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1

A Bayesian network model of proteins' association with promyelocytic leukemia (PML) nuclear bodies.  

PubMed

The modularity that nuclear organization brings has the potential to explain the function of aggregates of proteins and RNA. Promyelocytic leukemia nuclear bodies are implicated in important regulatory processes. To understand the complement of proteins associated with these intra-nuclear bodies, we construct a Bayesian network model that integrates sequence and protein-protein interaction data. The model predicts association with promyelocytic leukemia nuclear bodies accurately when interaction data is available. At a false positive rate of 10%, the true positive rate is almost 50%, indicated by an independent nuclear proteome reference set. The model provides strong support for further expanding the protein complement with several important regulators and a richer functional repertoire. Using special support vector machine (SVM)-nodes (equipped with string kernels), the Bayesian network is also able to produce predictions on the basis of sequence only, with an accuracy superior to that of baseline models. Supplementary Material is available online at www.liebertonline.com. PMID:20426694

Bodén, Mikael; Dellaire, Graham; Burrage, Kevin; Bailey, Timothy L

2010-04-01

2

Arsenic-Induced PML Targeting onto Nuclear Bodies: Implications for the Treatment of Acute Promyelocytic Leukemia  

Microsoft Academic Search

Acute promyelocytic leukemia (APL) is associated with the t(15;17) translocation, which generates a PML\\/RARalpha fusion protein between PML, a growth suppressor localized on nuclear matrix-associated bodies, and RARalpha , a nuclear receptor for retinoic acid (RA). PML\\/RARalpha was proposed to block myeloid differentiation through inhibition of nuclear receptor response, as does a dominant negative RARalpha mutant. In addition, in APL

Jun Zhu; Marcel H. M. Koken; Frederique Quignon; Mounira K. Chelbi-Alix; Laurent Degos; Zhen Yi Wang; Zhu Chen; Hugues de The

1997-01-01

3

The transcription coactivator CBP is a dynamic component of the promyelocytic leukemia nuclear body.  

PubMed

The transcription coactivator and histone acetyltransferase CAMP response element-binding protein (CBP) has been demonstrated to accumulate in promyelocytic leukemia (PML) bodies. We show that this accumulation is cell type specific. In cells where CBP does not normally accumulate in PML bodies, it can be induced to accumulate in PML bodies through overexpression of either CBP or Pml, but not Sp100. Using fluorescence recovery after photobleaching, we demonstrate that CBP moves rapidly into and out of PML bodies. In contrast, Pml and Sp100 are relatively immobile in the nucleoplasm and within PML nuclear bodies. They possess the characteristics expected of proteins that would play a structural role in the integrity of these subnuclear domains. Our results are consistent with CBP being a dynamic component of PML bodies and that the steady-state level in these structures can be modulated by Pml. PMID:11238464

Boisvert, F M; Kruhlak, M J; Box, A K; Hendzel, M J; Bazett-Jones, D P

2001-03-01

4

Identifying gene locus associations with promyelocytic leukemia nuclear bodies using immuno-TRAP  

PubMed Central

Important insights into nuclear function would arise if gene loci physically interacting with particular subnuclear domains could be readily identified. Immunofluorescence microscopy combined with fluorescence in situ hybridization (immuno-FISH), the method that would typically be used in such a study, is limited by spatial resolution and requires prior assumptions for selecting genes to probe. Our new technique, immuno-TRAP, overcomes these limitations. Using promyelocytic leukemia nuclear bodies (PML NBs) as a model, we used immuno-TRAP to determine if specific genes localize within molecular dimensions with these bodies. Although we confirmed a TP53 gene–PML NB association, immuno-TRAP allowed us to uncover novel locus-PML NB associations, including the ABCA7 and TFF1 loci and, most surprisingly, the PML locus itself. These associations were cell type specific and reflected the cell’s physiological state. Combined with microarrays or deep sequencing, immuno-TRAP provides powerful opportunities for identifying gene locus associations with potentially any nuclear subcompartment.

Ching, Reagan W.; Ahmed, Kashif; Boutros, Paul C.; Penn, Linda Z.

