhibiting features of senescence but not apoptosis, ultimately abrogating APL-initiating activity. Apart from triggering PML-RARA degradation, arsenic trioxide also targets normal PML to enhance NB reformation, which may explain its clinical potency, alone or with RA. This Pml-Trp53 checkpoint initiated by therapy-triggered NB restoration is specific for PML-RARA-driven APL, but not the RA-resistant promyelocytic leukemia zinc finger (PLZF)-RARA variant. Yet, as NB biogenesis is druggable, it could be therapeutically exploited in non-APL malignancies.

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

    Institute of Scientific and Technical Information of China (English)

    Philippe; Kastner; Susan; Chan

    2011-01-01

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

  10. c-fms expression in acute leukemias with complex phenotypes.

    Science.gov (United States)

    Torrès, H; Dubreuil, P; Falzetti, F; Courcoul, M A; Lopez, M; Falcinelli, F; Birg, F; Tabilio, A; Mannoni, P

    1990-10-01

    The c-fms proto-oncogene product, which is the receptor for the macrophage colony-stimulating factor CSF-1, is always found expressed in acute myeloid leukemia cells, irrespective of their stage of differentiation according to the FAB classification (Dubreuil P, Torrès H, Courcoul M, Birg F, Mannoni P. Blood 1988;72:1081-1085). We have extended this study and looked for c-fms expression in poorly differentiated myeloid leukemias, in a series of acute leukemias of either T or B origin and in biphenotypic leukemias. We now report that expression of c-fms is still related to the myeloid origin of the leukemic proliferation, but that it can also be found in some acute leukemias presenting clonal rearrangements of the T cell receptor gene. Thus expression of the c-fms/CSF-1 receptor may not be exclusively a marker for myeloid proliferations.

  11. America's Infant-Mortality Puzzle.

    Science.gov (United States)

    Eberstadt, Nicholas

    1991-01-01

    Conventional explanations attributing the high infant mortality rate in United States to the prevalence of poverty and lack of adequate health care do not tell the whole story. Contributions of parental behavior, lifestyles, and public health care availability versus utilization must be examined in determining public policies to address the…

  12. Infant Mortality: The Shared Concern.

    Science.gov (United States)

    Heagarty, Margaret C.

    1990-01-01

    Addresses the causes for and implications of infant mortality. Besides the more immediate causes such as disease, nutrition, and lifestyle, there are the additional hurdles of government bureaucracy, lack of funds, and institutional attitudes that block access to prenatal care. Suggests structural solutions, including a consistent, individual,…

  13. Testosterone deficiency and cardiovascular mortality

    Institute of Scientific and Technical Information of China (English)

    Abraham Morgentaler

    2015-01-01

    New concerns have been raised regarding cardiovascular (CV) risks with testosterone (T) therapy (TTh). These concerns are based primarily on two widely reported retrospective studies. However, methodological flaws and data errors invalidate both studies as credible evidence of risk. One showed reduced adverse events by half in T‑treated men but reversed this result using an unproven statistical approach. The authors subsequently acknowledged serious data errors including nearly 10% contamination of the dataset by women. The second study mistakenly used the rate of T prescriptions written by healthcare providers to men with recent myocardial infarction (MI) as a proxy for the naturally occurring rate of MI. Numerous studies suggest T is beneficial, including decreased mortality in association with TTh, reduced MI rate with TTh in men with the greatest MI risk prognosis, and reduced CV and overall mortality with higher serum levels of endogenous T. Randomized controlled trials have demonstrated benefits of TTh in men with coronary artery disease and congestive heart failure. Improvement in CV risk factors such as fat mass and glycemic control have been repeatedly demonstrated in T‑deficient men treated with T. The current evidence does not support the belief that TTh is associated with increased CV risk or CV mortality. On the contrary, a wealth of evidence accumulated over several decades suggests that low serum T levels are associated with increased risk and that higher endogenous T, as well as TTh itself, appear to be beneficial for CV mortality and risk.

  14. Child mortality in rural India

    NARCIS (Netherlands)

    B. van der Klaauw (Bas); L. Wang (Lihong)

    2011-01-01

    textabstractThis paper focuses on infant and child mortality in rural areas of India. We construct a flexible duration model, which allows for frailty at multiple levels and interactions between the child's age and individual, socioeconomic, and environmental characteristics. The model is estimated

  15. Excess mortality following hip fracture

    DEFF Research Database (Denmark)

    Abrahamsen, B; van Staa, T; Ariely, R;

    2009-01-01

    Summary This systematic literature review has shown that patients experiencing hip fracture after low-impact trauma are at considerable excess risk for death compared with nonhip fracture/community control populations. The increased mortality risk may persist for several years thereafter, highlig...

  16. CAR-pNK Cell Immunotherapy in CD7 Positive Leukemia and Lymphoma

    Science.gov (United States)

    2016-12-04

    Acute Myeloid Leukemia; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma; T-cell Prolymphocytic Leukemia; T-cell Large Granular Lymphocytic Leukemia; Peripheral T-cell Lymphoma, NOS; Angioimmunoblastic T-cell Lymphoma; Extranodal NK/T-cell Lymphoma, Nasal Type; Enteropathy-type Intestinal T-cell Lymphoma; Hepatosplenic T-cell Lymphoma

  17. Reduced-intensity conditioning allogeneic hematopoietic-cell transplantation for older patients with acute myeloid leukemia.

    Science.gov (United States)

    Goyal, Gaurav; Gundabolu, Krishna; Vallabhajosyula, Saraschandra; Silberstein, Peter T; Bhatt, Vijaya Raj

    2016-06-01

    Elderly patients (>60 years) with acute myeloid leukemia have a poor prognosis with a chemotherapy-alone approach. Allogeneic hematopoietic-cell transplantation (HCT) can improve overall survival (OS). However, myeloablative regimens can have unacceptably high transplant-related mortality (TRM) in an unselected group of older patients. Reduced-intensity conditioning (RIC) or nonmyeloablative (NMA) conditioning regimens preserve the graft-versus-leukemia effects but reduce TRM. NMA regimens result in minimal cytopenia and may not require stem cell support for restoring hematopoiesis. RIC regimens, intermediate in intensity between NMA and myeloablative regimens, can cause prolonged myelosuppresion and usually require stem cell support. A few retrospective and prospective studies suggest a possibility of lower risk of relapse with myeloablative HCT in fit older patients with lower HCT comorbidity index; however, RIC and NMA HCTs have an important role in less-fit patients and those with significant comorbidities because of lower TRM. Whether early tapering of immunosuppression, monitoring of minimal residual disease, and post-transplant maintenance therapy can improve the outcomes of RIC and NMA HCT in elderly patients will require prospective trials.

  18. TLR Stimulation of Bone Marrow Lymphoid Precursors from Childhood Acute Leukemia Modifies Their Differentiation Potentials

    Directory of Open Access Journals (Sweden)

    Elisa Dorantes-Acosta

    2013-01-01

    Full Text Available Acute leukemias are the most frequent childhood malignancies worldwide and remain a leading cause of morbidity and mortality of relapsed patients. While remarkable progress has been made in characterizing genetic aberrations that may control these hematological disorders, it has also become clear that abnormalities in the bone marrow microenvironment might hit precursor cells and contribute to disease. However, responses of leukemic precursor cells to inflammatory conditions or microbial components upon infection are yet unexplored. Our previous work and increasing evidence indicate that Toll-like receptors (TLRs in the earliest stages of lymphoid development in mice and humans provide an important mechanism for producing cells of the innate immune system. Using highly controlled co-culture systems, we now show that lymphoid precursors from leukemic bone marrow express TLRs and respond to their ligation by changing cell differentiation patterns. While no apparent contribution of TLR signals to tumor progression was recorded for any of the investigated diseases, the replenishment of innate cells was consistently promoted upon in vitro TLR exposure, suggesting that early recognition of pathogen-associated molecules might be implicated in the regulation of hematopoietic cell fate decisions in childhood acute leukemia.

  19. Identification of Differentially Expressed Genes Associated with Prognosis of B Acute Lymphoblastic Leukemia

    Directory of Open Access Journals (Sweden)

    Idalia Garza-Veloz

    2015-01-01

    Full Text Available Background. Acute lymphoblastic leukemia type B (B-ALL is a neoplastic disorder with high mortality rates. The aim of this study was to validate the expression profile of 45 genes associated with signaling pathways involved in leukemia and to evaluate their association with the prognosis of B-ALL. Methods. 219 samples of peripheral blood mononuclear cells obtained from 73 B-ALL patients were studied at diagnosis, four, and eight weeks after starting treatment. Gene expression was analyzed by quantitative real-time polymerase chain reaction. Results. Normalized delta Cq values of 23 genes showed differences between B-ALL and controls at diagnosis time (P values < 0.05. There were significant associations between B-ALL patients relapse/death and the expression levels of IL2RA, SORT1, DEFA1, and FLT3 genes at least in one of the times evaluated (P values < 0.05 and odds ratio ranges: 3.73–27. The association between FLT3 deregulation and relapse/death was a constant in the times studied and their overexpression significantly increased the odds of relapse/death in a range of 3.73 and 6.05 among study population (P values < 0.05. Conclusions. Overexpression of FLT3 and DEFA1 genes retained independent prognostic significance for B-ALL outcome, reflected as increased risks of relapse/death among the study population.

  20. Identification of Differentially Expressed Genes Associated with Prognosis of B Acute Lymphoblastic Leukemia

    Science.gov (United States)

    Jaime-Perez, Jose Carlos; Carrillo-Sanchez, Karol; Ramos-Del Hoyo, Maria Guadalupe; Lugo-Trampe, Angel; Gutierrez-Aguirre, Cesar Homero; Gonzalez-Llano, Oscar; Salazar-Riojas, Rosario; Hidalgo-Miranda, Alfredo; Gomez-Almaguer, David

    2015-01-01

    Background. Acute lymphoblastic leukemia type B (B-ALL) is a neoplastic disorder with high mortality rates. The aim of this study was to validate the expression profile of 45 genes associated with signaling pathways involved in leukemia and to evaluate their association with the prognosis of B-ALL. Methods. 219 samples of peripheral blood mononuclear cells obtained from 73 B-ALL patients were studied at diagnosis, four, and eight weeks after starting treatment. Gene expression was analyzed by quantitative real-time polymerase chain reaction. Results. Normalized delta Cq values of 23 genes showed differences between B-ALL and controls at diagnosis time (P values < 0.05). There were significant associations between B-ALL patients relapse/death and the expression levels of IL2RA, SORT1, DEFA1, and FLT3 genes at least in one of the times evaluated (P values < 0.05 and odds ratio ranges: 3.73–27). The association between FLT3 deregulation and relapse/death was a constant in the times studied and their overexpression significantly increased the odds of relapse/death in a range of 3.73 and 6.05 among study population (P values < 0.05). Conclusions. Overexpression of FLT3 and DEFA1 genes retained independent prognostic significance for B-ALL outcome, reflected as increased risks of relapse/death among the study population. PMID:25802479

  1. Increased childhood liver cancer mortality and arsenic in drinking water in northern Chile.

    Science.gov (United States)

    Liaw, Jane; Marshall, Guillermo; Yuan, Yan; Ferreccio, Catterina; Steinmaus, Craig; Smith, Allan H

    2008-08-01

    Arsenic in drinking water is an established cause of lung, bladder, and skin cancers in adults and may also cause adult kidney and liver cancers. Some evidence for these effects originated from region II of Chile, which had a period of elevated arsenic levels in drinking water, in particular from 1958 to 1970. This unique exposure scenario provides a rare opportunity to investigate the effects of early-life arsenic exposure on childhood mortality; to our knowledge, this is the first study of childhood cancer mortality and high concentrations of arsenic in drinking water. In this article, we compare cancer mortality rates under the age of 20 in region II during 1950 to 2000 with those of unexposed region V, dividing subjects into those born before, during, or after the peak exposure period. Mortality from the most common childhood cancers, leukemia and brain cancer, was not increased in the exposed population. However, we found that childhood liver cancer mortality occurred at higher rates than expected. For those exposed as young children, liver cancer mortality between ages 0 and 19 was especially high: the relative risk (RR) for males born during this period was 8.9 [95% confidence interval (95% CI), 1.7-45.8; P = 0.009]; for females, the corresponding RR was 14.1 (95% CI, 1.6-126; P = 0.018); and for males and females pooled, the RR was 10.6 (95% CI, 2.9-39.2; P water during early childhood may result in an increase in childhood liver cancer mortality.

