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Sample records for leukemia nuclear bodies

  1. Nucleus accumbens associated 1 is recruited within the promyelocytic leukemia nuclear body through SUMO modification

    PubMed Central

    Tatemichi, Yoshinori; Shibazaki, Masahiko; Yasuhira, Shinji; Kasai, Shuya; Tada, Hiroshi; Oikawa, Hiroki; Suzuki, Yuji; Takikawa, Yasuhiro; Masuda, Tomoyuki; Maesawa, Chihaya

    2015-01-01

    Nucleus accumbens associated 1 (NACC1) is a cancer-associated BTB/POZ (pox virus and zinc finger/bric-a-brac tramtrack broad complex) gene, and is involved in several cellular functions in neurons, cancer and stem cells. Some of the BTB/POZ proteins associated with cancer biology are SUMOylated, which appears to play an important role in transcription regulation. We show that NACC1 is SUMOylated on a phylogenetically conserved lysine (K167) out of three consensus SUMOylation motif sites. Amino acid substitution in the SIM sequence (SIM/M) within the BTB/POZ domain partially reduced K167 SUMOylation activity of NACC1. Overexpression of GFP-NACC1 fusion protein leads to formation of discrete nuclear foci similar to promyelocytic leukemia nuclear bodies (PML-NB), which colocalized with SUMO paralogues (SUMO1/2/3). Both NACC1 nuclear body formation and colocalization with SUMO paralogues were completely suppressed in the GFP-NACC1-SIM/M mutant, whereas they were partially maintained in the NACC1 K167R mutant. Confocal immunofluorescence analysis showed that endogenous and exogenous NACC1 proteins colocalized with endogenous PML protein. A pull-down assay revealed that the consensus motifs of the SUMO acceptor site at K167 and the SIM within the BTB/POZ domain were both necessary for efficient binding to PML protein. Our study demonstrates that NACC1 can be modified by SUMO paralogues, and cooperates with PML protein. PMID:25891951

  2. Live Cell Dynamics of Promyelocytic Leukemia Nuclear Bodies upon Entry into and Exit from Mitosis

    PubMed Central

    Chen, Yi-Chun M.; Kappel, Constantin; Beaudouin, Joel; Eils, Roland

    2008-01-01

    Promyelocytic leukemia nuclear bodies (PML NBs) have been proposed to be involved in tumor suppression, viral defense, DNA repair, and/or transcriptional regulation. To study the dynamics of PML NBs during mitosis, we developed several U2OS cell lines stably coexpressing PML-enhanced cyan fluorescent protein with other individual marker proteins. Using three-dimensional time-lapse live cell imaging and four-dimensional particle tracking, we quantitatively demonstrated that PML NBs exhibit a high percentage of directed movement when cells progressed from prophase to prometaphase. The timing of this increased dynamic movement occurred just before or upon nuclear entry of cyclin B1, but before nuclear envelope breakdown. Our data suggest that entry into prophase leads to a loss of tethering between regions of chromatin and PML NBs, resulting in their increased dynamics. On exit from mitosis, Sp100 and Fas death domain-associated protein (Daxx) entered the daughter nuclei after a functional nuclear membrane was reformed. However, the recruitment of these proteins to PML NBs was delayed and correlated with the timing of de novo PML NB formation. Together, these results provide insight into the dynamic changes associated with PML NBs during mitosis. PMID:18480407

  3. Assembly of Epstein-Barr Virus Capsid in Promyelocytic Leukemia Nuclear Bodies

    PubMed Central

    Wang, Wen-Hung; Kuo, Chung-Wen; Chang, Li-Kwan; Hung, Chen-Chia; Chang, Tzu-Hsuan

    2015-01-01

    ABSTRACT The Epstein-Barr virus (EBV) capsid contains a major capsid protein, VCA; two minor capsid proteins, BDLF1 and BORF1; and a small capsid protein, BFRF3. During the lytic cycle, these capsid proteins are synthesized and imported into the host nucleus for capsid assembly. This study finds that EBV capsid proteins colocalize with promyelocytic leukemia (PML) nuclear bodies (NBs) in P3HR1 cells during the viral lytic cycle, appearing as nuclear speckles under a confocal laser scanning microscope. In a glutathione S-transferase pulldown study, we show that BORF1 interacts with PML-NBs in vitro. BORF1 also colocalizes with PML-NBs in EBV-negative Akata cells after transfection and is responsible for bringing VCA and the VCA-BFRF3 complex from the cytoplasm to PML-NBs in the nucleus. Furthermore, BDLF1 is dispersed throughout the cell when expressed alone but colocalizes with PML-NBs when BORF1 is also present in the cell. In addition, this study finds that knockdown of PML expression by short hairpin RNA does not influence the intracellular levels of capsid proteins but reduces the number of viral particles produced by P3HR1 cells. Together, these results demonstrate that BORF1 plays a critical role in bringing capsid proteins to PML-NBs, which may likely be the assembly sites of EBV capsids. The mechanisms elucidated in this study are critical to understanding the process of EBV capsid assembly. IMPORTANCE Capsid assembly is an important event during the Epstein-Barr virus (EBV) lytic cycle, as this process is required for the production of virions. In this study, confocal microscopy revealed that the EBV capsid protein BORF1 interacts with promyelocytic leukemia (PML) nuclear bodies (NBs) in the host nucleus and is responsible for transporting the other EBV capsid proteins, including VCA, BDLF1, and BFRF3, to these subnuclear locations prior to initiation of capsid assembly. This study also found that knockdown of PML expression by short hairpin RNA

  4. Trafficking of the Transcription Factor Nrf2 to Promyelocytic Leukemia-Nuclear Bodies

    PubMed Central

    Malloy, Melanie Theodore; McIntosh, Deneshia J.; Walters, Treniqka S.; Flores, Andrea; Goodwin, J. Shawn; Arinze, Ifeanyi J.

    2013-01-01

    Ubiquitylation of Nrf2 by the Keap1-Cullin3/RING box1 (Cul3-Rbx1) E3 ubiquitin ligase complex targets Nrf2 for proteasomal degradation in the cytoplasm and is an extensively studied mechanism for regulating the cellular level of Nrf2. Although mechanistic details are lacking, reports abound that Nrf2 can also be degraded in the nucleus. Here, we demonstrate that Nrf2 is a target for sumoylation by both SUMO-1 and SUMO-2. HepG2 cells treated with As2O3, which enhances attachment of SUMO-2/3 to target proteins, increased SUMO-2/3-modification (polysumoylation) of Nrf2. We show that Nrf2 traffics, in part, to promyelocytic leukemia-nuclear bodies (PML-NBs). Cell fractions harboring key components of PML-NBs did not contain biologically active Keap1 but contained modified Nrf2 as well as RING finger protein 4 (RNF4), a poly-SUMO-specific E3 ubiquitin ligase. Overexpression of wild-type RNF4, but not the catalytically inactive mutant, decreased the steady-state levels of Nrf2, measured in the PML-NB-enriched cell fraction. The proteasome inhibitor MG-132 interfered with this decrease, resulting in elevated levels of polysumoylated Nrf2 that was also ubiquitylated. Wild-type RNF4 accelerated the half-life (t½) of Nrf2, measured in PML-NB-enriched cell fractions. These results suggest that RNF4 mediates polyubiquitylation of polysumoylated Nrf2, leading to its subsequent degradation in PML-NBs. Overall, this work identifies Nrf2 as a target for sumoylation and provides a novel mechanism for its degradation in the nucleus, independent of Keap1. PMID:23543742

  5. Epstein - Barr virus latent membrane protein 1 suppresses reporter activity through modulation of promyelocytic leukemia protein-nuclear bodies

    PubMed Central

    2011-01-01

    The Epstein-Barr virus (EBV) encoded Latent Membrane Protein 1 (LMP1) has been shown to increase the expression of promyelocytic leukemia protein (PML) and the immunofluorescent intensity of promyelocytic leukemia nuclear bodies (PML NBs). PML NBs have been implicated in the modulation of transcription and the association of reporter plasmids with PML NBs has been implicated in repression of reporter activity. Additionally, repression of various reporters in the presence of LMP1 has been noted. This study demonstrates that LMP1 suppresses expression of reporter activity in a dose responsive manner and corresponds with the LMP1 induced increase in PML NB intensity. Disruption of PML NBs with arsenic trioxide or a PML siRNA restores reporter activity. These data offer an explanation for previously conflicting data on LMP1 signaling and calls attention to the possibility of false-positives and false-negatives when using reporter assays as a research tool in cells expressing LMP1. PMID:21975125

  6. SUMO-dependent compartmentalization in promyelocytic leukemia protein nuclear bodies prevents the access of LRH-1 to chromatin.

    PubMed

    Chalkiadaki, Angeliki; Talianidis, Iannis

    2005-06-01

    Posttranslational modification by SUMO elicits a repressive effect on many transcription factors. In principle, sumoylation may either influence transcription factor activity on promoters, or it may act indirectly by targeting the modified factors to specific cellular compartments. To provide direct experimental evidence for the above, not necessarily mutually exclusive models, we analyzed the role of SUMO modification on the localization and the activity of the orphan nuclear receptor LRH-1. We demonstrate, by using fluorescence resonance energy transfer (FRET) and fluorescence recovery after photobleaching (FRAP) assays, that sumoylated LRH-1 is exclusively localized in promyelocytic leukemia protein (PML) nuclear bodies and that this association is a dynamic process. Release of LRH-1 from nuclear bodies correlated with its desumoylation, pointing to the pivotal role of SUMO conjugation in keeping LRH-1 in these locations. SUMO-dependent shuttling of LRH-1 into PML bodies defines two spatially separated pools of the protein, of which only the soluble, unmodified one is associated with actively transcribed target genes. The results suggest that SUMO-PML nuclear bodies may primarily function as dynamic molecular reservoirs, controlling the availability of certain transcription factors to active chromatin domains. PMID:15923626

  7. Arsenic mediated disruption of promyelocytic leukemia protein nuclear bodies induces ganciclovir susceptibility in Epstein-Barr positive epithelial cells

    SciTech Connect

    Sides, Mark D.; Block, Gregory J.; Shan, Bin; Esteves, Kyle C.; Lin, Zhen; Flemington, Erik K.; Lasky, Joseph A.

    2011-06-20

    Promyelocytic leukemia protein nuclear bodies (PML NBs) have been implicated in host immune response to viral infection. PML NBs are targeted for degradation during reactivation of herpes viruses, suggesting that disruption of PML NB function supports this aspect of the viral life cycle. The Epstein-Barr virus (EBV) Latent Membrane Protein 1 (LMP1) has been shown to suppress EBV reactivation. Our finding that LMP1 induces PML NB immunofluorescence intensity led to the hypothesis that LMP1 may modulate PML NBs as a means of maintaining EBV latency. Increased PML protein and morphometric changes in PML NBs were observed in EBV infected alveolar epithelial cells and nasopharyngeal carcinoma cells. Treatment with low dose arsenic trioxide disrupted PML NBs, induced expression of EBV lytic proteins, and conferred ganciclovir susceptibility. This study introduces an effective modality to induce susceptibility to ganciclovir in epithelial cells with implications for the treatment of EBV associated pathologies.

  8. Arsenic mediated disruption of promyelocytic leukemia protein nuclear bodies induces ganciclovir susceptibility in Epstein-Barr positive epithelial cells.

    PubMed

    Sides, Mark D; Block, Gregory J; Shan, Bin; Esteves, Kyle C; Lin, Zhen; Flemington, Erik K; Lasky, Joseph A

    2011-07-20

    Promyelocytic leukemia protein nuclear bodies (PML NBs) have been implicated in host immune response to viral infection. PML NBs are targeted for degradation during reactivation of herpes viruses, suggesting that disruption of PML NB function supports this aspect of the viral life cycle. The Epstein-Barr virus (EBV) Latent Membrane Protein 1 (LMP1) has been shown to suppress EBV reactivation. Our finding that LMP1 induces PML NB immunofluorescence intensity led to the hypothesis that LMP1 may modulate PML NBs as a means of maintaining EBV latency. Increased PML protein and morphometric changes in PML NBs were observed in EBV infected alveolar epithelial cells and nasopharyngeal carcinoma cells. Treatment with low dose arsenic trioxide disrupted PML NBs, induced expression of EBV lytic proteins, and conferred ganciclovir susceptibility. This study introduces an effective modality to induce susceptibility to ganciclovir in epithelial cells with implications for the treatment of EBV associated pathologies. PMID:21605886

  9. Signal-dependent Regulation of Transcription by Histone Deacetylase 7 Involves Recruitment to Promyelocytic Leukemia Protein Nuclear Bodies

    PubMed Central

    Gao, Chengzhuo; Cheng, Xiwen; Lam, Minh; Liu, Yu; Liu, Qing; Chang, Kun-Sang

    2008-01-01

    Promyelocytic leukemia protein (PML) nuclear bodies (NBs) are dynamic subnuclear compartments that play roles in several cellular processes, including apoptosis, transcriptional regulation, and DNA repair. Histone deacetylase (HDAC) 7 is a potent corepressor that inhibits transcription by myocyte enhancer factor 2 (MEF2) transcription factors. We show here that endogenous HDAC7 and PML interact and partially colocalize in PML NBs. Tumor necrosis factor (TNF)-α treatment recruits HDAC7 to PML NBs and enhances association of HDAC7 with PML in human umbilical vein endothelial cells. Consequently, TNF-α promotes dissociation of HDAC7 from MEF2 transcription factors and the promoters of MEF2 target genes such as matrix metalloproteinase (MMP)-10, leading to accumulation of MMP-10 mRNA. Conversely, knockdown of PML enhances the association between HDAC7 and MEF2 and decreases MMP-10 mRNA accumulation. Accordingly, ectopic expression of PML recruits HDAC7 to PML NBs and leads to activation of MEF2 reporter activity. Notably, small interfering RNA knockdown of PML decreases basal and TNF-α-induced MMP-10 mRNA accumulation. Our results reveal a novel mechanism by which PML sequesters HDAC7 to relieve repression and up-regulate gene expression. PMID:18463162

  10. Dynamic Response of IFI16 and Promyelocytic Leukemia Nuclear Body Components to Herpes Simplex Virus 1 Infection

    PubMed Central

    2015-01-01

    ABSTRACT Intrinsic immunity is an aspect of antiviral defense that operates through diverse mechanisms at the intracellular level through a wide range of constitutively expressed cellular proteins. In the case of herpesviruses, intrinsic resistance involves the repression of viral gene expression during the very early stages of infection, a process that is normally overcome by viral tegument and/or immediate-early proteins. Thus, the balance between cellular repressors and virus-counteracting proteins determines whether or not a cell becomes productively infected. One aspect of intrinsic resistance to herpes simplex virus 1 (HSV-1) is conferred by components of promyelocytic leukemia nuclear bodies (PML NBs), which respond to infection by accumulating at sites that are closely associated with the incoming parental HSV-1 genomes. Other cellular proteins, including IFI16, which has been implicated in sensing pathogen DNA and initiating signaling pathways that lead to an interferon response, also respond to viral genomes in this manner. Here, studies of the dynamics of the response of PML NB components and IFI16 to invading HSV-1 genomes demonstrated that this response is extremely rapid, occurring within the first hour after addition of the virus, and that human Daxx (hDaxx) and IFI16 respond more rapidly than PML. In the absence of HSV-1 regulatory protein ICP0, which counteracts the recruitment process, the newly formed, viral-genome-induced PML NB-like foci can fuse with existing PML NBs. These data are consistent with a model involving viral genome sequestration into such structures, thereby contributing to the low probability of initiation of lytic infection in the absence of ICP0. IMPORTANCE Herpesviruses have intimate interactions with their hosts, with infection leading either to the productive lytic cycle or to a quiescent infection in which viral gene expression is suppressed while the viral genome is maintained in the host cell nucleus. Whether a cell

  11. Trafficking of the transcription factor Nrf2 to promyelocytic leukemia-nuclear bodies: implications for degradation of NRF2 in the nucleus.

    PubMed

    Malloy, Melanie Theodore; McIntosh, Deneshia J; Walters, Treniqka S; Flores, Andrea; Goodwin, J Shawn; Arinze, Ifeanyi J

    2013-05-17

    Ubiquitylation of Nrf2 by the Keap1-Cullin3/RING box1 (Cul3-Rbx1) E3 ubiquitin ligase complex targets Nrf2 for proteasomal degradation in the cytoplasm and is an extensively studied mechanism for regulating the cellular level of Nrf2. Although mechanistic details are lacking, reports abound that Nrf2 can also be degraded in the nucleus. Here, we demonstrate that Nrf2 is a target for sumoylation by both SUMO-1 and SUMO-2. HepG2 cells treated with As2O3, which enhances attachment of SUMO-2/3 to target proteins, increased SUMO-2/3-modification (polysumoylation) of Nrf2. We show that Nrf2 traffics, in part, to promyelocytic leukemia-nuclear bodies (PML-NBs). Cell fractions harboring key components of PML-NBs did not contain biologically active Keap1 but contained modified Nrf2 as well as RING finger protein 4 (RNF4), a poly-SUMO-specific E3 ubiquitin ligase. Overexpression of wild-type RNF4, but not the catalytically inactive mutant, decreased the steady-state levels of Nrf2, measured in the PML-NB-enriched cell fraction. The proteasome inhibitor MG-132 interfered with this decrease, resulting in elevated levels of polysumoylated Nrf2 that was also ubiquitylated. Wild-type RNF4 accelerated the half-life (t½) of Nrf2, measured in PML-NB-enriched cell fractions. These results suggest that RNF4 mediates polyubiquitylation of polysumoylated Nrf2, leading to its subsequent degradation in PML-NBs. Overall, this work identifies Nrf2 as a target for sumoylation and provides a novel mechanism for its degradation in the nucleus, independent of Keap1. PMID:23543742

  12. Leukemia

    MedlinePlus

    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. ...

  13. Total body irradiation in chronic myeloid leukemia

    SciTech Connect

    Advani, S.H.; Dinshaw, K.A.; Nair, C.N.; Ramakrishnan, G.

    1983-04-01

    Total body irradiation (TBI), given as 10 rad daily for five days a week for a total dose of 150 rad has been used in an attempt to control the chronic phase of chronic myeloid leukemia (CML). Thirteen patients with CML received fractionated TBI leading to rapid and good control of WBC count without any adverse reaction. The chronic phase of CML could also be controlled with TBI, even in three patients who were resistant to busulfan. Following TBI, WBC count remained under control for a period of 32 weeks as compared to 40 weeks following vusulfan alone. Repeat TBI was also well tolerated with good response. It appears that TBI is an effective and safe therapy for controlling the chronic phase of CML.

  14. Role of Promyelocytic Leukemia (Pml) Sumolation in Nuclear Body Formation, 11s Proteasome Recruitment, and as2O3-Induced Pml or Pml/Retinoic Acid Receptor α Degradation

    PubMed Central

    Lallemand-Breitenbach, Valérie; Zhu, Jun; Puvion, Francine; Koken, Marcel; Honoré, Nicole; Doubeikovsky, Alexandre; Duprez, Estelle; Pandolfi, Pier Paolo; Puvion, Edmond; Freemont, Paul; de Thé, Hugues

    2001-01-01

    Promyelocytic leukemia (PML) is the organizer of nuclear matrix domains, PML nuclear bodies (NBs), with a proposed role in apoptosis control. In acute promyelocytic leukemia, PML/retinoic acid receptor (RAR) α expression disrupts NBs, but therapies such as retinoic acid or arsenic trioxide (As2O3) restore them. PML is conjugated by the ubiquitin-related peptide SUMO-1, a process enhanced by As2O3 and proposed to target PML to the nuclear matrix. We demonstrate that As2O3 triggers the proteasome-dependent degradation of PML and PML/RARα and that this process requires a specific sumolation site in PML, K160. PML sumolation is dispensable for its As2O3-induced matrix targeting and formation of primary nuclear aggregates, but is required for the formation of secondary shell-like NBs. Interestingly, only these mature NBs harbor 11S proteasome components, which are further recruited upon As2O3 exposure. Proteasome recruitment by sumolated PML only likely accounts for the failure of PML-K160R to be degraded. Therefore, studying the basis of As2O3-induced PML/RARα degradation we show that PML sumolation directly or indirectly promotes its catabolism, suggesting that mature NBs could be sites of intranuclear proteolysis and opening new insights into NB alterations found in viral infections or transformation. PMID:11413191

  15. Leukemia

    MedlinePlus

    ... version of this page please turn Javascript on. Leukemia What Is Leukemia? Leukemia is a cancer of the blood cells. ... diagnosed with leukemia are over 50 years old. Leukemia Starts in Bone Marrow Click for more information ...

  16. SUMO Ligase Protein Inhibitor of Activated STAT1 (PIAS1) Is a Constituent Promyelocytic Leukemia Nuclear Body Protein That Contributes to the Intrinsic Antiviral Immune Response to Herpes Simplex Virus 1

    PubMed Central

    Brown, James R.; Conn, Kristen L.; Wasson, Peter; Charman, Matthew; Tong, Lily; Grant, Kyle; McFarlane, Steven

    2016-01-01

    ABSTRACT Aspects of intrinsic antiviral immunity are mediated by promyelocytic leukemia nuclear body (PML-NB) constituent proteins. During herpesvirus infection, these antiviral proteins are independently recruited to nuclear domains that contain infecting viral genomes to cooperatively promote viral genome silencing. Central to the execution of this particular antiviral response is the small ubiquitin-like modifier (SUMO) signaling pathway. However, the participating SUMOylation enzymes are not fully characterized. We identify the SUMO ligase protein inhibitor of activated STAT1 (PIAS1) as a constituent PML-NB protein. We show that PIAS1 localizes at PML-NBs in a SUMO interaction motif (SIM)-dependent manner that requires SUMOylated or SUMOylation-competent PML. Following infection with herpes simplex virus 1 (HSV-1), PIAS1 is recruited to nuclear sites associated with viral genome entry in a SIM-dependent manner, consistent with the SIM-dependent recruitment mechanisms of other well-characterized PML-NB proteins. In contrast to that of Daxx and Sp100, however, the recruitment of PIAS1 is enhanced by PML. PIAS1 promotes the stable accumulation of SUMO1 at nuclear sites associated with HSV-1 genome entry, whereas the accumulation of other evaluated PML-NB proteins occurs independently of PIAS1. We show that PIAS1 cooperatively contributes to HSV-1 restriction through mechanisms that are additive to those of PML and cooperative with those of PIAS4. The antiviral mechanisms of PIAS1 are counteracted by ICP0, the HSV-1 SUMO-targeted ubiquitin ligase, which disrupts the recruitment of PIAS1 to nuclear domains that contain infecting HSV-1 genomes through mechanisms that do not directly result in PIAS1 degradation. IMPORTANCE Adaptive, innate, and intrinsic immunity cooperatively and efficiently restrict the propagation of viral pathogens. Intrinsic immunity mediated by constitutively expressed cellular proteins represents the first line of intracellular defense against

  17. Serum metabonomics of acute leukemia using nuclear magnetic resonance spectroscopy

    PubMed Central

    Musharraf, Syed Ghulam; Siddiqui, Amna Jabbar; Shamsi, Tahir; Choudhary, M. Iqbal; Rahman, Atta-ur

    2016-01-01

    Acute leukemia is a critical neoplasm of white blood cells. In order to differentiate between the metabolic alterations associated with two subtypes of acute leukemia, acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML), we investigated the serum of ALL and AML patients and compared with two controls (healthy and aplastic anemia) using 1H NMR (nuclear magnetic resonance) spectroscopy. Thirty-seven putative metabolites were identified using Carr-Purcell-Meiboom-Gill (CPMG) sequence. The use of PLS-DA and OPLS-DA models gave results with 84.38% and 90.63% classification rate, respectively. The metabolites responsible for classification are mainly lipids, lactate and glucose. Compared with controls, ALL and AML patients showed serum metabonomic differences involving aberrant metabolism pathways including glycolysis, TCA cycle, lipoprotein changes, choline and fatty acid metabolisms. PMID:27480133

  18. Serum metabonomics of acute leukemia using nuclear magnetic resonance spectroscopy.

    PubMed

    Musharraf, Syed Ghulam; Siddiqui, Amna Jabbar; Shamsi, Tahir; Choudhary, M Iqbal; Rahman, Atta-Ur

    2016-01-01

    Acute leukemia is a critical neoplasm of white blood cells. In order to differentiate between the metabolic alterations associated with two subtypes of acute leukemia, acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML), we investigated the serum of ALL and AML patients and compared with two controls (healthy and aplastic anemia) using (1)H NMR (nuclear magnetic resonance) spectroscopy. Thirty-seven putative metabolites were identified using Carr-Purcell-Meiboom-Gill (CPMG) sequence. The use of PLS-DA and OPLS-DA models gave results with 84.38% and 90.63% classification rate, respectively. The metabolites responsible for classification are mainly lipids, lactate and glucose. Compared with controls, ALL and AML patients showed serum metabonomic differences involving aberrant metabolism pathways including glycolysis, TCA cycle, lipoprotein changes, choline and fatty acid metabolisms. PMID:27480133

  19. Chronic myelogenous leukemia (CML)

    MedlinePlus

    CML; Chronic myeloid leukemia; Chronic granulocytic leukemia; Leukemia - chronic granulocytic ... nuclear disaster. It takes many years to develop leukemia from radiation exposure. Most people treated for cancer ...

  20. Nuclear bodies: Built to boost.

    PubMed

    Sawyer, Iain A; Dundr, Miroslav

    2016-06-01

    The classic archetypal function of nuclear bodies is to accelerate specific reactions within their crowded space. In this issue, Tatomer et al. (2016. J. Cell Biol http://dx.doi.org/10.1083/jcb.201504043) provide the first direct evidence that the histone locus body acts to concentrate key factors required for the proper processing of histone pre-mRNAs. PMID:27241912

  1. Childhood leukemia and fallout from the Nevada nuclear tests

    SciTech Connect

    Land, C.E.; McKay, F.W.; Machado, S.G.

    1984-01-13

    Cancer mortality data from the National Center for Health Statistics, covering the period 1950 through 1978, were used to test a reported association between childhood leukemia and exposure to radioactive fallout from nuclear weapons tests in Nevada between 1951 and 1958. No pattern of temporal and geographic variation in risk supportive of the reported association was found. Comparison of these results with those presented in support of an association of risk with fallout suggests that the purported association merely reflects an anomalously low leukemia rate in southern Utah during the period 1944 to 1949. 14 references, 4 figures, 7 tables.

  2. Leukemia.

    PubMed

    Juliusson, Gunnar; Hough, Rachael

    2016-01-01

    Leukemias are a group of life threatening malignant disorders of the blood and bone marrow. In the adolescent and young adult (AYA) population, the acute leukemias are most prevalent, with chronic myeloid leukemia being infrequently seen. Factors associated with more aggressive disease biology tend to increase in frequency with increasing age, whilst tolerability of treatment strategies decreases. There are also challenges regarding the effective delivery of therapy specific to the AYA group, consequences on the unique psychosocial needs of this age group, including compliance. This chapter reviews the current status of epidemiology, pathophysiology, treatment strategies and outcomes of AYA leukemia, with a focus on acute lymphoblastic leukemia and acute myeloid leukemia. PMID:27595359

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

    ClinicalTrials.gov

    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

  4. Nucleolus: the fascinating nuclear body

    PubMed Central

    Sirri, Valentina; Urcuqui-Inchima, Silvio; Roussel, Pascal

    2007-01-01

    Nucleoli are the prominent contrasted structures of the cell nucleus. In the nucleolus, ribosomal RNAs are synthesized, processed and assembled with ribosomal proteins. RNA polymerase I synthesizes the ribosomal RNAs and this activity is cell cycle regulated. The nucleolus reveals the functional organization of the nucleus in which the compartmentation of the different steps of ribosome biogenesis is observed whereas the nucleolar machineries are in permanent exchange with the nucleoplasm and other nuclear bodies. After mitosis, nucleolar assembly is a time and space regulated process controlled by the cell cycle. In addition, by generating a large volume in the nucleus with apparently no RNA polymerase II activity, the nucleolus creates a domain of retention/sequestration of molecules normally active outside the nucleolus. Viruses interact with the nucleolus and recruit nucleolar proteins to facilitate virus replication. The nucleolus is also a sensor of stress due to the redistribution of the ribosomal proteins in the nucleoplasm by nucleolus disruption. The nucleolus plays several crucial functions in the nucleus: in addition to its function as ribosome factory of the cells it is a multifunctional nuclear domain, and nucleolar activity is linked with several pathologies. Perspectives on the evolution of this research area are proposed. PMID:18046571

  5. Nuclear body formation and PML body remodeling by the human cytomegalovirus protein UL35

    SciTech Connect

    Salsman, Jayme; Wang Xueqi; Frappier, Lori

    2011-06-05

    The human cytomegalovirus (HCMV) UL35 gene encodes two proteins, UL35 and UL35a. Expression of UL35 in transfected cells results in the formation of UL35 nuclear bodies that associate with promyelocytic leukemia (PML) protein. PML forms the basis for PML nuclear bodies that are important for suppressing viral lytic gene expression. Given the important relationship between PML and viral infection, we have further investigated the association of UL35 with PML bodies. We demonstrate that UL35 bodies form independently of PML and subsequently recruit PML, Sp100 and Daxx. In contrast, UL35a did not form bodies; however, it could bind UL35 and inhibit the formation of UL35 bodies. The HCMV tegument protein pp71 promoted the formation of UL35 bodies and the cytoplasmic localization of UL35a. Similarly, UL35a shifted pp71 to the cytoplasm. These results indicate that the interplay between UL35, UL35a and pp71 affects their subcellular localization and likely their functions throughout infection.

  6. Arsenic-induced SUMO-dependent recruitment of RNF4 into PML nuclear bodies.

    PubMed

    Geoffroy, Marie-Claude; Jaffray, Ellis G; Walker, Katherine J; Hay, Ronald T

    2010-12-01

    In acute promyelocytic leukemia (APL), the promyelocytic leukemia (PML) protein is fused to the retinoic acid receptor alpha (RAR). Arsenic is an effective treatment for this disease as it induces SUMO-dependent ubiquitin-mediated proteasomal degradation of the PML-RAR fusion protein. Here we analyze the nuclear trafficking dynamics of PML and its SUMO-dependent ubiquitin E3 ligase, RNF4 in response to arsenic. After administration of arsenic, PML immediately transits into nuclear bodies where it undergoes SUMO modification. This initial recruitment of PML into nuclear bodies is not dependent on RNF4, but RNF4 quickly follows PML into the nuclear bodies where it is responsible for ubiquitylation of SUMO-modified PML and its degradation by the proteasome. While arsenic restricts the mobility of PML, FRAP analysis indicates that RNF4 continues to rapidly shuttle into PML nuclear bodies in a SUMO-dependent manner. Under these conditions FRET studies indicate that RNF4 interacts with SUMO in PML bodies but not directly with PML. These studies indicate that arsenic induces the rapid reorganization of the cell nucleus by SUMO modification of nuclear body-associated PML and uptake of the ubiquitin E3 ligase RNF4 leading to the ubiquitin-mediated degradation of PML. PMID:20943951

  7. Many-Body Interactions and Nuclear Structure

    SciTech Connect

    Hjorth-Jensen, M.; Dean, David Jarvis; Hagen, Gaute; Kvaal, S.

    2010-01-01

    This article presents several challenges to nuclear many-body theory and our understanding of the stability of nuclear matter. In order to achieve this, we present five different cases, starting with an idealized toy model. These cases expose problems that need to be understood in order to match recent advances in nuclear theory with current experimental programs in low-energy nuclear physics. In particular, we focus on our current understanding, or lack thereof, of many-body forces, and how they evolve as functions of the number of particles. We provide examples of discrepancies between theory and experiment and outline some selected perspectives for future research directions.

  8. Body composition and phase angle in Russian children in remission from acute lymphoblastic leukemia

    NASA Astrophysics Data System (ADS)

    Tseytlin, G. Ja; Khomyakova, I. A.; Nikolaev, D. V.; Konovalova, M. V.; Vashura, A. Yu; Tretyak, A. V.; Godina, E. Z.; Rudnev, S. G.

    2010-04-01

    Elevated degree of body fatness and changes in other body composition parameters are known to be common effects of treatment for acute lymphoblastic leukemia (ALL) in children. In order to study peculiarities of somatic growth and development in ALL survivors, we describe the results of BIA body composition analysis of 112 boys and 108 girls aged 5-18 years in remission from ALL (remission time range 1-13 years) compared to data from the same number of age- and sex-matched healthy controls (n=220). Detrimental effect on height in ALL boys was observed, whereas girls experienced additional weight gain compared to healthy subjects. In ALL patients, resistance, body fat, and percent body fat were significantly increased. The reactance, phase angle, absolute and relative values of skeletal muscle and body cell mass were significantly decreased. Principal component analysis revealed an early prevalence of adiposity traits in the somatic growth and development of ALL girls compared to healthy controls.