2013-01-01

5

Targeting Promyelocytic Leukemia Protein: A Means to Regulating PML Nuclear Bodies  

PubMed Central

The promyelocytic leukemia protein (PML) is involved in many cellular processes including cell cycle progression, DNA damage response, transcriptional regulation, viral infection, and apoptosis. These cellular activities often rely on the localization of PML to unique subnuclear structures known as PML nuclear bodies (NBs). More than 50 cellular proteins are known to traffic in and out of PML NBs, either transiently or constitutively. In order to understand the dynamics of these NBs, it is important to delineate the regulation of PML itself. PML is subject to extensive regulation at transcriptional, post-transcriptional, and post-translational levels. Many of these modes of regulation depend on the cellular context and the presence of extracellular signals. This review focuses on the current knowledge of regulation of PML under normal cellular conditions as well as the role for regulation of PML in viral infection and cancer.

Reineke, Erin L.; Kao, Hung-Ying

2009-01-01

6

The Alphaherpesvirus Serine/Threonine Kinase Us3 Disrupts Promyelocytic Leukemia Protein Nuclear Bodies?†  

PubMed Central

Us3, a serine/threonine kinase encoded by all alphaherpesviruses, plays diverse roles during virus infection, including preventing virus-induced apoptosis, facilitating nuclear egress of capsids, stimulating mRNA translation and promoting cell-to-cell spread of virus infection. Given this diversity, the full spectrum of Us3 function may not yet be recognized. We noted, in transiently transfected cells, that herpes simplex virus type 2 (HSV-2) Us3 disrupted promyelocytic leukemia protein nuclear bodies (PML-NBs). However, PML-NB disruption was not observed in cells expressing catalytically inactive HSV-2 Us3. Analysis of PML-NBs in Vero cells transfected with pseudorabies virus (PRV) Us3 and those in Vero cells infected with Us3-null or -repaired PRV strains indicated that PRV Us3 expression also leads to the disruption of PML-NBs. While loss of PML-NBs in response to Us3 expression was prevented by the proteasome inhibitor MG132, Us3-mediated degradation of PML was not observed in infected cells or in transfected cells expressing enhanced green fluorescent protein (EGFP)-tagged PML isoform IV. These findings demonstrate that Us3 orthologues derived from distantly related alphaherpesviruses cause a disruption of PML-NBs in a kinase- and proteasome-dependent manner but, unlike the alphaherpesvirus ICP0 orthologues, do not target PML for degradation.

Jung, Masany; Finnen, Renee L.; Neron, Casey E.; Banfield, Bruce W.

2011-01-01

7

Pondering the puzzle of PML (promyelocytic leukemia) nuclear bodies: Can we fit the pieces together using an RNA regulon?  

PubMed Central

Summary The promyelocytic leukemia protein PML and its associated nuclear bodies are hot topics of investigation. This interest arises for multiple reasons including the tight link between the integrity of PML nuclear bodies and several disease states and the impact of the PML protein and PML nuclear bodies on proliferation, apoptosis and viral infection. Unfortunately, an understanding of the molecular underpinnings of PML nuclear body function remains elusive. Here, a general overview of the PML field is provided and is extended to discuss whether some of the basic tenets of “PML-ology” are still valid. For instance, recent findings suggest that some components of PML nuclear bodies form bodies in the absence of the PML protein. Also, a new model for PML nuclear body function is proposed which provides a unifying framework for its effects on diverse biochemical pathways such as Akt signaling and the p53-Mdm2 axis. In this model, the PML protein acts as an inhibitor of gene expression post-transcriptionally via inhibiting a network node in the eIF4E RNA regulon. An example is given for how the PML RNA regulon model provided the basis for the development of a new anti-cancer strategy being tested in the clinic.

Borden, Katherine L.B.