  2. Peptic ulcers: mortality and hospitalization.

    Science.gov (United States)

    Riley, R

    1991-01-01

    This study analyzes data on peptic ulcer disease based on deaths for 1951-1988 and hospital separations for 1969-1988. The source of the data are mortality and morbidity statistics provided to Statistics Canada by the provinces. The age-standardized mortality rates (ASMR) for peptic ulcer disease decreased from 1951 to 1988 by 69.4% for men (8.5 to 2.6 per 100,000 population), and 31.8% for women (2.2 to 1.5). Separation rates from hospitals during 1969-1988 for peptic ulcer disease also decreased by 59.8% for men (242.7 to 97.6 per 100,000 population) and 35.6% for women (103.2 to 66.5). Age-specific rates for both mortality and hospital separations increased with age. Epidemiological studies indicate that the incidence of peptic ulcer disease is declining in the general population. The downward trends in mortality and hospitalization rates for peptic ulcer disease reflect this change in incidence, but additional factors probably contribute as well to this decline. Male rates for both mortality and hospital separations were much higher than female rates at the beginning of the study period; but toward the end, the gap between the sexes narrowed considerably, mainly because the male rates declined substantially while the female rates decline moderately. The slower decline in the rates for women may be related to such factors as the increasing labour force participation among women and the slower decline in the population of female smokers.

  3. Boswellia sacra essential oil induces tumor cell-specific apoptosis and suppresses tumor aggressiveness in cultured human breast cancer cells

    Directory of Open Access Journals (Sweden)

    Suhail Mahmoud M

    2011-12-01

    Full Text Available Abstract Background Gum resins obtained from trees of the Burseraceae family (Boswellia sp. are important ingredients in incense and perfumes. Extracts prepared from Boswellia sp. gum resins have been shown to possess anti-inflammatory and anti-neoplastic effects. Essential oil prepared by distillation of the gum resin traditionally used for aromatic therapy has also been shown to have tumor cell-specific anti-proliferative and pro-apoptotic activities. The objective of this study was to optimize conditions for preparing Boswellea sacra essential oil with the highest biological activity in inducing tumor cell-specific cytotoxicity and suppressing aggressive tumor phenotypes in human breast cancer cells. Methods Boswellia sacra essential oil was prepared from Omani Hougari grade resins through hydrodistillation at 78 or 100 oC for 12 hours. Chemical compositions were identified by gas chromatography-mass spectrometry; and total boswellic acids contents were quantified by high-performance liquid chromatography. Boswellia sacra essential oil-mediated cell viability and death were studied in established human breast cancer cell lines (T47D, MCF7, MDA-MB-231 and an immortalized normal human breast cell line (MCF10-2A. Apoptosis was assayed by genomic DNA fragmentation. Anti-invasive and anti-multicellular tumor properties were evaluated by cellular network and spheroid formation models, respectively. Western blot analysis was performed to study Boswellia sacra essential oil-regulated proteins involved in apoptosis, signaling pathways, and cell cycle regulation. Results More abundant high molecular weight compounds, including boswellic acids, were present in Boswellia sacra essential oil prepared at 100 oC hydrodistillation. All three human breast cancer cell lines were sensitive to essential oil treatment with reduced cell viability and elevated cell death, whereas the immortalized normal human breast cell line was more resistant to essential oil

  4. Septic arthritis as the first sign of Candida tropicalis fungaemia in an acute lymphoid leukemia patient

    Directory of Open Access Journals (Sweden)

    Vicari Perla

    2003-01-01

    Full Text Available Fungal infections caused by Candida species have increased in incidence during the past two decades in England, North America and Europe. Candidal arthritis is rare in patients who are not intravenous drug users or are who not using a prostheses. We report the case of a 24-year-old man with acute lymphoid leukemia, who developed Candida tropicalis arthritis during an aplastic period after chemotherapy. This is the eighth case described in the literature of C. tropicalis causing arthritis without intra-articular inoculation. We call attention to an unusual first sign of fungal infection: septic arthritis without intra-articular inoculation. However, this case differs from the other seven, since despite therapy a fast and lethal evolution was observed. We reviewed reported cases, incidence, risk factors, mortality and treatment of neutropenic patients with fungal infections.

  5. Transient ischemic attack as an unusual initial manifestation of acute promyelocytic leukemia.

    Science.gov (United States)

    Liu, Lifeng; Yuan, Xiaoling

    2016-07-01

    Patients with acute promyelocytic leukemia (APL) are prone to both bleeding and thrombosis. Both of these have a significant impact on the morbidity and mortality of patients with this disease. Here we report a case of a 41-year-old male, who presented with transient ischemic attack (TIA) and early neurological deterioration (END) as initial manifestations prior to an ultimate diagnosis of APL. This patient had no cerebrovascular risk factors or familial cerebrovascular disease. The patient experienced an acute ischemic stroke, verified by magnetic resonance imaging (MRI), in less than 24 h after his second hospital admission. Some APL patients suffer from cerebral ischemia as an initial manifestation or during induction therapy, and patients presenting this condition may continue to deteriorate until their death during hospitalization. Thus, APL should be considered as a possible underlying disease in patients with TIA without cerebrovascular risk factors. Delayed diagnosis and treatment of APL can be fatal.

  6. Pulmonary mucormycosis with embolism: two autopsied cases of acute myeloid leukemia.

    Science.gov (United States)

    Kogure, Yasunori; Nakamura, Fumihiko; Shinozaki-Ushiku, Aya; Watanabe, Akira; Kamei, Katsuhiko; Yoshizato, Tetsuichi; Nannya, Yasuhito; Fukayama, Masashi; Kurokawa, Mineo

    2014-01-01

    Mucormycosis is an increasingly important cause of morbidity and mortality for patients with hematological malignancies. The diagnosis of mucormycosis usually requires mycological evidence through tissue biopsy or autopsy because the signs and symptoms are nonspecific and there are currently no biomarkers to identify the disease. We herein present two autopsied cases of acute myeloid leukemia with prolonged neutropenia who developed invasive mucormycosis accompanied by pulmonary artery embolism. Our cases were featured by unexplained fever and rapidly progressive dyspnea. Computed tomography scan detected nodular lesions or nonspecific consolidations in the lungs. Cultures, cytological study, and serum fungal markers consistently gave negative results. Autopsy revealed embolism of the pulmonary artery which consisted of fibrin clots by filamentous fungi. Genomic DNA was extracted from the paraffin-embedded clots and was applied to polymerase chain reaction amplification, leading to the diagnosis of infection by Rhizopus microsporus. We should carefully search for life-threatening pulmonary embolism when patients with hematological malignancies develop pulmonary mucormycosis.

  7. Expression of CD133 in acute leukemia.

    Science.gov (United States)

    Tolba, Fetnat M; Foda, Mona E; Kamal, Howyda M; Elshabrawy, Deena A

    2013-06-01

    There have been conflicting results regarding a correlation between CD133 expression and disease outcome. To assess CD133 expression in patients with acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) and to evaluate its correlation with the different clinical and laboratory data as well as its relation to disease outcome, the present study included 60 newly diagnosed acute leukemic patients; 30 ALL patients with a male to female ratio of 1.5:1 and their ages ranged from 9 months to 48 years, and 30 AML patients with a male to female ratio of 1:1 and their ages ranged from 17 to 66 years. Flow cytometric assessment of CD133 expression was performed on blast cells. In ALL, no correlations were elicited between CD133 expression and some monoclonal antibodies, but in AML group, there was a significant positive correlation between CD133 and HLA-DR, CD3, CD7 and TDT, CD13 and CD34. In ALL group, patients with negative CD133 expression achieved complete remission more than patients with positive CD133 expression. In AML group, there was no statistically significant association found between positive CD133 expression and treatment outcome. The Kaplan-Meier curve illustrated a high significant negative correlation between CD133 expression and the overall survival of the AML patients. CD133 expression is an independent prognostic factor in acute leukemia, especially ALL patients and its expression could characterize a group of acute leukemic patients with higher resistance to standard chemotherapy and relapse. CD133 expression was highly associated with poor prognosis in acute leukemic patients.

  8. High-Risk Childhood Acute Lymphoblastic Leukemia

    Science.gov (United States)

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

    2009-01-01

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

  9. Lenalidomide, Cytarabine, and Idarubicin in Treating Patients With Acute Myeloid Leukemia

    Science.gov (United States)

    2014-12-22

    Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); RUNX1-RUNX1T1; Adult Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-MLL; Adult Acute Promyelocytic Leukemia With t(15;17)(q22;q12); PML-RARA; Alkylating Agent-Related Acute Myeloid Leukemia; de Novo Myelodysplastic Syndrome; Previously Treated Myelodysplastic Syndrome; Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndrome; Untreated Adult Acute Myeloid Leukemia

  10. Structural and Functional Characterization of Two Alternative Splicing Variants of Mouse Endothelial Cell-Specific Chemotaxis Regulator (ECSCR

    Directory of Open Access Journals (Sweden)

    Yongchang Chang

    2012-04-01

    Full Text Available Endothelial cells (ECs that line the lumen of blood vessels are important players in blood vessel formation, and EC migration is a key component of the angiogenic process. Thus, identification of genes that are specifically or preferentially expressed in vascular ECs and in-depth understanding of their biological functions may lead to discovery of new therapeutic targets. We have previously reported molecular characterization of human endothelial cell-specific molecule 2 (ECSM2/endothelial cell-specific chemotaxis regulator (ECSCR. In the present study, we cloned two mouse full-length cDNAs by RT-PCR, which encode two putative ECSCR isoform precursors with considerable homology to the human ECSCR. Nucleotide sequence and exon-intron junction analyses suggested that they are alternative splicing variants (ECSCR isoform-1 and -2, differing from each other in the first and second exons. Quantitative RT-PCR results revealed that isoform-2 is the predominant form, which was most abundant in heart, lung, and muscles, and moderately abundant in uterus and testis. In contrast, the expression of isoform-1 seemed to be more enriched in testis. To further explore their potential cellular functions, we expressed GFP- and FLAG-tagged ECSCR isoforms, respectively, in an ECSCR deficient cell line (HEK293. Interestingly, the actual sizes of either ECSCR-GFP or -FLAG fusion proteins detected by immunoblotting are much larger than their predicted sizes, suggesting that both isoforms are glycoproteins. Fluorescence microscopy revealed that both ECSCR isoforms are localized at the cell surface, which is consistent with the structural prediction. Finally, we performed cell migration assays using mouse endothelial MS1 cells overexpressing GFP alone, isoform-1-GFP, and isoform-2-GFP, respectively. Our results showed that both isoforms significantly inhibited vascular epidermal growth factor (VEGF-induced cell migration. Taken together, we have provided several lines

  11. Effects of KIR ligand incompatibility on clinical outcomes of umbilical cord blood transplantation without ATG for acute leukemia in complete remission.

    Science.gov (United States)

    Tanaka, J; Morishima, Y; Takahashi, Y; Yabe, T; Oba, K; Takahashi, S; Taniguchi, S; Ogawa, H; Onishi, Y; Miyamura, K; Kanamori, H; Aotsuka, N; Kato, K; Kato, S; Atsuta, Y; Kanda, Y

    2013-11-29

    To clarify the effect of killer cell immunoglobulin-like receptor (KIR) ligand incompatibility on outcomes of acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) patients in complete remission after single cord blood transplantation (CBT), we assessed the outcomes of CBT registered in the Japan Society for Hematopoietic Cell Transplantation (JSHCT) database. A total of 643 acute leukemia (357 AML and 286 ALL) patient and donor pairs were categorized according to their KIR ligand incompatibility by determining whether or not they expressed HLA-C, Bw4 or A3/A11 by DNA typing. A total of 128 patient-donor pairs were KIR ligand-incompatible in the graft-versus-host (GVH) direction and 139 patient-donor pairs were incompatible in the host-versus-graft (HVG) direction. Univariate and multivariate analyses showed no significant differences between the KIR ligand-incompatible and compatible groups in the GVH direction for both AML and ALL patients of overall survival, disease-free survival, relapse incidence, non-relapse mortality and acute GVH disease. However, KIR incompatibility in the HVG direction ameliorated engraftment in ALL patients (hazard ratio 0.66, 95% confidence interval 0.47-0.91, P=0.013). Therefore, there were no effects of KIR ligand incompatibility in the GVH direction on single CBT outcomes for acute leukemia patients without anti-thymocyte globulin use. However, it is necessary to pay attention to KIR incompatibility in the HVG direction for engraftment.