  9. Childhood Leukemia

    MedlinePlus

    Leukemia is cancer of the white blood cells. It is the most common type of childhood cancer. ... blood cells help your body fight infection. In leukemia, the bone marrow produces abnormal white blood cells. ...

  10. PML nuclear bodies: assembly and oxidative stress-sensitive sumoylation.

    PubMed

    Sahin, Umut; de Thé, Hugues; Lallemand-Breitenbach, Valérie

    2014-01-01

    PML Nuclear Bodies (NBs) have fascinated cell biologists due to their exquisitely dynamic nature and their involvement in human diseases, notably acute promyelocytic leukemia. NBs, as well as their master organizer--the PML protein--exhibit multiple connections with stress responses. Initially viewed as a tumor suppressor, PML recently re-emerged as a multifaceted protein, capable of controlling numerous aspects of cellular homeostasis. NBs recruit many functionally diverse proteins and function as stress-regulated sumoylation factories. SUMO-initiated partner retention can subsequently facilitate a variety of other post-translational modifications, as well as partner degradation. With this newly elucidated central role of stress-enhanced sumoylation, it should now be possible to build a working model for the different NB-regulated cellular activities. Moreover, pharmacological manipulation of NB formation by interferons or oxidants holds the promise of clearing many undesirable proteins for clinical management of malignant, viral or neurodegenerative diseases. PMID:25482067

  11. 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

    ClinicalTrials.gov

    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

  12. Interferon gamma regulates accumulation of the proteasome activator PA28 and immunoproteasomes at nuclear PML bodies.

    PubMed

    Fabunmi, R P; Wigley, W C; Thomas, P J; DeMartino, G N

    2001-01-01

    PA28 is an interferon (gamma) (IFN(gamma)) inducible proteasome activator required for presentation of certain major histocompatibility (MHC) class I antigens. Under basal conditions in HeLa and Hep2 cells, a portion of nuclear PA28 is concentrated at promyelocytic leukemia oncoprotein (PML)-containing bodies also commonly known as PODs or ND10. IFN(gamma) treatment greatly increased the number and size of the PA28- and PML-containing bodies, and the effect was further enhanced in serum-deprived cells. PML bodies are disrupted in response to certain viral infections and in diseases such as acute promyelocytic leukemia (APL). Like PML, PA28 was delocalized from PML bodies by expression of the cytomegalovirus protein, IE1, and in NB4 cells, an APL model line. Moreover, retinoic acid treatment, which causes remission of APL in patients and reformation of PML-containing bodies in NB4 cells, relocalized PA28 to this site. In contrast, the proteasome, the functional target of PA28, was not detected at PML bodies under basal conditions in HeLa and Hep2 cells, but IFN(gamma) promoted accumulation of 'immunoproteasomes' at this site. These results establish PA28 as a novel component of nuclear PML bodies, and suggest that PA28 may assemble or activate immunoproteasomes at this site as part of its role in proteasome-dependent MHC class I antigen presentation. PMID:11112687

  13. What Is Acute Myeloid Leukemia?

    MedlinePlus

    ... about acute myeloid leukemia? What is acute myeloid leukemia? Cancer starts when cells in a part of ... the body from doing their jobs. Types of leukemia Not all leukemias are the same. There are ...

  14. Relativistic nuclear many-body theory

    SciTech Connect

    Serot, B.D. ); Walecka, J.D. . Continuous Electron Beam Accelerator Facility)

    1991-09-11

    Nonrelativistic models of nuclear systems have provided important insight into nuclear physics. In future experiments, nuclear systems will be examined under extreme conditions of density and temperature, and their response will be probed at momentum and energy transfers larger than the nucleon mass. It is therefore essential to develop reliable models that go beyond the traditional nonrelativistic many-body framework. General properties of physics, such as quantum mechanics, Lorentz covariance, and microscopic causality, motivate the use of quantum field theories to describe the interacting, relativistic, nuclear many-body system. Renormalizable models based on hadronic degrees of freedom (quantum hadrodynamics) are presented, and the assumptions underlying this framework are discussed. Some applications and successes of quantum hadrodynamics are described, with an emphasis on the new features arising from relativity. Examples include the nuclear equation of state, the shell model, nucleon-nucleus scattering, and the inclusion of zero-point vacuum corrections. Current issues and problems are also considered, such as the construction of improved approximations, the full role of the quantum vacuum, and the relationship between quantum hadrodynamics and quantum chromodynamics. We also speculate on future developments. 103 refs., 18 figs.

  15. The Role of Nuclear Bodies in Gene Expression and Disease

    PubMed Central

    Morimoto, Marie; Boerkoel, Cornelius F.

    2013-01-01

    This review summarizes the current understanding of the role of nuclear bodies in regulating gene expression. The compartmentalization of cellular processes, such as ribosome biogenesis, RNA processing, cellular response to stress, transcription, modification and assembly of spliceosomal snRNPs, histone gene synthesis and nuclear RNA retention, has significant implications for gene regulation. These functional nuclear domains include the nucleolus, nuclear speckle, nuclear stress body, transcription factory, Cajal body, Gemini of Cajal body, histone locus body and paraspeckle. We herein review the roles of nuclear bodies in regulating gene expression and their relation to human health and disease. PMID:24040563

  16. Hyperfractionated total body irradiation for bone marrow transplantation. Results in seventy leukemia patients with allogeneic transplants

    SciTech Connect

    Shank, B.; Chu, F.C.H.; Dinsmore, R.; Kapoor, N.; Kirkpatrick, D.; Teitelbaum, H.; Reid, A.; Bonfiglio, P.; Simpson, L.; O'Reilly, R.J.

    1983-11-01

    From May, 1979 to March, 1981, 76 leukemia patients were prepared for bone marrow transplantation (BMT) with a new hyperfractionated total body irradiation (TBI) regimen (1320 cGy in 11 fractions, 3x/day), followed by cyclophosphamide, 60 mg/kg, for two days. Partial lung shielding was done on each treatment, with supplemental electron beam treatments of the chest wall to compensate, and of the testes, a sanctuary site. This regimen was initiated to potentially reduce fatal interstitial pneumonitis as well as decrease leukemic relapse. Overall actuarial survival at 1 year for acute non-lymphocytic leukemia (ANLL) patients is 63%, while relapse-free survival at 1 year is 53%. On the other hand, for acute lymphocytic leukemia (ALL) patients, there is no significant difference between relapse or remission patients with regard to overall survival or relapse-free survival, when relapse is defined as > 5% blasts in the marrow at the time of cytoreduction. Overall actuarial survival at 1 year for ALL is 61% and relapse-free survival is 45% at 1 year. Fatal interstitial pneumonitis has dropped to 18% compared with 50% in our previous single-dose TBI regimen (1000 cGy), in which the same doses of cyclophosphamide were given prior to TBI. In conclusion, not only has fatal interstitial pneumonitis been reduced by hyperfractionation and partial lung blocking, but there may be a survival advantage in ALL patients in relapse, who have a survival equal to that of remission patients. This may indicate a greater cell kill with the higher dose (1320 cGy) attained with this regimen, in these patients with a higher leukemic cell burden.

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

    PubMed

    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. PMID:25840335

  18. A view of nuclear Polycomb bodies

    PubMed Central

    Pirrotta, Vincenzo; Li, Hua-Bing

    2012-01-01

    Polycomb Group (PcG) proteins are concentrated in nuclear foci called PcG bodies. Although the some of these foci are due to the tendency of PcG binding sites in the genome to occur in linear clusters, distant PcG sites can contact one another and in some cases congregate in the same PcG body when they are repressed. Experiments using transgenes containing PcG binding sites reveal that co-localization depends on the presence of insulator elements rather than of Polycomb Response Elements (PREs) and that it can occur also when the transgenes are in the active state. A model is proposed according to which insulator proteins mediate shuttling of PcG target genes between PcG bodies when repressed to transcription factories when transcriptionally active. PMID:22178420

  19. Childhood leukemia and cancers near German nuclear reactors: significance, context, and ramifications of recent studies.

    PubMed

    Nussbaum, Rudi H

    2009-01-01

    A government-sponsored study of childhood cancer in the proximity of German nuclear power plants (German acronym KiKK) found that children < 5 years living < 5 km from plant exhaust stacks had twice the risk for contracting leukemia as those residing > 5 km. The researchers concluded that since "this result was not to be expected under current radiation-epidemiological knowledge" and confounders could not be identified, the observed association of leukemia incidence with residential proximity to nuclear plants "remains unexplained." This unjustified conclusion illustrates the dissonance between evidence and assumptions. There exist serious flaws and gaps in the knowledge on which accepted models for population exposure and radiation risk are based. Studies with results contradictory to those of KiKK lack statistical power to invalidate its findings. The KiKK study's ramifications add to the urgency for a public policy debate regarding the health impact of nuclear power generation. PMID:19650588

  20. 21 CFR 892.1130 - Nuclear whole body counter.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Nuclear whole body counter. 892.1130 Section 892...) MEDICAL DEVICES RADIOLOGY DEVICES Diagnostic Devices § 892.1130 Nuclear whole body counter. (a) Identification. A nuclear whole body counter is a device intended to measure the amount of radionuclides in...

  1. 21 CFR 892.1330 - Nuclear whole body scanner.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Nuclear whole body scanner. 892.1330 Section 892...) MEDICAL DEVICES RADIOLOGY DEVICES Diagnostic Devices § 892.1330 Nuclear whole body scanner. (a) Identification. A nuclear whole body scanner is a device intended to measure and image the distribution...

  2. 21 CFR 892.1330 - Nuclear whole body scanner.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Nuclear whole body scanner. 892.1330 Section 892...) MEDICAL DEVICES RADIOLOGY DEVICES Diagnostic Devices § 892.1330 Nuclear whole body scanner. (a) Identification. A nuclear whole body scanner is a device intended to measure and image the distribution...

  3. 21 CFR 892.1130 - Nuclear whole body counter.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Nuclear whole body counter. 892.1130 Section 892...) MEDICAL DEVICES RADIOLOGY DEVICES Diagnostic Devices § 892.1130 Nuclear whole body counter. (a) Identification. A nuclear whole body counter is a device intended to measure the amount of radionuclides in...

  4. 21 CFR 892.1330 - Nuclear whole body scanner.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ...) MEDICAL DEVICES RADIOLOGY DEVICES Diagnostic Devices § 892.1330 Nuclear whole body scanner. (a) Identification. A nuclear whole body scanner is a device intended to measure and image the distribution of... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Nuclear whole body scanner. 892.1330 Section...

  5. 21 CFR 892.1330 - Nuclear whole body scanner.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ...) MEDICAL DEVICES RADIOLOGY DEVICES Diagnostic Devices § 892.1330 Nuclear whole body scanner. (a) Identification. A nuclear whole body scanner is a device intended to measure and image the distribution of... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Nuclear whole body scanner. 892.1330 Section...

  6. 21 CFR 892.1330 - Nuclear whole body scanner.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ...) MEDICAL DEVICES RADIOLOGY DEVICES Diagnostic Devices § 892.1330 Nuclear whole body scanner. (a) Identification. A nuclear whole body scanner is a device intended to measure and image the distribution of... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Nuclear whole body scanner. 892.1330 Section...

  7. What Is Acute Lymphocytic Leukemia (ALL)?

    MedlinePlus

    ... key statistics about acute lymphocytic leukemia? What is acute lymphocytic leukemia? Cancer starts when cells in the body begin ... leukemias). The rest of this document focuses on acute lymphocytic leukemia (ALL) in adults. For information on ALL in ...

  8. Nuclear Few-Body Physics at FAIR

    NASA Astrophysics Data System (ADS)

    Nilsson, Thomas

    2011-05-01

    The FAIR facility, to be constructed at the GSI site in Darmstadt, will be addressing a wealth of outstanding questions within the realm of subatomic, atomic and plasma physics through a combination of novel accelerators, storage rings and innovative experimental set-ups. One of the key installations is the fragment separator Super-FRS that will be able to deliver an unprecedented range of radioactive ion beams (RIBs) in the energy range of 0-1.5 GeV/u to the envisaged experiments collected within the NuSTAR collaboration. This will in particular permit new experimental investigations of nuclear few-body systems at extreme isospins, also reaching beyond the drip-lines, using the NuSTAR-R3B set-up. The outcome of pilot experiments on unbound systems are reported, as well as crucial detector upgrades.

  9. Childhood Leukemia in the Vicinity of the Geesthacht Nuclear Establishments near Hamburg, Germany

    PubMed Central

    Hoffmann, Wolfgang; Terschueren, Claudia; Richardson, David B.

    2007-01-01

    Background During 1990–1991 a childhood leukemia cluster was observed in the sparsely populated region surrounding two nuclear establishments southeast of Hamburg, Germany. Since then, several new cases have been reported. Recently a possible accidental release of radionuclides in 1986 was hypothesized. Objective The objective of this study was to analyze the childhood leukemia incidence in this area since 1990. Methods All incident cases (< 15 years of age) were ascertained during 1990–2005 within a 5-km radius of the Krümmel nuclear power plant. We derived standardized incidence ratios (SIRs) using county and national leukemia incidence rates as referents. We stratified analyses by calendar period and attained age, and by subdividing the study region into areas north versus south of the Elbe river. Results Fourteen cases were ascertained in the study area, whereas 4.0 were expected based on national referent rates [1990–2005: SIR = 3.5; 95% confidence interval (CI), 1.9–5.9]. The excess was not confined to the early 1990s; for the more recent time period 1999–2005, the SIR is still elevated (SIR = 2.7; 95% CI, 0.9–6.2). SIRs of greatest magnitude were observed for children 0–4 years of age (SIR = 4.9; 95% CI, 2.4–9.0) and for residents south of the Elbe (SIR = 7.5; 95% CI, 2.8–16.4). Conclusions The incidence in this region is significantly higher than the childhood leukemia incidence for Germany as a whole. To date, no unique hazards have been identified in this population. The fact that the elevated rates have persisted in this community for > 15 years warrants further investigation. PMID:17589605

  10. What Is Chronic Lymphocytic Leukemia?

    MedlinePlus

    ... blood, and lymphoid tissue What is chronic lymphocytic leukemia? Cancer starts when cells in the body begin ... the lymph nodes, liver, and spleen. What is leukemia? Leukemia is a cancer that starts in the ...

  11. Outcomes for newly diagnosed patients with acute myeloid leukemia dosed on actual or adjusted body weight

    PubMed Central

    Bivona, Cory; Rockey, Michelle; Henry, Dave; Grauer, Dennis; Abhyankar, Sunil; Aljitawi, Omar; Ganguly, Siddhartha; McGuirk, Joseph; Singh, Anurag; Lin, Tara L.

    2015-01-01

    Purpose Data from solid tumor malignancies suggest that actual body weight (ABW) dosing improves overall outcomes. There is the potential to compromise efficacy when chemotherapy dosages are reduced, but the impact of dose adjustment on clinical response and toxicity in hematologic malignancies is unknown. The purpose of this study was to evaluate the outcomes of utilizing a percent of ABW for acute myeloid leukemia (AML) induction chemotherapy dosing. Methods This retrospective, single-center study included 146 patients who received 7 + 3 induction (cytarabine and anthracycline) for treatment of AML. Study design evaluated the relationship between percentage of ABW dosing and complete response (CR) rates in patients newly diagnosed with AML. Results Percentage of ABW dosing did not influence CR rates in patients undergoing induction chemotherapy for AML (p = 0.83); nor did it influence rate of death at 30 days or relapse at 6 months (p = 0.94). When comparing patients dosed at 90–100 % of ABW compared to <90 % ABW, CR rates were not significantly different in patients classified as poor risk (p = 0.907). All favorable risk category patients obtained CR. Conclusions Preemptive dose reductions for obesity did not influence CR rates for patients with AML undergoing induction chemotherapy and did not influence the composite endpoint of death at 30 days or disease relapse at 6 months. PMID:26231954

  12. Increased Body Mass Index during Therapy for Childhood Acute Lymphoblastic Leukemia: A Significant and Underestimated Complication.

    PubMed

    Atkinson, Helen C; Marsh, Julie A; Rath, Shoshana R; Kotecha, Rishi S; Gough, Hazel; Taylor, Mandy; Walwyn, Thomas; Gottardo, Nicholas G; Cole, Catherine H; Choong, Catherine S

    2015-01-01

    Objective & Design. We undertook a retrospective review of children diagnosed with acute lymphoblastic leukemia (ALL) and treated with modern COG protocols (n = 80) to determine longitudinal changes in body mass index (BMI) and the prevalence of obesity compared with a healthy reference population. Results. At diagnosis, the majority of patients (77.5%) were in the healthy weight category. During treatment, increases in BMI z-scores were greater for females than males; the prevalence of obesity increased from 10.3% to 44.8% (P < 0.004) for females but remained relatively unchanged for males (9.8% to 13.7%, P = 0.7). Longitudinal analysis using linear mixed-effects identified associations between BMI z-scores and time-dependent interactions with sex (P = 0.0005), disease risk (P < 0.0001), age (P = 0.0001), and BMI z-score (P < 0.0001) at diagnosis and total dose of steroid during maintenance (P = 0.01). Predicted mean BMI z-scores at the end of therapy were greater for females with standard risk ALL irrespective of age at diagnosis and for males younger than 4 years of age at diagnosis with standard risk ALL. Conclusion. Females treated on standard risk protocols and younger males may be at greatest risk of becoming obese during treatment for ALL. These subgroups may benefit from intervention strategies to manage BMI during treatment for ALL. PMID:26101530

  13. Expression of Leukemia-Associated Nup98 Fusion Proteins Generates an Aberrant Nuclear Envelope Phenotype

    PubMed Central

    Fahrenkrog, Birthe; Martinelli, Valérie; Nilles, Nadine; Fruhmann, Gernot; Chatel, Guillaume; Juge, Sabine; Sauder, Ursula; Di Giacomo, Danika; Mecucci, Cristina; Schwaller, Jürg

    2016-01-01

    Chromosomal translocations involving the nucleoporin NUP98 have been described in several hematopoietic malignancies, in particular acute myeloid leukemia (AML). In the resulting chimeric proteins, Nup98's N-terminal region is fused to the C-terminal region of about 30 different partners, including homeodomain (HD) transcription factors. While transcriptional targets of distinct Nup98 chimeras related to immortalization are relatively well described, little is known about other potential cellular effects of these fusion proteins. By comparing the sub-nuclear localization of a large number of Nup98 fusions with HD and non-HD partners throughout the cell cycle we found that while all Nup98 chimeras were nuclear during interphase, only Nup98-HD fusion proteins exhibited a characteristic speckled appearance. During mitosis, only Nup98-HD fusions were concentrated on chromosomes. Despite the difference in localization, all tested Nup98 chimera provoked morphological alterations in the nuclear envelope (NE), in particular affecting the nuclear lamina and the lamina-associated polypeptide 2α (LAP2α). Importantly, such aberrations were not only observed in transiently transfected HeLa cells but also in mouse bone marrow cells immortalized by Nup98 fusions and in cells derived from leukemia patients harboring Nup98 fusions. Our findings unravel Nup98 fusion-associated NE alterations that may contribute to leukemogenesis. PMID:27031510

  14. Fludarabine Phosphate and Total-Body Irradiation Followed by Donor Peripheral Blood Stem Cell Transplant in Treating Patients With Acute Lymphoblastic Leukemia or Chronic Myelogenous Leukemia That Has Responded to Treatment With Imatinib Mesylate, Dasatinib, or Nilotinib

    ClinicalTrials.gov

    2016-07-18

    Adult Acute Lymphoblastic Leukemia in Remission; Blastic Phase Chronic Myelogenous Leukemia; Childhood Acute Lymphoblastic Leukemia in Remission; Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Chronic Phase Chronic Myelogenous Leukemia; Philadelphia Chromosome Positive Adult Precursor Acute Lymphoblastic Leukemia; Philadelphia Chromosome Positive Childhood Precursor Acute Lymphoblastic Leukemia; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Relapsing Chronic Myelogenous Leukemia

  15. PML nuclear body disruption impairs DNA double-strand break sensing and repair in APL

    PubMed Central

    di Masi, A; Cilli, D; Berardinelli, F; Talarico, A; Pallavicini, I; Pennisi, R; Leone, S; Antoccia, A; Noguera, N I; Lo-Coco, F; Ascenzi, P; Minucci, S; Nervi, C

    2016-01-01

    Proteins involved in DNA double-strand break (DSB) repair localize within the promyelocytic leukemia nuclear bodies (PML-NBs), whose disruption is at the root of the acute promyelocytic leukemia (APL) pathogenesis. All-trans-retinoic acid (RA) treatment induces PML-RARα degradation, restores PML-NB functions, and causes terminal cell differentiation of APL blasts. However, the precise role of the APL-associated PML-RARα oncoprotein and PML-NB integrity in the DSB response in APL leukemogenesis and tumor suppression is still lacking. Primary leukemia blasts isolated from APL patients showed high phosphorylation levels of H2AX (γ-H2AX), an initial DSBs sensor. By addressing the consequences of ionizing radiation (IR)-induced DSB response in primary APL blasts and RA-responsive and -resistant myeloid cell lines carrying endogenous or ectopically expressed PML-RARα, before and after treatment with RA, we found that the disruption of PML-NBs is associated with delayed DSB response, as revealed by the impaired kinetic of disappearance of γ-H2AX and 53BP1 foci and activation of ATM and of its substrates H2AX, NBN, and CHK2. The disruption of PML-NB integrity by PML-RARα also affects the IR-induced DSB response in a preleukemic mouse model of APL in vivo. We propose the oncoprotein-dependent PML-NB disruption and DDR impairment as relevant early events in APL tumorigenesis. PMID:27468685

  16. PML nuclear body disruption impairs DNA double-strand break sensing and repair in APL.

    PubMed

    di Masi, A; Cilli, D; Berardinelli, F; Talarico, A; Pallavicini, I; Pennisi, R; Leone, S; Antoccia, A; Noguera, N I; Lo-Coco, F; Ascenzi, P; Minucci, S; Nervi, C

    2016-01-01

    Proteins involved in DNA double-strand break (DSB) repair localize within the promyelocytic leukemia nuclear bodies (PML-NBs), whose disruption is at the root of the acute promyelocytic leukemia (APL) pathogenesis. All-trans-retinoic acid (RA) treatment induces PML-RARα degradation, restores PML-NB functions, and causes terminal cell differentiation of APL blasts. However, the precise role of the APL-associated PML-RARα oncoprotein and PML-NB integrity in the DSB response in APL leukemogenesis and tumor suppression is still lacking. Primary leukemia blasts isolated from APL patients showed high phosphorylation levels of H2AX (γ-H2AX), an initial DSBs sensor. By addressing the consequences of ionizing radiation (IR)-induced DSB response in primary APL blasts and RA-responsive and -resistant myeloid cell lines carrying endogenous or ectopically expressed PML-RARα, before and after treatment with RA, we found that the disruption of PML-NBs is associated with delayed DSB response, as revealed by the impaired kinetic of disappearance of γ-H2AX and 53BP1 foci and activation of ATM and of its substrates H2AX, NBN, and CHK2. The disruption of PML-NB integrity by PML-RARα also affects the IR-induced DSB response in a preleukemic mouse model of APL in vivo. We propose the oncoprotein-dependent PML-NB disruption and DDR impairment as relevant early events in APL tumorigenesis. PMID:27468685

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

    PubMed Central

    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.

    2015-01-01

    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 (HCT) who received TBI (1200-1500cGY) for acute leukemia from 2003 to 2010. The two cohorts were comparable for median age, performance score, type of leukemia, first complete remission, Ph+ ALL, HLA matched siblings, stem cell source, anti-thymocyte globulin use, TBI dose, and type of graft-versus-host disease (GVHD) prophylaxis. The sequence of TBI did not significantly affect TRM (24% vs. 23% at 3y, p=0.67; relative risk [RR] 1.01, p=0.91), leukemia relapse (27% vs. 29% at 3y, p=0.34; RR 0.89, p=0.18), leukemia-free survival (49% vs. 48% at3y, p=0.27; RR 0.93, p=0.29), chronic GVHD (45% vs. 47% at 1y, p=0.39; RR 0.9, p=0.11) or overall survival (53% vs. 52% at 3y, p=0.62; RR 0.96, p=0.57) for CyTBI and TBICy respectively. Corresponding cumulative incidences of sinusoidal obstruction syndrome were 4% and 6% at 100 days (p=0.08). This study demonstrates that the sequence of Cy and TBI does not impact transplant outcomes and complications in patients with acute leukemia undergoing HCT with myeloablative conditioning. PMID:25840335

  18. Father's occupational exposure to radiation and the raised level of childhood leukemia near the Sellafield Nuclear Plant

    SciTech Connect

    Gardner, M.J. )

    1991-08-01

    The first indications that childhood leukemia rates may be raised near the Sellafield nuclear plant in West Cumbria, England, came from largely anecdotal evidence in a television program Windscale: The Nuclear Laundry shown during 1983. During subsequent years, various epidemiological studies have investigated the claim in more detail. Geographical analyses of childhood leukemia incidence in the northern region and mortality in England and Wales using routinely available data made the first contribution. As a result, it was confirmed that leukemia rates in the area, particularly the neighboring village of Seascale, were high compared to other districts, although not totally extreme. Cohort studies of children born in Seascale or attending schools in Seascale were carried out to resolve some of the difficulties of interpretation of geographical analysis. Cohort studies indicated that the excess of leukemia was concentrated among children born in Seascale and was not found among those moving in after birth and suggested that any causal factors may be acting before birth or very early in life. A case-control study of leukemia (and lymphoma) among young people in West Cumbria has examined potentially important individual factors in detail. The study demonstrated a relationship between the raised incidence of leukemia in children and father's recorded external radiation dose during work at Sellafield before his child's conception. The association can effectively explain statistically the observed geographical excess.

  19. 21 CFR 892.1130 - Nuclear whole body counter.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Nuclear whole body counter. 892.1130 Section 892.1130 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES RADIOLOGY DEVICES Diagnostic Devices § 892.1130 Nuclear whole body counter....

  20. 21 CFR 892.1130 - Nuclear whole body counter.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Nuclear whole body counter. 892.1130 Section 892.1130 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES RADIOLOGY DEVICES Diagnostic Devices § 892.1130 Nuclear whole body counter....

  1. 21 CFR 892.1130 - Nuclear whole body counter.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Nuclear whole body counter. 892.1130 Section 892.1130 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES RADIOLOGY DEVICES Diagnostic Devices § 892.1130 Nuclear whole body counter....

  2. Acute Lymphocytic Leukemia

    MedlinePlus

    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 ...

  3. Chronic Myeloid Leukemia

    MedlinePlus

    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. ...

  4. Acute Myeloid Leukemia

    MedlinePlus

    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 ...

  5. Chronic Lymphocytic Leukemia

    MedlinePlus

    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. Leukemia risk associated with chronic external exposure to ionizing radiation in a French cohort of nuclear workers.

    PubMed

    Metz-Flamant, C; Samson, E; Caër-Lorho, S; Acker, A; Laurier, D

    2012-11-01

    Leukemia is one of the earliest cancer effects observed after acute exposure to relatively high doses of ionizing radiation. Leukemia mortality after external exposure at low doses and low-dose rates has been investigated at the French Atomic Energy Commission (CEA) and Nuclear Fuel Company (AREVA NC) after an additional follow-up of 10 years. The cohort included radiation-monitored workers employed for at least one year during 1950-1994 at CEA or AREVA NC and followed during 1968-2004. Association between external exposure and leukemia mortality was estimated with excess relative risk (ERR) models and time-dependent modifying factors were investigated with time windows. The cohort included 36,769 workers, followed for an average of 28 years, among whom 73 leukemia deaths occurred. Among the workers with a positive recorded dose, the mean cumulative external dose was 21.7 mSv. Results under a 2-year lag assumption suggested that the risk of leukemia (except chronic lymphatic leukemia) increased significantly by 8% per 10 mSv. The magnitude of the association for myeloid leukemia was larger. The higher ERR/Sv for doses received 2-14 years earlier suggest that time since exposure modifies the effect. The ERR/Sv also appeared higher for doses received at exposure rates ≥20 mSv per year. These results are consistent with those found in other studies of nuclear workers. However, confidence intervals are still wide. Further analyses should be conducted in pooled cohorts of nuclear workers. PMID:23050984

  7. Relativistic effects in nuclear many-body systems

    SciTech Connect

    Coester, F.

    1985-01-01

    Different approaches to the formulation of relativistic many-body dynamics yield different perspectives of nature and the magnitude of ''relativistic effects''. The effects of Lorentz invariance appear to be relatively unimportant. Important dynamical features of spinorial many-body formalisms are effects of subnuclear degrees of freedom which are represented in the many-body forces of the covariant nuclear Hamiltonian. 24 refs.

  8. SUMO5, a Novel Poly-SUMO Isoform, Regulates PML Nuclear Bodies

    PubMed Central

    Liang, Ya-Chen; Lee, Chia-Chin; Yao, Ya-Li; Lai, Chien-Chen; Schmitz, M. Lienhard; Yang, Wen-Ming

    2016-01-01

    Promyelocytic leukemia nuclear bodies (PML-NBs) are PML-based nuclear structures that regulate various cellular processes. SUMOylation, the process of covalently conjugating small ubiquitin-like modifiers (SUMOs), is required for both the formation and the disruption of PML-NBs. However, detailed mechanisms of how SUMOylation regulates these processes remain unknown. Here we report that SUMO5, a novel SUMO variant, mediates the growth and disruption of PML-NBs. PolySUMO5 conjugation of PML at lysine 160 facilitates recruitment of PML-NB components, which enlarges PML-NBs. SUMO5 also increases polySUMO2/3 conjugation of PML, resulting in RNF4-mediated disruption of PML-NBs. The acute promyelocytic leukemia oncoprotein PML-RARα blocks SUMO5 conjugation of PML, causing cytoplasmic displacement of PML and disruption of PML-NBs. Our work not only identifies a new member of the SUMO family but also reveals the mechanistic basis of the PML-NB life cycle in human cells. PMID:27211601

  9. SUMO5, a Novel Poly-SUMO Isoform, Regulates PML Nuclear Bodies.

    PubMed

    Liang, Ya-Chen; Lee, Chia-Chin; Yao, Ya-Li; Lai, Chien-Chen; Schmitz, M Lienhard; Yang, Wen-Ming

    2016-01-01

    Promyelocytic leukemia nuclear bodies (PML-NBs) are PML-based nuclear structures that regulate various cellular processes. SUMOylation, the process of covalently conjugating small ubiquitin-like modifiers (SUMOs), is required for both the formation and the disruption of PML-NBs. However, detailed mechanisms of how SUMOylation regulates these processes remain unknown. Here we report that SUMO5, a novel SUMO variant, mediates the growth and disruption of PML-NBs. PolySUMO5 conjugation of PML at lysine 160 facilitates recruitment of PML-NB components, which enlarges PML-NBs. SUMO5 also increases polySUMO2/3 conjugation of PML, resulting in RNF4-mediated disruption of PML-NBs. The acute promyelocytic leukemia oncoprotein PML-RARα blocks SUMO5 conjugation of PML, causing cytoplasmic displacement of PML and disruption of PML-NBs. Our work not only identifies a new member of the SUMO family but also reveals the mechanistic basis of the PML-NB life cycle in human cells. PMID:27211601

  10. Haploidentical hematopoietic stem cell transplantation without total body irradiation for pediatric acute leukemia: a single-center experience

    PubMed Central

    Mu, Yanshun; Qin, Maoquan; Wang, Bin; Li, Sidan; Zhu, Guanghua; Zhou, Xuan; Yang, Jun; Wang, Kai; Lin, Wei; Zheng, Huyong

    2016-01-01

    Hematopoietic stem cell transplantation (HSCT) is a promising method for therapy of pediatric patients with acute leukemia. However, less availability of matched donors limited its wide application. Recently, haploidentical HSCT has become a great resource. Here, we have retrospectively reported our experience of 20 pediatric patients with acute leukemia who underwent haploidentical HSCT without total body irradiation (TBI) myeloablative regimen in our center from November 2007 to June 2014. All the patients attained successful HSCT engraftment in terms of myeloid and platelet recovery. Thirteen patients developed grade I–IV acute graft-versus-host disease (a-GVHD). The incidence of grade I–II a-GVHD, grade III–IV a-GVHD, and chronic GVHD (c-GVHD) was 45%, 20%, and 25%, respectively. The mean myeloid and platelet recovery time was 13.20±2.41 and 19.10±8.37 days. The median follow-up time was 43.95±29.26 months. During the follow-up, three patients died. The overall survival (OS) rate was 85%. The present study indicated that haploidentical HSCT without TBI myeloablative regimen significantly improved the OS rate of pediatric patients with acute leukemia. PMID:27217774

  11. Phosphorothioate Antisense Oligonucleotides Induce the Formation of Nuclear Bodies

    PubMed Central

    Lorenz, Peter; Baker, Brenda F.; Bennett, C. Frank; Spector, David L.