2008-01-01

8

Functional Reorganization of Promyelocytic Leukemia Nuclear Bodies during BK Virus Infection  

PubMed Central

BK virus (BKV) is the causative agent for polyomavirus-associated nephropathy, a severe disease found in renal transplant patients due to reactivation of a persistent BKV infection. BKV replication relies on the interactions of BKV with many nuclear components, and subnuclear structures such as promyelocytic leukemia nuclear bodies (PML-NBs) are known to play regulatory roles during a number of DNA virus infections. In this study, we investigated the relationship between PML-NBs and BKV during infection of primary human renal proximal tubule epithelial (RPTE) cells. While the levels of the major PML-NB protein components remained unchanged, BKV infection of RPTE cells resulted in dramatic alterations in both the number and the size of PML-NBs. Furthermore, two normally constitutive components of PML-NBs, Sp100 and hDaxx, became dispersed from PML-NBs. To define the viral factors responsible for this reorganization, we examined the cellular localization of the BKV large tumor antigen (TAg) and viral DNA. TAg colocalized with PML-NBs during early infection, while a number of BKV chromosomes were adjacent to PML-NBs during late infection. We demonstrated that TAg alone was not sufficient to reorganize PML-NBs and that active viral DNA replication is required. Knockdown of PML protein did not dramatically affect BKV growth in culture. BKV infection, however, was able to rescue the growth of an ICP0-null herpes simplex virus 1 mutant whose growth defect was partially due to its inability to disrupt PML-NBs. We hypothesize that the antiviral functions of PML-NBs are inactivated through reorganization during normal BKV infection.

Jiang, Mengxi; Entezami, Pouya; Gamez, Monica; Stamminger, Thomas; Imperiale, Michael J.

2011-01-01

9

Nucleocytoplasmic shuttling of p62/SQSTM1 and its role in recruitment of nuclear polyubiquitinated proteins to promyelocytic leukemia bodies.  

PubMed

p62, also known as sequestosome1 (SQSTM1), A170, or ZIP, is a multifunctional protein implicated in several signal transduction pathways. p62 is induced by various forms of cellular stress, is degraded by autophagy, and acts as a cargo receptor for autophagic degradation of ubiquitinated targets. It is also suggested to shuttle ubiquitinated proteins for proteasomal degradation. p62 is commonly found in cytosolic protein inclusions in patients with protein aggregopathies, it is up-regulated in several forms of human tumors, and mutations in the gene are linked to classical adult onset Paget disease of the bone. To this end, p62 has generally been considered to be a cytosolic protein, and little attention has been paid to possible nuclear roles of this protein. Here, we present evidence that p62 shuttles continuously between nuclear and cytosolic compartments at a high rate. The protein is also found in nuclear promyelocytic leukemia bodies. We show that p62 contains two nuclear localization signals and a nuclear export signal. Our data suggest that the nucleocytoplasmic shuttling of p62 is modulated by phosphorylations at or near the most important nuclear localization signal, NLS2. The aggregation of p62 in cytosolic bodies also regulates the transport of p62 between the compartments. We found p62 to be essential for accumulation of polyubiquitinated proteins in promyelocytic leukemia bodies upon inhibition of nuclear protein export. Furthermore, p62 contributed to the assembly of proteasome-containing degradative compartments in the vicinity of nuclear aggregates containing polyglutamine-expanded Ataxin1Q84 and to the degradation of Ataxin1Q84. PMID:20018885

Pankiv, Serhiy; Lamark, Trond; Bruun, Jack-Ansgar; Øvervatn, Aud; Bjørkøy, Geir; Johansen, Terje

2009-12-15

10

Association of hepatitis B virus polymerase with promyelocytic leukemia nuclear bodies mediated by the S100 family protein p11.  

PubMed

Hepatitis B virus (HBV) polymerase (Pol) interacts with cellular chaperone proteins and thereby performs multiple functions necessary for viral replication. Yeast two-hybrid analysis was applied to identify additional cellular targets required for HBV Pol function. HBV Pol interacted with S100A10 (p11), a Ca(2+)-modulated protein previously shown to bind to annexin II. The interaction between HBV Pol and p11 was confirmed by co-immunoprecipitation of the two proteins synthesized either in vitro or in transfected cells and by inhibition of the DNA polymerase activity of HBV Pol by p11. Immunofluorescence analysis of transfected human cell lines revealed that, although most HBV Pol and p11 was restricted to the cytoplasm, a small proportion of each protein colocalized as nuclear speckles; HBV Pol was not detected in the nucleus in the absence of p11. The HBV Pol-p11 nuclear speckles coincided with nuclear bodies containing the promyelocytic leukemia protein PML. Furthermore, the association of HBV Pol-p11 with PML was increased by exposure of cells to EGTA and inhibited by valinomycin. These results suggest a role for p11 in modulation of HBV Pol function and implicate PML nuclear bodies and intracellular Ca(2+) in viral replication. PMID:12767936