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

    Science.gov (United States)

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

    2016-04-01

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

  13. Effects of total body irradiation-based conditioning allogenic sem cell transplantation for pediatric acute leukemia: A single-institution study

    Energy Technology Data Exchange (ETDEWEB)

    Park, Jong Moo; Choi, Eun Kyung; Kim, Jong Hoon [Dept.of Radiation Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); and others

    2014-09-15

    To evaluate the effects of total body irradiation (TBI), as a conditioning regimen prior to allogeneic stem cell transplantation (allo-SCT), in pediatric acute leukemia patients. From January 2001 to December 2011, 28 patients, aged less than 18 years, were treated with TBI-based conditioning for allo-SCT in our institution. Of the 28 patients, 21 patients were diagnosed with acute lymphoblastic leukemia (ALL, 75%) and 7 were diagnosed with acute myeloid leukemia (AML, 25%). TBI was completed 4 days or 1 day before stem cell infusion. Patients underwent radiation therapy with bilateral parallel opposing fields and 6-MV X-rays. The Kaplan-Meier method was used to calculate survival outcomes. The 2-year event-free survival and overall survival rates were 66% and 56%, respectively (71.4% and 60.0% in AML patients vs. 64.3% and 52.4% in ALL patients, respectively). Treatment related mortality rate were 25%. Acute and chronic graft-versus-host disease was a major complication; other complications included endocrine dysfunction and pulmonary complications. Common complications from TBI were nausea (89%) and cataracts (7.1%). The efficacy and toxicity data in this study of TBI-based conditioning to pediatric acute leukemia patients were comparable with previous studies. However, clinicians need to focus on the acute and chronic complications related to allo-SCT.

  14. Liver Involvement with Acute Myeloid Leukemia

    Directory of Open Access Journals (Sweden)

    Emily Mathews

    2008-03-01

    Full Text Available Liver involvement with acute myeloid leukemia (AML is rarely reported. The majority of published cases suggest a cholestatic picture and obstructive jaundice at presentation. On the contrary, our patient presented with transaminitis without cholestasis. Elevated liver function tests persisted in our patient despite cholecystectomy; however, they normalized with chemotherapy administration, suggesting that AML was the causative effect of the hepatitis-like picture. Our review of the literature revealed that most reported cases of AML with liver involvement had short-lived remissions and an overall ominous prognosis. In our opinion, patients who have liver involvement with AML should be offered alternative investigational therapies with a low hepatic toxicity profile.

  15. Epigenetic Modifications in Pediatric Acute Lymphoblastic Leukemia

    Directory of Open Access Journals (Sweden)

    Michael James Burke

    2014-05-01

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

  16. Blood group change in acute myeloid leukemia

    Science.gov (United States)

    Nambiar, Rakul K.; Prakash, N. P.; Vijayalakshmi, K.

    2017-01-01

    Blood group antigens are either sugars or proteins found attached to the red blood cell membrane. ABO blood group antigens are the most clinically important antigens because they are the most immunogenic. As red blood cell antigens are inherited traits, they are usually not altered throughout the life of an individual. There have been occasional case reports of ABO blood group antigen change in malignant conditions. We report two such cases of ABO antigen alteration associated with acute myeloid leukemia. These patients had suppression of their blood group antigens during their leukemic phase, and the antigens were reexpressed when the patients attained remission.

  17. Clofarabine, Cytarabine, and Filgrastim Followed by Infusion of Non-HLA Matched Ex Vivo Expanded Cord Blood Progenitors in Treating Patients With Acute Myeloid Leukemia

    Science.gov (United States)

    2014-08-13

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Acute Promyelocytic Leukemia (M3); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Recurrent Adult Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  18. The Effect of Uncertainty in Exposure Estimation on the Exposure-Response Relation between 1,3-Butadiene and Leukemia

    Directory of Open Access Journals (Sweden)

    George Maldonado

    2009-09-01

    Full Text Available Abstract: In a follow-up study of mortality among North American synthetic rubber industry workers, cumulative exposure to 1,3-butadiene was positively associated with leukemia. Problems with historical exposure estimation, however, may have distorted the association. To evaluate the impact of potential inaccuracies in exposure estimation, we conducted uncertainty analyses of the relation between cumulative exposure to butadiene and leukemia. We created the 1,000 sets of butadiene estimates using job-exposure matrices consisting of exposure values that corresponded to randomly selected percentiles of the approximate probability distribution of plant-, work area/job group-, and year specific butadiene ppm. We then analyzed the relation between cumulative exposure to butadiene and leukemia for each of the 1,000 sets of butadiene estimates. In the uncertainty analysis, the point estimate of the RR for the first non zero exposure category (>0–<37.5 ppm-years was most likely to be about 1.5. The rate ratio for the second exposure category (37.5–<184.7 ppm-years was most likely to range from 1.5 to 1.8. The RR for category 3 of exposure (184.7–<425.0 ppm-years was most likely between 2.1 and 3.0. The RR for the highest exposure category (425.0+ ppm-years was likely to be between 2.9 and 3.7. This range off RR point estimates can best be interpreted as a probability distribution that describes our uncertainty in RR point estimates due to uncertainty in exposure estimation. After considering the complete probability distributions of butadiene exposure estimates, the exposure-response association of butadiene and leukemia was maintained. This exercise was a unique example of how uncertainty analyses can be used to investigate and support an observed measure of effect when occupational exposure estimates are employed in the absence of direct exposure measurements.

  19. 妊娠合并白血病的临床处理%Management of leukemia during pregnancy

    Institute of Scientific and Technical Information of China (English)

    邹萍

    2011-01-01

    妊娠合并白血病发生率不高,但由于并发症严重,易导致母婴死亡,临床处理较为棘手.白血病对妊娠母体及胎儿具有显著性的损害,而妊娠状态对白血病可能并无明显影响.妊娠合并白血病的临床处理需要严格区分妊娠状态,早孕患者建议立即停止妊娠后积极治疗白血病,中晚孕患者应积极足量化疗,辅以支持疗法,争取在短期内完全缓解.影响患者预后的主要因素是及时诊断并尽早开始强力化疗以提高缓解率和可能的治愈率.%The incidence of leukemia during pregnancy is not high, but its serious complications result easily in maternal and infant mortality, making it a difficult clinical problem. Leukemia causes significant damage to the pregnant mother and fetus while pregnancy may not significantly affect the leukemia. Clinical treatment of leukemia during pregnancy requires strict discrimination of the pregnancy stale. Patients with early pregnancy should give up the fetus and receive chemotherapy;patients in late pregnancy should undergo adequate chemotherapy,combined with a supportive therapy,in order tn achieve complete remission in a short term. The main prognostic factors are an early diagnosis and an early start of chemotherapy to improve the response rate and obtain a possible cure.

  20. Decitabine Followed by Idarubicin and Cytarabine in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia or Myelodysplastic Syndromes

    Science.gov (United States)

    2013-10-09

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts

  1. Germ cell-specific sustained activation of Wnt signalling perturbs spermatogenesis in aged mice, possibly through non-coding RNAs

    Science.gov (United States)

    Kumar, Manish; Atkins, Joshua; Cairns, Murray; Ali, Ayesha; Tanwar, Pradeep S.

    2016-01-01

    Dysregulated Wnt signalling is associated with human infertility and testicular cancer. However, the role of Wnt signalling in male germ cells remains poorly understood. In this study, we first confirmed the activity of Wnt signalling in mouse, dog and human testes. To determine the physiological importance of the Wnt pathway, we developed a mouse model with germ cell-specific constitutive activation of βcatenin. In young mutants, similar to controls, germ cell development was normal. However, with age, mutant testes showed defective spermatogenesis, progressive germ cell loss, and flawed meiotic entry of spermatogonial cells. Flow sorting confirmed reduced germ cell populations at the leptotene/zygotene stages of meiosis in mutant group. Using thymidine analogues-based DNA double labelling technique, we further established decline in germ cell proliferation and differentiation. Overactivation of Wnt/βcatenin signalling in a spermatogonial cell line resulted in reduced cell proliferation, viability and colony formation. RNA sequencing analysis of testes revealed significant alterations in the non-coding regions of mutant mouse genome. One of the novel non-coding RNAs was switched on in mutant testes compared to controls. QPCR analysis confirmed upregulation of this unique non-coding RNA in mutant testis. In summary, our results highlight the significance of Wnt signalling in male germ cells. PMID:27992363

  2. The companion cell-specific Arabidopsis disaccharide carrier AtSUC2 is expressed in nematode-induced syncytia.

    Science.gov (United States)

    Juergensen, Katja; Scholz-Starke, Joachim; Sauer, Norbert; Hess, Paul; van Bel, Aart J E; Grundler, Florian M W

    2003-01-01

    Cyst nematodes induce a metabolically highly active syncytial cell complex in host roots. The syncytia are symplastically isolated. Because they form a strong sink, assimilates must be imported via the apoplast, thus suggesting that specific membrane-bound sugar transport proteins are expressed and activated. To identify possible candidate genes, transgenic Arabidopsis plants expressing different reporter genes under the control of different promoters from Arabidopsis sugar transporter genes were infected with the beet cyst nematode (Heterodera schachtii). With polymerase chain reaction, 13 additional sugar transporters were tested for their presence in the syncytia through the use of a syncytium-specific cDNA library. Analysis of the infected roots showed that the promoter of the sucrose (Suc) transporter AtSUC2 gene that codes for a companion cell-specific Suc transporter in noninfected plants was found to be expressed in syncytia. Its expression patterns in beta-glucuronidase and green fluorescent protein plants were monitored. Syncytium-specific gene expression was confirmed by reverse transcriptase-polymerase chain reaction. Results support the idea that AtSUC2 mediates the transmembrane transfer of Suc. AtSUC2 is the first disaccharide carrier described to be activated by pathogens.

  3. CD8+ T cells specific for the islet autoantigen IGRP are restricted in their T cell receptor chain usage

    Science.gov (United States)

    Fuchs, Yannick F.; Eugster, Anne; Dietz, Sevina; Sebelefsky, Christian; Kühn, Denise; Wilhelm, Carmen; Lindner, Annett; Gavrisan, Anita; Knoop, Jan; Dahl, Andreas; Ziegler, Anette-G.; Bonifacio, Ezio

    2017-01-01

    CD8+ T cells directed against beta cell autoantigens are considered relevant for the pathogenesis of type 1 diabetes. Using single cell T cell receptor sequencing of CD8+ T cells specific for the IGRP265-273 epitope, we examined whether there was expansion of clonotypes and sharing of T cell receptor chains in autoreactive CD8+ T cell repertoires. HLA-A*0201 positive type 1 diabetes patients (n = 19) and controls (n = 18) were analysed. TCR α- and β-chain sequences of 418 patient-derived IGRP265-273-multimer+ CD8+ T cells representing 48 clonotypes were obtained. Expanded populations of IGRP265-273-specific CD8+ T cells with dominant clonotypes that had TCR α-chains shared across patients were observed. The SGGSNYKLTF motif corresponding to TRAJ53 was contained in 384 (91.9%) cells, and in 20 (41.7%) patient-derived clonotypes. TRAJ53 together with TRAV29/DV5 was found in 15 (31.3%) clonotypes. Using next generation TCR α-chain sequencing, we found enrichment of one of these TCR α-chains in the memory CD8+ T cells of patients as compared to healthy controls. CD8+ T cell clones bearing the enriched motifs mediated antigen-specific target cell lysis. We provide the first evidence for restriction of T cell receptor motifs in the alpha chain of human CD8+ T cells with specificity to a beta cell antigen. PMID:28300170

  4. Hematopoietic lineage cell specific protein 1 (HS1) is a functionally important signaling molecule in platelet activation.