    1998-01-01

    Antisense oligonucleotides are powerful tools for the in vivo regulation of gene expression. We have characterized the intracellular distribution of fluorescently tagged phosphorothioate oligodeoxynucleotides (PS-ONs) at high resolution under conditions in which PS-ONs have the potential to display antisense activity. Under these conditions PS-ONs predominantly localized to the cell nucleus where they accumulated in 20–30 bright spherical foci designated phosphorothioate bodies (PS bodies), which were set against a diffuse nucleoplasmic population excluding nucleoli. PS bodies are nuclear structures that formed in cells after PS-ON delivery by transfection agents or microinjection but were observed irrespectively of antisense activity or sequence. Ultrastructurally, PS bodies corresponded to electron-dense structures of 150–300 nm diameter and resembled nuclear bodies that were found with lower frequency in cells lacking PS-ONs. The environment of a living cell was required for the de novo formation of PS bodies, which occurred within minutes after the introduction of PS-ONs. PS bodies were stable entities that underwent noticeable reorganization only during mitosis. Upon exit from mitosis, PS bodies were assembled de novo from diffuse PS-ON pools in the daughter nuclei. In situ fractionation demonstrated an association of PS-ONs with the nuclear matrix. Taken together, our data provide evidence for the formation of a nuclear body in cells after introduction of phosphorothioate oligodeoxynucleotides. PMID:9571236

  12. Histone Deacetylase 7 Promotes PML Sumoylation and Is Essential for PML Nuclear Body Formation▿ †

    PubMed Central

    Gao, Chengzhuo; Ho, Chun-Chen; Reineke, Erin; Lam, Minh; Cheng, Xiwen; Stanya, Kristopher J.; Liu, Yu; Chakraborty, Sharmistha; Shih, Hsiu-Ming; Kao, Hung-Ying

    2008-01-01

    Promyelocytic leukemia protein (PML) sumoylation has been proposed to control the formation of PML nuclear bodies (NBs) and is crucial for PML-dependent cellular processes, including apoptosis and transcriptional regulation. However, the regulatory mechanisms of PML sumoylation and its specific roles in the formation of PML NBs remain largely unknown. Here, we show that histone deacetylase 7 (HDAC7) knockdown reduces the size and the number of the PML NBs in human umbilical vein endothelial cells (HUVECs). HDAC7 coexpression stimulates PML sumoylation independent of its HDAC activity. Furthermore, HDAC7 associates with the E2 SUMO ligase, Ubc9, and stimulates PML sumoylation in vitro, suggesting that it possesses a SUMO E3 ligase-like activity to promote PML sumoylation. Importantly, HDAC7 knockdown inhibits tumor necrosis factor alpha-induced PML sumoylation and the formation of PML NBs in HUVECs. These results demonstrate a novel function of HDAC7 and provide a regulatory mechanism of PML sumoylation. PMID:18625722

  13. Three-body equations for nuclear reactions

    SciTech Connect

    Chao, S.H.

    1980-01-01

    The problem of calculating three-body differential cross sections for two-body interactions which are local in configuration space is considered. The integral equations of Faddeev and recent modifications are reviewed. The difficulties both in solving and interpreting the various equations are discussed. An alternative set of exact operator equations is proposed. This new set of operator equations involve the two-body potentials directly rather than the two-body t-matrices. The solutions represent quantities different from those of previous equations. The formal structure of the operator equations is similar to but different from the Faddeev equations. It is demonstrated that the equations contain no terms which correspond to disconnected diagrams. The transformation of the equations to the Faddeev equations is given. Integral equations are obtained using the momentum representation. Only Cauchy-type singularities occur in the Green's function, and the equations have unique solutions. No off-energy shell t-matrices are required. Transition amplitudes are obtained from the solutions by quadrature, so that effects which result from the nature of the final state can be separated from the three-body effects. The angular momentum reduction of Omnes is used to obtain two-dimensional coupled integral equations. A method of numerical solution is developed using a generalization of the approximate product integration method due to Young. Examples corresponding to the reactions /sup 16/O(d,p)/sup 17/O g.s and /sup 16/O(d,d)/sup 16/O in two dimensions and /sup 16/O(d,p)/sup 17/O* (0.87 MeV) in three dimensions for a deuteron enegy of 5 MeV are considered using Gaussian potentials. The convergence of the summation over angular momentum is examined and a comparison is made with experiment to obtain the spectroscopic factor for the 0.87 MeV state of /sup 17/O.

  14. Computational nuclear quantum many-body problem: The UNEDF project

    SciTech Connect

    Fann, George I

    2013-01-01

    The UNEDF project was a large-scale collaborative effort that applied high-performance computing to the nuclear quantum many-body problem. The primary focus of the project was on constructing, validating, and applying an optimized nuclear energy density functional, which entailed a wide range of pioneering developments in microscopic nuclear structure and reactions, algorithms, high-performance computing, and uncertainty quantification. UNEDF demonstrated that close associations among nuclear physicists, mathematicians, and computer scientists can lead to novel physics outcomes built on algorithmic innovations and computational developments. This review showcases a wide range of UNEDF science results to illustrate this interplay.

  15. Insights into the nuclear export of murine leukemia virus intron-containing RNA

    PubMed Central

    Pessel-Vivares, Lucie; Houzet, Laurent; Lainé, Sébastien; Mougel, Marylène

    2015-01-01

    The retroviral genome consists of an intron-containing transcript that has essential cytoplasmic functions in the infected cell. This viral transcript can escape splicing, circumvent the nuclear checkpoint mechanisms and be transported to the cytoplasm by hijacking the host machinery. Once in the cytoplasm, viral unspliced RNA acts as mRNA to be translated and as genomic RNA to be packaged into nascent viruses. The murine leukemia virus (MLV) is among the first retroviruses discovered and is classified as simple Retroviridae due to its minimal encoding capacity. The oncogenic and transduction abilities of MLV are extensively studied, whereas surprisingly the crucial step of its nuclear export has remained unsolved until 2014. Recent work has revealed the recruitment by MLV of the cellular NXF1/Tap-dependent pathway for export. Unconventionally, MLV uses of Tap to export both spliced and unspliced viral RNAs. Unlike other retroviruses, MLV does not harbor a unique RNA signal for export. Indeed, multiple sequences throughout the MLV genome appear to promote export of the unspliced MLV RNA. We review here the current understanding of the export mechanism and highlight the determinants that influence MLV export. As the molecular mechanism of MLV export is elucidated, we will gain insight into the contribution of the export pathway to the cytoplasmic fate of the viral RNA. PMID:26158194

  16. Fingertip and whole body exposure to nuclear medicine personnel

    SciTech Connect

    Lis, G.A.; Zu'bi, S.M.; Brahmavar, S.M.

    1981-06-01

    We calculate radiation exposure to the nuclear medicine technologist for all common sources of exposure. Special attention is given to exposure received by fingertips. We include typical exposure rates for patient injections, reagent preparations, generator handling and elution, patient positioning, and other phases of nuclear medicine. The cumulative exposure to fingertips and whole body is estimated. When every precaution is taken to minimize exposure in our laboratory, the unavoidable annual exposure to the fingertips is 11 R; to the whole body it is 1 R from all sources. When precautions are not taken, the annual exposure to the fingertips may exceed 170 R and the whole body dose may then approach 2 R. Our nuclear medicine laboratory averages about 1000 injections per technologist per year.

  17. The Nuclear Three-Body Continuum

    NASA Astrophysics Data System (ADS)

    Brune, Carl R.

    2001-04-01

    Experiments in the three-nucleon (3N) continuum provide important insights into the underlying nuclear forces, as theoretical calculations of 3N systems using realistic nucleon-nucleon (NN) and 3N interactions are now routinely possible. This talk will focus on experimental results at low energies, below ≈ 50 MeV. Measurements of p-d and n-d elastic scattering are generally in agreement with theoretical predictions, with the exception of large discrepancies found for the polarization observables Ay and iT_11. Studies of breakup reactions, such as n+darrow n+n+p, offer greater flexibility in the final state kinematics, providing additional sensitivity to quantities such as NN scattering lengths and perhaps to 3N forces. Some possibilities for future experiments will also be discussed.

  18. Targeting SMN to Cajal bodies and nuclear gems during neuritogenesis

    PubMed Central

    Navascues, Joaquin; Berciano, Maria T.; Tucker, Karen E.

    2006-01-01

    Neurite outgrowth is a central feature of neuronal differentiation. PC12 cells are a good model system for studying the peripheral nervous system and the outgrowth of neurites. In addition to the dramatic changes observed in the cytoplasm, neuronal differentiation is also accompanied by striking changes in nuclear morphology. The large and sustained increase in nuclear transcription during neuronal differentiation requires synthesis of a large number of factors involved in pre-mRNA processing. We show that the number and composition of the nuclear subdomains called Cajal bodies and gems changes during the course of N-ras-induced neuritogenesis in the PC12-derived cell line UR61. The Cajal bodies found in undifferentiated cells are largely devoid of the survival of motor neurons (SMN) protein product. As cells shift to a differentiated state, SMN is not only globally upregulated, but is progressively recruited to Cajal bodies. Additional SMN foci (also known as Gemini bodies, gems) can also be detected. Using dual-immunogold labeling electron microscopy and mouse embryonic fibroblasts lacking the coilin protein, we show that gems clearly represent a distinct category of nuclear body. PMID:15164213

  19. A case-control study of leukemia at a naval nuclear shipyard.

    PubMed

    Stern, F B; Waxweiler, R A; Beaumont, J J; Lee, S T; Rinsky, R A; Zumwalde, R D; Halperin, W E; Bierbaum, P J; Landrigan, P J; Murray, W E

    1986-06-01

    A matched case-control study was conducted of 53 leukemia deaths and of 212 controls within a previously studied cohort of 24,545 on-shore workers employed between January 1, 1952 and August 15, 1977 at the Portsmouth (New Hampshire) Naval Shipyard. The study sought to ascertain a priori whether there was an association between leukemia deaths and occupational exposure to either ionizing radiation or organic solvents. To obtain information on individual exposures, radiation dose histories and detailed work histories by job and shop were evaluated for each subject. No statistically significant associations were found either between ionizing radiation or presumed solvent exposure and myelogenous or lymphatic leukemia. However, when specific job categories and shops were examined without benefit of a priori hypotheses, two occupations, electrician and welder, were found to be associated with leukemia. For electricians, the Mantel-Haenszel odds ratio (ORMH) was significantly elevated for all leukemias (ORMH = 3.00, 95% confidence interval (CI) = 1.29-6.98), particularly for lymphatic leukemia (ORMH = 6.00, 95% CI = 1.47-24.45). For welders, the odds ratio was not significantly elevated for all leukemias (ORMH = 2.25, 95% CI = 0.92-5.53), but was significantly elevated for myeloid leukemia (ORMH = 3.83, 95% CI = 1.28-11.46). These findings persisted when potential confounders were adjusted by means of a conditional logistic regression model. PMID:3458360

  20. Nuclear Astrophysics from View Point of Few-Body Problems

    NASA Astrophysics Data System (ADS)

    Tumino, A.; Spitaleri, C.; Bertulani, C.; Mukhamedzhanov, A. M.

    2013-08-01

    Few-body systems provide very useful tools to solve different problems for nuclear astrophysics. This is the case of indirect techniques, developed to overcome some of the limits of direct measurements at astrophysical energies. Here the Coulomb dissociation, the asymptotic normalization coefficient and the Trojan Horse method are discussed.

  1. Murine acute leukemia cell line with megakaryocytic differentiation (MK-8057) induced by whole-body irradiation in C sup 3 H/He mice: Cytological properties and kinetics of its leukemic stem cells

    SciTech Connect

    Hirabayashi, Y.; Inoue, T.; Yoshida, K.; Sasaki, H.; Kubo, S.; Kanisawa, M.; Seki, M. )

    1991-01-01

    Five cases of murine leukemia with megakaryocytic differentiation were observed among the 417 cases of radiation-induced leukemias which developed in 30% of C{sup 3}H/HeMs mice exposed at 8 to 10 weeks to 0.5 to 5 gy total body irradiation. Cells from individual leukemic colonies in the spleen of the irradiated mice, and cells from colonies in methylcellulose (MC) culture in vitro, derived from one of these leukemias, MK-8057, were injected into mice; both types of cells caused the deaths of the recipient mice by inducing the same type of leukemia. MK-8057 can be maintained in Dexter-type liquid culture with a feeder layer of irradiated bone marrow cells. There was a linear reciprocal relationship between the increasing number of MK-8057 cells injected versus the survival of the recipient mice. A reciprocal relationship also was seen between an increasing number of leukemic stem cells, corresponding to the number of MK-8057 cells, and the survival of mice injected with MK-8057. Giant nuclear megakaryocytes developed during the course of colony growth in the spleen as they did in the MC culture. Such megakaryocytes were acetylcholinesterase positive, whereas leukemic cells in the peripheral blood showed no sign of platelet production nor of a positive reaction to acetylcholinesterase. Cells maintained in culture were entirely positive in platelet glycoprotein IIb/IIIa when anti-human antibody was used. The larger cells in a splenic cell suspension derived from a moribund mouse were separated and enriched by velocity sedimentation using centrifugal elutriation (CE), and then subjected to flow cytometry using propidium iodide staining. Cells with up to 32N-DNA content were detected. After separating MK-8057 by counter-flow CE, the larger cell fraction produced more leukemic colonies when injected into irradiated mice than did the small cell fraction.

  2. In situ SUMOylation analysis reveals a modulatory role of RanBP2 in the nuclear rim and PML bodies

    SciTech Connect

    Saitoh, Noriko . E-mail: hisa@gpo.kumamoto-u.ac.jp; Uchimura, Yasuhiro; Tachibana, Taro; Sugahara, Satoko; Saitoh, Hisato; Nakao, Mitsuyoshi . E-mail: mnakao@gpo.kumamoto-u.ac.jp

    2006-05-01

    SUMO modification plays a critical role in a number of cellular functions including nucleocytoplasmic transport, gene expression, cell cycle and formation of subnuclear structures such as promyelocytic leukemia (PML) bodies. In order to identify the sites where SUMOylation takes place in the cell, we developed an in situ SUMOylation assay using a semi-intact cell system and subsequently combined it with siRNA-based knockdown of nucleoporin RanBP2, also known as Nup358, which is one of the known SUMO E3 proteins. With the in situ SUMOylation assay, we found that both nuclear rim and PML bodies, besides mitotic apparatuses, are major targets for active SUMOylation. The ability to analyze possible SUMO conjugation sites would be a valuable tool to investigate where SUMO E3-like activities and/or SUMO substrates exist in the cell. Specific knockdown of RanBP2 completely abolished SUMOylation along the nuclear rim and dislocated RanGAP1 from the nuclear pore complexes. Interestingly, the loss of RanBP2 markedly reduced the number of PML bodies, in contrast to other, normal-appearing nuclear compartments including the nuclear lamina, nucleolus and chromatin, suggesting a novel link between RanBP2 and PML bodies. SUMOylation facilitated by RanBP2 at the nuclear rim may be a key step for the formation of a particular subnuclear organization. Our data imply that SUMO E3 proteins like RanBP2 facilitate spatio-temporal SUMOylation for certain nuclear structure and function.

  3. Effect of fractionated versus unfractionated total body irradiation on the growth of the BN acute myelocytic leukemia

    SciTech Connect

    Hagenbeek, A.; Martens, A.C.M.

    1981-08-01

    The efficacy of various total body irradiation (TBI) regimens prior to bone marrow transplantation was evaluated in a rat model for acute myelocytic leukemia (Dq = 85.1 cGy gamma ; N = 3.7). Using high dose rate gamma-irradiation (115 cGy/min), fractionated TBI with large total daily doses (400 to 600 cGy), either given as acute doses or as split doses at 8 hr intervals, was most effective. Split doses (2 fractions per day) offered no additional advantage. At the most, a 4 log leukemic cell kill was induced. No lethal toxicity was observed. Nine-hundred cGy flash TBI had a similar anti-tumor effect, but with this regimen almost half of the rats died from radiation-induced toxicity (lungs and gastro-intestinal tract). The results are explained in terms of differences between normal and leukemic cells as regards (a) repair of sublethal damage; and (b) repopulation. Low dose rate continuous gamma-irradiation (0.26 cGy/min) with total doses ranging from 900 to 2000 cGy was also quite effective. Maximally a 4 log cell kill was obtained. With 2000 cGy, 50% of the rats died from the gastro-intestinal tract-syndrome. In addition to the major role played by chemotherapy, TBI is mainly of importance in sterilizing the various sanctuaries in the body which contain leukemic cells anatomically resistant to most cytostatic agents.

  4. The SUMO protease SENP6 is a direct regulator of PML nuclear bodies

    PubMed Central

    Hattersley, Neil; Shen, Linnan; Jaffray, Ellis G.; Hay, Ronald T.

    2011-01-01

    Promyelocytic leukemia protein (PML) is the core component of PML-nuclear bodies (PML NBs). The small ubiquitin-like modifier (SUMO) system (and, in particular, SUMOylation of PML) is a critical component in the formation and regulation of PML NBs. SUMO protease SENP6 has been shown previously to be specific for SUMO-2/3–modified substrates and shows preference for SUMO polymers. Here, we further investigate the substrate specificity of SENP6 and show that it is also capable of cleaving mixed chains of SUMO-1 and SUMO-2/3. Depletion of SENP6 results in accumulation of endogenous SUMO-2/3 and SUMO-1 conjugates, and immunofluorescence analysis shows accumulation of SUMO and PML in an increased number of PML NBs. Although SENP6 depletion drastically increases the size of PML NBs, the organizational structure of the body is not affected. Mutation of the catalytic cysteine of SENP6 results in its accumulation in PML NBs, and biochemical analysis indicates that SUMO-modified PML is a substrate of SENP6. PMID:21148299

  5. Recent Developments in the Nuclear Many-Body Problem

    NASA Astrophysics Data System (ADS)

    Furnstahl, R. J.

    2002-12-01

    The study of quantum chromodynamics (QCD) over the past quarter century has had relatively little impact on the traditional approach to the low-energy nuclear many-body problem. Recent developments are changing this situation. New experimental capabilities and theoretical approaches are opening windows into the richness of many-body phenomena in QCD. A common theme is the use of effective field theory (EFT) methods, which exploit the separation of scales in physical systems. At low energies, effective field theory can explain how existing phenomenology emerges from QCD and how to refine it systematically. More generally, the application of EFT methods to many-body problems promises insight into the analytic structure of observables, the identification of new expansion parameters, and a consistent organisation of many-body corrections, with reliable error estimates.

  6. Leukemia -- Eosinophilic

    MedlinePlus

    ... Leukemia - Eosinophilic: Overview Request Permissions Print to PDF Leukemia - Eosinophilic: Overview Approved by the Cancer.Net Editorial ... Platelets that help the blood to clot About leukemia Types of leukemia are named after the specific ...

  7. Leukemia - B-Cell Prolymphocytic Leukemia and Hairy Cell Leukemia

    MedlinePlus

    ... Leukemia: Introduction Request Permissions Print to PDF Leukemia - B-cell Prolymphocytic Leukemia and Hairy Cell Leukemia: Introduction ... Research and Advocacy Survivorship Blog About Us Leukemia - B-cell Prolymphocytic Leukemia and Hairy Cell Leukemia Guide ...

  8. Aberrant nuclear factor-kappa B activity in acute myeloid Leukemia: from molecular pathogenesis to therapeutic target

    PubMed Central

    Zhou, Jianbiao; Ching, Ying Qing; Chng, Wee-Joo

    2015-01-01

    The overall survival of patients with acute myeloid leukemia (AML) has not been improved significantly over the last decade. Molecularly targeted agents hold promise to change the therapeutic landscape in AML. The nuclear factor kappa B (NF-κB) controls a plethora of biological process through switching on and off its long list of target genes. In AML, constitutive NF-κB has been detected in 40% of cases and its aberrant activity enable leukemia cells to evade apoptosis and stimulate proliferation. These facts suggest that NF-κB signaling pathway plays a fundamental role in the development of AML and it represents an attractive target for the intervention of AML. This review summarizes our current knowledge of NF-κB signaling transduction including canonical and non-canonical NF-κB pathways. Then we specifically highlight what factors contribute to the aberrant activation of NF-κB activity in AML, followed by an overview of 8 important clinical trials of the first FDA approved proteasome inhibitor, Bortezomib (Velcade®), which is a NF-κB inhibitor too, in combination with other therapeutic agents in patients with AML. Finally, this review discusses the future directions of NF-κB inhibitor in treatment of AML, especially in targeting leukemia stem cells (LSCs). PMID:25823927

  9. Aberrant nuclear factor-kappa B activity in acute myeloid leukemia: from molecular pathogenesis to therapeutic target.

    PubMed

    Zhou, Jianbiao; Ching, Ying Qing; Chng, Wee-Joo

    2015-03-20

    The overall survival of patients with acute myeloid leukemia (AML) has not been improved significantly over the last decade. Molecularly targeted agents hold promise to change the therapeutic landscape in AML. The nuclear factor kappa B (NF-κB) controls a plethora of biological process through switching on and off its long list of target genes. In AML, constitutive NF-κB has been detected in 40% of cases and its aberrant activity enable leukemia cells to evade apoptosis and stimulate proliferation. These facts suggest that NF-κB signaling pathway plays a fundamental role in the development of AML and it represents an attractive target for the intervention of AML. This review summarizes our current knowledge of NF-κB signaling transduction including canonical and non-canonical NF-κB pathways. Then we specifically highlight what factors contribute to the aberrant activation of NF-κB activity in AML, followed by an overview of 8 important clinical trials of the first FDA approved proteasome inhibitor, Bortezomib (Velcade), which is a NF-κB inhibitor too, in combination with other therapeutic agents in patients with AML. Finally, this review discusses the future directions of NF-κB inhibitor in treatment of AML, especially in targeting leukemia stem cells (LSCs). PMID:25823927

  10. Relationship between leukemia incidence and residing and/or working near the Pilgrim 1 nuclear power plant in Plymouth, Massachusetts

    SciTech Connect

    Morris, M.S.

    1992-01-01

    To determine whether a strong association between leukemia incidence between 1978 and 1986 and potential for exposure to radiation emitted from the Pilgrim 1 nuclear power plant in Plymouth, Massachusetts was a spurious finding resulting from either (1) failure to account for temporal variation in the level of radioactivity released from the plant or (2) inattention to certain potentially confounding factors, additional age/sex-matched case-control analyses controlled for the effects of socioeconomic status (SES), work history, and cigarette smoking were performed with data collected in the Southeastern Massachusetts Health Investigation -- a study of leukemia among residents aged 13 and older of 22 southeastern Massachusetts towns. None of the additional analyses, including incorporation of emissions data into the exposure-assessment scheme and crude attempts to control for (1) medical-radiation exposure, (2) potential for exposure to pesticides sprayed on cranberry bogs, or (3) workplace exposure to radiation, chemical solvents, dust, or fumes, altered the finding of a statistically significant dose-response relationship between leukemia incidence and potential for exposure to radioactive emissions. The trend in the association over time was not entirely consistent, however, with the hypothesis that unusually large amounts of radioactivity reportedly released from the plant during the mid-1970s were responsible for the observed effects. Recommendations were made for further study of the Plymouth-area population for studies of this problem elsewhere.

  11. RNA transcription modulates phase transition-driven nuclear body assembly

    PubMed Central

    Berry, Joel; Weber, Stephanie C.; Vaidya, Nilesh; Haataja, Mikko; Brangwynne, Clifford P.

    2015-01-01

    Nuclear bodies are RNA and protein-rich, membraneless organelles that play important roles in gene regulation. The largest and most well-known nuclear body is the nucleolus, an organelle whose primary function in ribosome biogenesis makes it key for cell growth and size homeostasis. The nucleolus and other nuclear bodies behave like liquid-phase droplets and appear to condense from the nucleoplasm by concentration-dependent phase separation. However, nucleoli actively consume chemical energy, and it is unclear how such nonequilibrium activity might impact classical liquid–liquid phase separation. Here, we combine in vivo and in vitro experiments with theory and simulation to characterize the assembly and disassembly dynamics of nucleoli in early Caenorhabditis elegans embryos. In addition to classical nucleoli that assemble at the transcriptionally active nucleolar organizing regions, we observe dozens of “extranucleolar droplets” (ENDs) that condense in the nucleoplasm in a transcription-independent manner. We show that growth of nucleoli and ENDs is consistent with a first-order phase transition in which late-stage coarsening dynamics are mediated by Brownian coalescence and, to a lesser degree, Ostwald ripening. By manipulating C. elegans cell size, we change nucleolar component concentration and confirm several key model predictions. Our results show that rRNA transcription and other nonequilibrium biological activity can modulate the effective thermodynamic parameters governing nucleolar and END assembly, but do not appear to fundamentally alter the passive phase separation mechanism. PMID:26351690

  12. RNA transcription modulates phase transition-driven nuclear body assembly.

    PubMed

    Berry, Joel; Weber, Stephanie C; Vaidya, Nilesh; Haataja, Mikko; Brangwynne, Clifford P

    2015-09-22

    Nuclear bodies are RNA and protein-rich, membraneless organelles that play important roles in gene regulation. The largest and most well-known nuclear body is the nucleolus, an organelle whose primary function in ribosome biogenesis makes it key for cell growth and size homeostasis. The nucleolus and other nuclear bodies behave like liquid-phase droplets and appear to condense from the nucleoplasm by concentration-dependent phase separation. However, nucleoli actively consume chemical energy, and it is unclear how such nonequilibrium activity might impact classical liquid-liquid phase separation. Here, we combine in vivo and in vitro experiments with theory and simulation to characterize the assembly and disassembly dynamics of nucleoli in early Caenorhabditis elegans embryos. In addition to classical nucleoli that assemble at the transcriptionally active nucleolar organizing regions, we observe dozens of "extranucleolar droplets" (ENDs) that condense in the nucleoplasm in a transcription-independent manner. We show that growth of nucleoli and ENDs is consistent with a first-order phase transition in which late-stage coarsening dynamics are mediated by Brownian coalescence and, to a lesser degree, Ostwald ripening. By manipulating C. elegans cell size, we change nucleolar component concentration and confirm several key model predictions. Our results show that rRNA transcription and other nonequilibrium biological activity can modulate the effective thermodynamic parameters governing nucleolar and END assembly, but do not appear to fundamentally alter the passive phase separation mechanism. PMID:26351690

  13. Decitabine and Total-Body Irradiation Followed By Donor Bone Marrow Transplant and Cyclophosphamide in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

    ClinicalTrials.gov

    2016-07-08

    Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome; 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); de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia

  14. Calorie restriction reduces the incidence of myeloid leukemia induced by a single whole-body radiation in C3H/He mice.

    PubMed

    Yoshida, K; Inoue, T; Nojima, K; Hirabayashi, Y; Sado, T

    1997-03-18

    Dietary restriction, especially caloric restriction, is a major modifier in experimental carcinogenesis and is known to decrease significantly the incidence of neoplasms. Gross and Dreyfuss [Gross, L. & Dreyfuss, Y. (1984) Proc. Natl. Acad. Sci. USA 81, 7596-7598; Gross, L. & Dreyfuss, Y. (1986) Proc. Natl. Acad. Sci. USA 83, 7928-7931] reported that a 36% restriction in caloric intake dramatically decreased the radiation-induced solid tumors and/or leukemias. Their protocol predominantly produced lymphatic neoplasms. It is of interest to observe the effect of caloric restriction on radiation-induced myeloid leukemia, because the disease was observed to have been increased in the survivors of the atomic bombs in Hiroshima and Nagasaki. The spontaneous incidence of myeloid leukemia in C3H/He male mice is 1%, and the incidence increased to 23.3% when 3 Gy of whole-body x-ray irradiation was given. However, the incidence of myeloid leukemia was found to be significantly decreased by caloric restriction; it was reduced to 7.9% and 10.7% when restriction was started before (6 weeks old) and after (10 weeks old) irradiation, respectively. In addition, the onset of the myeloid leukemia in both restricted groups was prolonged to a greater extent as compared with the control diet group. Caloric restriction demonstrated a significant prolongation of the life span in the groups on a restricted diet after having been exposed to irradiation, either before or after dietary restriction, in comparison with mice that were only irradiated. PMID:9122244

  15. Oxidative stress-induced assembly of PML nuclear bodies controls sumoylation of partner proteins.

    PubMed

    Sahin, Umut; Ferhi, Omar; Jeanne, Marion; Benhenda, Shirine; Berthier, Caroline; Jollivet, Florence; Niwa-Kawakita, Michiko; Faklaris, Orestis; Setterblad, Niclas; de Thé, Hugues; Lallemand-Breitenbach, Valérie

    2014-03-17

    The promyelocytic leukemia (PML) protein organizes PML nuclear bodies (NBs), which are stress-responsive domains where many partner proteins accumulate. Here, we clarify the basis for NB formation and identify stress-induced partner sumoylation as the primary NB function. NB nucleation does not rely primarily on intermolecular interactions between the PML SUMO-interacting motif (SIM) and SUMO, but instead results from oxidation-mediated PML multimerization. Oxidized PML spherical meshes recruit UBC9, which enhances PML sumoylation, allow partner recruitment through SIM interactions, and ultimately enhance partner sumoylation. Intermolecular SUMO-SIM interactions then enforce partner sequestration within the NB inner core. Accordingly, oxidative stress enhances NB formation and global sumoylation in vivo. Some NB-associated sumoylated partners also become polyubiquitinated by RNF4, precipitating their proteasomal degradation. As several partners are protein-modifying enzymes, NBs could act as sensors that facilitate and confer oxidative stress sensitivity not only to sumoylation but also to other post-translational modifications, thereby explaining alterations of stress response upon PML or NB loss. PMID:24637324

  16. Myeloid Cell Nuclear Differentiation Antigen (MNDA) Expression Distinguishes Extramedullary Presentations of Myeloid Leukemia From Blastic Plasmacytoid Dendritic Cell Neoplasm.

    PubMed

    Johnson, Ryan C; Kim, Jinah; Natkunam, Yasodha; Sundram, Uma; Freud, Aharon G; Gammon, Bryan; Cascio, Michael J

    2016-04-01

    Myeloid neoplasms constitute one of the most common malignancies in adults. In most cases these proliferations initially manifest in the blood and marrow; however, extramedullary involvement may precede blood or marrow involvement in a subset of cases, making a definitive diagnosis challenging by morphologic and immunohistochemical assessment alone. Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare, aggressive entity that frequently presents in extramedullary sites and can show morphologic and immunophenotypic overlap with myeloid neoplasms. Given that BPDCN and myeloid neoplasms may both initially present in extramedullary sites and that novel targeted therapies may be developed that exploit the unique molecular signature of BPDCN, new immunophenotypic markers that can reliably separate myeloid neoplasms from BPDCN are desirable. We evaluated the utility of myeloid cell nuclear differentiation antigen (MNDA) expression in a series of extramedullary myeloid leukemias (EMLs) and BPDCN. Forty biopsies containing EML and 19 biopsies containing BPDCN were studied by MNDA immunohistochemistry. The majority of myeloid neoplasms showed nuclear expression of MNDA (65%). In contrast, all cases of BPDCN lacked MNDA expression. These findings show that MNDA is expressed in the majority of EMLs and support the inclusion of MNDA immunohistochemistry in the diagnostic evaluation of blastic hematopoietic infiltrates, particularly when the differential diagnosis is between myeloid leukemia and BPDCN. PMID:26796502

  17. Applying twisted boundary conditions for few-body nuclear systems

    NASA Astrophysics Data System (ADS)

    Körber, Christopher; Luu, Thomas

    2016-05-01

    We describe and implement twisted boundary conditions for the deuteron and triton systems within finite volumes using the nuclear lattice EFT formalism. We investigate the finite-volume dependence of these systems with different twist angles. We demonstrate how various finite-volume information can be used to improve calculations of binding energies in such a framework. Our results suggests that with appropriate twisting of boundaries, infinite-volume binding energies can be reliably extracted from calculations using modest volume sizes with cubic length L ≈8 -14 fm. Of particular importance is our derivation and numerical verification of three-body analogs of "i-periodic" twist angles that eliminate the leading-order finite-volume effects to the three-body binding energy.