Choi, Juhyun; Chang, Jin-Sook; Song, Min-Sup; Ahn, Byung-Yoon; Park, Young; Lim, Dae-Sik; Han, Ye Sun

2003-06-13

11

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

SciTech Connect

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.

Sides, Mark D. [Department of Medicine, Section of Pulmonary Disease and Critical Care, Tulane University School of Medicine, New Orleans, LA (United States); Block, Gregory J. [University of Washington Institute for Stem Cell and Regenerative Medicine, Seattle, WA (United States); Shan, Bin; Esteves, Kyle C. [Department of Medicine, Section of Pulmonary Disease and Critical Care, Tulane University School of Medicine, New Orleans, LA (United States); Lin, Zhen; Flemington, Erik K. [Department of Pathology, Tulane University School of Medicine, New Orleans, LA (United States); Lasky, Joseph A., E-mail: jlasky@tulane.edu [Department of Medicine, Section of Pulmonary Disease and Critical Care, Tulane University School of Medicine, New Orleans, LA (United States)

2011-06-20

12

Acute promyelocytic leukemia, arsenic, and PML bodies  

PubMed Central

Acute promyelocytic leukemia (APL) is driven by a chromosomal translocation whose product, the PML/retinoic acid (RA) receptor ? (RARA) fusion protein, affects both nuclear receptor signaling and PML body assembly. Dissection of APL pathogenesis has led to the rediscovery of PML bodies and revealed their role in cell senescence, disease pathogenesis, and responsiveness to treatment. APL is remarkable because of the fortuitous identification of two clinically effective therapies, RA and arsenic, both of which degrade PML/RARA oncoprotein and, together, cure APL. Analysis of arsenic-induced PML or PML/RARA degradation has implicated oxidative stress in the biogenesis of nuclear bodies and SUMO in their degradation.

Le Bras, Morgane; Lallemand-Breitenbach, Valerie

2012-01-01

13

Components of Promyelocytic Leukemia Nuclear Bodies (ND10) Act Cooperatively To Repress Herpesvirus Infection  

PubMed Central

Upon the entry of the viral genome into the nucleus, herpes simplex virus type 1 (HSV-1) gene expression is rapidly repressed by constitutively expressed cellular proteins. This intrinsic antiviral defense is normally counteracted by ICP0, which allows virus infection to proceed efficiently. Replication of ICP0-null mutant HSV-1, however, is severely repressed by mechanisms that are conferred, at least in part, by nuclear domain 10 (ND10) components, including hDaxx, the promyelocytic leukemia (PML) protein, and Sp100. To investigate if these ND10 components repress viral gene expression in a cooperative manner, we simultaneously depleted host cells for hDaxx, PML, and Sp100 by multiple short hairpin RNA (shRNA) knockdown from a single lentivirus vector. We found that replication and gene expression of ICP0-null mutant HSV-1 were cooperatively repressed by hDaxx, PML, and Sp100 immediately upon infection, and all stages of virus replication were inhibited. Plaque-forming efficiency was enhanced at least 50-fold in the triple-depleted cells, a much larger increase than achieved by depletion of any single ND10 protein. Similar effects were also observed during infection of triple-depleted cells with human cytomegalovirus (HCMV). Moreover, using a cell culture model of quiescent infection, we found that triple depletion resulted in a much larger number of viral genomes escaping repression. However, triple depletion was unable to fully overcome the ICP0-null phenotype, implying the presence of additional repressive host factors, possibly components of the SUMO modification or DNA repair pathways. We conclude that several ND10 components cooperate in an additive manner to regulate HSV-1 and HCMV infection.