    Science.gov (United States)

    Kahner, Bryan N; Dorsam, Robert T; Mada, Sripal R; Kim, Soochong; Stalker, Timothy J; Brass, Lawrence F; Daniel, James L; Kitamura, Daisuke; Kunapuli, Satya P

    2007-10-01

    Collagen activates platelets through an intracellular signaling cascade downstream of glycoprotein VI (GPVI). We have investigated the contribution of hematopoietic lineage cell-specific protein 1 (HS1) downstream of GPVI in platelet activation. Stimulation of GPVI leads to tyrosine phosphorylation of HS1, which is blocked by Src-family kinase inhibitors. Coimmunoprecipitation experiments revealed that HS1 associates with Syk and phosphatidylinositol 3-kinases. HS1-null mice displayed increased bleeding times and increased time to occlusion in the FeCl(3) in vivo thrombosis model compared with their wild-type littermates. In addition, aggregation and secretion responses were diminished in HS1-null mouse platelets after stimulation of GPVI and protease-activated receptor 4 (PAR-4) agonists compared with wild-type littermate mouse platelets. Finally, Akt phosphorylation was diminished after GPVI or PAR-4 stimulation in platelets from HS1-null mice compared with their wild-type littermates. These results demonstrate that phosphorylation of the HS1 protein occurs downstream of GPVI stimulation and that HS1 plays a significant functional role in platelet activation downstream of GPVI and PARs.

  5. Single cell subtractive transcriptomics for identification of cell-specifically expressed candidate genes of pyrrolizidine alkaloid biosynthesis.

    Science.gov (United States)

    Sievert, Christian; Beuerle, Till; Hollmann, Julien; Ober, Dietrich

    2015-09-01

    Progress has recently been made in the elucidation of pathways of secondary metabolism. However, because of its diversity, genetic information concerning biosynthetic details is still missing for many natural products. This is also the case for the biosynthesis of pyrrolizidine alkaloids. To close this gap, we tested strategies using tissues that express this pathway in comparison to tissues in which this pathway is not expressed. As many pathways of secondary metabolism are known to be induced by jasmonates, the pyrrolizidine alkaloid-producing species Heliotropium indicum, Symphytum officinale, and Cynoglossum officinale of the Boraginales order were treated with methyl jasmonate. An effect on pyrrolizidine alkaloid levels and on transcript levels of homospermidine synthase, the first specific enzyme of pyrrolizidine alkaloid biosynthesis, was not detectable. Therefore, a method was developed by making use of the often observed cell-specific production of secondary compounds. H. indicum produces pyrrolizidine alkaloids exclusively in the shoot. Homospermidine synthase is expressed only in the cells of the lower leaf epidermis and the epidermis of the stem. Suggesting that the whole pathway of pyrrolizidine alkaloid biosynthesis might be localized in these cells, we have isolated single cells of the upper and lower epidermis by laser-capture microdissection. The resulting cDNA preparations have been used in a subtractive transcriptomic approach. Quantitative real-time polymerase chain reaction has shown that the resulting library is significantly enriched for homospermidine-synthase-coding transcripts providing a valuable source for the identification of further genes involved in pyrrolizidine alkaloid biosynthesis.

  6. Confocal microscopy-based three-dimensional cell-specific modeling for large deformation analyses in cellular mechanics.

    Science.gov (United States)

    Slomka, Noa; Gefen, Amit

    2010-06-18

    This study introduces a new confocal microscopy-based three-dimensional cell-specific finite element (FE) modeling methodology for simulating cellular mechanics experiments involving large cell deformations. Three-dimensional FE models of undifferentiated skeletal muscle cells were developed by scanning C2C12 myoblasts using a confocal microscope, and then building FE model geometries from the z-stack images. Strain magnitudes and distributions in two cells were studied when the cells were subjected to compression and stretching, which are used in pressure ulcer and deep tissue injury research to induce large cell deformations. Localized plasma membrane and nuclear surface area (NSA) stretches were observed for both the cell compression and stretching simulation configurations. It was found that in order to induce large tensile strains (>5%) in the plasma membrane and NSA, one needs to apply more than approximately 15% of global cell deformation in cell compression tests, or more than approximately 3% of tensile strains in the elastic plate substrate in cell stretching experiments. Utilization of our modeling can substantially enrich experimental cellular mechanics studies in classic cell loading designs that typically involve large cell deformations, such as static and cyclic stretching, cell compression, micropipette aspiration, shear flow and hydrostatic pressure, by providing magnitudes and distributions of the localized cellular strains specific to each setup and cell type, which could then be associated with the applied stimuli.

  7. Cell-specific RNA aptamer against human CCR5 specifically targets HIV-1 susceptible cells and inhibits HIV-1 infectivity.

    Science.gov (United States)

    Zhou, Jiehua; Satheesan, Sangeetha; Li, Haitang; Weinberg, Marc S; Morris, Kevin V; Burnett, John C; Rossi, John J

    2015-03-19

    The C-C chemokine receptor type 5 (CCR5) is a receptor expressed by T cells and macrophages that serves as a coreceptor for macrophage-tropic HIV-1. Loss of CCR5 is associated with resistance to HIV-1. Here, we combine the live-cell-based SELEX with high-throughput sequencing technology to generate CCR5 RNA aptamers capable of specifically targeting HIV-1 susceptible cells (as small interfering RNA [siRNA] delivery agent) and inhibiting HIV-1 infectivity (as antiviral agent) via block of the CCR5 required for HIV-1 to enter cells. One of the best candidates, G-3, efficiently bound and was internalized into human CCR5-expressing cells. The G-3 specifically neutralized R5 virus infection in primary peripheral blood mononuclear cells, and in vivo generated human CD4(+) T cells with a nanomolar inhibitory concentration 50%. G-3 was also capable of transferring functional siRNAs to CCR5-expressing cells. Collectively, the cell-specific, internalizing, CCR5-targeted aptamers and aptamer-siRNA conjugates offer promise for overcoming some of the current challenges of drug resistance in HIV-1 by providing cell-type- or tissue-specific delivery of various therapeutic moieties.

  8. Symptom-Adapted Physical Activity Intervention in Minimizing Physical Function Decline in Older Patients With Acute Myeloid Leukemia Undergoing Chemotherapy

    Science.gov (United States)

    2016-07-26

    Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Recurrent Adult Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  9. The incidences and mortalities of major cancers in China, 2009

    Institute of Scientific and Technical Information of China (English)

    Wanqing Chen; Rongshou Zheng; Siwei Zhang; Ping Zhao; Guanglin Li; Lingyou Wu; Jie He

    2013-01-01

    In 2012,the National Central Cancer Registry (NCCR) of China collected cancer registration information for the year 2009 from local cancer registries and analyzed it to describe the incidences and mortalities of cancers in China.Based on the data quality criteria from NCCR,data from 104 registries covering 85,470,522 people (57,489,009 in urban areas and 27,981,513 in rural areas) were checked and evaluated.The data from 72 registries were qualified and accepted for the cancer registry annual report in 2012.The total cancer incident cases and cancer deaths were 244,366 and 154,310,respectively.The morphologically verified cases accounted for 67.23% and 3.14% of the incident cases only had information from death certifications.The crude incidence in the Chinese cancer registration areas was 285.91/100,000 (317.97/100,000 in males and 253.09/100,000 in females).The age-standardized rates for incidences based on the Chinese standard population (ASRIC) and the world standard population (ASRIW) were 146.87/100,000 and 191.72/100,000,respectively,with a cumulative incidence of 22.08%.The cancer mortality in the Chinese cancer registration areas was 180.54/100,000 (224.20/100,000 in males and 135.85/100,000 in females).The age-standardized rates for mortalities based on the Chinese standard population (ASRMC) and the world standard population (ASRMW) were 85.06/100,000 and 115.65/100,000,respectively,and the cumulative mortality was 12.94%.Lung cancer,gastric cancer,colorectal cancer,liver cancer,esophageal cancer,pancreatic cancer,encephaloma,lymphoma,female breast cancer,and cervical cancer were the most common cancers,accounting for 75% of all cancer cases.Lung cancer,gastric cancer,liver cancer,esophageal cancer,colorectal cancer,pancreatic cancer,breast cancer,encephaloma,leukemia,and lymphoma accounted for 80% of all cancer deaths.The cancer registration's population coverage has been increasing,and its data quality is improving.As the basis of the

  10. The incidence and mortality of major cancers in China, 2012

    Institute of Scientific and Technical Information of China (English)

    Wanqing Chen; Rongshou Zheng; Hongmei Zeng; Siwei Zhang

    2016-01-01

    Background: The National Central Cancer Registry (NCCR) collected population-based cancer registration data in 2012 from local registries and estimated the cancer incidence and mortality in China. Methods: In the middle of 2015, 261 cancer registries submitted reports on new cancer cases and deaths occurred in 2012. Qualiifed data from 193 registries were used for analysis after evaluation. Crude rates, number of cases, and age-standardized rates stratiifed by area (urban/rural), sex, age group, and cancer type were calculated according to the national population in 2012. Results: The covered population were 198,060,406 from 193 qualiifed cancer registries (74 urban and 119 rural reg-istries). The major indicators of quality control, percentage of cases morphologically veriifed (MV%), death certiifcate-only cases (DCO%), and the mortality to incidence (M/I) ratio, were 69.13%, 2.38%, and 0.62, respectively. It was esti-mated that there were 3,586,200 new cancer cases and 2,186,600 cancer deaths in 2012 in China with an incidence of 264.85/100,000 [age-standardized rate of incidence by the Chinese standard population (ASRIC) of 191.89/100,000] and a mortality of 161.49/100,000 [age-standardized rate of mortality by the Chinese standard population (ASRMC) of 112.34/100,000]. The ten most common cancer sites were the lung, stomach, liver, colorectum, esophagus, female breast, thyroid, cervix, brain, and pancreas, accounting for approximately 77.4%of all new cancer cases. The ten lead-ing causes of cancer death were lung cancer, liver cancer, gastric cancer, esophageal cancer, colorectal cancer, pancre-atic cancer, female breast cancer, brain tumor, leukemia, and lymphoma, accounting for 84.5%of all cancer deaths. Conclusions: Continuous cancer registry data provides basic information in cancer control programs. The cancer burden in China is gradually increasing, both in urban and rural areas, in males and females. Effcient cancer preven-tion and control, such as

  11. Comparing pandemic to seasonal influenza mortality: moderate impact overall but high mortality in young children.

    NARCIS (Netherlands)

    Wijngaard, C.C. van den; Asten, L. van; Koopmans, M.P.G.; Pelt, W. van; Nagelkerke, N.J.D.; Wielders, C.C.H.; Lier, A. van; Hoek, W. van der; Meijer, A.; Donker, G.A.; Dijkstra, F.; Harmsen, C.; Sande, M.A.B. van der; Kretzschmar, M.

    2012-01-01

    Background: We assessed the severity of the 2009 influenza pandemic by comparing pandemic mortality to seasonal influenza mortality. However, reported pandemic deaths were laboratory-confirmed - and thus an underestimation - whereas seasonal influenza mortality is often more inclusively estimated. F

  12. Vorinostat, Cytarabine, and Etoposide in Treating Patients With Relapsed and/or Refractory Acute Leukemia or Myelodysplastic Syndromes or Myeloproliferative Disorders

    Science.gov (United States)

    2013-05-01

    Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Acute Promyelocytic Leukemia (M3); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative; Blastic Phase Chronic Myelogenous Leukemia; Chronic Eosinophilic Leukemia; Chronic Myelomonocytic Leukemia; Chronic Neutrophilic Leukemia; de Novo Myelodysplastic Syndromes; Essential Thrombocythemia; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Polycythemia Vera; Previously Treated Myelodysplastic Syndromes; Primary Myelofibrosis; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes

  13. Mortality level, trends and differentials in Malawi.

    Science.gov (United States)

    Palamuleni, M E

    1994-01-01

    "This article examines the levels, and trends and differentials in mortality in Malawi.... The study has shown that (i) the level of mortality is very high in Malawi; (ii) mortality has declined during the period under review; (iii) there was reduction in the rate of mortality decline in the seventies; and (iv) [there are] interesting differences in mortality in terms of rural-urban localities, regions and age-sex differentials. The observed levels, trends and differentials in mortality are however consistent with the level of social and economic development in the country."

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

    Directory of Open Access Journals (Sweden)

    Rashmi Kushwaha

    2014-01-01

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

  15. Reduced-intensity stem-cell transplantation for adult acute lymphoblastic leukemia: a retrospective study of 33 patients.