  18. Iodine I 131 Monoclonal Antibody BC8, Fludarabine Phosphate, Cyclophosphamide, Total-Body Irradiation and Donor Bone Marrow Transplant in Treating Patients With Advanced Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, or High-Risk Myelodysplastic Syndrome

    ClinicalTrials.gov

    2016-07-18

    Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Myeloid Leukemia in Remission; Chronic Myelomonocytic Leukemia; Previously Treated Myelodysplastic Syndrome; Refractory Anemia With Excess Blasts; Refractory Anemia With Ring Sideroblasts; Refractory Cytopenia With Multilineage Dysplasia; Refractory Cytopenia With Multilineage Dysplasia and Ring Sideroblasts

  19. Comparison of total body irradiation vs chlorambucil and prednisone for remission induction of active chronic lymphocytic leukemia: an ECOG study. Part I: total body irradiation-response

    SciTech Connect

    Rubin, P.I.; Bennett, J.M.; Begg, C.; Bozdech, M.J.; Silber, R.

    1981-12-01

    Twenty-six evaluable patients were entered into two fractionated total body irradiation (TBI) programs; 11 patients received a course of 150 rad TBI (x 3 if tolerated) and 15 patients received a lower dose course of 50 rad (x 3 if tolerated). Complete remissions (CR) were not produced by either course; however, the higher dose course (Plan I) yielded a partial response (PR) rate of 73%, while the lower dose course yielded a PR of 47%. Although fraction size seemed trivial in both TBI plans, an unexpected high degree of hematologic toxicity was encountered, and was parallel to the response rates: in Plan I 73% of patients experienced severe to life-threatening depression of platelets or granulocytes, whereas in Plan II this rate was 47%. This was of short duration with rapid return of blood counts to normal levels. One death can be attributed to TBI. The chemotherapy arm of the study demonstrated superiority in terms of complete responses. Twenty-three percent of patients treated by cholrambucil and prednisone attained CR, in contrast to 0% of TBI patients. PR for chemotherapy was similar to that obtained with TBI. Chemotherapy also proved superior in terms of overall response rate, number of patients in remission, and in the median duration of response, but not in the median duration of survival. Fractional TBI techniques for active chronic lymphocytic leukemia (CLL) should be interrupted when the platelet count dips below 100,000 and the granulocyte count is lower than 2,000. Future studies should combine TBI radiation therapy and chemotherapy.

  20. PML nuclear bodies: regulation, function and therapeutic perspectives.

    PubMed

    Sahin, Umut; Lallemand-Breitenbach, Valérie; de Thé, Hugues

    2014-11-01

    PML nuclear bodies (NBs) were first described by electron microscopy and rediscovered through their treatment-reversible disruption in a rare leukaemia. They recruit multiple partner proteins and now emerge as interferon- and oxidative stress-responsive sumoylation factories. NBs mediate interferon-induced viral restriction, enhance proteolysis, finely tune metabolism and enforce stress-induced senescence. Apart from being markers of cellular stress, PML NBs could be harnessed pharmacologically in a number of conditions, including cancer, viral infection or neurodegenerative diseases. PMID:25138686

  1. Leukemia in the proximity of a German boiling-water nuclear reactor: evidence of population exposure by chromosome studies and environmental radioactivity.

    PubMed

    Schmitz-Feuerhake, I; Dannheim, B; Heimers, A; Oberheitmann, B; Schröder, H; Ziggel, H

    1997-12-01

    Exceptional elevation of children's leukemia appearing 5 years after the 1983 startup of the Krümmel nuclear power plant, accompanied by a significant increase of adult leukemia cases, led to investigations of radiation exposures of the population living near the plant. The rate of dicentric chromosomes in peripheral lymphocytes of seven parents of children with leukemia and in 14 other inhabitants near the plant was significantly elevated and indicated ongoing exposures over the years of its operation. These findings led to the hypothesis that chronic reactor leakages had occurred. This assumption is support by identification of artificial radioactivity in air, rainwater, soil and vegetation by the environmental monitoring program at the nuclear power plant. Calculations of the corresponding source terms show that emissions must have been well above authorized annual limits. Bone marrow doses supposedly result primarily through incorporation of bone-seeking beta- and alpha-emitters. PMID:9467072

  2. Feasibility of total body irradiation in chronic lymphocytic leukemia and low-grade non-Hodgkin's lymphomas.

    PubMed

    Roncadin, M; Arcicasa, M; Bortolus, R; Trovó, M G; Carbone, A; Tirelli, U; De Paoli, A; Franchin, G; Grigoletto, E

    1991-01-01

    Combined total body irradiation (TBI) and Prednimustine were prospectively evaluated in 30 patients affected either with chronic lymphocytic leukemia (CLL) or with low-grade non-Hodgkin's lymphoma (NHL) eleven patients were previously treated. Between January 1984 and May 1987, 20 evaluable patients with CLL, median age 66 years (range 43-82), classified according to Rai (4 in stage I, 10 in stage II, 4 in stage III, 2 in stage IV) and 10 evaluable patients with NHL low-grade malignancy according to the Working Formulation, Stages III and IV, median age 54 years (range 32-71) were treated using a 6 MeV Linear Accelerator, applying two opposite alternating fields including total body, with a fraction of 15 cGy, 2 fractions weekly (3-day interval) for a total dose of 150 cGy given over 5 weeks. Prednimustine (100 mg/m2, orally, for 5 consecutive days, every 3-4 weeks, for 6-9 courses) was administered 2 months after TBI treatment, as consolidation therapy. By May 1989, a total of 85% hematological responses (defined as normalization of the differential white cell count, of the total blood cell count and of bone marrow infiltration) were obtained after combined treatment in CLL patients; moreover 3 CR (according to the WHO criteria), 75% with splenomegaly reduction and 40% with lymphadenopathy reduction were seen. Ninety percent objective responses (5 CR and 4 PR) were observed in the NHL patients, with 50% having splenomegaly reduction and 67% lymphadenopathy reduction. The median response time in the two groups was, respectively, 14 and 23 months. The overall toxicity (WHO grades 1,2,3,4) after combined treatment was 65% and 70% in the two patient groups. WHO grade III toxicity, completely reversible, was verified in only 16.6% of the cases; all cases, except one, were previously treated. Additionally, 1 toxic death (grade IV thrombocytopenia and leukopenia) was observed in a heavily pretreated patient affected with CLL after TBI alone. Prednimustine regimen was

  3. An Adenovirus DNA Replication Factor, but Not Incoming Genome Complexes, Targets PML Nuclear Bodies

    PubMed Central

    Komatsu, Tetsuro; Nagata, Kyosuke

    2015-01-01

    ABSTRACT Promyelocytic leukemia protein nuclear bodies (PML-NBs) are subnuclear domains implicated in cellular antiviral responses. Despite the antiviral activity, several nuclear replicating DNA viruses use the domains as deposition sites for the incoming viral genomes and/or as sites for viral DNA replication, suggesting that PML-NBs are functionally relevant during early viral infection to establish productive replication. Although PML-NBs and their components have also been implicated in the adenoviral life cycle, it remains unclear whether incoming adenoviral genome complexes target PML-NBs. Here we show using immunofluorescence and live-cell imaging analyses that incoming adenovirus genome complexes neither localize at nor recruit components of PML-NBs during early phases of infection. We further show that the viral DNA binding protein (DBP), an early expressed viral gene and essential DNA replication factor, independently targets PML-NBs. We show that DBP oligomerization is required to selectively recruit the PML-NB components Sp100 and USP7. Depletion experiments suggest that the absence of one PML-NB component might not affect the recruitment of other components toward DBP oligomers. Thus, our findings suggest a model in which an adenoviral DNA replication factor, but not incoming viral genome complexes, targets and modulates PML-NBs to support a conducive state for viral DNA replication and argue against a generalized concept that PML-NBs target incoming viral genomes. IMPORTANCE The immediate fate upon nuclear delivery of genomes of incoming DNA viruses is largely unclear. Early reports suggested that incoming genomes of herpesviruses are targeted and repressed by PML-NBs immediately upon nuclear import. Genome localization and/or viral DNA replication has also been observed at PML-NBs for other DNA viruses. Thus, it was suggested that PML-NBs may immediately sense and target nuclear viral genomes and hence serve as sites for deposition of incoming viral

  4. Lipid droplets go nuclear.

    PubMed

    Farese, Robert V; Walther, Tobias C

    2016-01-01

    Lipid droplets (LDs) are sometimes found in the nucleus of some cells. In this issue, Ohsaki et al. (2016. J. Cell Biol. http://dx.doi.org/10.1083/jcb.201507122) show that the nuclear membrane, promyelocytic leukemia bodies, and the protein PML-II play a role in nuclear LD formation, suggesting functional relationships between these structures. PMID:26728852

  5. Treosulfan, Fludarabine Phosphate, and Total Body Irradiation Before Donor Stem Cell Transplant in Treating Patients With Myelodysplastic Syndrome or Acute Myeloid Leukemia

    ClinicalTrials.gov

    2016-06-20

    Acute Myeloid Leukemia in Remission; Chronic Myelomonocytic Leukemia; Minimal Residual Disease; Myelodysplastic Syndrome; Myelodysplastic/Myeloproliferative Neoplasm; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable

  6. Decreased nuclear matrix DNA topoisomerase II in human leukemia cells resistant to VM-26 and m-AMSA

    SciTech Connect

    Fernandes, D.J. ); Danks, M.K.; Beck, W.T. )

    1990-05-01

    CEM leukemia cells selected for resistance to VM-26 (CEM/VM-1) are cross-resistant to various other DNA topoisomerase II inhibitors but not to Vinca alkaloids. Since DNA topoisomerase II is a major protein of the nuclear matrix, the authors asked if alterations in nuclear matrix topoisomerase II might be important in this form of multidrug resistance. Pretreatment of drug-sensitive CEM cells for 2 h with either 5 {mu}M VM-26 or 3 {mu}M m-AMSA reduced the specific activity of newly replicated DNA on the nuclear matrix by 75 and 50%, respectively, relative to that of the bulk DNA. The decatenating and unknotting activities of DNA topoisomerase II were 6- and 7-fold lower, respectively, in the nuclear matrix preparations from the CEM/VM-1 cells compared to parental CEM cells. Western blot analysis revealed that the amount of immunoreactive topoisomerase II in the nuclear matrices of the CEM/VM-1 cells decreased 3.2-fold relative to that in CEM cells. Increasing the NaCl concentration used in the matrix isolation procedure from 0.2 to 1.8 M resulted in a progressive decrease in the specific activity of topoisomerase II in matrices of CEM/VM-1 but not CEM cells, which suggested that the association of the enzyme with the matrix is altered in the resistant cells. These data support the hypothesis that resistance to VM-26 and m-AMSA is directly related to the decreased activity of nuclear matrix topoisomerase II. In CEM/VM-1 cells the interaction of either VM-26 or m-AMSA with nuclear matrix topoisomerase II is specifically diminished.

  7. Visualized kinematics code for two-body nuclear reactions

    NASA Astrophysics Data System (ADS)

    Lee, E. J.; Chae, K. Y.

    2016-05-01

    The one or few nucleon transfer reaction has been a great tool for investigating the single-particle properties of a nucleus. Both stable and exotic beams are utilized to study transfer reactions in normal and inverse kinematics, respectively. Because many energy levels of the heavy recoil from the two-body nuclear reaction can be populated by using a single beam energy, identifying each populated state, which is not often trivial owing to high level-density of the nucleus, is essential. For identification of the energy levels, a visualized kinematics code called VISKIN has been developed by utilizing the Java programming language. The development procedure, usage, and application of the VISKIN is reported.

  8. Association between body mass index at diagnosis and pediatric leukemia mortality and relapse: a systematic review and meta-analysis.

    PubMed

    Amankwah, Ernest K; Saenz, Ashleigh M; Hale, Gregory A; Brown, Patrick A

    2016-05-01

    Obesity is a risk factor for mortality and relapse of certain cancers. However, existing evidence for pediatric leukemia is inconsistent. The aim of this systematic review and meta-analysis was to evaluate the association between obesity at diagnosis and pediatric acute leukemia mortality and relapse. This study systematically searched MEDLINE and EMBASE from inception to February 5, 2015. Random-effect models were used to generate pooled estimates of study-specific hazard ratios (HR) and 95% confidence intervals (CI). Eleven studies were included. An increased risk of mortality with a high BMI at diagnosis was observed (overall survival: HR = 1.30, 95% CI = 1.16-1.46 and event-free survival: HR = 1.46, 95% CI = 1.29-1.64). Only two studies reported HR for relapse; one reported a reduced risk, while the other reported an increased risk. A high BMI at diagnosis is associated with poor overall and event-free survival among pediatric acute leukemia patients. Targeted therapeutic approaches for obese pediatric leukemia patients may potentially improve survival outcomes. PMID:26453440

  9. The use of potential of bone marrow allograft and whole-body irradiation in the treatment of leukemia

    SciTech Connect

    Thomas, E.D.

    1982-10-15

    A brief history of the clinical application of marrow transplantation based on knowledge gained from ten years work utilizing the dog as an animal model is summarized. The techniques for marrow transplantation, donor selection, and conditioning of the recipient are described. Thirteen of the first 110 endstage leukemic patients who received allogeneic grafts and six of 16 patients who received syngeneic grafts are alive 6-11 years after grafting. Encouraged by the apparent ''cure'' of leukemia in these poor-risk patients, the Seattle transplant group in 1976 decided to give patients transplants earlier in the course of their disease. Patients with acute lymphoblastic leukemia in second or subsequent relapse were considered to have a poor prognosis. Twenty-two such patients received transplants, with seven surviving in remission 3-5 years later. Nineteen patients with acute nonlymphoblastic leukemia received transplants in first remission and 11 are living in remission 3.5-5.5 years after grafting. The median survival will not be less than 42 months. The problems associated with graft-versus-host disease and recurrence of leukemia and methods aimed at eliminating these problems are discussed.

  10. Similar Survival for Patients Undergoing Reduced-Intensity Total Body Irradiation (TBI) Versus Myeloablative TBI as Conditioning for Allogeneic Transplant in Acute Leukemia

    SciTech Connect

    Mikell, John L.; Waller, Edmund K.; Switchenko, Jeffrey M.; Rangaraju, Sravanti; Ali, Zahir; Graiser, Michael; Hall, William A.; Langston, Amelia A.; Esiashvili, Natia; Khoury, H. Jean; Khan, Mohammad K.

    2014-06-01

    Purpose: Hematopoietic stem cell transplantation (HSCT) is the mainstay of treatment for adults with acute leukemia. Total body irradiation (TBI) remains an important part of the conditioning regimen for HCST. For those patients unable to tolerate myeloablative TBI (mTBI), reduced intensity TBI (riTBI) is commonly used. In this study we compared outcomes of patients undergoing mTBI with those of patients undergoing riTBI in our institution. Methods and Materials: We performed a retrospective review of all patients with acute leukemia who underwent TBI-based conditioning, using a prospectively acquired database of HSCT patients treated at our institution. Patient data including details of the transplantation procedure, disease status, Karnofsky performance status (KPS), response rates, toxicity, survival time, and time to progression were extracted. Patient outcomes for various radiation therapy regimens were examined. Descriptive statistical analysis was performed. Results: Between June 1985 and July 2012, 226 patients with acute leukemia underwent TBI as conditioning for HSCT. Of those patients, 180 had full radiation therapy data available; 83 had acute lymphoblastic leukemia and 94 had acute myelogenous leukemia; 45 patients received riTBI, and 135 received mTBI. Median overall survival (OS) was 13.7 months. Median relapse-free survival (RFS) for all patients was 10.2 months. Controlling for age, sex, KPS, disease status, and diagnosis, there were no significant differences in OS or RFS between patients who underwent riTBI and those who underwent mTBI (P=.402, P=.499, respectively). Median length of hospital stay was shorter for patients who received riTBI than for those who received mTBI (16 days vs 23 days, respectively; P<.001), and intensive care unit admissions were less frequent following riTBI than mTBI (2.22% vs 12.69%, respectively, P=.043). Nonrelapse survival rates were also similar (P=.186). Conclusions: No differences in OS or RFS were seen between

  11. The leukemia associated nuclear corepressor ETO homologue genes MTG16 and MTGR1 are regulated differently in hematopoietic cells

    PubMed Central

    2012-01-01

    Background MTG16, MTGR1 and ETO are nuclear transcriptional corepressors of the human ETO protein family. MTG16 is implicated in hematopoietic development and in controlling erythropoiesis/megakaryopoiesis. Furthermore, ETO homologue genes are 3'participants in leukemia fusions generated by chromosomal translocations responsible of hematopoietic dysregulation. We tried to identify structural and functional promoter elements of MTG16 and MTGR1 genes in order to find associations between their regulation and hematopoiesis. Results 5' deletion examinations and luciferase reporter gene studies indicated that a 492 bp sequence upstream of the transcription start site is essential for transcriptional activity by the MTG16 promoter. The TATA- and CCAAT-less promoter with a GC box close to the start site showed strong reporter activity when examined in erythroid/megakaryocytic cells. Mutation of an evolutionary conserved GATA -301 consensus binding site repressed promoter function. Furthermore, results from in vitro antibody-enhanced electrophoretic mobility shift assay and in vivo chromatin immunoprecipitation indicated binding of GATA-1 to the GATA -301 site. A role of GATA-1 was also supported by transfection of small interfering RNA, which diminished MTG16 expression. Furthermore, expression of the transcription factor HERP2, which represses GATA-1, produced strong inhibition of the MTG16 promoter reporter consistent with a role of GATA-1 in transcriptional activation. The TATA-less and CCAAT-less MTGR1 promoter retained most of the transcriptional activity within a -308 to -207 bp region with a GC-box-rich sequence containing multiple SP1 binding sites reminiscent of a housekeeping gene with constitutive expression. However, mutations of individual SP1 binding sites did not repress promoter function; multiple active SP1 binding sites may be required to safeguard constitutive MTGR1 transcriptional activity. The observed repression of MTG16/MTGR1 promoters by the

  12. Projection techniques to approach the nuclear many-body problem

    NASA Astrophysics Data System (ADS)

    Sun, Yang

    2016-04-01

    Our understanding of angular-momentum-projection goes beyond quantum-number restoration for symmetry-violated states. The angular-momentum-projection method can be viewed as an efficient way of truncating the shell-model space which is otherwise too large to handle. It defines a transformation from the intrinsic system, where dominant excitation modes in the low-energy region are identified with the concept of spontaneous symmetry breaking, to the laboratory frame with well-organized configuration states according to excitations. An energy-dictated, physically-guided shell-model truncation can then be carried out within the projected space and the Hamiltonian is thereby diagonalized in a compact basis. The present article reviews the theory of angular-momentum-projection applied in the nuclear many-body problem. Angular momentum projection emerges naturally if a deformed state is treated quantum-mechanically. To demonstrate how different physical problems in heavy, deformed nuclei can be efficiently described with different truncation schemes, we introduce the projected shell model and show examples of calculation in a basis with axial symmetry, a basis with triaxiality, and a basis with both quasiparticle and phonon excitations. Technical details of how to calculate the projected matrix elements and how to build a workable model with the projection techniques are given in the appendix.

  13. Hybrid detectors improved time-lapse confocal microscopy of PML and 53BP1 nuclear body colocalization in DNA lesions.

    PubMed

    Foltánková, Veronika; Matula, Pavel; Sorokin, Dmitry; Kozubek, Stanislav; Bártová, Eva

    2013-04-01

    We used hybrid detectors (HyDs) to monitor the trajectories and interactions of promyelocytic leukemia (GFP-PML) nuclear bodies (NBs) and mCherry-53BP1-positive DNA lesions. 53BP1 protein accumulates in NBs that occur spontaneously in the genome or in γ-irradiation-induced foci. When we induced local DNA damage by ultraviolet irradiation, we also observed accumulation of 53BP1 proteins into discrete bodies, instead of the expected dispersed pattern. In comparison with photomultiplier tubes, which are used for standard analysis by confocal laser scanning microscopy, HyDs significantly eliminated photobleaching of GFP and mCherry fluorochromes during image acquisition. The low laser intensities used for HyD-based confocal analysis enabled us to observe NBs for the longer time periods, necessary for studies of the trajectories and interactions of PML and 53BP1 NBs. To further characterize protein interactions, we used resonance scanning and a novel bioinformatics approach to register and analyze the movements of individual PML and 53BP1 NBs. The combination of improved HyD-based confocal microscopy with a tailored bioinformatics approach enabled us to reveal damage-specific properties of PML and 53BP1 NBs. PMID:23410959

  14. Tyrosine kinase inhibitor, methyl 2,5-dihydromethylcinnimate, induces PML nuclear body formation and apoptosis in tumor cells

    SciTech Connect

    Komura, Naoyuki; Asakawa, Mayako; Umezawa, Kazuo . E-mail: umezawa@applc.keio.ac.jp; Segawa, Kaoru

    2007-08-01

    Promyelocytic leukemia (PML) nuclear bodies (PML-NBs) are the nuclear structure consisting of various proteins such as PML, SUMO-1, and p53. PML-NBs are implicated in the regulation of tumor suppression, antiviral responses, and apoptosis. In this study, we searched for bioactive metabolites that would promote the formation of PML-NBs in tumor cells. As a result, methyl 2,5-dihydromethylcinnimate (2,5-MeC), a tyrosine kinase inhibitor, enhanced expression and/or stability of PML proteins and induced PML-NB formation in p53 null H1299 cells established from non-small cell lung cancer (NSCLC) and wild-type p53-expressing U2OS cells derived from osteosarcoma. Furthermore, it enhanced apoptosis by exogenously expressed wild type p53 and the expression of p53-responsive genes, such as PUMA and p21, in H1299 cells. 2,5-MeC also activated endogenous p53 and induced apoptosis in U2OS cells. The results suggest that 2,5-MeC is likely to be a promising candidate drug for the clinical treatment of terminal cancer-expressing wild-type p53.

  15. Cell cycle-dependent alteration in NAC1 nuclear body dynamics and morphology

    NASA Astrophysics Data System (ADS)

    Wu, Pei-Hsun; Hung, Shen-Hsiu; Ren, Tina; Shih, Ie-Ming; Tseng, Yiider

    2011-02-01

    NAC1, a BTB/POZ family member, has been suggested to participate in maintaining the stemness of embryonic stem cells and has been implicated in the pathogenesis of human cancer. In ovarian cancer, NAC1 upregulation is associated with disease aggressiveness and with the development of chemoresistance. Like other BTB/POZ proteins, NAC1 forms discrete nuclear bodies in non-dividing cells. To investigate the biological role of NAC1 nuclear bodies, we characterized the expression dynamics of NAC1 nuclear bodies during different phases of the cell cycle. Fluorescence recovery after photobleaching assays revealed that NAC1 was rapidly exchanged between the nucleoplasm and NAC1 nuclear bodies in interphase cells. The number of NAC1 bodies significantly increased and their size decreased in the S phase as compared to the G0/G1 and G2 phases. NAC1 nuclear bodies disappeared and NAC1 became diffuse during mitosis. NAC1 nuclear bodies reappeared immediately after completion of mitosis. These results indicate that a cell cycle-dependent regulatory mechanism controls NAC1 body formation in the nucleus and suggest that NAC1 body dynamics are associated with mitosis or cytokinesis.

  16. Detecting body cavity bombs with nuclear quadrupole resonance

    NASA Astrophysics Data System (ADS)

    Collins, Michael London

    Nuclear Quadrupole Resonance (NQR) is a technology with great potential for detecting hidden explosives. Past NQR research has studied the detection of land mines and bombs concealed within luggage and packages. This thesis focuses on an NQR application that has received less attention and little or no publicly available research: detecting body cavity bombs (BCBs). BCBs include explosives that have been ingested, inserted into orifices, or surgically implanted. BCBs present a threat to aviation and secure facilities. They are extremely difficult to detect with the technology currently employed at security checkpoints. To evaluate whether or not NQR can be used to detect BCBs, a computational model is developed to assess how the dielectric properties of biological tissue affect the radio frequency magnetic field employed in NQR (0.5-5MHz). The relative permittivity of some biological tissue is very high (over 1,000 at 1MHz), making it conceivable that there is a significant effect on the electromagnetic field. To study this effect, the low-frequency approximation known as the Darwin model is employed. First, the electromagnetic field of a coil is calculated in free space. Second, a dielectric object or set of objects is introduced, and the free-space electric field is modified to accommodate the dielectric object ensuring that the relevant boundary conditions are obeyed. Finally, the magnetic field associated with the corrected electric field is calculated. This corrected magnetic field is evaluated with an NQR simulation to estimate the impact of dielectric tissue on NQR measurements. The effect of dielectric tissue is shown to be small, thus obviating a potential barrier to BCB detection. The NQR model presented may assist those designing excitation and detection coils for NQR. Some general coil design considerations and strategies are discussed.

  17. Few-Body Problem in Nuclear Reactions: Beyond the horizon of the three-body Faddeev equations

    NASA Astrophysics Data System (ADS)

    Oryu, Shinsho; Hiratsuka, Yasuhisa; Watanabe, Takashi

    2016-06-01

    Recent progress in few-body problem physics based on the three-body Faddeev equations is reviewed for three-related fields. The first field involves the description of light nuclear reactions in terms of multi-channel three-body Faddeev equations. The second field is the investigation of the two- and three-body threshold behaviors for the NNπ system using the three-body Faddeev equations, where the πD and the NN' or N-(Nπ) scattering lengths are calculated, and also we show that the NN' potential has a long range term of 1/r2 form. The third is a new Coulomb treatment in terms of a generalized screening range to describe on-shell Coulomb amplitudes which is useful in the threebody Faddeev equations. This procedure reproduces both of the Coulomb phase shift and the wave function from the electron-electron to the heavy-ion-heavy-ion systems.

  18. Identification of Three Redundant Segments Responsible for Herpes Simplex Virus 1 ICP0 To Fuse with ND10 Nuclear Bodies

    PubMed Central

    Zheng, Yi

    2015-01-01

    ABSTRACT Infected cell protein 0 (ICP0) of herpes simplex virus 1 (HSV-1) is a key regulator in both lytic and latent infections. In lytic infection, an important early event is the colocalization of ICP0 to nuclear domain 10 (ND10), the discrete nuclear bodies that impose restrictions on viral expression. ICP0 contains an E3 ubiquitin ligase that degrades promyelocytic leukemia protein (PML) and Sp100, two major components of ND10, and disperses ND10 to alleviate repression. We previously reported that the association between ICP0 and ND10 is a dynamic process that includes three steps: adhesion, fusion, and retention. ICP0 residues 245 to 474, defined as ND10 entry signal (ND10-ES), is a region required for the fusion step. Without ND10-ES, ICP0 adheres at the ND10 surface but fails to enter. In the present study, we focus on characterizing ND10-ES. Here we report the following. (i) Fusion of ICP0 with ND10 relies on specific sequences located within ND10-ES. Replacement of ND10-ES by the corresponding region from ORF61 of varicella-zoster virus did not rescue ND10 fusion. (ii) Three tandem ND10 fusion segments (ND10-FS1, ND10-FS2, and ND10-FS3), encompassing 200 amino acids within ND10-ES, redundantly facilitate fusion. Each of the three segments is sufficient to independently drive the fusion process, but none of the segments by themselves are necessary for ND10 fusion. Only when all three segments are deleted is fusion blocked. (iii) The SUMO interaction motif located within ND10-FS2 is not required for ND10 fusion but is required for the complete degradation of PML, suggesting that PML degradation and ND10 fusion are regulated by different molecular mechanisms. IMPORTANCE ND10 nuclear bodies are part of the cell-intrinsic antiviral defenses that restrict viral gene expression upon virus infection. As a countermeasure, infected cell protein 0 (ICP0) of herpes simplex virus 1 (HSV-1) localizes to ND10s, degrades the ND10 organizer, and disperses ND10 components

  19. CUPLIKE NUCLEI (PROMINENT NUCLEAR INVAGINATIONS) IN ACUTE MYELOID LEUKEMIA ARE HIGHLY ASSOCIATED WITH FLT3-ITD AND NPM1 MUTATIONS

    PubMed Central

    Chen, Weina; Konoplev, Sergej; Medeiros, L. Jeffrey; Koeppen, Hartmut; Leventaki, Vasiliki; Vadhan-Raj, Saroj; Jones, Dan; Kantarjian, Hagop M.; Falini, Brunangelo; Bueso-Ramos, Carlos E.

    2012-01-01

    BACKGROUND A small subset of acute myeloid leukemia (AML) cases has cuplike nuclei. Others have shown that these neoplasms have distinctive clinicopathologic and molecular features. METHODS We searched for AML cases with cuplike nuclei at our institution over a 10-year interval. We used a strict definition for cuplike nuclei, ≥10% blasts with nuclear invaginations ≥25% of the nuclear area. We reviewed relevant data and compared the results with a control group of AML without cuplike nuclei. RESULTS We identified 22 cases of AML with cuplike nuclei, classified as AML without maturation (FAB AML M1). Compared with a control group AML M1cases, AMLs with cuplike nuclei were significantly associated with FLT3-ITD mutations (86 vs. 38%, p=0.002), NPM1 mutations (86 vs. 19%, p<0.0001), both mutations (77% vs. 14%, p<0.0001), normal karyotype (86 vs. 40%, p=0.003), bone marrow blast count (90% vs. 84%, p=0.016), myeloperoxidase positivity (95% vs. 30% blasts, p=0.001), higher D-dimer levels (>5000 vs. 569 ng/mL, p=0.001), and absence of CD7 (91% vs. 52%, p=0.007), CD34 (82% vs. 5%, p<0.0001), and HLA-DR (59% vs. 10%, p=0.001). There were no differences in age, sex, or peripheral blood counts. The positive predictive value of recognizing AML with cuplike nuclei for FLT3-ITD, NPM1, and both mutations was 81%, 86%, and 77%, respectively. CONCLUSIONS Cuplike nuclei in AML are highly associated with the presence of NPM1 and FLT3-ITD mutations and a number of clinicopathologic and immunophenotypic features. The recognition of AML with cuplike nuclei may be helpful in streamlining the workup of these neoplasms. PMID:19672946

  20. Nuclear Bodies: Random Aggregates of Sticky Proteins or Crucibles of Macromolecular Assembly?

    PubMed Central

    Matera, A. Gregory; Izaguire-Sierra, Mario; Praveen, Kavita; Rajendra, T.K.

    2011-01-01

    The principles of self-assembly and self-organization are major tenets of molecular and cellular biology. Governed by these principles, the eukaryotic nucleus is composed of numerous subdomains and compartments, collectively described as nuclear bodies. Emerging evidence reveals that associations within and between various nuclear bodies and genomic loci are dynamic and can change in response to cellular signals. This review will discuss recent progress in our understanding of how nuclear body components come together, what happens when they form, and what benefit these subcellular structures may provide to the tissues or organisms in which they are found. PMID:19922869

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

    ClinicalTrials.gov

    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)

  2. Academic difficulties and occupational outcomes of adult survivors of childhood leukemia who have undergone allogeneic hematopoietic stem cell transplantation and fractionated total body irradiation conditioning.

    PubMed

    Freycon, Fernand; Trombert-Paviot, Béatrice; Casagranda, Léonie; Frappaz, Didier; Mialou, Valérie; Armari-Alla, Corinne; Gomez, Frederic; Faure-Conter, Cécile; Plantaz, Dominique; Berger, Claire

    2014-04-01

    We studied academic and employment outcomes in 59 subjects who underwent allogeneic hematopoietic stem cell transplantation (a-HSCT) with fractionated total body irradiation (fTBI) for childhood leukemia, comparing them with, first, the general French population and, second, findings in 19 who underwent a-HSCT with chemotherapy conditioning. We observed an average academic delay of 0.98 years among the 59 subjects by Year 10 of secondary school (French class Troisième), which was higher than the 0.34-year delay in the normal population (P < .001) but not significantly higher than the delay of 0.68 years in our cohort of 19 subjects who underwent a-HSCT with chemotherapy. The delay was dependent on age at leukemia diagnosis, but not at fTBI. This delay increased to 1.32 years by the final year of secondary school (Year 13, Terminale) for our 59 subjects versus 0.51 years in the normal population (P = .0002), but did not differ significantly from the 1.08-year delay observed in our cohort of 19 subjects. The number of students who received their secondary school diploma (Baccalaureate) was similar to the expected rate in the general French population for girls (observed/expected = 1.02) but significantly decreased for boys (O/E = 0.48; CI: 95%[0.3-0.7]). Compared with 13.8% of the general population, 15.3% of the cancer survivors received no diploma (P = NS). Reported job distribution did not differ significantly between our cohort of childhood cancer survivors and the general population except that more female survivors were employed in intermediate-level professional positions. Academic difficulties after fTBI are common and their early identification will facilitate educational and professional achievement. PMID:24087985

  3. Three-Body Nuclear Systems in Pionless Effective Field Theory

    NASA Astrophysics Data System (ADS)

    Vanasse, Jared

    2016-03-01

    New perturbative techniques for three-body systems with contact interactions are discussed. Their application to pionless effective field theory (EF{Tnot π }) for nd scattering is shown, and their extension to bound states addressed. With the extension to bound states a leading-order EF{Tnot π } calculation of the triton charge radius and novel treatments of three-body forces are discussed.