Glass, Mandy

2013-01-01

14

Components of promyelocytic leukemia nuclear bodies (ND10) act cooperatively to repress herpesvirus infection.  

PubMed

Upon the entry of the viral genome into the nucleus, herpes simplex virus type 1 (HSV-1) gene expression is rapidly repressed by constitutively expressed cellular proteins. This intrinsic antiviral defense is normally counteracted by ICP0, which allows virus infection to proceed efficiently. Replication of ICP0-null mutant HSV-1, however, is severely repressed by mechanisms that are conferred, at least in part, by nuclear domain 10 (ND10) components, including hDaxx, the promyelocytic leukemia (PML) protein, and Sp100. To investigate if these ND10 components repress viral gene expression in a cooperative manner, we simultaneously depleted host cells for hDaxx, PML, and Sp100 by multiple short hairpin RNA (shRNA) knockdown from a single lentivirus vector. We found that replication and gene expression of ICP0-null mutant HSV-1 were cooperatively repressed by hDaxx, PML, and Sp100 immediately upon infection, and all stages of virus replication were inhibited. Plaque-forming efficiency was enhanced at least 50-fold in the triple-depleted cells, a much larger increase than achieved by depletion of any single ND10 protein. Similar effects were also observed during infection of triple-depleted cells with human cytomegalovirus (HCMV). Moreover, using a cell culture model of quiescent infection, we found that triple depletion resulted in a much larger number of viral genomes escaping repression. However, triple depletion was unable to fully overcome the ICP0-null phenotype, implying the presence of additional repressive host factors, possibly components of the SUMO modification or DNA repair pathways. We conclude that several ND10 components cooperate in an additive manner to regulate HSV-1 and HCMV infection. PMID:23221561

Glass, Mandy; Everett, Roger D

2012-12-05

15

Contribution of the C-terminal Regions of Promyelocytic Leukemia Protein (PML) Isoforms II and V to PML Nuclear Body Formation*  

PubMed Central

Promyelocytic leukemia protein (PML) nuclear bodies are dynamic and heterogeneous nuclear protein complexes implicated in various important functions, most notably tumor suppression. PML is the structural component of PML nuclear bodies and has several nuclear splice isoforms that share a common N-terminal region but differ in their C termini. Previous studies have suggested that the coiled-coil motif within the N-terminal region is sufficient for PML nuclear body formation by mediating homo/multi-dimerization of PML molecules. However, it has not been investigated whether any of the C-terminal variants of PML may contribute to PML body assembly. Here we report that the unique C-terminal domains of PML-II and PML-V can target to PML-NBs independent of their N-terminal region. Strikingly, both domains can form nuclear bodies in the absence of endogenous PML. The C-terminal domain of PML-II interacts transiently with unknown binding sites at PML nuclear bodies, whereas the C-terminal domain of PML-V exhibits hyperstable binding to PML bodies via homo-dimerization. This strong interaction is mediated by a putative ?-helix in the C terminus of PML-V. Moreover, nuclear bodies assembled from the C-terminal domain of PML-V also recruit additional PML body components, including Daxx and Sp100. These observations establish the C-terminal domain of PML-V as an additional important contributor to the assembly mechanism(s) of PML bodies.

Geng, Yunyun; Monajembashi, Shamci; Shao, Anwen; Cui, Di; He, Weiyong; Chen, Zhongzhou; Hemmerich, Peter; Tang, Jun

2012-01-01

16

Contribution of the C-terminal regions of promyelocytic leukemia protein (PML) isoforms II and V to PML nuclear body formation.  