    Science.gov (United States)

    Hamaki, T; Kami, M; Kanda, Y; Yuji, K; Inamoto, Y; Kishi, Y; Nakai, K; Nakayama, I; Murashige, N; Abe, Y; Ueda, Y; Hino, M; Inoue, T; Ago, H; Hidaka, M; Hayashi, T; Yamane, T; Uoshima, N; Miyakoshi, S; Taniguchi, S

    2005-03-01

    Efficacy of reduced-intensity stem-cell transplantation (RIST) for acute lymphoblastic leukemia (ALL) was investigated in 33 patients (median age, 55 years). RIST sources comprised 20 HLA-identical related donors, five HLA-mismatched related, and eight unrelated donors. Six patients had undergone previous transplantation. Disease status at RIST was first remission (n=13), second remission (n=6), and induction failure or relapse (n=14). All patients tolerated preparatory regimens and achieved neutrophil engraftment (median, day 12.5). Acute and chronic graft-versus-host disease (GVHD) developed in 45 and 64%, respectively. Six patients received donor lymphocyte infusion (DLI), for prophylaxis (n=1) or treatment of recurrent ALL (n=5). Nine patients died of transplant-related mortality, with six deaths due to GVHD. The median follow-up of surviving patients was 11.6 months (range, 3.5-37.3 months). The 1-year relapse-free and overall survival rates were 29.8 and 39.6%, respectively. Of the 14 patients transplanted in relapse, five remained relapse free for longer than 6 months. Cumulative rates of progression and progression-free mortality at 3 years were 50.9 and 30.4%, respectively. These findings suggest the presence of a graft-versus-leukemia effect for ALL. RIST for ALL is worth considering for further evaluation.

  16. Physical Inactivity and Mortality Risk

    Directory of Open Access Journals (Sweden)

    Peter Kokkinos

    2011-01-01

    Full Text Available In recent years a plethora of epidemiologic evidence accumulated supports a strong, independent and inverse, association between physical activity and the fitness status of an individual and mortality in apparently healthy individuals and diseased populations. These health benefits are realized at relatively low fitness levels and increase with higher physical activity patterns or fitness status in a dose-response fashion. The risk reduction is at least in part attributed to the favorable effect of exercise or physical activity on the cardiovascular risk factors, namely, blood pressure, diabetes mellitus and obesity. In this review, we examine evidence from epidemiologic and interventional studies in support of the association between exercise and physical activity and health. In addition, we present the exercise effects on the aforementioned risk factors. Finally, we include select dietary approaches and their impact on risk factors and overall mortality risk.

  17. Educational differences in cardiovascular mortality

    DEFF Research Database (Denmark)

    Kjøllesdal, M. K. R.; Ariansen, I.; Mortensen, L. H.;

    2016-01-01

    Aims: To explore the confounding effects of early family factors shared by siblings and cardiovascular risk factors in midlife on the educational differences in mortality from cardiovascular disease (CVD). Methods: Data from national and regional health surveys in Norway (1974–2003) were linked...... with data from the Norwegian Family Based Life Course Study, the National Educational Registry and the Cause of Death Registry. The study population consisted of participants with at least one full sibling among the health survey participants (n=271,310). Data were available on CVD risk factors, including...... weight, height, blood pressure, total cholesterol and smoking. Results: The hazards ratio (HR) of CVD mortality was 3.44 (95% confidence interval (CI) 2.98–3.96) in the lowest educational group relative to the highest. The HRs were little altered in the within-sibship analyses. Adjusted for risk factors...

  18. Leukemia stem cells in drug resistance and metastasis

    Institute of Scientific and Technical Information of China (English)

    DENG Chao-hua; ZHANG Qiu-ping

    2010-01-01

    Objective To review the central role of leukemia stem cells (LSCs) in drug resistance and metastasis, aiming to provide key insights into leukemogenic pathology and developing novel therapeutic strategies against the relapse of leukemia.Data sources The data used in this review were obtained mainly from the studies reported in PubMed using the key terms "tumor-initiating cells", "leukemia stem cells", "drug resistance" and "metastasis".Study selection Relevant articles on studies of leukemia stem cells were selected.Results Increasing numbers of studies have suggested the importance of cancer stem cells (CSCs) in the initiation and maintenance of cancer, especially in leukemia. This review has summarized the origin, characteristics, isolation and identification of LSCs. It highlights the crucial role of LSCs in drug resistance and metastasis of leukemia by illustrating possible mechanisms and aims to provide novel therapeutic strategies for LSCs-targeted treatment.Conclusion LSCs play a crucial role in drug resistance and metastasis of leukemia and new promising LSCs-targeted therapies warrant investigation in both experimental models and clinical practice.

  19. Radiological terrorism and estimate leukemia incidence

    Energy Technology Data Exchange (ETDEWEB)

    Saint' Yves, Thalis Leon de Avila [Instituto de Radioprotecao e Dosimetria (IRD/CNEN-RJ), Rio de Janeiro, RJ (Brazil); Instituto Nacional do Cancer (INCa), Rio de Janeiro, RJ (Brazil); Maia, Arlei; Andrade, Edson R. de [Centro Tecnologico do Exercito (CTEX), Rio de Janeiro, RJ (Brazil)

    2011-07-01

    Radiological dispersal devices (RDD) are widely used as a terrorist tool leading to major environmental and public health concerns. This work is focused on simulating a dispersive scenario where an amount of most common radionuclide for this purpose is released. In order to estimate the total effective dose from such release, an affected urban area was chosen as a potential public mass concentration during World Cup in 2014 and Olympics in 2016 in Rio de Janeiro. Specialized simulation software called HotSpot Health Physics Code using a semi-empirical Gaussian model, was used to simulate dispersion of Cs-137 following detonation of a RDD. The simulation was designed to determine dose curves as a function of distance from the hot site. Additionally, it was determined the relative risk of leukemia incidence as well as statistical correlation between malignancies and exposure to radiation, based on probability of causation calculations. Results was suggestive that exists dependence on age at exposure time and the probability of leukemia development. This study emphasizes the importance of fast response, using a user-friendly computational method that may help, at first sight, to guide the response from the basic actions to the complete decision making process looking after health effects on public and environmental detriment. (author)

  20. Targeting CD20 in chronic lymphocytic leukemia

    Directory of Open Access Journals (Sweden)

    Nahas MR

    2015-03-01

    Full Text Available Myrna R Nahas, Jon E ArnasonBeth Israel Deaconess Medical Center, Boston, MA, USAAbstract: Chronic lymphocytic leukemia (CLL, the most common leukemia in adults, is standardly managed with chemotherapy in combination with the anti-CD20 antibody rituximab. In this review, we discuss the history, use, and evolution of rituximab in the treatment of CLL and explore the next generation CD20 antibodies ofatumumab and obinutuzumab with a focus on recent clinical trials. Increased understanding of the importance of B cell receptor (BCR signaling in CLL has resulted in the development of several drugs with significant clinical activity that are ideally suited for combination with CD20 therapy as is being currently explored. Moving forward, these developments have the potential to result in treatment regimens that do not include traditional chemotherapeutic agents, which is of particular importance in CLL given the late onset of diagnosis and potential frailty of the patients.Keywords: CLL, monoclonal antibody, rituximab, ofatumumab, obinutuzumab

  1. Molecular Genetic Markers in Acute Myeloid Leukemia

    Directory of Open Access Journals (Sweden)

    Sophia Yohe

    2015-03-01

    Full Text Available Genetics play an increasingly important role in the risk stratification and management of acute myeloid leukemia (AML patients. Traditionally, AML classification and risk stratification relied on cytogenetic studies; however, molecular detection of gene mutations is playing an increasingly important role in classification, risk stratification, and management of AML. Molecular testing does not take the place of cytogenetic testing results, but plays a complementary role to help refine prognosis, especially within specific AML subgroups. With the exception of acute promyelocytic leukemia, AML therapy is not targeted but the intensity of therapy is driven by the prognostic subgroup. Many prognostic scoring systems classify patients into favorable, poor, or intermediate prognostic subgroups based on clinical and genetic features. Current standard of care combines cytogenetic results with targeted testing for mutations in FLT3, NPM1, CEBPA, and KIT to determine the prognostic subgroup. Other gene mutations have also been demonstrated to predict prognosis and may play a role in future risk stratification, although some of these have not been confirmed in multiple studies or established as standard of care. This paper will review the contribution of cytogenetic results to prognosis in AML and then will focus on molecular mutations that have a prognostic or possible therapeutic impact.

  2. [Infections in the child with acute leukemia].

    Science.gov (United States)

    Carrillo, J M; Jiménez, E; Jiménez, R

    1981-01-01

    One hundred and twenty-five febrile episodes in 82 children with acute leukemia were studied; 46% of the patients were from urban and 54% from rural areas. The origin of the fever was identified in 91% of the episodes, prevailing pneumonia, septicemia, chickenpox and herpes zoster. The etiological agent was identified in 46% of the cases. A viral predominance was evident, and among them varicela-zoster, following in importance gram-negative bacteria. Histoplasma capsulatum and Pneumocystis carinii were isolated in two occassions each. Sepsis was found more frequently in children with active leukemia than in those in remission (p less than 0.001). Forty-four febrile episodes occurred in patients with less than 1,000 neutrophils/ul. The daily-risk rate of infection was higher in children fom rural than in those from urban areas (p less than 0.001). After clinical and laboratory studies, methicillin and gentamicin were used, in addition to carbenicillin or trimethoprim-sulfamethoxazole is selected cases. This treatment was effective in 86% of the cases. Twelve (15%) children died, 6 of whom were in remission at that moment.

  3. An evolutionary perspective on chronic myelomonocytic leukemia.

    Science.gov (United States)

    Itzykson, R; Solary, E

    2013-07-01

    Chronic myelomonocytic leukemia (CMML) shares with other myeloid diseases a number of somatic gene mutations. These mutations can now be integrated within the framework of evolution theory to address the mechanisms of the disease. Several evidences indicate that the disease emerges in adult hematopoietic stem cells (HSC) through the age-dependent accumulation of DNA damage, leading stochastically to a driver mutation that confers a competitive advantage to the cell. A mutation in TET2 gene could be one of these driver mutations provoking the emergence of clonality. After a long latency, secondary lesions, such as mutations in the SRSF2 gene, contribute to progression to full-blown malignancy, with abnormal differentiation. Additional mutations accumulate and branching arising mostly through mitotic recombination generates clonal heterogeneity. Modifications in the microenvironment probably affect this clonal dynamics, whereas epigenetic alterations, such as hypermethylation of the TIF1γ gene promoter, may generate phenotypic diversification of otherwise clonal populations. The preserved although deregulated myeloid differentiation that characterizes CMML, with granulomonocyte expansion and various cytopenias, may depend on early clonal dominance in the hematopietic cell hierarchy. Progression to acute myeloid leukemia observed in 25-30% of the patients may arise from the massive expansion of a clone with novel genetic lesions, providing a high fitness to previously minor subclones when in chronic phase of the disease. This review discusses the various models of disease emergence and progression and how this recent knowledge could drive rational therapeutic strategies.

  4. Cytogenetics of pediatric acute myeloid leukemia.

    Science.gov (United States)

    Manola, Kalliopi N

    2009-11-01

    Acute myeloid leukemia (AML) is a clinically and genetically heterogeneous disease accounting for 15-20% of all childhood acute leukemias, while it is responsible for more than half of the leukemic deaths in these patients. This article focuses on the significance of cytogenetic analysis in pediatric AML supporting the importance of cytogenetic analysis in the pathogenesis, diagnosis, prognosis, follow-up and treatment selection in childhood AML. It reviews in detail the types and frequencies of most common chromosomal aberrations, their molecular background, their correlation with French American British (FAB) subtypes and age distribution and their prognostic relevance. It also summarizes some less frequent or rare chromosome aberrations in which the prognostic classification has not been determined yet owning to the small number of patients and the variable treatment modalities used in different study groups. Furthermore, it discusses the association of specific chromosome rearrangements with prenatal exposure to carcinogenic agents or therapeutic agents and highlights the ongoing and future research on pediatric AML in the evolving field of Cytogenetics.