  4. Towards many-body based nuclear reaction modelling

    NASA Astrophysics Data System (ADS)

    Hilaire, Stéphane; Goriely, Stéphane

    2016-06-01

    The increasing need for cross sections far from the valley of stability poses a challenge for nuclear reaction models. So far, predictions of cross sections have relied on more or less phenomenological approaches, depending on parameters adjusted to available experimental data or deduced from systematic expressions. While such predictions are expected to be reliable for nuclei not too far from the experimentally known regions, it is clearly preferable to use more fundamental approaches, based on sound physical principles, when dealing with very exotic nuclei. Thanks to the high computer power available today, all the ingredients required to model a nuclear reaction can now be (and have been) microscopically (or semi-microscopically) determined starting from the information provided by a nucleon-nucleon effective interaction. This concerns nuclear masses, optical model potential, nuclear level densities, photon strength functions, as well as fission barriers. All these nuclear model ingredients, traditionally given by phenomenological expressions, now have a microscopic counterpart implemented in the TALYS nuclear reaction code. We are thus now able to perform fully microscopic cross section calculations. The quality of these ingredients and the impact of using them instead of the usually adopted phenomenological parameters will be discussed. Perspectives for the coming years will be drawn on the improvements one can expect.

  5. Total body irradiation as preparation for bone marrow transplantation in treatment of acute leukemia and aplastic anemia

    SciTech Connect

    Serota, F.T.; Burkey, E.D.; August, C.S.; D'Angio, G.J.

    1983-12-01

    In an attempt to improve survival while minimizing toxicity, many bone marrow transplant centers are now studying the use of cytoreduction regimens with an increased amount of radiation in single-dose or fractionated-exposure schedules for patients with leukemia and aplastic anemia. In order to review the current results, the literature prior to September, 1982 was surveyed and data were tabulated for each transplant center regarding the number of patients receiving transplants, diagnoses, cytoreduction regimen, clinical status, remission duration, relapse rate, causes of death and incidence of interstitial pneumonia. The incidence and severity of cataracts, growth failure, hypothyroidism and second malignant neoplasms were noted, and the data obtained from the literature search were updated and expanded by telephone questionnaire when possible. Marked variation in the technique of tranplantation was found among the participating institutions, making it difficult to determine the contribution of the various TBI doses, dose rates and fractionation schedules to the efficacy and toxicity of the combined regimen. In order to define the risk-benefit ratio of the various TBI regimens more clearly, prospective controlled, randomized studies will be required.

  6. Quantitative nuclear magnetic resonance to measure body composition in infants and children

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Quantitative Nuclear Magnetic Resonance (QMR) is being used in human adults to obtain measures of total body fat (FM) with high precision. The current study assessed a device specially designed to accommodate infants and children between 3 and 50 kg (EchoMRI-AH™). Body composition of 113 infants and...

  7. Acute myelogenous leukemia (AML) - children

    MedlinePlus

    Acute myelogenous leukemia - children; AML; Acute myeloid leukemia - children; Acute granulocytic leukemia - children; Acute myeloblastic leukemia - children; Acute non-lymphocytic leukemia (ANLL) - children

  8. Leukemia-Associated Nup214 Fusion Proteins Disturb the XPO1-Mediated Nuclear-Cytoplasmic Transport Pathway and Thereby the NF-κB Signaling Pathway.

    PubMed

    Saito, Shoko; Cigdem, Sadik; Okuwaki, Mitsuru; Nagata, Kyosuke

    2016-07-01

    Nuclear-cytoplasmic transport through nuclear pore complexes is mediated by nuclear transport receptors. Previous reports have suggested that aberrant nuclear-cytoplasmic transport due to mutations or overexpression of nuclear pore complexes and nuclear transport receptors is closely linked to diseases. Nup214, a component of nuclear pore complexes, has been found as chimeric fusion proteins in leukemia. Among various Nup214 fusion proteins, SET-Nup214 and DEK-Nup214 have been shown to be engaged in tumorigenesis, but their oncogenic mechanisms remain unclear. In this study, we examined the functions of the Nup214 fusion proteins by focusing on their effects on nuclear-cytoplasmic transport. We found that SET-Nup214 and DEK-Nup214 interact with exportin-1 (XPO1)/CRM1 and nuclear RNA export factor 1 (NXF1)/TAP, which mediate leucine-rich nuclear export signal (NES)-dependent protein export and mRNA export, respectively. SET-Nup214 and DEK-Nup214 decreased the XPO1-mediated nuclear export of NES proteins such as cyclin B and proteins involved in the NF-κB signaling pathway by tethering XPO1 onto nuclear dots where Nup214 fusion proteins are localized. We also demonstrated that SET-Nup214 and DEK-Nup214 expression inhibited NF-κB-mediated transcription by abnormal tethering of the complex containing p65 and its inhibitor, IκB, in the nucleus. These results suggest that SET-Nup214 and DEK-Nup214 perturb the regulation of gene expression through alteration of the nuclear-cytoplasmic transport system. PMID:27114368

  9. Chromatin insulator bodies are nuclear structures that form in response to osmotic stress and cell death.

    PubMed

    Schoborg, Todd; Rickels, Ryan; Barrios, Josh; Labrador, Mariano

    2013-07-22

    Chromatin insulators assist in the formation of higher-order chromatin structures by mediating long-range contacts between distant genomic sites. It has been suggested that insulators accomplish this task by forming dense nuclear foci termed insulator bodies that result from the coalescence of multiple protein-bound insulators. However, these structures remain poorly understood, particularly the mechanisms triggering body formation and their role in nuclear function. In this paper, we show that insulator proteins undergo a dramatic and dynamic spatial reorganization into insulator bodies during osmostress and cell death in a high osmolarity glycerol-p38 mitogen-activated protein kinase-independent manner, leading to a large reduction in DNA-bound insulator proteins that rapidly repopulate chromatin as the bodies disassemble upon return to isotonicity. These bodies occupy distinct nuclear territories and contain a defined structural arrangement of insulator proteins. Our findings suggest insulator bodies are novel nuclear stress foci that can be used as a proxy to monitor the chromatin-bound state of insulator proteins and provide new insights into the effects of osmostress on nuclear and genome organization. PMID:23878275

  10. SUMOylation regulates the nuclear mobility of CREB binding protein and its association with nuclear bodies in live cells

    SciTech Connect

    Ryan, Colm M.; Kindle, Karin B.; Collins, Hilary M.; Heery, David M.

    2010-01-01

    The lysine acetyltransferase CREB binding protein (CBP) is required for chromatin modification and transcription at many gene promoters. In fixed cells, a large proportion of CBP colocalises to PML or nuclear bodies. Using live cell imaging, we show here that YFP-tagged CBP expressed in HEK293 cells undergoes gradual accumulation in nuclear bodies, some of which are mobile and migrate towards the nuclear envelope. Deletion of a short lysine-rich domain that contains the major SUMO acceptor sites of CBP abrogated its ability to be SUMO modified, and prevented its association with endogenous SUMO-1/PML speckles in vivo. This SUMO-defective CBP showed enhanced ability to co-activate AML1-mediated transcription. Deletion mapping revealed that the SUMO-modified region was not sufficient for targeting CBP to PML bodies, as C-terminally truncated mutants containing this domain showed a strong reduction in accumulation at PML bodies. Fluorescence recovery after photo-bleaching (FRAP) experiments revealed that YFP-CBP{Delta}998-1087 had a retarded recovery time in the nucleus, as compared to YFP-CBP. These results indicate that SUMOylation regulates CBP function by influencing its shuttling between nuclear bodies and chromatin microenvironments.

  11. Characterization of a nuclear compartment shared by nuclear bodies applying ectopic protein expression and correlative light and electron microscopy

    SciTech Connect

    Richter, Karsten; Reichenzeller, Michaela; Goerisch, Sabine M.; Schmidt, Ute; Scheuermann, Markus O.; Herrmann, Harald; Lichter, Peter . E-mail: m.macleod@dkfz.de

    2005-02-01

    To investigate the accessibility of interphase nuclei for nuclear body-sized particles, we analyzed in cultured cells from human origin by correlative fluorescence and electron microscopy (EM) the bundle-formation of Xenopus-vimentin targeted to the nucleus via a nuclear localization signal (NLS). Moreover, we investigated the spatial relationship of speckles, Cajal bodies, and crystalline particles formed by Mx1 fused to yellow fluorescent protein (YFP), with respect to these bundle arrays. At 37 deg C, the nucleus-targeted, temperature-sensitive Xenopus vimentin was deposited in focal accumulations. Upon shift to 28 deg C, polymerization was induced and filament arrays became visible. Within 2 h after temperature shift, arrays were found to be composed of filaments loosely embedded in the nucleoplasm. The filaments were restricted to limited areas of the nucleus between focal accumulations. Upon incubation at 28 deg C for several hours, NLS vimentin filaments formed bundles looping throughout the nuclei. Speckles and Cajal bodies frequently localized in direct neighborhood to vimentin bundles. Similarly, small crystalline particles formed by YFP-tagged Mx1 also located next to vimentin bundles. Taking into account that nuclear targeted vimentin locates in the interchromosomal domain (ICD), we conclude that nuclear body-sized particles share a common nuclear space which is controlled by higher order chromatin organization.

  12. Nuclear density functional theory with a semi-contact 3-body interaction

    NASA Astrophysics Data System (ADS)

    Lacroix, Denis; Bennaceur, Karim

    2016-01-01

    Theories combining nuclear density functional approach (DFT) and effects beyond the independent particle/quasi-particle limit have attracted much attention recently. In particular, such theories, generically referred as "beyond mean-field" (BMF) seem unavoidable to account for both single-particle effects and complex quantum internal phenomena in nuclear finite many-body nuclear systems. It has been realized recently that BMF theories might lead to specific difficulties when applied within the nuclear DFT context. An example is the appearance of divergences in configuration mixing approaches. A short summary of the difficulties is given here. One source of problem is the use of energy functional of non-integer powers of the density. We show that such dependence can be mimicked by a suitable choice of a three-body interaction. Application on infinite nuclear matter in various spin-isospin channels will be given.

  13. Total body irradiation in a patient with fragile X syndrome for acute lymphoblastic leukemia in preparation for stem cell transplantation: A case report and literature review.

    PubMed

    Collins, D T; Mannina, E M; Mendonca, M

    2015-10-01

    Fragile X syndrome (FXS) is a congenital disorder caused by expansion of CGG trinucleotide repeat at the 5' end of the fragile X mental retardation gene 1 (FMR1) on the X chromosome that leads to chromosomal instability and diminished serum levels of fragile X mental retardation protein (FMRP). Afflicted individuals often have elongated features, marfanoid habitus, macroorchidism and intellectual impairment. Evolving literature suggests the condition may actually protect from malignancy while chromosomal instability would presumably elevate the risk. Increased sensitivity to ionizing radiation should also be predicted by unstable sites within the DNA. Interestingly, in this report, we detail a patient with FXS diagnosed with acute lymphoblastic leukemia treated with induction followed by subsequent cycles of hyper-CVAD (cyclophosphamide, vincristine, doxorubicin, dexamethasone) with a complete response who then was recommended to undergo peripheral stem cell transplantation. The patient underwent total body irradiation (TBI) as a component of his conditioning regimen and despite the concern of his clinicians, developed minimal acute toxicity and successful engraftment. The pertinent literature regarding irradiation of patients with FXS is also reviewed. PMID:26097012

  14. Survival and Neurocognitive Outcomes After Cranial or Craniospinal Irradiation Plus Total-Body Irradiation Before Stem Cell Transplantation in Pediatric Leukemia Patients With Central Nervous System Involvement

    SciTech Connect

    Hiniker, Susan M.; Agarwal, Rajni; Modlin, Leslie A.; Gray, Christine C.; Harris, Jeremy P.; Million, Lynn; Kiamanesh, Eileen F.; Donaldson, Sarah S.

    2014-05-01

    Purpose: To evaluate survival and neurocognitive outcomes in pediatric acute lymphoblastic leukemia (ALL) patients with central nervous system (CNS) involvement treated according to an institutional protocol with stem cell transplantation (SCT) and a component of craniospinal irradiation (CSI) in addition to total-body irradiation (TBI) as preparative regimen. Methods and Materials: Forty-one pediatric ALL patients underwent SCT with TBI and received additional cranial irradiation or CSI because of CNS leukemic involvement. Prospective neurocognitive testing was performed before and after SCT in a subset of patients. Cox regression models were used to determine associations of patient and disease characteristics and treatment methods with outcomes. Results: All patients received a cranial radiation boost; median total cranial dose was 24 Gy. Eighteen patients (44%) received a spinal boost; median total spinal dose for these patients was 18 Gy. Five-year disease-free survival (DFS) for all patients was 67%. Those receiving CSI had a trend toward superior DFS compared with those receiving a cranial boost alone (hazard ratio 3.23, P=.14). Patients with isolated CNS disease before SCT had a trend toward superior DFS (hazard ratio 3.64, P=.11, 5-year DFS 74%) compared with those with combined CNS and bone marrow disease (5-year DFS 59%). Neurocognitive testing revealed a mean post-SCT overall intelligence quotient of 103.7 at 4.4 years. Relative deficiencies in processing speed and/or working memory were noted in 6 of 16 tested patients (38%). Pre- and post-SCT neurocognitive testing revealed no significant change in intelligence quotient (mean increase +4.7 points). At a mean of 12.5 years after transplant, 11 of 13 long-term survivors (85%) had completed at least some coursework at a 2- or 4-year college. Conclusion: The addition of CSI to TBI before SCT in pediatric ALL with CNS involvement is effective and well-tolerated. Craniospinal irradiation plus TBI is worthy

  15. The translation initiation factor 3 subunit eIF3K interacts with PML and associates with PML nuclear bodies

    SciTech Connect

    Salsman, Jayme; Pinder, Jordan; Tse, Brenda; Corkery, Dale; Dellaire, Graham

    2013-10-15

    The promyelocytic leukemia protein (PML) is a tumor suppressor protein that regulates a variety of important cellular processes, including gene expression, DNA repair and cell fate decisions. Integral to its function is the ability of PML to form nuclear bodies (NBs) that serve as hubs for the interaction and modification of over 90 cellular proteins. There are seven canonical isoforms of PML, which encode diverse C-termini generated by alternative pre-mRNA splicing. Recruitment of specific cellular proteins to PML NBs is mediated by protein–protein interactions with individual PML isoforms. Using a yeast two-hybrid screen employing peptide sequences unique to PML isoform I (PML-I), we identified an interaction with the eukaryotic initiation factor 3 subunit K (eIF3K), and in the process identified a novel eIF3K isoform, which we term eIF3K-2. We further demonstrate that eIF3K and PML interact both in vitro via pull-down assays, as well as in vivo within human cells by co-immunoprecipitation and co-immunofluorescence. In addition, eIF3K isoform 2 (eIF3K-2) colocalizes to PML bodies, particularly those enriched in PML-I, while eIF3K isoform 1 associates poorly with PML NBs. Thus, we report eIF3K as the first known subunit of the eIF3 translation pre-initiation complex to interact directly with the PML protein, and provide data implicating alternative splicing of both PML and eIF3K as a possible regulatory mechanism for eIF3K localization at PML NBs. - Highlights: • The PML-I C-terminus, encoded by exon 9, interacts with translation factor eIF3K. • We identify a novel eIF3K isoform that excludes exon 2 (eIF3K-2). • eIF3K-2 preferentially associates with PML bodies enriched in PML-I vs. PML-IV. • Alternative splicing of eIF3K regulates association with PML bodies.

  16. Nuclear-Spin-Independent Short-Range Three-Body Physics in Ultracold Atoms

    SciTech Connect

    Gross, Noam; Shotan, Zav; Khaykovich, Lev; Kokkelmans, Servaas

    2010-09-03

    We investigate three-body recombination loss across a Feshbach resonance in a gas of ultracold {sup 7}Li atoms prepared in the absolute ground state and perform a comparison with previously reported results of a different nuclear-spin state [N. Gross et al., Phys. Rev. Lett. 103, 163202 (2009)]. We extend the previously reported universality in three-body recombination loss across a Feshbach resonance to the absolute ground state. We show that the positions and widths of recombination minima and Efimov resonances are identical for both states which indicates that the short-range physics is nuclear-spin independent.

  17. A novel single cell method to identify the genetic composition at a single nuclear body.

    PubMed

    Anchel, David; Ching, Reagan W; Cotton, Rachel; Li, Ren; Bazett-Jones, David P

    2016-01-01

    Gene loci make specific associations with compartments of the nucleus (e.g. the nuclear envelope, nucleolus, and transcription factories) and this association may determine or reflect a mechanism of genetic control. With current methods, it is not possible to identify sets of genes that converge to form a "gene hub" as there is a reliance on loci-specific probes, or immunoprecipitation of a particular protein from bulk cells. We introduce a method that will allow for the identification of loci contained within the vicinity of a single nuclear body in a single cell. For the first time, we demonstrate that the DNA sequences originating from a single sub-nuclear structure in a single cell targeted by two-photon irradiation can be determined, and mapped to a particular locus. Its application to single PML nuclear bodies reveals ontologically related loci that frequently associate with each other and with PML bodies in a population of cells, and a possible nuclear body targeting role for specific transcription factor binding sites. PMID:27389808

  18. A novel single cell method to identify the genetic composition at a single nuclear body

    PubMed Central

    Anchel, David; Ching, Reagan W.; Cotton, Rachel; Li, Ren; Bazett-Jones, David P.

    2016-01-01

    Gene loci make specific associations with compartments of the nucleus (e.g. the nuclear envelope, nucleolus, and transcription factories) and this association may determine or reflect a mechanism of genetic control. With current methods, it is not possible to identify sets of genes that converge to form a “gene hub” as there is a reliance on loci-specific probes, or immunoprecipitation of a particular protein from bulk cells. We introduce a method that will allow for the identification of loci contained within the vicinity of a single nuclear body in a single cell. For the first time, we demonstrate that the DNA sequences originating from a single sub-nuclear structure in a single cell targeted by two-photon irradiation can be determined, and mapped to a particular locus. Its application to single PML nuclear bodies reveals ontologically related loci that frequently associate with each other and with PML bodies in a population of cells, and a possible nuclear body targeting role for specific transcription factor binding sites. PMID:27389808

  19. What Is Childhood Leukemia?

    MedlinePlus

    ... key statistics for childhood leukemia? What is childhood leukemia? Cancer starts when cells start to grow out ... start making antibodies to fight them. Types of leukemia in children Leukemia is often described as being ...

  20. Nuclear Import of Moloney Murine Leukemia Virus DNA Mediated by Adenovirus Preterminal Protein Is Not Sufficient for Efficient Retroviral Transduction in Nondividing Cells

    PubMed Central

    Lieber, André; Kay, Mark A.; Li, Zong-Yi

    2000-01-01

    Moloney murine leukemia virus (MoMLV)-derived vectors require cell division for efficient transduction, which may be related to an inability of the viral DNA-protein complex to cross the nuclear membrane. In contrast, adenoviruses (Ad) can efficiently infect nondividing cells. This property may be due to the presence of multiple nuclear translocation signals in a number of Ad proteins, which are associated with the incoming viral genomes. Of particular interest is the Ad preterminal protein (pTP), which binds alone or in complex with the Ad polymerase to specific sequences in the Ad inverted terminal repeat. The goal of this study was to test whether coexpression of pTP with retroviral DNA carrying pTP-binding sites would facilitate nuclear import of the viral preintegration complex and transduction of quiescent cells. In preliminary experiments, we demonstrated that the karyophylic pTP can coimport plasmid DNA into the nuclei of growth-arrested cells. Retroviral transduction studies were performed with G1/S-arrested LTA cells or stationary-phase human primary fibroblasts. These studies demonstrated that pTP or pTP-Ad polymerase conferred nuclear import of retroviral DNA upon arrested cells when the retrovirus vector contained the corresponding binding motifs. However, pTP-mediated nuclear translocation of MoMLV DNA in nondividing cells was not sufficient for stable transduction. Additional cellular factors activated during S phase or DNA repair synthesis were required for efficient retroviral integration. PMID:10623734

  1. Childhood Leukemia

    MedlinePlus

    ... acute types. Symptoms include Infections Fever Loss of appetite Tiredness Easy bruising or bleeding Swollen lymph nodes Night sweats Shortness of breath Pain in the bones or joints Risk factors for childhood leukemia include having a brother ...

  2. Marrow transplantation for acute nonlymphoblastic leukemia in first remission: toxicity and long-term follow-up of patients conditioned with single dose or fractionated total body irradiation.

    PubMed

    Deeg, H J; Sullivan, K M; Buckner, C D; Storb, R; Appelbaum, F R; Clift, R A; Doney, K; Sanders, J E; Witherspoon, R P; Thomas, E D

    1986-12-01

    Seventy-five patients with acute nonlymphoblastic leukemia (ANL) in first remission were treated with cyclophosphamide, 60 mg/kg on each of two consecutive days followed by total body irradiation (TBI) at an exposure rate of 4-6 cGy/min from two opposing 60Co sources. The first 22 patients were given 9.2 Gy of TBI as a single dose. Subsequently 53 patients were randomized to receive either 10 Gy single dose TBI (n = 27) or 6 x 2 Gy fractionated TBI (n = 26). All patients received marrow transplants from HLA-identical siblings and all had sustained engraftment. Patients given 10 Gy of TBI had more early toxicity, especially veno-occlusive disease of the liver, than patients given 9.2 or 6 x 2 Gy of TBI. Idiopathic interstitial pneumonitis appeared to be more frequent in patients given 9.2 or 10 Gy single-dose TBI than in patients given 6 x 2 Gy fractionated TBI. Patients have now been followed from 5 to 9 years. Survival (+/- 95% confidence limits) at 5 years is 54 +/- 31% among patients given 9.2 Gy single dose TBI, 33 +/- 31% among patients given 10 Gy single dose TBI, and 54 +/- 26% among patients given 6 x 2 Gy fractionated TBI (P = 0.04). These results indicate that about half the patients with ANL transplanted while in first chemotherapy-induced remission can be expected to become long-term survivors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3332129

  3. Nuclear magnetic resonance for measurement of body composition in infants and children

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Measurement of body composition in infants and children is currently challenging. Air Displacement Plethysmography (ADP) has not been validated between ages 6 mo and 6 y and the requirement for stillness of the Dual-energy X-ray Absorptiometry (DXA) technique limits its use. Quantitative Nuclear Ma...

  4. Positronium formation as a three-body reaction. II. The second-order nuclear amplitudes

    SciTech Connect

    Shojaei, F.; Bolorizadeh, M. A.; Ghanbari-Adivi, E.; Brunger, M. J.

    2009-01-15

    We derive an exact analytic form for the second-order nuclear amplitudes, under the Faddeev three-body approach, which is applicable to the nonrelativistic high energy impact interaction where positronium is formed in the collision of a positron with an atom.

  5. Identification of a role for the nuclear receptor EAR-2 in the maintenance of clonogenic status within the leukemia cell hierarchy

    PubMed Central

    Ichim, CV; Atkins, HL; Iscove, NN; Wells, RA

    2016-01-01

    Identification of genes that regulate clonogenicity of acute myelogenous leukemia (AML) cells is hindered by the difficulty of isolating pure populations of cells with defined proliferative abilities. By analyzing the growth of clonal siblings in low passage cultures of the cell line OCI/AML4 we resolved this heterogeneous population into strata of distinct clonogenic potential, permitting analysis of the transcriptional signature of single cells with defined proliferative abilities. By microarray analysis we showed that the expression of the orphan nuclear receptor EAR-2 (NR2F6) is greater in leukemia cells with extensive proliferative capacity than in those that have lost proliferative ability. EAR-2 is expressed highly in long-term hematopoietic stem cells, relative to short-term hematopoietic stem and progenitor cells, and is downregulated in AML cells after induction of differentiation. Exogenous expression of EAR-2 increased the growth of U937 cells and prevented the proliferative arrest associated with terminal differentiation, and blocked differentiation of U937 and 32Dcl3 cells. Conversely, silencing of EAR-2 by short-hairpin RNA initiated terminal differentiation of these cell lines. These data identify EAR-2 as an important factor in the regulation of clonogenicity and differentiation, and establish that analysis of clonal siblings allows the elucidation of differences in gene expression within the AML hierarchy. PMID:21637284

  6. CXXC5 (Retinoid-Inducible Nuclear Factor, RINF) is a Potential Therapeutic Target in High-Risk Human Acute Myeloid Leukemia

    PubMed Central

    Astori, Audrey; Fredly, Hanne; Aloysius, Thomas Aquinas; Bullinger, Lars; Mas, Véronique Mansat-De; de la Grange, Pierre; Delhommeau, François; Hagen, Karen Marie; Récher, Christian; Dusanter-Fourt, Isabelle; Knappskog, Stian; Lillehaug, Johan Richard

    2013-01-01

    The retinoid-responsive gene CXXC5 localizes to the 5q31.2 chromosomal region and encodes a retinoid-inducible nuclear factor (RINF) that seems important during normal myelopoiesis. We investigated CXXC5/RINF expression in primary human acute myeloid leukemia (AML) cells derived from 594 patients, and a wide variation in CXXC5/RINF mRNA levels was observed both in the immature leukemic myeloblasts and in immature acute lymphoblastic leukemia cells. Furthermore, patients with low-risk cytogenetic abnormalities showed significantly lower levels compared to patients with high-risk abnormalities, and high RINF/CXXC5/ mRNA levels were associated with decreased overall survival for patients receiving intensive chemotherapy for newly diagnosed AML. This association with prognosis was seen both when investigating (i) an unselected patient population as well as for patients with (ii) normal cytogenetic and (iii) core-binding factor AML. CXXC5/RINF knockdown in AML cell lines caused increased susceptibility to chemotherapy-induced apoptosis, and regulation of apoptosis also seemed to differ between primary human AML cells with high and low RINF expression. The association with adverse prognosis together with the antiapoptotic effect of CXXC5/RINF suggests that targeting of CXXC5/RINF should be considered as a possible therapeutic strategy, especially in high-risk patients who show increased expression in AML cells compared with normal hematopoietic cells. PMID:23988457

  7. Human Homolog of Drosophila Ariadne (HHARI) is a marker of cellular proliferation associated with nuclear bodies

    SciTech Connect

    Elmehdawi, Fatima; Wheway, Gabrielle; Szymanska, Katarzyna; Adams, Matthew; High, Alec S.; Johnson, Colin A.; Robinson, Philip A.

    2013-02-01

    HHARI (also known as ARIH1) is an ubiquitin-protein ligase and is the cognate of the E2, UbcH7 (UBE2L3). To establish a functional role for HHARI in cellular proliferation processes, we performed a reverse genetics screen that identified n=86/522 (16.5%) ubiquitin conjugation components that have a statistically significant effect on cell proliferation, which included HHARI as a strong hit. We then produced and validated a panel of specific antibodies that establish HHARI as both a nuclear and cytoplasmic protein that is expressed in all cell types studied. HHARI was expressed at higher levels in nuclei, and co-localized with nuclear bodies including Cajal bodies (p80 coilin, NOPP140), PML and SC35 bodies. We confirmed reduced cellular proliferation after ARIH1 knockdown with individual siRNA duplexes, in addition to significantly increased levels of apoptosis, an increased proportion of cells in G2 phase of the cell cycle, and significant reductions in total cellular RNA levels. In head and neck squamous cell carcinoma biopsies, there are higher levels of HHARI expression associated with increased levels of proliferation, compared to healthy control tissues. We demonstrate that HHARI is associated with cellular proliferation, which may be mediated through its interaction with UbcH7 and modification of proteins in nuclear bodies. -- Highlights: ► We produce and validate new antibody reagents for the ubiquitin-protein ligase HHARI. ► HHARI colocalizes with nuclear bodies including Cajal, PML and SC35 bodies. ► We establish new functions in cell proliferation regulation for HHARI. ► Increased HHARI expression associates with squamous cell carcinoma and proliferation.

  8. Nuclear actin is partially associated with Cajal bodies in human cells in culture and relocates to the nuclear periphery after infection of cells by adenovirus 5

    SciTech Connect

    Gedge, L.J.E.; Morrison, E.E.; Blair, G.E.; Walker, J.H. . E-mail: J.H.Walker@leeds.ac.uk

    2005-02-15

    Cajal bodies are intra-nuclear structures enriched in proteins involved in transcription and mRNA processing. In this study, immunofluorescence microscopy experiments using a highly specific antibody to actin revealed nuclear actin spots that colocalized in part with p80 coilin-positive Cajal bodies. Actin remained associated with Cajal bodies in cells extracted to reveal the nuclear matrix. Adenovirus infection, which is known to disassemble Cajal bodies, resulted in loss of actin from these structures late in infection. In infected cells, nuclear actin was observed to relocate to structures at the periphery of the nucleus, inside the nuclear envelope. Based on these findings, it is suggested that actin may play an important role in the organization or function of the Cajal body.

  9. Nuclear export and expression of human T-cell leukemia virus type 1 tax/rex mRNA are RxRE/Rex dependent.

    PubMed

    Bai, X T; Sinha-Datta, U; Ko, N L; Bellon, M; Nicot, C

    2012-04-01

    Human T-cell leukemia virus type 1 (HTLV-1) is a complex retrovirus associated with the lymphoproliferative disease adult T-cell leukemia/lymphoma (ATL) and the neurodegenerative disorder tropical spastic paraparesis/HTLV-1-associated myelopathy (TSP/HAM). Replication of HTLV-1 is under the control of two major trans-acting proteins, Tax and Rex. Previous studies suggested that Tax activates transcription from the viral long terminal repeat (LTR) through recruitment of cellular CREB and transcriptional coactivators. Other studies reported that Rex acts posttranscriptionally and allows the cytoplasmic export of unspliced or incompletely spliced viral mRNAs carrying gag/pol and env only. As opposed to HIV's Rev-responsive element (RRE), the Rex-responsive element (RxRE) is present in all viral mRNAs in HTLV-1. However, based on indirect observations, it is believed that nuclear export and expression of the doubly spliced tax/rex RNA are Rex independent. In this study, we demonstrate that Rex does stimulate Tax expression, through nuclear-cytoplasmic export of the tax/rex RNA, even though a Rex-independent basal export mechanism exists. This effect was dependent upon the RxRE element and the RNA-binding activity of Rex. In addition, Rex-mediated export of tax/rex RNA was CRM1 dependent and inhibited by leptomycin B treatment. RNA immunoprecipitation (RNA-IP) experiments confirmed Rex binding to the tax/rex RNA in both transfected cells with HTLV-1 molecular clones and HTLV-1-infected T cells. Since both Rex and p30 interact with the tax/rex RNA and with one another, this may offer a temporal and dynamic regulation of HTLV-1 replication. Our results shed light on HTLV-1 replication and reveal a more complex regulatory network than previously anticipated. PMID:22318152

  10. Detection of O-propargyl-puromycin with SUMO and ubiquitin by click chemistry at PML-nuclear bodies during abortive proteasome activities.

    PubMed

    Uozumi, Naoki; Matsumoto, Hotaru; Saitoh, Hisato

    2016-05-27

    The amino-nucleoside antibiotic, puromycin, acts by covalently linking to elongating polypeptide chains on ribosomes to generate prematurely terminated immature polypeptides. The trafficking of puromycin-conjugated (puromycylated) immature polypeptides within cell has, however, remained elusive. In this study, using O-propargyl-puromycin (OP-Puro), the distribution of puromycylated polypeptides was assessed in HeLa cells by click chemistry. Under standard culture conditions, OP-Puro signals were detected in the cytoplasm and nucleus with the highest concentrations in the nucleolus. Intriguingly, when proteasome activities were aborted using MG132, OP-Puro signals began to accumulate at promyelocytic leukemia nuclear bodies (PML-NBs) in addition to the nucleolus. We also found promiscuous association of OP-Puro signals with SUMO-2/3 and ubiquitin at PML-NBs, but not at the nucleolus, during abortive proteasome activities. This study reveals a previously unknown distribution of OP-Puro that argues for a nuclear function in regulating immature protein homeostasis. PMID:27125456

  11. Large Atomic and Nuclear Three-Body Systems:. Scattering and Binding

    NASA Astrophysics Data System (ADS)

    Tomio, Lauro; Yamashita, M. T.; Frederico, T.