  5. ERYTHEMA NODOSUM REVEALING ACUTE MYELOID LEUKEMIA

    Directory of Open Access Journals (Sweden)

    Chebbi Wafa

    2013-07-01

    Full Text Available Introduction: Erythema nodosum (EN is the most common type of panniculitis. It may be idiopathic or secondary to various etiologies. However, the occurrence of erythema nodosum in malignant hemopathy had rarely been reported. Case report: A 42 year-old woman presented with a four week history of recurrent multiple painful erythematous nodules developed on the lower limbs associated with arthralgia of the ankles and fever. The clinical features of skin lesions with contusiform color evolution allowed establishing the diagnosis of EN. No underlying cause was found. The skin lesions were improved with non-steroidal anti-inflammatory drugs and colchicine. Three months later, the patient consulted for recurrence of EN associated with fever, inflammatory polyarthralgia and hepatosplenomegaly. The peripheral blood count revealed pancytopenia. A bone marrow examination confirmed the diagnosis of acute myeloid leukemia type 2. Initiation of chemotherapy was followed by the complete disappearance of skin lesions of EN. Conclusion: Paraneoplastic erythema nodosum is a rare entity. In the literature, a few cases of association with leukemia have been reported. Exploration for solid neoplasms or hemopathy in case of recurrent EN or resistance to conventional treatment should be systematic

  6. Targeting the acute myeloid leukemia stem cells.

    Science.gov (United States)

    Krause, Alexandre; Luciana, M; Krause, Fontanari; Rego, Eduardo M

    2010-02-01

    The idea that within the bulk of leukemic cells there are immature progenitors which are intrinsically resistant to chemotherapy and able to repopulate the tumor after treatment is not recent. Nevertheless, the term leukemia stem cells (LSCs) has been adopted recently to describe these immature progenitors based on the fact that they share the most relevant features of the normal hematopoetic stem cells (HSCs), i.e. the self-renewal potential and quiescent status. LSCs differ from their normal counterparts and from the more differentiated leukemic cells regarding the default status of pathways regulating apoptosis, cell cycle, telomere maintenance and transport pumps activity. In addition, unique features regarding the interaction of these cells with the microenvironment have been characterized. Therapeutic strategies targeting these unique features are at different stages of development but the reported results are promising. The aim of this review is, by taking acute myeloid leukemia (AML) as a bona fide example, to discuss some of the mechanisms used by the LSCs to survive and the strategies which could be used to eradicate these cells.

  7. Secondary autoimmune cytopenias in chronic lymphocytic leukemia.

    Science.gov (United States)

    Rogers, Kerry A; Woyach, Jennifer A

    2016-04-01

    Secondary autoimmune cytopenias in chronic lymphocytic leukemia are distinct clinical entities that require specific management. These autoimmune disorders have a complex pathogenesis that involves both the leukemic cells and the immune environment in which they exist. The mechanism is not the same in all cases, and to varying degrees involves the chronic lymphocytic leukemia (CLL) cells in antibody production, antigen presentation, and stimulation of T cells and bystander polyclonal B cells. Diagnosis of autoimmune cytopenias can be challenging as it is difficult to differentiate between autoimmunity and bone marrow failure due to disease progression. There is a need to distinguish these causes, as prognosis and treatment are not the same. Evidence regarding treatment of secondary autoimmune cytopenias is limited, but many effective options exist and treatment can be selected with severity of disease and patient factors in mind. With new agents to treat CLL coming into widespread clinical use, it will be important to understand how these will change the natural history and treatment of autoimmune cytopenias.

  8. Testosterone Therapy and Mortality Risk

    Science.gov (United States)

    Eisenberg, Michael L.; Li, Shufeng; Herder, Danielle; Lamb, Dolores J.; Lipshultz, Larry I.

    2014-01-01

    INTRODUCTION Recent data suggests and increased risk of cardiovascular events and mortality in men on testosterone therapy (TT). To date there are no long term, prospective studies to determine safety. In such cases, retrospective observational studies can be helpful. We examined our patient database to determine if TT altered a man’s risk of all cause mortality. METHODS We queried our hormone database for all men with a serum testosterone level and then examined charts to determine testosterone status. In all, 509 men had charts available for review. We linked our patient records to the National Death Index to determine morality. RESULTS Of the 509 men who met inclusion criteria, 284 were on testosterone therapy and 225 did not use testosterone. Age (mean 54 years) and follow up time (mean 10 years) were similar for both groups. In all, 19 men died—10 (4.4%) of the men not on TT and 9 (3.2%) of the men on TT. After adjusting for age and year of evaluation, there was no significant difference in the risk of death based on TT (HR 1.0, 95% CI 0.39 – 2.57, p=1.0). CONCLUSIONS There appears to be no change in mortality risk overall for men utilizing long-term testosterone therapy. PMID:25078049

  9. Acute Lymphoblastic Leukemia Presented as Multiple Breast Masses

    Energy Technology Data Exchange (ETDEWEB)

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

    2009-10-15

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

  10. In vitro radiosensitivity of human leukemia cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Weichselbaum, R.R.; Greenberger, J.S.; Schmidt, A.; Karpas, A.; Moloney, W.C.; Little, J.B.

    1981-05-01

    The in vitro radiobiologic survival values (n, D0) of four tumor lines derived from human hematopoietic tumors were studied. These cell lines were HL50 (n . 1.3, D0 . 117 rad(1.17 Gy)), promyelocytic leukemia; K562 (n . 1.4, D0 . 165 rad(1.65 Gy)), erythroleukemia; 45 (n . 1.1, D0 . 147 rad(1.47 Gy)), acute lymphocyte leukemia; and 176 (n . 4.0, D0 . 76 rad(0.76 Gy)), acute monomyelogenous leukemia. More cell lines must be examined before the exact relationship between in vitro radiosensitivity and clinical radiocurability is firmly established.

  11. Role of autophagy in acute myeloid leukemia therapy

    Institute of Scientific and Technical Information of China (English)

    Su-Ping Zhang; Yu-Na Niu; Na Yuan; Ai-Hong Zhang; Dan Chao; Qiu-Ping Xu; Li-Jun Wang

    2013-01-01

    Despite its dual role in determining cell fate in a wide array of solid cancer cell lines,autophagy has been robustly shown to suppress or kill acute myeloid leukemia cells via degradation of the oncogenic fusion protein that drives leukemogenesis.However,autophagy also induces the demise of acute leukemia cells that do not express the known fusion protein,though the molecular mechanism remains elusive.Nevertheless,since it can induce cooperation with apoptosis and differentiation in response to autophagic signals,autophagy can be manipulated for a better therapy on acute myeloid leukemia.

  12. Second analysis of mortality of nuclear industry workers in Japan

    Energy Technology Data Exchange (ETDEWEB)

    Murata, Motoi; Ohshima, Sumio; Kudo, Shin-ichi [Radiation Effects Association, Tokyo (Japan)] [and others

    2002-07-01

    A cohort study of nuclear industry workers was begun in 1990 to determine the possible health effect of low dose radiation exposure. A follow-up study of about 244,000 male workers was conducted using residence registration records. About 176,000 subjects were successfully followed up, and 5,527 deaths were ascertained during the period of observation 1986 through 1997. Underlying causes of death were identified by record linkage with magnetic tape records of national vital statistics data. The standardized mortality ratio (SMR) was calculated with Japanese males in general as the reference population. Tests for trends in death rates were made against cumulative radiation dose. The SMR (and its 95% confidence interval) was 0.90 (0.87-0.92) for all causes, 0.80 (0.77-0.84) for non-neoplastic diseases and 0.94 (0.90-0.98) for all cancer, respectively. The lower SMR was ascribed to possible healthy worker effects, etc. In the trend analyses, the death rate for neither all cancers sites nor leukemia showed any positive correlation with radiation dose, while significantly positive correlations were found for cancers of the esophagus (p<0.001), stomach (p<0.05) and rectum (p<0.05), and also for external causes (p<0.001). In lifestyle survey studies of 49,000 workers, both smoking and drinking habits were positively correlated with radiation dose. These lifestyle characteristics may have been important factors affecting the present results.

  13. Mortality and reduced growth hormone secretion

    DEFF Research Database (Denmark)

    Stochholm, Kirstine; Christiansen, Jens; Laursen, Torben

    2007-01-01

    BACKGROUND: Data regarding the mortality rates of patients with growth hormone deficiency (GHD), whether or not treated with growth hormone (GH), are limited, but an increased mortality rate among hypopituitary patients compared with the general population has been documented. Cardiovascular...

  14. Mortality hazard rates and life expectancy

    NARCIS (Netherlands)

    J.S. Cramer; R. Kaas

    2013-01-01

    We consider the relation between mortality hazards and life expectancy for men and women in the Netherlands and in England. Halving the lifetime mortality hazards increases life expectancy at birth by only 9%.

  15. CDC WONDER: Mortality - Multiple Cause of Death

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Mortality - Multiple Cause of Death data on CDC WONDER are county-level national mortality and population data spanning the years 1999-2009. Data are based on...

  16. CDC WONDER: Mortality - Multiple Cause of Death

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Mortality - Multiple Cause of Death data on CDC WONDER are county-level national mortality and population data spanning the years 1999-2006. These data are...

  17. CDC WONDER: Mortality - Underlying Cause of Death

    Data.gov (United States)

    U.S. Department of Health & Human Services — The CDC WONDER Mortality - Underlying Cause of Death online database is a county-level national mortality and population database spanning the years since 1979. Data...

  18. Cancer incidence and mortality trends in Australian adolescents and young adults, 1982–2007

    Directory of Open Access Journals (Sweden)

    Haggar Fatima A

    2012-04-01

    Full Text Available Abstract Background Increasing incidence and lack of survival improvement in adolescents and young adults (AYAs with cancer have led to increased awareness of the cancer burden in this population. The objective of this study was to describe overall and type-specific cancer incidence and mortality trends among AYAs in Western Australia from 1982–2007. Methods Age–adjusted incidence and mortality rates were calculated for all malignancies combined and for each of the most common diagnostic groups, using five-year age–specific rates. Joinpoint regression analysis was used to derive annual percentage changes (APC for incidence and mortality rates. Results The annual incidence rate for all cancers combined increased in males from 1982 until 2000 (APC = 1.5%, 95%CI: 0.9%; 2.1% and then plateaued, whilst rates for females remained stable across the study period (APC = −0.1%; 95%CI: −0.2%; 0.4% across the study period. For males, significant incidence rate increases were observed for germ cell tumors, lymphoblastic leukemia and thyroid cancer. In females, the incidence of Hodgkin’s lymphoma, colorectal and breast cancers increased. Significant incidence rate reductions were noted for cervical, central nervous system and lung cancers. Mortality rates for all cancers combined decreased from 1982 to 2005 for both males (APC = −2.6%, 95%CI:−3.3%;−2.0% and females (APC = −4.6%, 95%CI:−5.1%;−4.1%. With the exception of bone sarcoma and lung cancer in females, mortality rates for specific cancer types decreased significantly for both sexes during the study period. Conclusions Incidence of certain AYA cancers increased, whilst it decreased for others. Mortality rates decreased for most cancers, with the largest improvement observed for breast carcinomas. Further research is needed to identify the reasons for the increasing incidence of certain cancers.

  19. Mortality risk in a historical cohort of nuclear power plant workers in Germany: results from a second follow-up.

    Science.gov (United States)

    Merzenich, Hiltrud; Hammer, Gaël P; Tröltzsch, Katrin; Ruecker, Kai; Buncke, Johanna; Fehringer, Franz; Blettner, Maria

    2014-05-01

    Possible health effects of low and protracted doses of ionizing radiation are relevant for persons who are exposed to an occupational context like nuclear industry workers. A historical cohort study was therefore conducted to examine mortality risks following occupational radiation exposure among 4,844 German nuclear power plant workers. This cohort included workers from ten nuclear power plants with an observational period from 1991 until 1997. The results of an enlarged cohort with 8,972 workers from all 17 nuclear power plants in West Germany are now available. During the extended follow-up period from 1991 to 2008, a total of 310 deaths among men were observed. The standardized mortality ratio (SMR) from all causes of deaths was estimated at 0.50 [95 % confidence interval (CI) 0.45-0.56]. A total of 126 deaths due to cancer occurred (SMR = 0.65; 95 % CI 0.51-0.82) and seven deaths due to leukemia (SMR = 1.23; 95 % CI 0.42-2.84). Overall, a reduced mortality compared to the general population of West Germany was observed indicating a healthy worker effect. In the dose-response analysis, no statistically significant risk due to ionizing radiation was seen. The hazard ratio (HR/mSv) for leukemia excluding chronic lymphocytic leukemia was estimated at 1.004 (95 % CI 0.997-1.011). In conclusion, the cohort is small and made up of young workers, most of whom were still employed at the end of the observational period in 2008. Results of the external analysis are difficult to interpret as influenced by a healthy worker effect. In the internal analysis, no excess of risk due to radiation was detected.

  20. Purkinje cell-specific ablation of Cav2.1 channels is sufficient to cause cerebellar ataxia in mice.

    Science.gov (United States)

    Todorov, Boyan; Kros, Lieke; Shyti, Reinald; Plak, Petra; Haasdijk, Elize D; Raike, Robert S; Frants, Rune R; Hess, Ellen J; Hoebeek, Freek E; De Zeeuw, Chris I; van den Maagdenberg, Arn M J M

    2012-03-01

    The Cacna1a gene encodes the α(1A) subunit of voltage-gated Ca(V)2.1 Ca(2+) channels that are involved in neurotransmission at central synapses. Ca(V)2.1-α(1)-knockout (α1KO) mice, which lack Ca(V)2.1 channels in all neurons, have a very severe phenotype of cerebellar ataxia and dystonia, and usually die around postnatal day 20. This early lethality, combined with the wide expression of Ca(V)2.1 channels throughout the cerebellar cortex and nuclei, prohibited determination of the contribution of particular cerebellar cell types to the development of the severe neurobiological phenotype in Cacna1a mutant mice. Here, we crossed conditional Cacna1a mice with transgenic mice expressing Cre recombinase, driven by the Purkinje cell-specific Pcp2 promoter, to specifically ablate the Ca(V)2.1-α(1A) subunit and thereby Ca(V)2.1 channels in Purkinje cells. Purkinje cell Ca(V)2.1-α(1A)-knockout (PCα1KO) mice aged without difficulties, rescuing the lethal phenotype seen in α1KO mice. PCα1KO mice exhibited cerebellar ataxia starting around P12, much earlier than the first signs of progressive Purkinje cell loss, which appears in these mice between P30 and P45. Secondary cell loss was observed in the granular and molecular layers of the cerebellum and the volume of all individual cerebellar nuclei was reduced. In this mouse model with a cell type-specific ablation of Ca(V)2.1 channels, we show that ablation of Ca(V)2.1 channels restricted to Purkinje cells is sufficient to cause cerebellar ataxia. We demonstrate that spatial ablation of Ca(V)2.1 channels may help in unraveling mechanisms of human disease.

  1. Contribution of distinct homeodomain DNA binding specificities to Drosophila embryonic mesodermal cell-specific gene expression programs.

    Directory of Open Access Journals (Sweden)

    Brian W Busser

    Full Text Available Homeodomain (HD proteins are a large family of evolutionarily conserved transcription factors (TFs having diverse developmental functions, often acting within the same cell types, yet many members of this family paradoxically recognize similar DNA sequences. Thus, with multiple family members having the potential to recognize the same DNA sequences in cis-regulatory elements, it is difficult to ascertain the role of an individual HD or a subclass of HDs in mediating a particular developmental function. To investigate this problem, we focused our studies on the Drosophila embryonic mesoderm where HD TFs are required to establish not only segmental identities (such as the Hox TFs, but also tissue and cell fate specification and differentiation (such as the NK-2 HDs, Six HDs and identity HDs (I-HDs. Here we utilized the complete spectrum of DNA binding specificities determined by protein binding microarrays (PBMs for a diverse collection of HDs to modify the nucleotide sequences of numerous mesodermal enhancers to be recognized by either no or a single subclass of HDs, and subsequently assayed the consequences of these changes on enhancer function in transgenic reporter assays. These studies show that individual mesodermal enhancers receive separate transcriptional input from both I-HD and Hox subclasses of HDs. In addition, we demonstrate that enhancers regulating upstream components of the mesodermal regulatory network are targeted by the Six class of HDs. Finally, we establish the necessity of NK-2 HD binding sequences to activate gene expression in multiple mesodermal tissues, supporting a potential role for the NK-2 HD TF Tinman (Tin as a pioneer factor that cooperates with other factors to regulate cell-specific gene expression programs. Collectively, these results underscore the critical role played by HDs of multiple subclasses in inducing the unique genetic programs of individual mesodermal cells, and in coordinating the gene regulatory

  2. Contribution of distinct homeodomain DNA binding specificities to Drosophila embryonic mesodermal cell-specific gene expression programs.

    Science.gov (United States)

    Busser, Brian W; Gisselbrecht, Stephen S; Shokri, Leila; Tansey, Terese R; Gamble, Caitlin E; Bulyk, Martha L; Michelson, Alan M

    2013-01-01

    Homeodomain (HD) proteins are a large family of evolutionarily conserved transcription factors (TFs) having diverse developmental functions, often acting within the same cell types, yet many members of this family paradoxically recognize similar DNA sequences. Thus, with multiple family members having the potential to recognize the same DNA sequences in cis-regulatory elements, it is difficult to ascertain the role of an individual HD or a subclass of HDs in mediating a particular developmental function. To investigate this problem, we focused our studies on the Drosophila embryonic mesoderm where HD TFs are required to establish not only segmental identities (such as the Hox TFs), but also tissue and cell fate specification and differentiation (such as the NK-2 HDs, Six HDs and identity HDs (I-HDs)). Here we utilized the complete spectrum of DNA binding specificities determined by protein binding microarrays (PBMs) for a diverse collection of HDs to modify the nucleotide sequences of numerous mesodermal enhancers to be recognized by either no or a single subclass of HDs, and subsequently assayed the consequences of these changes on enhancer function in transgenic reporter assays. These studies show that individual mesodermal enhancers receive separate transcriptional input from both I-HD and Hox subclasses of HDs. In addition, we demonstrate that enhancers regulating upstream components of the mesodermal regulatory network are targeted by the Six class of HDs. Finally, we establish the necessity of NK-2 HD binding sequences to activate gene expression in multiple mesodermal tissues, supporting a potential role for the NK-2 HD TF Tinman (Tin) as a pioneer factor that cooperates with other factors to regulate cell-specific gene expression programs. Collectively, these results underscore the critical role played by HDs of multiple subclasses in inducing the unique genetic programs of individual mesodermal cells, and in coordinating the gene regulatory networks

  3. Arx polyalanine expansion in mice leads to reduced pancreatic α-cell specification and increased α-cell death.

    Directory of Open Access Journals (Sweden)

    Crystal L Wilcox

    Full Text Available ARX/Arx is a homeodomain-containing transcription factor necessary for the specification and early maintenance of pancreatic endocrine α-cells. Many transcription factors important to pancreas development, including ARX/Arx, are also crucial for proper brain development. Although null mutations of ARX in human patients result in the severe neurologic syndrome XLAG (X-linked lissencephaly associated with abnormal genitalia, the most common mutation is the expansion of the first polyalanine tract of ARX, which results primarily in the clinical syndrome ISSX (infantile spasms. Mouse models of XLAG, ISSX and other human ARX mutations demonstrate a direct genotype-phenotype correlation in ARX-related neurologic disorders. Furthermore, mouse models utilizing a polyalanine tract expansion mutation have illustrated critical developmental differences between null mutations and expansion mutations in the brain, revealing context-specific defects. Although Arx is known to be required for the specification and early maintenance of pancreatic glucagon-producing α-cells, the consequences of the Arx polyalanine expansion on pancreas development remain unknown. Here we report that mice with an expansion mutation in the first polyalanine tract of Arx exhibit impaired α-cell specification and maintenance, with gradual α-cell loss due to apoptosis. This is in contrast to the re-specification of α-cells into β- and δ-cells that occurs in mice null for Arx. Overall, our analysis of an Arx polyalanine expansion mutation on pancreatic development suggests that impaired α-cell function might also occur in ISSX patients.

  4. Temporal network based analysis of cell specific vein graft transcriptome defines key pathways and hub genes in implantation injury.

    Directory of Open Access Journals (Sweden)

    Manoj Bhasin

    Full Text Available Vein graft failure occurs between 1 and 6 months after implantation due to obstructive intimal hyperplasia, related in part to implantation injury. The cell-specific and temporal response of the transcriptome to vein graft implantation injury was determined by transcriptional profiling of laser capture microdissected endothelial cells (EC and medial smooth muscle cells (SMC from canine vein grafts, 2 hours (H to 30 days (D following surgery. Our results demonstrate a robust genomic response beginning at 2 H, peaking at 12-24 H, declining by 7 D, and resolving by 30 D. Gene ontology and pathway analyses of differentially expressed genes indicated that implantation injury affects inflammatory and immune responses, apoptosis, mitosis, and extracellular matrix reorganization in both cell types. Through backpropagation an integrated network was built, starting with genes differentially expressed at 30 D, followed by adding upstream interactive genes from each prior time-point. This identified significant enrichment of IL-6, IL-8, NF-κB, dendritic cell maturation, glucocorticoid receptor, and Triggering Receptor Expressed on Myeloid Cells (TREM-1 signaling, as well as PPARα activation pathways in graft EC and SMC. Interactive network-based analyses identified IL-6, IL-8, IL-1α, and Insulin Receptor (INSR as focus hub genes within these pathways. Real-time PCR was used for the validation of two of these genes: IL-6 and IL-8, in addition to Collagen 11A1 (COL11A1, a cornerstone of the backpropagation. In conclusion, these results establish causality relationships clarifying the pathogenesis of vein graft implantation injury, and identifying novel targets for its prevention.

  5. Peroxisome proliferator-activated receptor gamma B cell-specific deficient mice have an impaired antibody response1

    Science.gov (United States)

    Ramon, Sesquile; Bancos, Simona; Thatcher, Thomas H.; Murant, Thomas I.; Moshkani, Safiehkhatoon; Sahler, Julie M.; Bottaro, Andrea; Sime, Patricia J.; Phipps, Richard P.

    2012-01-01

    Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear hormone receptor superfamily. PPARγ, a ligand activated transcription factor, has important anti-inflammatory and anti-proliferative functions and it has been associated with diseases including diabetes, scarring and atherosclerosis among others. PPARγ is expressed in most bone marrow derived cells and influences their function. PPARγ ligands can stimulate human B cell differentiation and promote antibody production. A knowledge gap is that the role of PPARγ in B cells under physiological conditions is not known. We developed a new B cell-specific PPARγ (B-PPARγ) knockout mouse and explored the role of PPARγ during both the primary and secondary immune response. Here, we show that PPARγ deficiency in B cells decreases germinal center B cells and plasma cell development as well as the levels of circulating antigen-specific antibodies during a primary challenge. Inability to generate germinal center B cells and plasma cells is correlated to decreased MHC class II expression and decreased Bcl-6 and Blimp-1 levels. Furthermore, B-PPARγ-deficient mice have an impaired memory response, characterized by low titers of antigen-specific antibodies and low numbers of antigen-experienced antibody-secreting cells. However, B-PPARγ-deficient mice have no differences in B cell population distribution within neither primary nor secondary lymphoid organs during development. This is the first report to show under physiological conditions that PPARγ expression in B cells is required for an efficient B cell-mediated immune response as it regulates B cell differentiation and antibody production. PMID:23041568

  6. Peroxisome proliferator-activated receptor γ B cell-specific-deficient mice have an impaired antibody response.

    Science.gov (United States)

    Ramon, Sesquile; Bancos, Simona; Thatcher, Thomas H; Murant, Thomas I; Moshkani, Safiehkhatoon; Sahler, Julie M; Bottaro, Andrea; Sime, Patricia J; Phipps, Richard P

    2012-11-15

    Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear hormone receptor superfamily. PPARγ, a ligand-activated transcription factor, has important anti-inflammatory and antiproliferative functions, and it has been associated with diseases including diabetes, scarring, and atherosclerosis, among others. PPARγ is expressed in most bone marrow-derived cells and influences their function. PPARγ ligands can stimulate human B cell differentiation and promote Ab production. A knowledge gap is that the role of PPARγ in B cells under physiological conditions is not known. We developed a new B cell-specific PPARγ (B-PPARγ) knockout mouse and explored the role of PPARγ during both the primary and secondary immune response. In this article, we show that PPARγ deficiency in B cells decreases germinal center B cells and plasma cell development, as well as the levels of circulating Ag-specific Abs during a primary challenge. Inability to generate germinal center B cells and plasma cells is correlated to decreased MHC class II expression and decreased Bcl-6 and Blimp-1 levels. Furthermore, B-PPARγ-deficient mice have an impaired memory response, characterized by low titers of Ag-specific Abs and low numbers of Ag-experienced, Ab-secreting cells. However, B-PPARγ-deficient mice have no differences in B cell population distribution within primary or secondary lymphoid organs during development. This is the first report, to our knowledge, to show that, under physiological conditions, PPARγ expression in B cells is required for an efficient B cell-mediated immune response as it regulates B cell differentiation and Ab production.