    The universal character of non-relativistic large three-body bosonic systems is addressed, with focus on highly interesting situations that occur in low-energy nuclear and atomic physics. Investigations on the trajectory of the first excited Efimov state, in a renormalized zero-range three-body model for a system with two bound and one virtual two-body subsystems, are reported. The approach is applied to n-n-18C, where the n - n virtual energy and the three-body ground state are kept fixed. It is shown that the real part of the elastic s-wave phase-shift (δ 0R ) presents a zero, or a pole in k \\cot δ 0R , when the system has an Efimov excited or virtual state. A brief discussion is given on the relevance of the approach for ultracold atom physics with tunable scattering lengths.

  12. Thermalization and many-body localization in systems under dynamic nuclear polarization

    NASA Astrophysics Data System (ADS)

    De Luca, Andrea; Rodríguez-Arias, Inés; Müller, Markus; Rosso, Alberto

    2016-07-01

    We study the role of dipolar interactions in the standard protocol used to achieve dynamic nuclear polarization (DNP). We point out that a critical strength of interactions is required to obtain significant nuclear hyperpolarization. Otherwise, the electron spins do not thermalize among each other, due to the incipient many-body localization transition in the electron spin system. Only when the interactions are sufficiently strong, in the so-called spin-temperature regime, they establish an effective thermodynamic behavior in the out-of-equilibrium stationary state. The highest polarization is reached at a point where the spin temperature is just not able to establish itself anymore. We provide numerical predictions for the level of nuclear hyperpolarization and present an analytical technique to estimate the spin temperature as a function of interaction strength and quenched disorder. We show that, at sufficiently strong coupling, nuclear spins perfectly equilibrate to the spin temperature that establishes among the spins of radicals.

  13. Identification of a novel RNA giant nuclear body in cancer cells

    PubMed Central

    Gan, Xiaoxian; Gan, Yichao; Zheng, Weiwei; Kim, Byung-Wook; Xu, Xiaohua; Lu, Xiaoya; Dong, Qi; Zheng, Shu; Huang, Wendong; Xu, Rongzhen

    2016-01-01

    Constitutive synthesis of oncogenic mRNAs is essential for maintaining the uncontrolled growth of cancer cells. However, little is known about how these mRNAs are exported from the nucleus to the cytoplasm. Here, we report the identification of a RNA giant nuclear body (RNA-GNB) that is abundant in cancer cells but rare in normal cells. The RNA-GNB contains a RNA core surrounded by a protein shell. We identify 782 proteins from cancer-associated RNA-GNBs, 40% of which are involved in the nuclear mRNA trafficking. RNA-GNB is required for cell proliferation, and its abundance is positively associated with tumor burden and outcome of therapies. Our findings suggest that the RNA-GNB is a novel nuclear RNA trafficking organelle that may contribute to the nuclear mRNA exporting and proliferation of cancer cells. PMID:26678034

  14. Nuclear extrusion precedes discharge of genomic DNA fibers during tunicamycin-induced neutrophil extracellular trap-osis (NETosis)-like cell death in cultured human leukemia cells.

    PubMed

    Nakayama, Tomofumi; Saitoh, Noriko; Morotomi-Yano, Keiko; Yano, Ken-Ichi; Nakao, Mitsuyoshi; Saitoh, Hisato

    2016-05-01

    We previously reported that the nucleoside antibiotic tunicamycin (TN), a protein glycosylation inhibitor triggering unfolded protein response (UPR), induced neutrophil extracellular trap-osis (NETosis)-like cellular suicide and, thus, discharged genomic DNA fibers to extracellular spaces in a range of human myeloid cell lines under serum-free conditions. In this study, we further evaluated the effect of TN on human promyelocytic leukemia HL-60 cells using time-lapse microscopy. Our assay revealed a previously unappreciated early event induced by TN-exposure, in which, at 30-60 min after TN addition, the cells extruded their nuclei into the extracellular space, followed by discharge of DNA fibers to form NET-like structures. Intriguingly, neither nuclear extrusion nor DNA discharge was observed when cells were exposed to inducers of UPR, such as brefeldin A, thapsigargin, or dithiothreitol. Our findings revealed novel nuclear dynamics during TN-induced NETosis-like cellular suicide in HL-60 cells and suggested that the toxicological effect of TN on nuclear extrusion and DNA discharge was not a simple UPR. PMID:26888435

  15. Comparison of total body irradiation vs chlorambucil and prednisone for remission induction of active chronic lymphocytic leukemia: an ECOG study. Part I: total body irradiation-response and toxicity

    SciTech Connect

    Rubin, P.; Bennent, J.M.; Begg, C.; Bozdech, M.J.; Silber, R.

    1981-12-01

    Twenty-six evaluable patients were entered into two fractionated total body irradiation (TBI) programs; 11 patients received a course of 150 rad TBI (x 3 if tolerated) and 15 patients received a lower dose course of 50 rad (x 3 if tolerated). Complete remissions (CR) were not produced by either course; however, the higher dose course (Plan I) yielded a partial response (PR) rate of 73%, while the lower dose course yielded a PR of 47%. Although fraction size seemed trivial in both TBI plans, an unexpected high degree of hematologic toxicity was encountered, and was parallel to the response rates: in Plan I 73% of patients experienced severe to life-threatening depression of platelets, or granulocytes, whereas in Plan II this rate was 47%. This was of short duration with rapid return of blood counts to normal levels. One death can be attributed to TBI. The chemotherapy arm of the study demonstrated superiority in terms of complete responses. Twenty-three percent of patients treated by cholrambucil and prednisone attained CR, in contrast to 0% of TBI patients. PR for chemotherapy was similar to that obtained with TBI. Chemotherapy also proved superior in terms of overall response rate, number of patients in remission, and in the median duration of response, but not in the median duration of survival. Fractional TBI techniques for active chronic lymphocytic leukemia (CLL) should be interrupted when the platelet count dips below 100,000 and the granulocyte count is lower than 2,000. Future studies should continue TBI radiation therapy and chemotherapy.

  16. Applications of nuclear techniques for in vivo body composition studies at Brookhaven National Laboratory

    SciTech Connect

    Cohn, S.H.; Ellis, K.J.; Vartsky, D.; Vaswani, A.N.; Wielopolski, L.

    1981-01-01

    A series of technical developments and their clinical applications in various nuclear technologies at Brookhaven National Laboratory is described. These include the development of a portable neutron activation facility for measuring cadmium in vivo in kidney and liver, a technique for the measurement of body iron utilizing nuclear resonant scattering of gamma rays, a non-invasive measure of the skeletal levels of lead by an x-ray fluorescence technique, and the development of a pulsed Van de Graaff generator as a source of pulsed neutrons for the measurement of lung silicon. (ACR)

  17. Role of ND10 nuclear bodies in the chromatin repression of HSV-1.

    PubMed

    Gu, Haidong; Zheng, Yi

    2016-01-01

    Herpes simplex virus (HSV) is a neurotropic virus that establishes lifelong latent infection in human ganglion sensory neurons. This unique life cycle necessitates an intimate relation between the host defenses and virus counteractions over the long course of infection. Two important aspects of host anti-viral defense, nuclear substructure restriction and epigenetic chromatin regulation, have been intensively studied in the recent years. Upon viral DNA entering the nucleus, components of discrete nuclear bodies termed nuclear domain 10 (ND10), converge at viral DNA and place restrictions on viral gene expression. Meanwhile the infected cell mobilizes its histones and histone-associated repressors to force the viral DNA into nucleosome-like structures and also represses viral transcription. Both anti-viral strategies are negated by various HSV countermeasures. One HSV gene transactivator, infected cell protein 0 (ICP0), is a key player in antagonizing both the ND10 restriction and chromatin repression. On one hand, ICP0 uses its E3 ubiquitin ligase activity to target major ND10 components for proteasome-dependent degradation and thereafter disrupts the ND10 nuclear bodies. On the other hand, ICP0 participates in de-repressing the HSV chromatin by changing histone composition or modification and therefore activates viral transcription. Involvement of a single viral protein in two seemingly different pathways suggests that there is coordination in host anti-viral defense mechanisms and also cooperation in viral counteraction strategies. In this review, we summarize recent advances in understanding the role of chromatin regulation and ND10 dynamics in both lytic and latent HSV infection. We focus on the new observations showing that ND10 nuclear bodies play a critical role in cellular chromatin regulation. We intend to find the connections between the two major anti-viral defense pathways, chromatin remodeling and ND10 structure, in order to achieve a better

  18. Low Dose Total Body Irradiation Combined With Recombinant CD19-Ligand × Soluble TRAIL Fusion Protein is Highly Effective Against Radiation-resistant B-precursor Acute Lymphoblastic Leukemia in Mice☆

    PubMed Central

    Uckun, Fatih M.; Myers, Dorothea E.; Ma, Hong; Rose, Rebecca; Qazi, Sanjive

    2015-01-01

    In high-risk remission B-precursor acute lymphoblastic leukemia (BPL) patients, relapse rates have remained high post-hematopoietic stem cell transplantation (HSCT) even after the use of very intensive total body irradiation (TBI)-based conditioning regimens, especially in patients with a high “minimal residual disease” (MRD) burden. New agents capable of killing radiation-resistant BPL cells and selectively augmenting their radiation sensitivity are therefore urgently needed. We report preclinical proof-of-principle that the potency of radiation therapy against BPL can be augmented by combining radiation with recombinant human CD19-Ligand × soluble TRAIL (“CD19L–sTRAIL”) fusion protein. CD19L–sTRAIL consistently killed radiation-resistant primary leukemia cells from BPL patients as well as BPL xenograft cells and their leukemia-initiating in vivo clonogenic fraction. Low dose total body irradiation (TBI) combined with CD19L–sTRAIL was highly effective against (1) xenografted CD19+ radiochemotherapy-resistant human BPL in NOD/SCID (NS) mice challenged with an otherwise invariably fatal dose of xenograft cells derived from relapsed BPL patients as well as (2) radiation-resistant advanced stage CD19+ murine BPL with lymphomatous features in CD22ΔE12xBCR-ABL double transgenic mice. We hypothesize that the incorporation of CD19L–sTRAIL into the pre-transplant TBI regimens of patients with very high-risk BPL will improve their survival outcome after HSCT. PMID:26097891

  19. Understanding Leukemia

    MedlinePlus

    ... a second cancer, including melanoma, sarcoma, colorectal cancer, lung cancer, basal cell cancer, squamous cell skin cancer or myeloma. {{ See your primary care doctor to keep up with other healthcare needs. Understanding Leukemia I page 21 {{ Talk with family and friends about how ...

  20. Nuclear-matter equation of state with consistent two- and three-body perturbative chiral interactions

    NASA Astrophysics Data System (ADS)

    Coraggio, L.; Holt, J. W.; Itaco, N.; Machleidt, R.; Marcucci, L. E.; Sammarruca, F.

    2014-04-01

    We compute the energy per particle of infinite symmetric nuclear matter from chiral NLO3 (next-to-next-to-next-to-leading order) two-body potentials plus NLO2 three-body forces. The low-energy constants of the chiral three-nucleon force that cannot be constrained by two-body observables are fitted to reproduce the triton binding energy and the H3-He3 Gamow-Teller transition matrix element. In this way, the saturation properties of nuclear matter are reproduced in a parameter-free approach. The equation of state is computed up to third order in many-body perturbation theory, with special emphasis on the role of the third-order particle-hole diagram. The dependence of these results on the cutoff scale and regulator function is studied. We find that the inclusion of three-nucleon forces consistent with the applied two-nucleon interaction leads to a reduced dependence on the choice of the regulator only for lower values of the cutoff.

  1. Three-body force effect on the properties of neutron-rich nuclear matter

    NASA Astrophysics Data System (ADS)

    Zuo, Wei; Bombarci, Ignazio; Lombardo, Umberto

    2016-05-01

    We review our research work in recent years on the properties of neutron-rich nuclear matter within the framework of the Brueckner theory extended to include a microscopic three-body force (TBF). We discuss specially the TBF effect on the equation of state and the singleparticle (s.p.) potentials. The TBF turns out to be crucial for describing the saturation properties of nuclear matter in nonrelativistic microscopic framework. The TBF effect on the EOS of neutron-rich nuclear matter is to result in a significant stiffening of its isovector part at supra-saturation densities. Within the Brueckner approach, the TBF may lead to a rearrangement contribution to the s.p. potentials, which enhances strongly the repulsion and momentum-dependence of the s.p. potentials at high densities and high momenta. Our results are also compared with the predictions by other ab initio approaches.

  2. MicroRNA-1301-Mediated RanGAP1 Downregulation Induces BCR-ABL Nuclear Entrapment to Enhance Imatinib Efficacy in Chronic Myeloid Leukemia Cells

    PubMed Central

    Lin, Tsung-Yao; Chen, Ku-Chung; Liu, Hsing-Jin Eugene; Liu, Ann-Jeng; Wang, Kun-Li; Shih, Chwen-Ming

    2016-01-01

    Chronic myeloid leukemia (CML) is a myeloproliferative disease. Imatinib (IM), the first line treatment for CML, is excessively expensive and induces various side effects in CML patients. Therefore, it is essential to investigate a new strategy for improving CML therapy. Our immunoblot data revealed that RanGTPase activating protein 1 (RanGAP1) protein levels increased by approximately 30-fold in K562 cells compared with those in normal cells. RanGAP1 is one of the important components of RanGTPase system, which regulates the export of nuclear protein. However, whether RanGAP1 level variation influences BCR-ABL nuclear export is still unknown. In this report, using shRNA to downregulate RanGAP1 expression level augmented K562 cell apoptosis by approximately 40% after treatment with 250 nM IM. Immunofluorescence assay also indicated that three-fold of nuclear BCR-ABL was detected. These data suggest that BCR-ABL nuclear entrapment induced by RanGAP1 downregulation can be used to improve IM efficacy. Moreover, our qRT-PCR data indicated a trend of inverse correlation between the RanGAP1 and microRNA (miR)-1301 levels in CML patients. MiR-1301, targeting the RanGAP1 3′ untranslated region, decreased by approximately 100-fold in K562 cells compared with that in normal cells. RanGAP1 downregulation by miR-1301 transfection impairs BCR-ABL nuclear export to increase approximately 60% of cell death after treatment of 250 nM IM. This result was almost the same as treatment with 1000 nM IM alone. Furthermore, immunofluorescence assay demonstrated that Tyr-99 of nuclear P73 was phosphorylated accompanied with nuclear entrapment of BCR-ABL after transfection with RanGAP1 shRNA or miR-1301 in IM-treated K562 cells. Altogether, we demonstrated that RanGAP1 downregulation can mediate BCR-ABL nuclear entrapment to activate P73-dependent apoptosis pathway which is a novel strategy for improving current IM treatment for CML. PMID:27228340

  3. Radiolabeled Monoclonal Antibody Therapy, Fludarabine Phosphate, and Low-Dose Total-Body Irradiation Followed by Donor Stem Cell Transplant and Immunosuppression Therapy in Treating Older Patients With Advanced Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndromes

    ClinicalTrials.gov

    2015-11-16

    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); Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Excess Blasts in Transformation; Refractory Anemia With Ringed Sideroblasts; Refractory Cytopenia With Multilineage Dysplasia; Secondary Myelodysplastic Syndromes; Untreated Adult Acute Myeloid Leukemia

  4. Iodine I 131 Monoclonal Antibody BC8, Fludarabine Phosphate, Total Body Irradiation, and Donor Stem Cell Transplant Followed by Cyclosporine and Mycophenolate Mofetil in Treating Patients With Advanced Acute Myeloid Leukemia or Myelodysplastic Syndrome

    ClinicalTrials.gov

    2015-11-16

    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); Childhood Myelodysplastic Syndromes; Chronic Myelomonocytic Leukemia; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Excess Blasts in Transformation; Refractory Anemia With Ringed Sideroblasts; Refractory Cytopenia With Multilineage Dysplasia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes

  5. Targeting of Nbp1 to the inner nuclear membrane is essential for spindle pole body duplication

    PubMed Central

    Kupke, Thomas; Di Cecco, Leontina; Müller, Hans-Michael; Neuner, Annett; Adolf, Frank; Wieland, Felix; Nickel, Walter; Schiebel, Elmar

    2011-01-01

    Spindle pole bodies (SPBs), like nuclear pore complexes, are embedded in the nuclear envelope (NE) at sites of fusion of the inner and outer nuclear membranes. A network of interacting proteins is required to insert a cytoplasmic SPB precursor into the NE. A central player of this network is Nbp1 that interacts with the conserved integral membrane protein Ndc1. Here, we establish that Nbp1 is a monotopic membrane protein that is essential for SPB insertion at the inner face of the NE. In vitro and in vivo studies identified an N-terminal amphipathic α-helix of Nbp1 as a membrane-binding element, with crucial functions in SPB duplication. The karyopherin Kap123 binds to a nuclear localization sequence next to this amphipathic α-helix and prevents unspecific tethering of Nbp1 to membranes. After transport into the nucleus, Nbp1 binds to the inner nuclear membrane. These data define the targeting pathway of a SPB component and suggest that the amphipathic α-helix of Nbp1 is important for SPB insertion into the NE from within the nucleus. PMID:21785410

  6. Role of fungal dynein in hyphal growth, microtubule organization, spindle pole body motility and nuclear migration.

    PubMed

    Inoue, S; Turgeon, B G; Yoder, O C; Aist, J R

    1998-06-01

    Cytoplasmic dynein is a microtubule-associated motor protein with several putative subcellular functions. Sequencing of the gene (DHC1) for cytoplasmic dynein heavy chain of the filamentous ascomycete, Nectria haematococca, revealed a 4,349-codon open reading frame (interrupted by two introns) with four highly conserved P-loop motifs, typical of cytoplasmic dynein heavy chains. The predicted amino acid sequence is 78.0% identical to the cytoplasmic dynein heavy chain of Neurospora crassa, 70.2% identical to that of Aspergillus nidulans and 24.8% identical to that of Saccharomyces cerevisiae. The genomic copy of DHC1 in N. haematococca wild-type strain T213 was disrupted by inserting a selectable marker into the central motor domain. Mutants grew at 33% of the wild-type rate, forming dense compact colonies composed of spiral and highly branched hyphae. Major cytological phenotypes included (1) absence of aster-like arrays of cytoplasmic microtubules focused at the spindle pole bodies of post-mitotic and interphase nuclei, (2) limited post-mitotic nuclear migration, (3) lack of spindle pole body motility at interphase, (4) failure of spindle pole bodies to anchor interphase nuclei, (5) nonuniform distribution of interphase nuclei and (6) small or ephemeral Spitzenkörper at the apices of hyphal tip cells. Microtubule distribution in the apical region of tip cells of the mutant was essentially normal. The nonuniform distribution of nuclei in hyphae resulted primarily from a lack of both post-mitotic nuclear migration and anchoring of interphase nuclei by the spindle pole bodies. The results support the hypothesis that DHC1 is required for the motility and functions of spindle pole bodies, normal secretory vesicle transport to the hyphal apex and normal hyphal tip cell morphogenesis. PMID:9580563

  7. Chromatin remodeling complexes in the assembly of long noncoding RNA-dependent nuclear bodies.

    PubMed

    Kawaguchi, Tetsuya; Hirose, Tetsuro

    2015-11-01

    Paraspeckles are subnuclear structures that assemble on nuclear paraspeckle assembly transcript 1 (NEAT1) long noncoding (lnc)RNA. Paraspeckle formation requires appropriate NEAT1 biogenesis and subsequent assembly with multiple prion-like domain (PLD) containing RNA-binding proteins. We found that SWI/SNF chromatin remodeling complexes function as paraspeckle components that interact with paraspeckle proteins (PSPs) and NEAT1. SWI/SNF complexes play an essential role in paraspeckle formation that does not require their ATP-dependent chromatin remodeling activity. Instead, SWI/SNF complexes facilitate organization of the PSP interaction network required for intact paraspeckle assembly. SWI/SNF complexes may collectively bind multiple PSPs to recruit them onto NEAT1. SWI/SNF complexes are also required for Sat III (Satellite III) lncRNA-dependent formation of nuclear stress bodies under heat shock conditions. Organization of the lncRNA-dependent omega speckle in Drosophila also depends on the chromatin remodeling complex. These findings raise the possibility that a common mechanism controls the formation of lncRNA-dependent nuclear body architecture. PMID:26709446

  8. Liposomal Nanoparticles of a Spleen Tyrosine Kinase P-Site Inhibitor Amplify the Potency of Low Dose Total Body Irradiation Against Aggressive B-Precursor Leukemia and Yield Superior Survival Outcomes in Mice☆

    PubMed Central

    Uckun, Fatih M.; Myers, Dorothea E.; Cheng, Jianjun; Qazi, Sanjive

    2015-01-01

    This study was designed to improve the efficacy of radiation therapy against radiation-resistant leukemia. We report that the potency of low dose radiation therapy against B-precursor acute lymphoblastic leukemia (BPL) can be markedly enhanced by combining radiation with a liposomal nanoparticle (LNP) formulation of the SYK-P-site inhibitor C61 (“C61-LNP”). C61-LNP plus low dose total body irradiation (TBI) was substantially more effective than TBI alone or C61-LNP alone in improving the event-free survival outcome NOD/SCID mice challenged with an otherwise invariably fatal dose of human ALL xenograft cells derived from relapsed BPL patients. C61-LNP plus low dose TBI also yielded progression-free survival, tumor-free survival and overall survival outcomes in CD22ΔE12 × BCR–ABL double transgenic mice with advanced stage, radiation-resistant BPL with lymphomatous features that were significantly superior to those of mice treated with TBI alone or C61-LNP alone. PMID:26285772

  9. Nuclear three-body problem in the complex energy plane: Complex-scaling Slater method

    NASA Astrophysics Data System (ADS)

    Kruppa, A. T.; Papadimitriou, G.; Nazarewicz, W.; Michel, N.

    2014-01-01

    Background: The physics of open quantum systems is an interdisciplinary area of research. The nuclear "openness" manifests itself through the presence of the many-body continuum representing various decay, scattering, and reaction channels. As the radioactive nuclear beam experimentation extends the known nuclear landscape toward the particle drip lines, the coupling to the continuum space becomes exceedingly more important. Of particular interest are weakly bound and unbound nuclear states appearing around particle thresholds. Theories of such nuclei must take into account their open quantum nature. Purpose: To describe open quantum systems, we introduce a complex-scaling (CS) approach in the Slater basis. We benchmark it with the complex-energy Gamow shell model (GSM) by studying energies and wave functions of the bound and unbound states of the two-neutron halo nucleus 6He viewed as an α +n+n cluster system. Methods: Both CS and GSM approaches are applied to a translationally invariant Hamiltonian with the two-body interaction approximated by the finite-range central Minnesota force. In the CS approach, we use the Slater basis, which exhibits the correct asymptotic behavior at large distances. To extract particle densities from the back-rotated CS solutions, we apply the Tikhonov regularization procedure, which minimizes the ultraviolet numerical noise. Results: We show that the CS-Slater method is both accurate and efficient. Its equivalence to the GSM approach has been demonstrated numerically for both energies and wave functions of 6He. One important technical aspect of our calculation was to fully retrieve the correct asymptotic behavior of a resonance state from the complex-scaled (square-integrable) wave function. While standard applications of the inverse complex transformation to the complex-rotated solution provide unstable results, the stabilization method fully reproduces the GSM benchmark. We also propose a method to determine the smoothing

  10. Nuclear Immunolocalization of Hexamerins in the Fat Body of Metamorphosing Honey Bees.

    PubMed

    Martins, Juliana Ramos; Bitondi, Márcia Maria Gentile

    2012-01-01

    Hexamerins are storage proteins with primordial functions in insect metamorphosis. They are actively secreted by the larval fat body and stored in the hemolymph. During metamorphosis, they return to the fat body to be processed. For decades, these proteins were thought to exclusively function as an amino acid source for tissue reconstruction during the non-feeding pupal and pharate adult stages and, in some species, for egg production. Recently, new findings have linked the hexamerins to caste polyphenism and gonad development in social insects. To explore the roles of hexamerins during the honey bee metamorphosis, we used specific antibodies in expression analysis by western blot, in situ immunolocalization by confocal laser-scanning microscopy and in vivo injections to lower their endogenous levels. Our expression analysis highlighted the changing expression patterns in the fat body and hemolymph during development, which is consistent with the temporal dynamics of hexamerin secretion, storage and depletion. Confocal microscopy showed hexamerin expression in the cytoplasm of both types of fat body cells, trophocytes and oenocytes. Notably, hexamerin foci were also found in the nuclei of these cells, thus confirming our western blot analysis of fat body nuclear-enriched fractions. We also observed that the decrease in soluble hexamerins in antibody-treated pharate adults led to a precocious adult ecdysis, perhaps in response to the lack (or decrease) in hexamerin-derived amino acids. Taken together, these findings indicate that hexamerins have other functions in addition to their well-established role as amino acid sources for development. PMID:26466725

  11. Nuclear Immunolocalization of Hexamerins in the Fat Body of Metamorphosing Honey Bees

    PubMed Central

    Martins, Juliana Ramos; Bitondi, Márcia Maria Gentile

    2012-01-01

    Hexamerins are storage proteins with primordial functions in insect metamorphosis. They are actively secreted by the larval fat body and stored in the hemolymph. During metamorphosis, they return to the fat body to be processed. For decades, these proteins were thought to exclusively function as an amino acid source for tissue reconstruction during the non-feeding pupal and pharate adult stages and, in some species, for egg production. Recently, new findings have linked the hexamerins to caste polyphenism and gonad development in social insects. To explore the roles of hexamerins during the honey bee metamorphosis, we used specific antibodies in expression analysis by western blot, in situ immunolocalization by confocal laser-scanning microscopy and in vivo injections to lower their endogenous levels. Our expression analysis highlighted the changing expression patterns in the fat body and hemolymph during development, which is consistent with the temporal dynamics of hexamerin secretion, storage and depletion. Confocal microscopy showed hexamerin expression in the cytoplasm of both types of fat body cells, trophocytes and oenocytes. Notably, hexamerin foci were also found in the nuclei of these cells, thus confirming our western blot analysis of fat body nuclear-enriched fractions. We also observed that the decrease in soluble hexamerins in antibody-treated pharate adults led to a precocious adult ecdysis, perhaps in response to the lack (or decrease) in hexamerin-derived amino acids. Taken together, these findings indicate that hexamerins have other functions in addition to their well-established role as amino acid sources for development. PMID:26466725

  12. Variants within the SP110 nuclear body protein modify risk of canine degenerative myelopathy.

    PubMed

    Ivansson, Emma L; Megquier, Kate; Kozyrev, Sergey V; Murén, Eva; Körberg, Izabella Baranowska; Swofford, Ross; Koltookian, Michele; Tonomura, Noriko; Zeng, Rong; Kolicheski, Ana L; Hansen, Liz; Katz, Martin L; Johnson, Gayle C; Johnson, Gary S; Coates, Joan R; Lindblad-Toh, Kerstin

    2016-05-31

    Canine degenerative myelopathy (DM) is a naturally occurring neurodegenerative disease with similarities to some forms of amyotrophic lateral sclerosis (ALS). Most dogs that develop DM are homozygous for a common superoxide dismutase 1 gene (SOD1) mutation. However, not all dogs homozygous for this mutation develop disease. We performed a genome-wide association analysis in the Pembroke Welsh Corgi (PWC) breed comparing DM-affected and -unaffected dogs homozygous for the SOD1 mutation. The analysis revealed a modifier locus on canine chromosome 25. A haplotype within the SP110 nuclear body protein (SP110) was present in 40% of affected compared with 4% of unaffected dogs (P = 1.5 × 10(-5)), and was associated with increased probability of developing DM (P = 4.8 × 10(-6)) and earlier onset of disease (P = 1.7 × 10(-5)). SP110 is a nuclear body protein involved in the regulation of gene transcription. Our findings suggest that variations in SP110-mediated gene transcription may underlie, at least in part, the variability in risk for developing DM among PWCs that are homozygous for the disease-related SOD1 mutation. Further studies are warranted to clarify the effect of this modifier across dog breeds. PMID:27185954

  13. Variants within the SP110 nuclear body protein modify risk of canine degenerative myelopathy

    PubMed Central

    Ivansson, Emma L.; Kozyrev, Sergey V.; Murén, Eva; Körberg, Izabella Baranowska; Swofford, Ross; Koltookian, Michele; Tonomura, Noriko; Zeng, Rong; Kolicheski, Ana L.; Hansen, Liz; Katz, Martin L.; Johnson, Gayle C.; Johnson, Gary S.; Coates, Joan R.; Lindblad-Toh, Kerstin

    2016-01-01

    Canine degenerative myelopathy (DM) is a naturally occurring neurodegenerative disease with similarities to some forms of amyotrophic lateral sclerosis (ALS). Most dogs that develop DM are homozygous for a common superoxide dismutase 1 gene (SOD1) mutation. However, not all dogs homozygous for this mutation develop disease. We performed a genome-wide association analysis in the Pembroke Welsh Corgi (PWC) breed comparing DM-affected and -unaffected dogs homozygous for the SOD1 mutation. The analysis revealed a modifier locus on canine chromosome 25. A haplotype within the SP110 nuclear body protein (SP110) was present in 40% of affected compared with 4% of unaffected dogs (P = 1.5 × 10−5), and was associated with increased probability of developing DM (P = 4.8 × 10−6) and earlier onset of disease (P = 1.7 × 10−5). SP110 is a nuclear body protein involved in the regulation of gene transcription. Our findings suggest that variations in SP110-mediated gene transcription may underlie, at least in part, the variability in risk for developing DM among PWCs that are homozygous for the disease-related SOD1 mutation. Further studies are warranted to clarify the effect of this modifier across dog breeds. PMID:27185954

  14. Leukemia revisited

    SciTech Connect

    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.

  15. The leukemias: Epidemiologic aspects

    SciTech Connect

    Linet, M.S.

    1984-01-01

    Particularly geared to physicians and cancer researchers, this study of the epidemiology and etiology of leukemia analyzes the four major leukemia subtypes in terms of genetic and familial determinant factors and examines the incidence, distribution and frequency of reported leukemia clusters. Linet discusses the connection between other types of malignancies, their treatments, and the subsequent development of leukemia and evaluates the impact on leukemia onset of such environmental factors as radiation therapy, drugs, and occupational hazards.

  16. Influence of nuclear interactions in body tissues on tumor dose in carbon-ion radiotherapy

    SciTech Connect

    Inaniwa, T. Kanematsu, N.; Tsuji, H.; Kamada, T.

    2015-12-15

    Purpose: In carbon-ion radiotherapy treatment planning, the planar integrated dose (PID) measured in water is applied to the patient dose calculation with density scaling using the stopping power ratio. Since body tissues are chemically different from water, this dose calculation can be subject to errors, particularly due to differences in inelastic nuclear interactions. In recent studies, the authors proposed and validated a PID correction method for these errors. In the present study, the authors used this correction method to assess the influence of these nuclear interactions in body tissues on tumor dose in various clinical cases. Methods: Using 10–20 cases each of prostate, head and neck (HN), bone and soft tissue (BS), lung, liver, pancreas, and uterine neoplasms, the authors first used treatment plans for carbon-ion radiotherapy without nuclear interaction correction to derive uncorrected dose distributions. The authors then compared these distributions with recalculated distributions using the nuclear interaction correction (corrected dose distributions). Results: Median (25%/75% quartiles) differences between the target mean uncorrected doses and corrected doses were 0.2% (0.1%/0.2%), 0.0% (0.0%/0.0%), −0.3% (−0.4%/−0.2%), −0.1% (−0.2%/−0.1%), −0.1% (−0.2%/0.0%), −0.4% (−0.5%/−0.1%), and −0.3% (−0.4%/0.0%) for the prostate, HN, BS, lung, liver, pancreas, and uterine cases, respectively. The largest difference of −1.6% in target mean and −2.5% at maximum were observed in a uterine case. Conclusions: For most clinical cases, dose calculation errors due to the water nonequivalence of the tissues in nuclear interactions would be marginal compared to intrinsic uncertainties in treatment planning, patient setup, beam delivery, and clinical response. In some extreme cases, however, these errors can be substantial. Accordingly, this correction method should be routinely applied to treatment planning in clinical practice.

  17. Ab initio nuclear many-body perturbation calculations in the Hartree-Fock basis

    NASA Astrophysics Data System (ADS)

    Hu, B. S.; Xu, F. R.; Sun, Z. H.; Vary, J. P.; Li, T.

    2016-07-01

    Starting from realistic nuclear forces, the chiral N3LO and JISP16, we have applied many-body perturbation theory (MBPT) to the structure of closed-shell nuclei, 4He and 16O. The two-body N3LO interaction is softened by a similarity renormalization group transformation while JISP16 is adopted without renormalization. The MBPT calculations are performed within the Hartree-Fock (HF) bases. The angular momentum coupled scheme is used, which can reduce the computational task. Corrections up to the third order in energy and up to the second order in radius are evaluated. Higher-order corrections in the HF basis are small relative to the leading-order perturbative result. Using the antisymmetrized Goldstone diagram expansions of the wave function, we directly correct the one-body density for the calculation of the radius, rather than calculate corrections to the occupation probabilities of single-particle orbits as found in other treatments. We compare our results with other methods where available and find good agreement. This supports the conclusion that our methods produce reasonably converged results with these interactions. We also compare our results with experimental data.

  18. Dynamic localization of tripartite motif-containing 22 in nuclear and nucleolar bodies

    SciTech Connect

    Sivaramakrishnan, Gayathri; Sun, Yang; Tan, Si Kee; Lin, Valerie C.L.

    2009-05-01

    Tripartite motif-containing 22 (TRIM22) exhibits antiviral and growth inhibitory properties, but there has been no study on the localization and dynamics of the endogenous TRIM22 protein. We report here that TRIM22 is dramatically induced by progesterone in MDA-MB-231-derived ABC28 cells and T47D cells. This induction was associated with an increase in TRIM22 nuclear bodies (NB), and an even more prominent increase in nucleolar TRIM22 bodies. Distinct endogenous TRIM22 NB were also demonstrated in several other cell lines including MCF7 and HeLa cells. These TRIM22 NB resemble Cajal bodies, co-localized with these structures and co-immunoprecipitated with p80-coilin. However, IFN{gamma}-induced TRIM22 in HeLa and MCF7 cells did not form NB, implying the forms and distribution of TRIM22 are regulated by specific cellular signals. This notion is also supported by the observation that TRIM22 NB undergoes dynamic cell-cycle dependent changes in distribution such that TRIM22 NB started to form in early G0/G1 but became dispersed in the S-phase. In light of its potential antiviral and antitumor properties, the findings here provide an interesting gateway to study the relationship between the different forms and functions of TRIM22.

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

    ClinicalTrials.gov

    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

  20. What Is Chronic Myeloid Leukemia?

    MedlinePlus

    ... leukemia? Next Topic Normal bone marrow and blood 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 ...

  1. Faddeev-type calculation of (d ,n ) transfer reactions in three-body nuclear systems

    NASA Astrophysics Data System (ADS)

    Deltuva, A.

    2015-12-01

    Exact Faddeev-type three-body equations are applied to the study of the proton transfer reactions (d ,n ) in the system consisting of a nuclear core and two nucleons. The integral equations for the three-body transition operators are solved in the momentum-space framework including the Coulomb interaction via the screening and renormalization method. For a weakly bound final nucleus the calculation of the (d ,n ) reaction is more demanding in terms of the screening radius as compared to the (d ,p ) reaction. Well-converged differential cross section results are obtained for 7Be (d ,n ) 8B, 12C (d ,n ) 13N, and 16O (d ,n ) 17$ reactions. A comparison with the corresponding (d ,p ) reactions is made. The calculations fail to reproduce the shape of the angular distribution for reactions on 12C but provide quite successful description for reactions on 16O, especially for the transfer to the 17F excited state 1 /2+ when using a nonlocal optical potential.

  2. An Introductory Guide to GREEN’S Function Methods in Nuclear Many-Body Problems

    NASA Astrophysics Data System (ADS)

    Kuo, T. T. S.; Tzeng, Yiharn

    We present an elementary and fairly detailed review of several Green’s function methods for treating nuclear and other many-body systems. We first treat the single-particle Green’s function, by way of which some details concerning linked diagram expansion, rules for evaluating Green’s function diagrams and solution of the Dyson’s integral equation for Green’s function are exhibited. The particle-particle hole-hole (pphh) Green’s function is then considered, and a specific time-blocking technique is discussed. This technique enables us to have a one-frequency Dyson’s equation for the pphh and similarly for other Green’s functions, thus considerably facilitating their calculation. A third type of Green’s function considered is the particle-hole Green’s function. RPA and high order RPA are treated, along with examples for setting up particle-hole RPA equations. A general method for deriving a model-space Dyson’s equation for Green’s functions is discussed. We also discuss a method for determining the normalization of Green’s function transition amplitudes based on its vertex function. Some applications of Green’s function methods to nuclear structure and recent deep inelastic lepton-nucleus scattering are addressed.

  3. Formation of nuclear bodies in hepatocytes of estrogen-treated roosters.

    PubMed Central

    Ochs, R L; Stein, T W; Andrade, L E; Gallo, D; Chan, E K; Tan, E M; Brasch, K

    1995-01-01

    As a model for cellular growth and stimulation without accompanying proliferation, we have examined the induction and formation of nuclear bodies (NBs) in hepatocytes of estrogen-treated roosters. Four-week-old roosters were injected with a single intramuscular dose of estradiol and then killed at time points of 8 h, 48 h, and 4 wk post-injection. For immunofluorescence analyses, livers were excised and isolated hepatocyte nuclei were fixed and then labeled with antibody to the coiled body-specific protein, p80-coilin. In control animals (no estradiol) or in animals 8 h post-injection, each hepatocyte nucleus contained an average of 1.0 coiled body (CB), which appeared randomly distributed in the nucleoplasm. At 48 h post-injection, there were an average of 2.7 CBs/nucleus and many of these appeared to be in contact with the nucleolus. Pairs of CBs were also observed. By 4 wk post-injection an average of 1.5 CBs/nucleus were detected, with no apparent relationship to the nucleolus observed. By serial-section electron microscopy of intact livers, two different types of round NBs were observed, sometimes in close proximity to each other and to the expanded interchromatin granule region in maximally stimulated cells. One type of NB was a classical CB that averaged 0.35 microns in diameter and the other NB type was ring shaped, averaged 0.25 microns in diameter, was composed of a fibrous shell surrounding a hollow interior, and appeared as a simple NB when sectioned tangentially through its outer shell. Immunoelectron microscopy revealed that CBs were the only class of NBs that contained p80-coilin. From these data, we conclude that CBs proliferate in response to estrogen stimulation, possibly arising from the nucleolar surface and then increasing in number by replicative division. Images PMID:7612968

  4. Intracellular Bacterial Pathogens Trigger the Formation of U Small Nuclear RNA Bodies (U Bodies) through Metabolic Stress Induction.

    PubMed

    Tsalikis, Jessica; Tattoli, Ivan; Ling, Arthur; Sorbara, Matthew T; Croitoru, David O; Philpott, Dana J; Girardin, Stephen E

    2015-08-21

    Invasive bacterial pathogens induce an amino acid starvation (AAS) response in infected host cells that controls host defense in part by promoting autophagy. However, whether AAS has additional significant effects on the host response to intracellular bacteria remains poorly characterized. Here we showed that Shigella, Salmonella, and Listeria interfere with spliceosomal U snRNA maturation in the cytosol. Bacterial infection resulted in the rerouting of U snRNAs and their cytoplasmic escort, the survival motor neuron (SMN) complex, to processing bodies, thus forming U snRNA bodies (U bodies). This process likely contributes to the decline in the cytosolic levels of U snRNAs and of the SMN complex proteins SMN and DDX20 that we observed in infected cells. U body formation was triggered by membrane damage in infected cells and was associated with the induction of metabolic stresses, such as AAS or endoplasmic reticulum stress. Mechanistically, targeting of U snRNAs to U bodies was regulated by translation initiation inhibition and the ATF4/ATF3 pathway, and U bodies rapidly disappeared upon removal of the stress, suggesting that their accumulation represented an adaptive response to metabolic stress. Importantly, this process likely contributed to shape the host response to invasive bacteria because down-regulation of DDX20 expression using short hairpin RNA (shRNA) amplified ATF3- and NF-κB-dependent signaling. Together, these results identify a critical role for metabolic stress and invasive bacterial pathogens in U body formation and suggest that this process contributes to host defense. PMID:26134566

  5. Drugs Approved for Leukemia

    MedlinePlus

    ... Ask about Your Treatment Research Drugs Approved for Leukemia This page lists cancer drugs approved by the ... not listed here. Drugs Approved for Acute Lymphoblastic Leukemia (ALL) Abitrexate (Methotrexate) Arranon (Nelarabine) Asparaginase Erwinia chrysanthemi ...

  6. Chronic lymphocytic leukemia (CLL)

    MedlinePlus

    CLL; Leukemia - chronic lymphocytic (CLL) ... Byrd JC, Flynn JM. Chronic lymphocytic leukemia. In: Niederhuber JE, Armitage JO, Doroshow JH, Kastan MB, Tepper JE, eds. Abeloff's Clinical Oncology. 5th ed. Philadelphia, PA: Elsevier ...

  7. Acute Lymphocytic Leukemia

    MedlinePlus

    ... hard for blood to do its work. In acute lymphocytic leukemia (ALL), also called acute lymphoblastic leukemia, there are too ... of white blood cells called lymphocytes or lymphoblasts. ALL is the most common type of cancer in ...

  8. 40 CFR 180.1149 - Inclusion bodies of the multi-nuclear polyhedrosis virus of Anagrapha falcifera; exemption from...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... polyhedrosis virus of Anagrapha falcifera; exemption from the requirement of a tolerance. 180.1149 Section 180... Inclusion bodies of the multi-nuclear polyhedrosis virus of Anagrapha falcifera; exemption from the... polyhedrosis virus of Anagrapha falcifera is exempted from the requirement of a tolerance in or on all...

  9. 40 CFR 180.1149 - Inclusion bodies of the multi-nuclear polyhedrosis virus of Anagrapha falcifera; exemption from...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... polyhedrosis virus of Anagrapha falcifera; exemption from the requirement of a tolerance. 180.1149 Section 180... Inclusion bodies of the multi-nuclear polyhedrosis virus of Anagrapha falcifera; exemption from the... polyhedrosis virus of Anagrapha falcifera is exempted from the requirement of a tolerance in or on all...

  10. 40 CFR 180.1149 - Inclusion bodies of the multi-nuclear polyhedrosis virus of Anagrapha falcifera; exemption from...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... polyhedrosis virus of Anagrapha falcifera; exemption from the requirement of a tolerance. 180.1149 Section 180... Inclusion bodies of the multi-nuclear polyhedrosis virus of Anagrapha falcifera; exemption from the... polyhedrosis virus of Anagrapha falcifera is exempted from the requirement of a tolerance in or on all...

  11. 40 CFR 180.1149 - Inclusion bodies of the multi-nuclear polyhedrosis virus of Anagrapha falcifera; exemption from...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... polyhedrosis virus of Anagrapha falcifera; exemption from the requirement of a tolerance. 180.1149 Section 180... Inclusion bodies of the multi-nuclear polyhedrosis virus of Anagrapha falcifera; exemption from the... polyhedrosis virus of Anagrapha falcifera is exempted from the requirement of a tolerance in or on all...

  12. 40 CFR 180.1149 - Inclusion bodies of the multi-nuclear polyhedrosis virus of Anagrapha falcifera; exemption from...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... polyhedrosis virus of Anagrapha falcifera; exemption from the requirement of a tolerance. 180.1149 Section 180... Inclusion bodies of the multi-nuclear polyhedrosis virus of Anagrapha falcifera; exemption from the... polyhedrosis virus of Anagrapha falcifera is exempted from the requirement of a tolerance in or on all...

  13. PREFACE: Many-body correlations from dilute to dense nuclear systems

    NASA Astrophysics Data System (ADS)

    Otsuka, Takaharu; Urban, Michael; Yamada, Taiichi

    2011-09-01

    The International EFES-IN2P3 conference on "Many body correlations from dilute to dense nuclear systems" was held at the Institut Henri Poincaré (IHP), Paris, France, from 15-18 February 2011, on the occasion of the retirement of our colleague Peter Schuck. Correlations play a decisive role in various many-body systems such as nuclear systems, condensed matter and quantum gases. Important examples include: pairing correlations (Cooper pairs) which give rise to nuclear superfluidity (analogous to superconductivity in condensed matter); particle-hole (RPA) correlations in the description of the ground state beyond mean-field theory; clusters; and α-particle correlations in certain nuclei. Also, the nucleons themselves can be viewed as clusters of three quarks. During the past few years, researchers have started to study how the character of these correlations changes with the variation of the density. For instance, the Cooper pairs in dense matter can transform into a Bose-Einstein condensate (BEC) of true bound states at low density (this is the BCS-BEC crossover studied in ultracold Fermi gases). Similar effects play a role in neutron matter at low density, e.g., in the "neutron skin" of exotic nuclei. The α-cluster correlation becomes particularly important at lower density, such as in the excited states of some nuclei (e.g., the α-condensate-like structure in the Hoyle state of 12C) or in the formation of compact stars. In addition to nuclear physics, topics from astrophysics (neutron stars), condensed matter, and quantum gases were discussed in 48 talks and 19 posters, allowing the almost 90 participants from different communities to exchange their ideas, experiences and methods. The conference dinner took place at the Musée d'Orsay, and all the participants enjoyed the very pleasant atmosphere. One session of the conference was dedicated to the celebration of Peter's retirement. We would like to take this opportunity to wish Peter all the best and we hope

  14. [The infant with leukemia].

    PubMed

    Kamps, W A; Sjamsoedin-Visser, E J; van Wering, E R

    1988-04-01

    Infant leukemia is rare and especially in newborn leukemoid reactions should be excluded by careful cytogenetic analysis before starting cytotoxic therapy. Infants have either acute lymphoblastic leukemia, monoblastic leukemia or acute undifferentiated leukemia. At present they have a bad outlook due to many coinciding unfavorable initial disease characteristics: high leukocyte count, liver and spleen enlargement, meningeal involvement, no expression of common ALL antigen, and a high frequency of pseudodiploid cells, that is with a translocation 4;II. The immaturity of organs and systems makes it difficult to treat these infants, and requires optimal supportive care. Therapeutic protocols for prospective clinical trials for leukemia in this age group are urgently needed. PMID:3287687

  15. The Role of Three-Nucleon Forces and Many-Body Processes in Nuclear Pairing

    SciTech Connect

    Holt, Jason D.

    2013-01-01

    We present microscopic valence-shell calculations of pairing gaps in the calcium isotopes, focusing on the role of three-nucleon (3N) forces and manybody processes. In most cases, we find a reduction in pairing strength when the leading chiral 3N forces are included, compared to results with lowmomentum two-nucleon (NN) interactions only. This is in agreement with a recent energy density functional study. At the NN level, calculations that include particle particle and hole hole ladder contributions lead to smaller pairing gaps compared with experiment. When particle hole contributions as well as the normal-ordered one- and two-body parts of 3N forces are consistently included to third order, we find reasonable agreement with experimental three-point mass differences. This highlights the important role of 3N forces and manybody processes for pairing in nuclei. Finally, we relate pairing gaps to the evolution of nuclear structure in neutron-rich calcium isotopes and study the predictions for the 2+ excitation energies, in particular for 54Ca.

  16. What Are the Risk Factors for Chronic Myeloid Leukemia?

    MedlinePlus

    ... of an atomic bomb blast or nuclear reactor accident) increases the risk of getting CML Age : The ... Myeloid (CML)? Causes, Risk Factors, and Prevention Early Detection, Diagnosis, and Staging Treating Leukemia - Chronic Myeloid (CML) ...

  17. Allogeneic hematopoietic cell transplantation after conditioning with I-131-anti-CD45 antibody plus fludarabine and low-dose total body irradiation for elderly patients with advanced acute myeloid leukemia or high-risk myelodysplastic syndrome.

    SciTech Connect

    Pagel, John M.; Gooley, T. A.; Rajendran, Joseph G.; Fisher, Darrell R.; Wilson, Wendy A.; Sandmaier, B. M.; Matthews, D. C.; Deeg, H. Joachim; Gopal, Ajay K.; Martin, P. J.; Storb, R.; Press, Oliver W.; Appelbaum, Frederick R.

    2009-12-24

    We conducted a study to estimate the maximum tolerated dose (MTD) of I-131-anti-CD45 antibody (Ab; BC8) that can be combined with a standard reduced-intensity conditioning regimen before allogeneic hematopoietic cell transplantation. Fifty-eight patients older than 50 years with advanced acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (MDS) were treated with (131)I-BC8 Ab and fludarabine plus 2 Gy total body irradiation. Eighty-six percent of patients had AML or MDS with greater than 5% marrow blasts at the time of transplantation. Treatment produced a complete remission in all patients, and all had 100% donor-derived CD3(+) and CD33(+) cells in the blood by day 28 after the transplantation. The MTD of I-131-BC8 Ab delivered to liver was estimated to be 24 Gy. Seven patients (12%) died of nonrelapse causes by day 100. The estimated probability of recurrent malignancy at 1 year is 40%, and the 1-year survival estimate is 41%. These results show that CD45-targeted radiotherapy can be safely combined with a reduced-intensity conditioning regimen to yield encouraging overall survival for older, high-risk patients with AML or MDS. This study was registered at www.clinicaltrials.gov as #NCT00008177.

  18. Leukemia risk following radiotherapy for breast cancer

    SciTech Connect

    Curtis, R.E.; Boice, J.D. Jr.; Stovall, M.; Flannery, J.T.; Moloney, W.C.

    1989-01-01

    To evaluate further the relationship between high-dose radiotherapy and leukemia incidence, a nested case-control study was conducted in a cohort of 22,753 women who were 18-month survivors of invasive breast cancer diagnosed from 1935 to 1972. Women treated for breast cancer after 1973 were excluded to minimize the possible confounding influence of treatment with chemotherapeutic agents. The cases had histologically confirmed leukemia reported to the Connecticut Tumor Registry (CTR) between 1935 and 1984. A total of 48 cases of leukemia following breast cancer were included in the study. Two controls were individually matched to each leukemia case on the basis of age, calendar year when diagnosed with breast cancer, and survival time. Leukemia diagnoses were verified by one hematologist. Radiation dose to active bone marrow was estimated by medical physicists on the basis of the original radiotherapy records of study subjects. Local radiation doses to each of the 16 bone marrow components for each patient were reconstructed; the dose averaged over the entire body was 530 rad (5.3 Gy). Based on this dosage and assuming a linear relationship between dose and affect, a relative risk (RR) in excess of 10 would have been expected. However, there was little evidence that radiotherapy increased the overall risk of leukemia (RR = 1.16; 90% confidence interval (CI), 0.6 to 2.1). The risk of chronic lymphocytic leukemia, one of the few malignancies without evidence for an association with ionizing radiation, was not significantly increased (RR = 1.8; n = 10); nor was the risk for all other forms of leukemia (RR = 1.0; n = 38). There was no indication that risk varied over categories of radiation dose.

  19. What You Need to Know about Leukemia

    MedlinePlus

    ... Publications Reports What You Need To Know About™ Leukemia This booklet is about leukemia. Leukemia is cancer of the blood and bone marrow ( ... This book covers: Basics about blood cells and leukemia Types of doctors who treat leukemia Treatments for ...

  20. Protein kinase A activation enhances β-catenin transcriptional activity through nuclear localization to PML bodies.

    PubMed

    Zhang, Mei; Mahoney, Emilia; Zuo, Tao; Manchanda, Parmeet K; Davuluri, Ramana V; Kirschner, Lawrence S

    2014-01-01

    The Protein Kinase A (PKA) and Wnt signaling cascades are fundamental pathways involved in cellular development and maintenance. In the osteoblast lineage, these pathways have been demonstrated functionally to be essential for the production of mineralized bone. Evidence for PKA-Wnt crosstalk has been reported both during tumorigenesis and during organogenesis, and the nature of the interaction is thought to rely on tissue and cell context. In this manuscript, we analyzed bone tumors arising from mice with activated PKA caused by mutation of the PKA regulatory subunit Prkar1a. In primary cells from these tumors, we observed relocalization of β-catenin to intranuclear punctuate structures, which were identified as PML bodies. Cellular redistribution of β-catenin could be recapitulated by pharmacologic activation of PKA. Using 3T3-E1 pre-osteoblasts as a model system, we found that PKA phosphorylation sites on β-catenin were required for nuclear re-localization. Further, β-catenin's transport to the nucleus was accompanied by an increase in canonical Wnt-dependent transcription, which also required the PKA sites. PKA-Wnt crosstalk in the cells was bi-directional, including enhanced interactions between β-catenin and the cAMP-responsive element binding protein (CREB) and transcriptional crosstalk between the Wnt and PKA signaling pathways. Increases in canonical Wnt/β-catenin signaling were associated with a decrease in the activity of the non-canonical Wnt/Ror2 pathway, which has been shown to antagonize canonical Wnt signaling. Taken together, this study provides a new understanding of the complex regulation of the subcellular distribution of β-catenin and its differential protein-protein interaction that can be modulated by PKA signaling. PMID:25299576

  1. Flavopiridol, Cytarabine, and Mitoxantrone in Treating Patients With Acute Leukemia

    ClinicalTrials.gov

    2013-10-07

    Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Myeloid Leukemia

  2. [Hairy cell leukemia].

    PubMed

    Dietrich, S; Andrulis, M; Zenz, T

    2015-04-01

    Hairy cell leukemia was initially described as a distinct entity in 1958. It is rare B-cell malignancy characterized by an indolent course. Advances in the treatment and understanding of the biology of hairy cell leukemia have made the disease exquisitely amenable to treatment. This review summarizes the present understanding of hairy cell leukemia with a particular focus on the development of novel and targeted approaches to treatment. PMID:25787322

  3. Divergence of the isospin-asymmetry expansion of the nuclear equation of state in many-body perturbation theory

    NASA Astrophysics Data System (ADS)

    Wellenhofer, Corbinian; Holt, Jeremy W.; Kaiser, Norbert

    2016-05-01

    The isospin-asymmetry dependence of the nuclear-matter equation of state obtained from microscopic chiral two- and three-body interactions in second-order many-body perturbation theory is examined in detail. The quadratic, quartic, and sextic coefficients in the Maclaurin expansion of the free energy per particle of infinite homogeneous nuclear matter with respect to the isospin asymmetry are extracted numerically using finite differences, and the resulting polynomial isospin-asymmetry parametrizations are compared to the full isospin-asymmetry dependence of the free energy. It is found that in the low-temperature and high-density regime where the radius of convergence of the expansion is generically zero, the inclusion of higher-order terms beyond the leading quadratic approximation leads overall to a significantly poorer description of the isospin-asymmetry dependence. In contrast, at high temperatures and densities well below nuclear saturation density, the interaction contributions to the higher-order coefficients are negligible and the deviations from the quadratic approximation are predominantly from the noninteracting term in the many-body perturbation series. Furthermore, we extract the leading logarithmic term in the isospin-asymmetry expansion of the equation of state at zero temperature from the analysis of linear combinations of finite differences. It is shown that the logarithmic term leads to a considerably improved description of the isospin-asymmetry dependence at zero temperature.

  4. The Sam68 nuclear body is composed of two RNase-sensitive substructures joined by the adaptor HNRNPL.

    PubMed

    Mannen, Taro; Yamashita, Seisuke; Tomita, Kozo; Goshima, Naoki; Hirose, Tetsuro

    2016-07-01

    The mammalian cell nucleus contains membraneless suborganelles referred to as nuclear bodies (NBs). Some NBs are formed with an architectural RNA (arcRNA) as the structural core. Here, we searched for new NBs that are built on unidentified arcRNAs by screening for ribonuclease (RNase)-sensitive NBs using 32,651 fluorescently tagged human cDNA clones. We identified 32 tagged proteins that required RNA for their localization in distinct nuclear foci. Among them, seven RNA-binding proteins commonly localized in the Sam68 nuclear body (SNB), which was disrupted by RNase treatment. Knockdown of each SNB protein revealed that SNBs are composed of two distinct RNase-sensitive substructures. One substructure is present as a distinct NB, termed the DBC1 body, in certain conditions, and the more dynamic substructure including Sam68 joins to form the intact SNB. HNRNPL acts as the adaptor to combine the two substructures and form the intact SNB through the interaction of two sets of RNA recognition motifs with the putative arcRNAs in the respective substructures. PMID:27377249

  5. Neuroimaging in Leukemia.

    PubMed

    Nabavizadeh, Seyed Ali; Stein, Joel; Mohan, Suyash

    2016-08-01

    Leukemias are a heterogeneous group of hematologic malignancies that results from uncontrolled neoplastic proliferation of undifferentiated or partially differentiated hematopoietic cells. Patients with acute leukemia can have a variety of craniocerebral complications, which can result from direct leukemic involvement, secondary to cerebrovascular or infectious complications of leukemia, or can be treatment related. Imaging plays a central role in evaluating the central nervous system during treatment in patients with leukemia. CT scan is usually considered an effective initial imaging modality to evaluate for cerebrovascular complications. MRI is considered the imaging modality of choice due to its versatility. PMID:27443999

  6. MicroRNAs as biomarkers in leukemia

    PubMed Central

    Wang, Xinxin; Zhu, Baohua; Huang, Zunnan; Chen, Liyong

    2014-01-01

    Current diagnostic and prognostic markers still exhibit biological limitation and seeking novel molecular biomarkers is crucial for early clinical diagnosis and in the development of novel strategies for leukemia therapy. Emerging evidence showed that dysregulated microRNAs (miRNAs) play important roles in cancer including leukemia. In this review, we summarized recent progress on the role of miRNAs in leukemia, mainly focusing on recent findings that suggest the potential of miRNAs as biomarkers for diagnosis and prognosis. Notably, the circulating miRNAs were also discussed for the fact that they can be detected in body fluids, and thus represent a novel source of promising biomarkers that may be applied to clinical settings.

  7. The Family Leukemia Association

    ERIC Educational Resources Information Center

    Pollitt, Eleanor

    1976-01-01

    An association of families of children with leukemia, the Family Leukemia Association (FLA), was recently established in Toronto. This paper discusses (a) philosophy of the FLA; (b) formative years of this organization; (c) problems encountered by leukemic children and their families; and (d) the FLA's past and future educational and social…

  8. Nilotinib and Imatinib Mesylate After Donor Stem Cell Transplant in Treating Patients With Acute Lymphoblastic Leukemia or Chronic Myelogenous Leukemia

    ClinicalTrials.gov

    2014-12-09

    Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Lymphoblastic Leukemia in Remission; Blastic Phase Chronic Myelogenous Leukemia; Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Chronic Myelogenous Leukemia; Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Chronic Phase Chronic Myelogenous Leukemia; Philadelphia Chromosome Positive Adult Precursor Acute Lymphoblastic Leukemia; Philadelphia Chromosome Positive Childhood Precursor Acute Lymphoblastic Leukemia; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Relapsing Chronic Myelogenous Leukemia; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Childhood Acute Lymphoblastic Leukemia

  9. Adipocytes impair leukemia treatment in mice

    PubMed Central

    Behan, James W.; Yun, Jason P.; Proektor, Marina P.; Ehsanipour, Ehsan A.; Arutyunyan, Anna; Moses, Ara S.; Avramis, Vassilios I.; Louie, Stan G.; Butturini, Anna; Heisterkamp, Nora; Mittelman, Steven D.

    2009-01-01

    Obesity is associated with increased cancer incidence and mortality. We have previously found that obesity in children is associated with a 50% increased recurrence of acute lymphoblastic leukemia (ALL) in high-risk patients. We have therefore developed novel in vivo and in vitro preclinical models to study the mechanism(s) of this association. Obesity increased relapse after monotherapy with vincristine (p=0.03) in obese mice injected with syngeneic ALL cells. This occurred even though the drug was dosed proportionally to body weight, equalizing blood and tissue drug levels. In co-culture, 3T3-L1 adipocytes significantly impaired the anti-leukemia efficacy of vincristine, as well as 3 other chemotherapies (p<0.05). Interestingly, this protection was independent of cell-cell contact, and it extended to human leukemia cell lines as well. Adipocytes prevented chemotherapy-induced apoptosis, and this was associated with increased expression of the two pro-survival signals Bcl-2 and Pim-2. These findings highlight the role of the adipocyte in fostering leukemia chemotherapy resistance, and may help explain the increased leukemia relapse rate in obese children and adults. Given the growing prevalence of obesity worldwide, these effects are likely to have increasing importance to cancer treatment. PMID:19773440

  10. Immunotherapy for Pediatric Leukemia

    PubMed Central

    Shah, Nirali N.; Dave, Hema; Wayne, Alan S.

    2013-01-01

    Substantial progress has been made in the treatment of leukemia in childhood. Despite this, leukemia remains a leading cause of pediatric cancer-related mortality and the prognosis is guarded for individuals with relapsed or refractory disease. Standard therapies are associated with a wide array of acute and long-term toxicities and further treatment intensification may not be tolerable or beneficial. The curative potential of allogeneic stem cell transplantation is due in part to the graft-versus-leukemia effect, which provides evidence for the therapeutic capacity of immune-based therapies. In recent years there have been significant advances in the development and application of immunotherapy in the treatment of leukemias, including the demonstration of activity in chemotherapy-resistant cases. This review summarizes immunotherapeutic approaches in the treatment of pediatric leukemia including current results and future directions. PMID:23847759

  11. Numerical Modeling of Thermal Pollution of Large Water Bodies from Thermal and Nuclear Power Plants

    NASA Astrophysics Data System (ADS)

    Lyubimova, Tatyana; Lepikhin, Anatoly; Lyakhin, Yury; Parshakova, Yanina; Tiunov, Alexey

    2016-04-01

    Currently, the major manufacturers of electrical energy are the thermal and nuclear power plants including the cooling ponds in the processing chains. For a wide range of both environmental and technological problems, the evaluation of the temperature fields in the cooling ponds at certain critical values of hydrological and meteorological parameters is important. The present paper deals with the evaluation of the thermal effect of one of the largest thermal power plant in Europe - Perm GRES - to its cooling pond which is the Kama Reservoir. Since the area of the possible impact is rather large and the reservoir itself is characterized by a very complex morphometry, numerical modeling of thermal spot propagation in the Kama River due to the discharge of warm water by Perm GRES for the entire area in the 3D-formulation with the desired detail setting morphometric characteristics of the water body meets very serious difficulties. Because of that, to solve the problem, a combined scheme of calculations based on the combination of hydrodynamic models in 2D and 3D formulations was used. At the first stage of the combined scheme implementation, 2D hydrodynamical model was developed for all possible area, using software SMS v.11.1. The boundary and initial conditions for this model were formulated on the basis of calculations made using 1D hydrodynamical model developed and applied for the entire Kama Reservoir. Application of 2D hydrodynamical model for solving the problem under consideration was needed to obtain the necessary information for setting the boundary conditions for the 3D model. Software package ANSYS Fluent v.6.3 was used for the realization of 3D model. 3D modeling was performed for different wind speeds and directions and quantitative characteristics of the discharge of warm water. To verify the models, the data of the detailed field measurements in the zones of thermal pollution of the Kama reservoir due to impact of the Perm GRES were used. A

  12. Targeted Therapy in Treating Patients With Relapsed or Refractory Acute Lymphoblastic Leukemia or Acute Myelogenous Leukemia

    ClinicalTrials.gov

    2016-07-28

    Chronic Myelomonocytic Leukemia; Myelodysplastic Syndrome; Recurrent Acute Myeloid Leukemia With Myelodysplasia-Related Changes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Refractory Adult Acute Lymphoblastic Leukemia

  13. Mitoxantrone resistance in HL-60 leukemia cells: Reduced nuclear topoisomerase II catalytic activity and drug-induced DNA cleavage in association with reduced expression of the topoisomerase II. beta. isoform

    SciTech Connect

    Harker, W.G.; Slade, D.L.; Parr, R.L. ); Drake, F.H. )

    1991-10-15

    Mitoxantrone-resistant variants of the human HL-60 leukemia cell line are cross-resistant to several natural product and synthetic antineoplastic agents. The resistant cells (HL-60/MX2) retain sensitivity to the Vinca alkaloids vincristine and vinblastine, drugs that are typically associated with the classical multidrug resistance phenotype. Mitoxantrone accumulation and retention are equivalent in the sensitive and resistant cell types, suggesting that mitoxantrone resistance inn HL-60/MX2 cells might be associated with an alteration in the type II DNA topoisomerases. The authors discovered that topoisomerase II catalytic activity in 1.0 M NaCl nuclear extracts from the HL-60/MX2 variant was reduced 4- to 5-fold compared to that in the parental HL-60 cells. Studies were designed to minimize the proteolytic degradation of the topoisomerase II enzymes by extraction of whole cells with hot SDS. When nuclear extracts from the two cell types were normalized for equivalent catalytic activity, mitoxantrone inhibited the decatenation of kDNA by these extracts to an equal extent but levels of mitoxantrone-induced cleavage of {sup 32}P-labeled pBR322 DNA by nuclear extracts from HL-60/MX2 cells were 3- to 4-fold lower than in comparable HL-60 extracts. Resistance to the topoisomerase II inhibitor mitoxantrone in HL-60/MX2 is associated with reduced nuclear and whole cell topoisomerase II catalytic activity, immunologically undetectable levels of the 180-kDa topoisomerase II isozyme, and reduced mitoxantrone-induced cleavage of radiolabeled DNA by topoisomerase II in nuclear extracts from these cells.