  7. Profilin is required for viral morphogenesis, syncytium formation, and cell-specific stress fiber induction by respiratory syncytial virus

    Directory of Open Access Journals (Sweden)

    Barik Sailen

    2003-05-01

    Full Text Available Abstract Background Actin is required for the gene expression and morphogenesis of respiratory syncytial virus (RSV, a clinically important Pneumovirus of the Paramyxoviridae family. In HEp-2 cells, RSV infection also induces actin stress fibers, which may be important in the immunopathology of the RSV disease. Profilin, a major regulator of actin polymerization, stimulates viral transcription in vitro. Thus, we tested the role of profilin in RSV growth and RSV-actin interactions in cultured cells (ex vivo. Results We tested three cell lines: HEp-2 (human, A549 (human, and L2 (rat. In all three, RSV grew well and produced fused cells (syncytium, and two RSV proteins, namely, the phosphoprotein P and the nucleocapsid protein N, associated with profilin. In contrast, induction of actin stress fibers by RSV occurred in HEp-2 and L2 cells, but not in A549. Knockdown of profilin by RNA interference had a small effect on viral macromolecule synthesis but strongly inhibited maturation of progeny virions, cell fusion, and induction of stress fibers. Conclusions Profilin plays a cardinal role in RSV-mediated cell fusion and viral maturation. In contrast, interaction of profilin with the viral transcriptional proteins P and N may only nominally activate viral RNA-dependent RNA polymerase. Stress fiber formation is a cell-specific response to infection, requiring profilin and perhaps other signaling molecules that are absent in certain cell lines. Stress fibers per se play no role in RSV replication in cell culture. Clearly, the cellular architecture controls multiple steps of host-RSV interaction, some of which are regulated by profilin.

  8. Treatment-related myelodysplastic syndrome (t-MDS)/acute myeloid leukemia (AML) in children with cancer: A single-center experience.

    Science.gov (United States)

    Tragiannidis, Athanasios; Gombakis, Nikolaos; Papageorgiou, Maria; Hatzipantelis, Emmanuel; Papageorgiou, Theodotis; Hatzistilianou, Maria

    2016-12-01

    Treatment-related myelodysplastic syndrome (t-MDS)/acute myeloid leukemia (AML) is a devastating early or late complication of treatment for childhood cancer related with a significant morbidity and mortality. We retrospectively studied survivors of childhood cancer. Overall, 287 patients were recorded in the databases and we identified three (1.04%) with t-MDS. The primary cancer diagnoses were Langerhans cell histiocytosis (one patient) and acute lymphoblastic leukemia (ALL; two patients). The mean age of patients was 12.1 years. All patients had received systemic antifungal treatment for invasive pulmonary aspergillosis successfully treated with voriconazole and liposomal amphotericin B before diagnosis of t-MDS. Two patients (66%) remain alive after a median follow-up period of 3.5 years.

  9. Mortality versus Morbidity in the Demographic Transition

    OpenAIRE

    Aksan, Anna-Maria; Chakraborty, Shankha

    2014-01-01

    The link between the mortality and epidemiological transitions is used to identify the effect of the former on the fertility transition: a mortality transition that is not accompanied by improving morbidity causes slower demographic and economic change. In a model where children may die from infectious disease, childhood health affects human capital and noninfectious-disease-related adult mortality. When child mortality falls from lower prevalence, as it did in western Europe, labor productiv...

  10. Neonatal tetanus mortality in coastal Kenya

    DEFF Research Database (Denmark)

    Bjerregaard, P; Steinglass, R; Mutie, D M

    1993-01-01

    In a house-to-house survey in Kilifi District, Kenya, mothers of 2556 liveborn children were interviewed about neonatal mortality, especially from neonatal tetanus (NNT). The crude birth rate was 60.5 per 1000 population, the neonatal mortality rate 21.1 and the NNT mortality rate 3.1 per 1000 li...

  11. High mortality in the Thule cohort

    DEFF Research Database (Denmark)

    Juel, K

    1994-01-01

    The objective was to study mortality in the Thule cohort in order to clarify whether it is a selected population and to ascertain the possibility of misinterpretation when national mortality rates are used as reference in the analysis of occupational mortality....

  12. Mortality in adult congenital heart disease

    NARCIS (Netherlands)

    C.L. Verheugt (Carianne); C.S.P.M. Uiterwaal (Cuno); E.T. van der Velde (Enno); F.J. Meijboom (Folkert); P.G. Pieper (Petronella); A.P.J. van Dijk (Arie); H.W. Vliegen (Hubert); D.E. Grobbee (Diederick); B.J.M. Mulder (Barbara)

    2010-01-01

    textabstractAimsMortality in adults with congenital heart disease is known to be increased, yet its extent and the major mortality risks are unclear.Methods and resultsThe Dutch CONCOR national registry for adult congenital heart disease was linked to the national mortality registry. Cox's regressio

  13. Advance Report of Final Mortality Statistics, 1985.

    Science.gov (United States)

    Monthly Vital Statistics Report, 1987

    1987-01-01

    This document presents mortality statistics for 1985 for the entire United States. Data analysis and discussion of these factors is included: death and death rates; death rates by age, sex, and race; expectation of life at birth and at specified ages; causes of death; infant mortality; and maternal mortality. Highlights reported include: (1) the…

  14. Identification and targeting leukemia stem cells: The path to the cure for acute myeloid leukemia

    Institute of Scientific and Technical Information of China (English)

    Jianbiao; Zhou; Wee-Joo; Chng

    2014-01-01

    Accumulating evidence support the notion that acute myeloid leukemia(AML) is organized in a hierarchical system, originating from a special proportion of leukemia stem cells(LSC). Similar to their normal counterpart, hematopoietic stem cells(HSC), LSC possess selfrenewal capacity and are responsible for the continued growth and proliferation of the bulk of leukemia cells in the blood and bone marrow. It is believed that LSC are also the root cause for the treatment failure and relapse of AML because LSC are often resistant to chemotherapy. In the past decade, we have made significant advancement in identification and understanding the molecular biology of LSC, but it remains a daunting task to specifically targeting LSC, while sparing normalHSC. In this review, we will first provide a historical overview of the discovery of LSC, followed by a summary of identification and separation of LSC by either cell surface markers or functional assays. Next, the review will focus on the current, various strategies for eradicating LSC. Finally, we will highlight future directions and challenges ahead of our ultimate goal for the cure of AML by targeting LSC.

  15. Bovine leukemia virus high tax molecular clone experimentally induces leukemia/lymphoma in sheep.

    Science.gov (United States)

    Okada, Kosuke; Nakae, Norihiro; Kuramochi, Konomi; Yin, Shan-ai; Ikeda, Manabu; Takami, Shigeaki; Hirata, Tou-ichi; Goryo, Masanobu; Numakunai, Shigeru; Takeshima, Shin-nosuke; Takahashi, Masahiko; Tajima, Shigeru; Konnai, Satoru; Onuma, Misao; Aida, Yoko

    2005-12-01

    Sheep were inoculated with high tax coded pBLV-IF (H group, Nos.1-5) of bovine leukemia virus (BLV), wild tax coded pBLV-IF (W group, Nos. 6-11), or control plasmid (C group, Nos. 12-14). During the observation period (4 to 46 months), 5 of 5 cases in H group and 3 of 6 cases (Nos. 6, 7, 9) in W group became positive for gp 51. Only 1 case in H group became leukemic, and one case each of H and W groups developed lymphoma. In No. 3, lesions were found in multiple organs including the lymph nodes, gastrointestinal tract following abomasum, and heart. In No. 6, lesions of lymphoma were found only in the jejunum and heart. Morphologically, small to middle-sized lymphocytic neoplastic (NP) cells were found in both cases, but lymphoblastic NP cells were found only in No. 3. By immunohistochemical examination, the phenotypes of NP cells were determined as CD1-, CD4-, CD5- -, CD8alpha-, sIgM+, lambda light chain+, B-B4+, MHC class II+ in both case. The results of this study indicate that inoculation of pBLV-IF can induce lymphocytic and lymphoblastic leukemia/lymphoma in sheep. Additionally, it is suggested that the expression rate of tax gene is not associated with the development of leukemia/lymphoma in sheep experimentally inoculated with pBLV-IF.

  16. Total Marrow and Lymphoid Irradiation and Chemotherapy Before Donor Stem Cell Transplant in Treating Patients With High-Risk Acute Lymphocytic or Myelogenous Leukemia

    Science.gov (United States)

    2016-09-07

    Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia

  17. Curcumin and Cholecalciferol in Treating Patients With Previously Untreated Stage 0-II Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

    Science.gov (United States)

    2016-10-04

    Contiguous Stage II Small Lymphocytic Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Stage 0 Chronic Lymphocytic Leukemia; Stage I Chronic Lymphocytic Leukemia; Stage I Small Lymphocytic Lymphoma; Stage II Chronic Lymphocytic Leukemia

  18. NALP3 inflammasome upregulation and CASP1 cleavage of the glucocorticoid receptor cause glucocorticoid resistance in leukemia cells

    NARCIS (Netherlands)

    S.W. Paugh (Steven); E.J. Bonten (Erik J.); D. Savic (Daniel); L.B. Ramsey (Laura B.); W.E. Thierfelder (William E.); P. Gurung (Prajwal); R.K.S. Malireddi (R. K. Subbarao); M. Actis (Marcelo); A. Mayasundari (Anand); J. Min (Jaeki); D.R. Coss (David R.); L.T. Laudermilk (Lucas T.); J.C. Panetta (John); J.R. McCorkle (J. Robert); Y. Fan (Yiping); K.R. Crews (Kristine R.); G. Stocco (Gabriele); M.R. Wilkinson (Mark R.); A.M. Ferreira (Antonio M.); C. Cheng (Cheng); W. Yang (Wenjian); S.E. Karol (Seth E.); C.A. Fernandez (Christian A.); B. Diouf (Barthelemy); C. Smith (Colton); J.K. Hicks (J Kevin); A. Zanut (Alessandra); A. Giordanengo (Audrey); D.J. Crona; J.J. Bianchi (Joy J.); L. Holmfeldt (Linda); C.G. Mullighan (Charles); M.L. den Boer (Monique); R. Pieters (Rob); S. Jeha (Sima); T.L. Dunwell (Thomas L.); F. Latif (Farida); D. Bhojwani (Deepa); W.L. Carroll (William L.); C.-H. Pui (Ching-Hon); R.M. Myers (Richard M.); R.K. Guy (R Kiplin); T.-D. Kanneganti (Thirumala-Devi); M.V. Relling (Mary); W.E. Evans (William)

    2015-01-01

    textabstractGlucocorticoids are universally used in the treatment of acute lymphoblastic leukemia (ALL), and resistance to glucocorticoids in leukemia cells confers poor prognosis. To elucidate mechanisms of glucocorticoid resistance, we determined the prednisolone sensitivity of primary leukemia ce

  19. Endometrial and acute myeloid leukemia cancer genomes characterized

    Science.gov (United States)

    Two studies from The Cancer Genome Atlas (TCGA) program reveal details about the genomic landscapes of acute myeloid leukemia (AML) and endometrial cancer. Both provide new insights into the molecular underpinnings of these cancers.

  20. Prognostic significance of serum immunoglobulin pareprotein in chronic lymphocytic leukemia

    Institute of Scientific and Technical Information of China (English)

    杨舒

    2012-01-01

    Objective To investigate the incidence of serum immunoglobulin (Ig) paraprotein in chronic lymphocytic leukemia(CLL) ,and to explore its clinical associated laboratory features and prognostic implication. Methods Serum protein electrophoresis and immunofixation