  14. Connecting neutron star observations to three-body forces in neutron matter and to the nuclear symmetry energy.

    PubMed

    Steiner, A W; Gandolfi, S

    2012-02-24

    Using a phenomenological form of the equation of state of neutron matter near the saturation density which has been previously demonstrated to be a good characterization of quantum Monte Carlo simulations, we show that currently available neutron star mass and radius measurements provide a significant constraint on the equation of state of neutron matter. At higher densities we model the equation of state by using polytropes and a quark matter model. We show that observations offer an important constraint on the strength of the three-body force in neutron matter, and thus some theoretical models of the three-body force may be ruled out by currently available astrophysical data. In addition, we obtain an estimate of the symmetry energy of nuclear matter and its slope that can be directly compared to the experiment and other theoretical calculations. PMID:22463511

  15. Body-fixed relativistic molecular Hamiltonian and its application to nuclear spin-rotation tensor: Linear molecules

    NASA Astrophysics Data System (ADS)

    Xiao, Yunlong; Liu, Wenjian

    2013-07-01

    The relativistic molecular Hamiltonian written in the body-fixed frame of reference is the basis for high-precision calculations of spectroscopic parameters involving nuclear vibrations and/or rotations. Such a Hamiltonian that describes electrons fully relativistically and nuclei quasi-relativistically is just developed for semi-rigid nonlinear molecules [Y. Xiao and W. Liu, J. Chem. Phys. 138, 134104 (2013)], 10.1063/1.4797496. Yet, the formulation should somewhat be revised for linear molecules thanks to some unusual features arising from the redundancy of the rotation around the molecular axis. Nonetheless, the resulting isomorphic Hamiltonian is rather similar to that for nonlinear molecules. Consequently, the relativistic formulation of nuclear spin-rotation (NSR) tensor for linear molecules is very much the same as that for nonlinear molecules. So is the relativistic mapping between experimental NSR and NMR.

  16. Sorafenib in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, or Chronic Myelogenous Leukemia

    ClinicalTrials.gov

    2013-01-08

    Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); 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 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 Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia

  17. Slovak Nuclear Regulatory Body Position in the Transport of Radioactive Waste

    SciTech Connect

    Homola, J.

    2003-02-27

    This paper describes safety requirements for transport of radioactive waste in Slovakia and the role of regulatory body in the transport licensing and assessment processes. Importance of radioactive waste shipments have been increased since 1999 by starting of NPP A-1 decommissioning and operation of near surface disposal facility. Also some information from history of shipment as well as future activities are given. Legal basis for radioactive waste transport is resulting from IAEA recommendations in this area. Different types of transport equipment were approved by regulatory body for both liquid and solid waste and transportation permits were issued to their shipment. Regulatory body attention during evaluation of transport safety is focused mainly on ability of individual packages to withstand different transport conditions and on safety analyses performed for transport equipment for liquid waste with high frequency of shipments. During past three years no event was occurred in connection with radioactive waste transport in Slovakia.

  18. Nuclear Effects of Supernova-Accelerated Cosmic Rays on Early Solar System Planetary Bodies

    NASA Astrophysics Data System (ADS)

    Meyer, B. S.; The, L.-S.; Johnson, J.

    2008-03-01

    The solar system apparently formed in the neighborhood of massive stars. Supernova explosions of these stars accelerate cosmic rays to 100s of TeVs. These cosmic rays could accelerate the beta decay of certain radioactive species in meteorite parent bodies.

  19. Three Lectures on Random Matrices and the Nuclear Many-body Problem

    SciTech Connect

    Weidenmueller, Hans A.

    2008-11-13

    In the first lecture, I give an overview of the random--matrix approach to the statistical theory of nuclear reactions, with application to recent data on a microwave billiard. In the second lecture, I discuss the preponderance of ground states with spin zero and of states with positive parity. In the third lecture, I discuss constrained ensembles of random matrices.

  20. UNEDF: Advanced Scientific Computing Transforms the Low-Energy Nuclear Many-Body Problem

    SciTech Connect

    Stoitsov, Mario; Nam, Hai Ah; Nazarewicz, Witold; Bulgac, Aurel; Hagen, Gaute; Kortelainen, E. M.; Pei, Junchen; Roche, K. J.; Schunck, N.; Thompson, I.; Vary, J. P.; Wild, S.

    2011-01-01

    The UNEDF SciDAC collaboration of nuclear theorists, applied mathematicians, and computer scientists is developing a comprehensive description of nuclei and their reactions that delivers maximum predictive power with quantified uncertainties. This paper illustrates significant milestones accomplished by UNEDF through integration of the theoretical approaches, advanced numerical algorithms, and leadership class computational resources.

  1. Predictive Nuclear Many-Body Theory with Ab Initio Methods: A Brief Survey and A Look Ahead

    NASA Astrophysics Data System (ADS)

    Hergert, Heiko

    2015-10-01

    The reach of ab initio many-body techniques has increased tremendously in recent years, owing to new developments in many-body theory as well as advances in their numerical implementation. Coupled Cluster, Self-Consistent Green's Function, and In-Medium Similarity Renormalization Group (IM-SRG) calculations are routinely performed for isotopes in the A ~ 100 region. Moreover, these techniques have been extended to tackle open-shell nuclei, either directly or through the auxiliary step of deriving valence-space interactions for use with existing Shell Model technology. One of the most powerful aspects of ab initio methods is their capability to provide results for energies and other observables with systematic uncertainties. Together with new accurate nuclear forces (and operators) derived from Chiral Effective Field Theory, they provide a consistent framework--and a road map--for a predictive description of nuclei. This will have a critical impact on the search for the limits of nuclear existence, tests of fundamental symmetries (e.g., the search for neutrinoless double beta decay), our understanding of quenching and effective charges in phenomenological Shell Model calculations etc. Using the Multi-Reference IM-SRG as a representative example, I will survey the current capabilities of ab initio methods with an emphasis on uncertainty quantification, highlight successes in the description of ground-state properties and spectra, and preview upcoming developments like the construction of consistent transition operators.

  2. Double decimation and sliding vacua in the nuclear many-body system

    NASA Astrophysics Data System (ADS)

    Brown, G. E.; Rho, Mannque

    2004-06-01

    We propose that effective field theories for nuclei and nuclear matter comprise of “double decimation”: (1) the chiral symmetry decimation (CSD) and (2) Fermi liquid decimation (FLD). The Brown-Rho scaling recently identified as the parametric dependence intrinsic in the “vector manifestation” of hidden local symmetry theory of Harada and Yamawaki results from the first decimation. This scaling governs dynamics down to the scale at which the Fermi surface is formed as a quantum critical phenomenon. The next decimation to the top of the Fermi sea where standard nuclear physics is operative makes up the FLD. Thus, nuclear dynamics are dictated by two fixed points, namely, the vector manifestation fixed point and the Fermi liquid fixed point. It has been a prevalent practice in nuclear physics community to proceed with the second decimation only, assuming density-independent masses, without implementing the first, CSD. We show why most nuclear phenomena can be reproduced by theories using either density-independent, or density-dependent masses, a grand conspiracy of nature that is an aspect that could be tied to the Cheshire Cat phenomenon in hadron physics. We identify what is left out in the FLD that does not incorporate the CSD. Experiments such as the dilepton production in relativistic heavy ion reactions, which are specifically designed to observe effects of dropping masses, could exhibit large effects from the reduced masses. However, they are compounded with effects that are not directly tied to chiral symmetry. We discuss a recent STAR/RHIC observation where BR scaling can be singled out in a pristine environment.

  3. Acute lymphoblastic leukemia (ALL)

    MedlinePlus

    ... WBC) count Platelet count Bone marrow biopsy Lumbar puncture (spinal tap) to check for leukemia cells in ... home Managing your pets during chemotherapy Bleeding problems Dry mouth Eating enough calories Safe eating during cancer ...

  4. Chronic Myeloid Leukemia

    MedlinePlus

    ... some patients with acute lymphoblastic leukemia (ALL). One theory that scientists propose about why this switch occurs ... a result called “graft-versus-tumor effect”). The theory being tested with a reduced-intensity transplant is ...

  5. Acute myeloid leukemia

    MedlinePlus

    ... a low number of platelets. A white blood cell count ( WBC ) can be high, low, or normal. Bone ... and overall health How high your white blood cell count was Certain genetic changes in the leukemia cells ...

  6. Drugs Approved for Leukemia

    Cancer.gov

    This page lists cancer drugs approved by the FDA for use in leukemia. The drug names link to NCI's Cancer Drug Information summaries. The list includes generic names, brand names, and common drug combinations, which are shown in capital letters.

  7. Hairy cell leukemia

    MedlinePlus

    ... 2014 Updated by: Yi-Bin Chen, MD, Leukemia/Bone Marrow Transplant Program, Massachusetts General Hospital, Boston, MA. Also reviewed ... M. is also a founding member of Hi-Ethics and subscribes to the principles of the Health ...

  8. CT findings in leukemia

    SciTech Connect

    Heiberg, E.; Wolverson, M.K.; Sundaram, M.; Shields, J.B.

    1984-12-01

    Review of 84 computed tomographic (CT) scans in leukemic patients demonstrate a wide spectrum of abnormalities. Findings caused by leukemia were lymphadenopathy, visceral enlargement, focal defects, and tissue infiltration. Hemorrhage was by far the most common complication and could usually be characterized on the noncontrast CT scan. The distinction between old hematomas, foci of infection, and leukemia infiltration could not be made with certainty without CT-guided aspiration. Unusual instances of sepsis, such as microabscesses of the liver and typhlitis, were seen.

  9. Flavopiridol in Treating Patients With Chronic Lymphocytic Leukemia

    ClinicalTrials.gov

    2013-01-16

    B-cell Chronic Lymphocytic Leukemia; Refractory Chronic Lymphocytic Leukemia; Stage I Chronic Lymphocytic Leukemia; Stage II Chronic Lymphocytic Leukemia; Stage III Chronic Lymphocytic Leukemia; Stage IV Chronic Lymphocytic Leukemia

  10. Low-Dose Total Body Irradiation and Donor Peripheral Blood Stem Cell Transplant Followed by Donor Lymphocyte Infusion in Treating Patients With Non-Hodgkin Lymphoma, Chronic Lymphocytic Leukemia, or Multiple Myeloma

    ClinicalTrials.gov

    2015-10-30

    Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Recurrent Adult Acute Lymphoblastic 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 Grade III Lymphomatoid Granulomatosis; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin 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 Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Refractory Multiple Myeloma; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Stage II Multiple Myeloma; Stage III Multiple Myeloma; Testicular Lymphoma; Waldenström Macroglobulinemia

  11. Myeloid leukemia after hematotoxins.

    PubMed Central

    Larson, R A; LeBeau, M M; Vardiman, J W; Rowley, J D

    1996-01-01

    One of the most serious consequences of cancer therapy is the development of a second cancer, especially leukemia. Several distinct subsets of therapy-related leukemia can now be distinguished. Classic therapy-related myeloid leukemia typically occurs 5 to 7 years after exposure to alkylating agents and/or irradiation, has a myelodysplastic phase with trilineage involvement, and is characterized by abnormalities of the long arms of chromosomes 5 and/or 7. Response to treatment is poor, and allogenic bone marrow transplantation is recommended. Leukemia following treatment with agents that inhibit topoisomerase II, however, has a shorter latency, no preleukemic phase, a monoblastic, myelomonocytic, or myeloblastic phenotype, and balanced translocations, most commonly involving chromosome bands 11q23 or 21q22. The MLL gene at 11q23 or the AML1 gene at 21q22 are almost uniformly rearranged. MLL is involved with many fusion gene partners. Therapy-related acute lymphoblastic leukemia also occurs with 11q23 rearrangements. Therapy-related leukemias with 11q23 or 21q22 rearrangements, inv(16) or t(15;17), have a more favorable response to treatment and a clinical course similar to their de novo counterparts. PMID:9118910

  12. [Large granular lymphocyte leukemia].

    PubMed

    Lazaro, Estibaliz; Caubet, Olivier; Menard, Fanny; Pellegrin, Jean-Luc; Viallard, Jean-François

    2007-11-01

    Large granular lymphocyte (LGL) leukemia is a clonal proliferation of cytotoxic cells, either CD3(+) (T-cell) or CD3(-) (natural killer, or NK). Both subtypes can manifest as indolent or aggressive disorders. T-LGL leukemia is associated with cytopenias and autoimmune diseases and most often has an indolent course and good prognosis. Rheumatoid arthritis and Felty syndrome are frequent. NK-LGL leukemias can be more aggressive. LGL expansion is currently hypothesized to be a virus (Ebstein Barr or human T-cell leukemia viruses) antigen-driven T-cell response that involves disruption of apoptosis. The diagnosis of T-LGL is suggested by flow cytometry and confirmed by T-cell receptor gene rearrangement studies. Clonality is difficult to determine in NK-LGL but use of monoclonal antibodies specific for killer cell immunoglobulin-like receptor (KIR) has improved this process. Treatment is required when T-LGL leukemia is associated with recurrent infections secondary to chronic neutropenia. Long-lasting remission can be obtained with immunosuppressive treatments such as methotrexate, cyclophosphamide, and cyclosporine A. NK-LGL leukemias may be more aggressive and refractory to conventional therapy. PMID:17596907

  13. Myeloid leukemia after hematotoxins

    SciTech Connect

    Larson, R.A.; LeBeau, M.M.; Vardiman, J.W.; Rowley, J.D.

    1996-12-01

    One of the most serious consequences of cancer therapy is the development of a second cancer, especially leukemia. Several distinct subsets of therapy-related leukemia can now be distinguished. Classic therapy-related myeloid leukemia typically occurs 5 to 7 years after exposure to alkylating agents and/or irradiation, has a myelodysplastic phase with trilineage involvement, and is characterized by abnormalities of the long arms of chromosomes 5 and/or 7. Response to treatment is poor, and allogeneic bone marrow transplantation is recommended. Leukemia following treatment with agents that inhibit topoisomerase 11, however, has a shorter latency, no preleukemic phase, a monoblastic, myelomonocytic, or myeloblastic phenotype, and balanced translocations, most commonly involving chromosome bands 11 q23 or 21 q22. The MLL gene at 11 q23 or the AML1 gene at 21 q22 are almost uniformly rearranged. MLL is involved with many fusion gene partners. Therapy-related acute lymphoblastic leukemia also occurs with 1 1 q23 rearrangements. Therapy-related leukemias with 11 q23 or 21 q22 rearrangements, inv(16) or t(15;17), have a more favorable response to treatment and a clinical course similar to their de novo counterparts. 32 refs., 4 tabs.

  14. Three-body Effects for the p(pe^-, ν_e)d Reaction in Nuclear Astrophysics.

    NASA Astrophysics Data System (ADS)

    Kim, Yeong E.; Zubarev, Alexander L.

    1996-05-01

    We have investigated three-body effect for p(pe^-, ν_e)d reaction in nuclear astrophysics. Solutions of three-body equation for the initial pep state show that two-proton dynamics does not depend on the electron degrees of freedom and hence the conventional adiabatic approximation is valid for energy sector (E_ep/E_pp) > 10-3 where E_ep and E_pp are the relative kinetic energies between e and p, and between p and p, respectively. For the energy sector (E_ep/E_pp) ≈ 10-3, an exact solution of the three-body equation is required. For the energy sector (E_ep/E_pp) < 10-3, it is shown that a Gamow-factor cancellation (GFC) can occur between two protons. Our estimate of the GFC effect indicates that the previous conventional estimate of the pep solar neutrino flux may be an underestimate at least by a factor of two. Implications of our results for the solar neutrino problem are described. At lower temperatures, the GFC effect becomes more significant, and p(pe^-, ν_e)d may dominate over p(p,e^+ ν_e)d. The enhancement of the reaction rate for p(pe^-, νe )d at lower temperatures due to the GFC effect may offer possible explanations for some of long-standing anomalies in astrophysical and geophysical problems.

  15. Tipifarnib and Bortezomib in Treating Patients With Acute Leukemia or Chronic Myelogenous Leukemia in Blast Phase

    ClinicalTrials.gov

    2015-04-14

    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 Erythroleukemia; Adult Pure Erythroid Leukemia; Blastic Phase; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Disease; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Myeloid Leukemia

  16. Nucleolar disruption and cajal body disassembly are nuclear hallmarks of DNA damage-induced neurodegeneration in purkinje cells.

    PubMed

    Baltanás, Fernando C; Casafont, Iñigo; Weruaga, Eduardo; Alonso, José R; Berciano, María T; Lafarga, Miguel

    2011-07-01

    The Purkinje cell (PC) degeneration (pcd) phenotype results from mutation in nna1 gene and is associated with the degeneration and death of PCs during the postnatal life. Although the pcd mutation is a model of the ataxic mouse, it shares clinical and pathological characteristics of inherited human spinocerebellar ataxias. PC degeneration in pcd mice provides a useful neuronal system to study nuclear mechanisms involved in DNA damage-dependent neurodegeneration, particularly the contribution of nucleoli and Cajal bodies (CBs). Both nuclear structures are engaged in housekeeping functions for neuronal survival, the biogenesis of ribosomes and the maturation of snRNPs and snoRNPs required for pre-mRNA and pre-rRNA processing, respectively. In this study, we use ultrastructural analysis, in situ transcription assay and molecular markers for DNA damage, nucleoli and CB components to demonstrate that PC degeneration involves the progressive accumulation of nuclear DNA damage associated with disruption of nucleoli and CBs, disassembly of polyribosomes into monoribosomes, ribophagy and shut down of nucleolar and extranucleolar transcription. Microarray analysis reveals that four genes encoding repressors of nucleolar rRNA synthesis (p53, Rb, PTEN and SNF2) are upregulated in the cerebellum of pcd mice. Collectively, these data support that nucleolar and CB alterations are hallmarks of DNA damage-induced neurodegeneration. PMID:21054627

  17. Coiled bodies contain U7 small nuclear RNA and associate with specific DNA sequences in interphase human cells.

    PubMed Central

    Frey, M R; Matera, A G

    1995-01-01

    Coiled bodies (CBs) are nuclear organelles whose structures appear to be highly conserved in evolution. In rapidly cycling cells, they are typically located in the nucleoplasm but are often found in contact with the nucleolus. The CBs in human cells contain a unique protein, called p80-coilin. Studies on amphibian oocyte nuclei have revealed a protein within the "sphere" organelle that shares significant structural similarity to p80-coilin. Spheres and CBs are also highly enriched in small nuclear ribonucleoproteins and other RNA-processing components. We present evidence that, like spheres, CBs contain U7 small nuclear RNA (snRNA) and associate with specific chromosomal loci. Using biotinylated 2'-O-methyl oligonucleotides complementary to the 5' end of U7 snRNA and fluorescence in situ hybridization, we show that U7 is distributed throughout the nucleoplasm, excluding nucleoli, and is concentrated in CBs. Interestingly, we found that CBs often associate with subsets of the histone, U1, and U2 snRNA gene loci in interphase HeLa-ATCC and HEp-2 monolayer cells. However, in a strain of suspension-grown HeLa cells, called HeLa-JS1000, we found a much lower rate of association between CBs and snRNA genes. Possible roles for CBs in the metabolism of these various histone and snRNAs are discussed. Images Fig. 1 Fig. 2 Fig. 3 PMID:7597053

  18. [Transport processes of low-level radioactive liquid effluent of nuclear power station in closed water body].

    PubMed

    Wu, Guo-Zheng; Xu, Zong-Xue

    2012-07-01

    The transport processes of low-level radioactive liquid effluent of Xianning nuclear power station in the closed water body Fushui Reservoir are simulated using the EFDC model. Six nuclides concentration distribution with different half-lives in the reservoir are analyzed under the condition of 97% guarantee rate incoming water and four-running nuclear power units. The results show that the nuclides concentration distribution is mainly affected by the flow field of the reservoir and the concentration is decided by the half-lives of nuclide and the volume of incoming water. In addition, the influence region is enlarged as increasing of half-life and tends to be stable when the half-life is longer than 5 years. Moreover, the waste water discharged from the outlet of the nuclear power plant has no effect on the water-intake for the outlet located at the upstream of the water-intake and the flow field flows to the dam of the reservoir. PMID:23002624

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

    ClinicalTrials.gov

    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

  20. Flavopiridol and Vorinostat in Treating Patients With Relapsed or Refractory Acute Leukemia or Chronic Myelogenous Leukemia or Refractory Anemia

    ClinicalTrials.gov

    2013-04-01

    Blastic Phase Chronic Myelogenous Leukemia; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts; Relapsing Chronic Myelogenous Leukemia; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Myeloid Leukemia

  1. Nuclear domain 10 of the viral aspect

    PubMed Central

    Rivera-Molina, Yisel A; Martínez, Francisco Puerta; Tang, Qiyi

    2013-01-01

    Nuclear domain 10 (ND10) are spherical bodies distributed throughout the nucleoplasm and measuring around 0.2-1.0 μm. First observed under an electron microscope, they were originally described as dense bodies found in the nucleus. They are known by a number of other names, including Promyelocytic Leukemia bodies (PML bodies), Kremer bodies, and PML oncogenic domains. ND10 are frequently associated with Cajal bodies and cleavage bodies. It has been suggested that they play a role in regulating gene transcription. ND10 were originally characterized using human autoantisera, which recognizes Speckled Protein of 100 kDa, from patients with primary biliary cirrhosis. At the immunohistochemical level, ND10 appear as nuclear punctate structures, with 10 indicating the approximate number of dots per nucleus observed. ND10 do not colocalize with kinetochores, centromeres, sites of mRNA processing, or chromosomes. Resistance of ND10 antigens to nuclease digestion and salt extraction suggest that ND10 are associated with the nuclear matrix. They are often identified by immunofluorescent assay using specific antibodies against PML, Death domain-associated protein, nuclear dot protein (NDP55), and so on. The role of ND10 has long been the subject of investigation, with the specific connection of ND10 and viral infection having been a particular focus for almost 20 years. This review summarizes the relationship of ND10 and viral infection. Some future study directions are also discussed. PMID:24255882

  2. Nuclear translocation of the 1,25D{sub 3}-MARRS (membrane associated rapid response to steroids) receptor protein and NF{kappa}B in differentiating NB4 leukemia cells

    SciTech Connect

    Wu, Wenqing; Beilhartz, Greg; Roy, Yvette; Richard, Cynthia L.; Curtin, Maureen; Brown, Lauren; Cadieux, Danielle; Coppolino, Marc; Farach-Carson, Mary C.; Nemere, Ilka; Meckling, Kelly A.

    2010-04-15

    1,25 Dihydroxyvitamin D{sub 3} (1,25D{sub 3}) primes NB4 promyelocytic leukemia cells to differentiate along the monocyte/macrophage lineage through a non-genomic mechanism. Here we show that NB4 cells express high levels of the recently identified membrane receptor for 1,25D{sub 3}, which is a distinct gene product from the classical nuclear vitamin D receptor. This 57 kDa protein, named 1,25D{sub 3}-MARRS (Membrane Activated Rapid Response to Steroids)/ERp57/PIA3 appears to associate in a complex with the transcription factor, nuclear factor kappa B (NF{kappa}B). In unstimulated cells, 1,25D{sub 3}-MARRS can be co-immunoprecipitated with antibodies directed at NF{kappa}B, and NF{kappa}B is co-precipitated when antibodies against 1,25D{sub 3}-MARRS or ERp57 are used. Confocal microscopy and subcellular fractionation studies demonstrate that both 1,25D{sub 3}-MARRS and NF{kappa}B begin translocating to the nucleus within minutes of co-stimulation with 1,25D{sub 3} and phorbol ester. The predominant nuclear localization of both proteins precedes the expression of the monocyte/macrophage phenotype and suggests that this event may be critical to the differentiation pathway. This suggests a role for 1,25D{sub 3}-MARRS in the nucleus as a regulator of gene expression. Here it may also regulate the activity of NF{kappa}B and other factors with which it may be interacting.

  3. Many-body correlations of QRPA in nuclear matrix elements of double-beta decay

    SciTech Connect

    Terasaki, J.

    2015-10-28

    We present two new ideas on the quasiparticle random-phase approximation (QRPA) approach for calculating nuclear matrix elements of double-beta decay. First, it is necessary to calculate overlaps of the QRPA states obtained on the basis of the ground states of different nuclei. We calculate this overlap using quasiboson vacua as the QRPA ground states. Second, we show that two-particle transfer paths are possible to use for the calculation under the closure approximation. A calculation is shown for {sup 150}Nd→{sup 150}Sm using these two new ideas, and their implication is discussed.

  4. HIV, leukemia, and new horizons in molecular therapy.

    PubMed

    Berkhout, Ben

    2013-08-01

    Cancer and human immunodeficiency virus (HIV) are both scary things to have in your body, but a new treatment is successfully using the latter against the former. Recent news reports, among others in the New York Times, talked about this new cure for leukemia by using HIV. This mini-review puts this news in perspective and provides a broader view as there appear to be several areas where clinical research on HIV and leukemia seem to connect. The topics covered range from antiviral gene therapy approaches using HIV-based lentiviral vectors to the risk of leukemia induction by these integrating vectors, and from an anti-leukemia transplantation strategy that turned out to provide a functional cure for HIV, to novel vaccination approaches. PMID:24016608

  5. Anticipation in familial leukemia.

    PubMed Central

    Horwitz, M.; Goode, E. L.; Jarvik, G. P.

    1996-01-01

    Anticipation refers to worsening severity or earlier age at onset with each generation for an inherited disease and primarily has been described for neurodegenerative illnesses resulting from expansion of trinucleotide repeats. We have tested for evidence of anticipation in familial leukemia. Of 49 affected individuals in nine families transmitting autosomal dominant acute myelogenous leukemia (AML), the mean age at onset is 57 years in the grandparental generation, 32 years in the parental generation, and 13 years in the youngest generation (P < .001). Of 21 parent-child pairs with AML, 19 show younger ages at onset in the child and demonstrate a mean decline in age at onset of 28 years (P < .001). Of 18 affected individuals from seven pedigrees with autosomal dominant chronic lymphocytic leukemia (CLL), the mean age at onset in the parental generation is 66 years versus 51 years in the youngest generation (P = .008). Of nine parent-child pairs with CLL, eight show younger ages at onset in the child and reveal a mean decline in age at onset of 21 years (P = .001). Inspection of rare pedigrees transmitting acute lymphocytic leukemia, chronic myelogenous leukemia, multiple types of leukemia, and lymphoma is also compatible with anticipation. Sampling bias is unlikely to explain these findings. This suggests that dynamic mutation of unstable DNA sequence repeats could be a common mechanism of inherited hematopoietic malignancy with implications for the role of somatic mutation in the more frequent sporadic cases. We speculate on three possible candidate genes for familial leukemia with anticipation: a locus on 21q22.1-22.2, CBL2 on 11q23.3, and CBFB or a nearby gene on 16q22. PMID:8900225

  6. High Precision Three-body Variational Method for Critical Nuclear Charge

    NASA Astrophysics Data System (ADS)

    Busuttil, Michael A.

    For an atom there exists a critical nuclear charge Zc that is just sufficient to bind the nucleus and its electrons into a stable configuration. A study of the critical charge for two-electron atoms is presented with the purpose of improving accuracy for Zc. To this end, high precision techniques involving the variational method with multiple basis sets in Hylleraas coordinates are employed. The method is particularly well adapted to the case where one electron is strongly bound and the other is at the limit of becoming unbound. The results are analysed in terms of fractional powers of (Z -- Zc) related to the analytic structure of the energy E( Z) and a 1/Z expansion for the energy. This results in a Zc of 0.91102808(5). Future work prompted by this study includes development of direct techniques to determine Zc utilizing the low-Z stability of the method; developing the framework and mathematical justification for a novel bootstrap analysis method used in curve-fitting; and investigating the inclusion of finite nuclear mass, relativistic effects, and other higher order corrections in the determination of Zc.

  7. HIRF: a novel nuclear factor that binds to the human T-cell leukemia virus type I internal regulatory element (HIRE).

    PubMed

    Ariumi, Y; Copeland, T D; Nosaka, T; Hatanaka, M

    1997-04-01

    The transcription of human T-cell leukemia virus type I (HTLV-I) provirus starts from a promoter located in the 5' long terminal repeat (LTR). We have identified a second promoter at the 3' end of the pol gene. This internal promoter expresses the Tax transactivator protein, but does not require Tax for its activity. Furthermore, we have found the novel enhancer motif AGTTCTGCCC, which are located near the initiation site. We have named the sequence HIRE (HTLV-I internal regulatory element). The HIRE binding protein is a ubiquitous protein. We purified this protein from the HTLV-I producing cell line MT-2 cells by DNA affinity chromatography. SDS-PAGE analysis revealed four major bands (70, 85, 115 and more than 200 kDa) and some minor bands on the gel. We renatured each major protein and showed the 70 and 115 kDa proteins bind to DNA, although the 115 kDa protein seemed to bind nonspecifically. We have designated these components as HIRF (HTLV-I internal regulatory factor). PMID:9209287

  8. UNEDF: Advanced Scientific Computing Collaboration Transforms the Low-Energy Nuclear Many-Body Problem

    SciTech Connect

    Nam, H.; Stoitsov, M.; Nazarewicz, W.; Bulgac, A.; Hagen, G.; Kortelainen, M.; Maris, P.; Pei, J. C.; Roche, K. J.; Schunck, N.; Thompson, I.; Vary, J. P.; Wild, S. M.

    2012-12-20

    The demands of cutting-edge science are driving the need for larger and faster computing resources. With the rapidly growing scale of computing systems and the prospect of technologically disruptive architectures to meet these needs, scientists face the challenge of effectively using complex computational resources to advance scientific discovery. Multi-disciplinary collaborating networks of researchers with diverse scientific backgrounds are needed to address these complex challenges. The UNEDF SciDAC collaboration of nuclear theorists, applied mathematicians, and computer scientists is developing a comprehensive description of nuclei and their reactions that delivers maximum predictive power with quantified uncertainties. This paper describes UNEDF and identifies attributes that classify it as a successful computational collaboration. Finally, we illustrate significant milestones accomplished by UNEDF through integrative solutions using the most reliable theoretical approaches, most advanced algorithms, and leadership-class computational resources.

  9. Studies of a nuclear matrix protein restricted to normal brain cells and lead-induced intranuclear inclusion bodies of kidney

    SciTech Connect

    Shelton, K.; Egle, P.; Redford, K.; Bigbee, J.

    1986-05-01

    A nuclear matrix protein, p32/6.3, with an unusual tissue distribution, has been identified. Protein from 21 tissues was surveyed by immunoprobing Western blots. In normal adult rats p32/6.3 is found only in grey matter from the cerebrum and the cerebellum, occurring in both neurons and astrocytes. Other brain cell types have not been examined. The protein appears to be developmentally regulated. It is detectable in the brain within a few days after birth and reaches adult levels within one to two weeks. Brain p32/6.3 has been found in all animals tested including rat, mouse, dog, cow, pig, chicken and human. This conservation indicates a fundamental role for p32/6.3 in the nucleus of brain cells. Possible functions for p32/6.3 may be indicated by a second novel occurrence. Chronic lead poisoning characteristically induces intranuclear inclusion bodies in the cells lining kidney proximal tubules. p32/6.3 is a major constituent of these inclusion bodies. They are also rich in lead and other metals including calcium, iron, zinc, copper and cadmium. These diverse observations suggest that p32/6.3 may have a role in metal homeostasis in the brain of normal animals.

  10. Yields of Soviet underground nuclear explosions at Novaya Zemlya, 1964-1976, from seismic body and surface waves

    PubMed Central

    Sykes, Lynn R.; Wiggins, Graham C.

    1986-01-01

    Surface and body wave magnitudes are determined for 15 U.S.S.R. underground nuclear weapons tests conducted at Novaya Zemlya between 1964 and 1976 and are used to estimate yields. These events include the largest underground explosions detonated by the Soviet Union. A histogram of body wave magnitude (mb) values indicates a clustering of explosions at a few specific yields. The most pronounced cluster consists of six explosions of yield near 500 kilotons. Several of these seem to be tests of warheads for major strategic systems that became operational in the late 1970s. The largest Soviet underground explosion is estimated to have a yield of 3500 ± 600 kilotons, somewhat smaller than the yield of the largest U.S. underground test. A preliminary estimation of the significance of tectonic release is made by measuring the amplitude of Love waves. The bias in mb for Novaya Zemlya relative to the Nevada test site is about 0.35, nearly identical to that of the eastern Kazakhstan test site relative to Nevada. PMID:16593645