PubMed

Promyelocytic leukemia protein (PML) nuclear bodies are dynamic and heterogeneous nuclear protein complexes implicated in various important functions, most notably tumor suppression. PML is the structural component of PML nuclear bodies and has several nuclear splice isoforms that share a common N-terminal region but differ in their C termini. Previous studies have suggested that the coiled-coil motif within the N-terminal region is sufficient for PML nuclear body formation by mediating homo/multi-dimerization of PML molecules. However, it has not been investigated whether any of the C-terminal variants of PML may contribute to PML body assembly. Here we report that the unique C-terminal domains of PML-II and PML-V can target to PML-NBs independent of their N-terminal region. Strikingly, both domains can form nuclear bodies in the absence of endogenous PML. The C-terminal domain of PML-II interacts transiently with unknown binding sites at PML nuclear bodies, whereas the C-terminal domain of PML-V exhibits hyperstable binding to PML bodies via homo-dimerization. This strong interaction is mediated by a putative ?-helix in the C terminus of PML-V. Moreover, nuclear bodies assembled from the C-terminal domain of PML-V also recruit additional PML body components, including Daxx and Sp100. These observations establish the C-terminal domain of PML-V as an additional important contributor to the assembly mechanism(s) of PML bodies. PMID:22773875

Geng, Yunyun; Monajembashi, Shamci; Shao, Anwen; Cui, Di; He, Weiyong; Chen, Zhongzhou; Hemmerich, Peter; Tang, Jun

2012-07-07

17

Progressive multifocal leukoencephalopathy and promyelocytic leukemia nuclear bodies: a review of clinical, neuropathological, and virological aspects of JC virus-induced demyelinating disease  

PubMed Central

Progressive multifocal leukoencephalopathy is a fatal viral-induced demyelinating disease that was once rare but has become more prevalent today. Over the past decades, much has been learned about the disease from molecular study of the etiological agent of the disease, JC virus. Recently, promyelocytic leukemia nuclear bodies (PML-NBs), punctuate structures for important nuclear functions in eukaryotic cells, were identified as an intranuclear target of JC virus infection. Neuropathologically, JC virus-infected glial cells display diffuse amphophilic viral inclusions by hematoxylin–eosin staining (full inclusions), a diagnostic hallmark of this disease. Recent results using immunohistochemistry, however, revealed the presence of punctate viral inclusions preferentially located along the inner nuclear periphery (dot-shaped inclusions). Dot-shaped inclusions reflect the accumulation of viral progeny at PML-NBs, which may be disrupted after viral replication. Structural changes to PML-NBs have been reported for a variety of human diseases, including cancers and neurodegenerative disorders. Thus, PML-NBs may provide clues to the further pathogenesis of JC virus-induced demyelinating disease. Here, we review what we have learned since the disease entity establishment, including a look at recent progress in understanding the relationship between JC virus, etiology and PML-NBs.

2010-01-01

18

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

PubMed

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

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

2013-03-29

19

Nucleation of nuclear bodies.  

PubMed

The nucleus is a complex organelle containing numerous highly dynamic, structurally stable domains and bodies, harboring functions that have only begun to be defined. However, the molecular mechanisms for their formation are still poorly understood. Recently it has been shown that a nuclear body can form de novo by self-organization. But little is known regarding what triggers the formation of a nuclear body and how subsequent assembly steps are orchestrated. Nuclear bodies are frequently associated with specific active gene loci that directly contribute to their formation. Both coding and noncoding RNAs can initiate the assembly of nuclear bodies with which they are physiologically associated. Thus, the formation of nuclear bodies occurs via recruitment and consequent accumulation of resident proteins in the nuclear bodies by nucleating RNA acting as a seeder. In this chapter I describe how to set up an experimental cell system to probe de novo biogenesis of a nuclear body by nucleating RNA and nuclear body components tethered on chromatin. PMID:23980018

Dundr, Miroslav

2013-01-01

20

Total body irradiation in chronic myeloid leukemia  

SciTech Connect

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.

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

1983-04-01

21

PML Nuclear Bodies  

PubMed Central

PML nuclear bodies are matrix-associated domains that recruit an astonishing variety of seemingly unrelated proteins. Since their discovery in the early 1960s, PML bodies have fascinated cell biologists because of their beauty and their tight association with cellular disorders. The identification of PML, a gene involved in an oncogenic chromosomal translocation, as the key organizer of these domains drew instant interest onto them. The multiple levels of PML body regulation by a specific posttranslational modification, sumoylation, have raised several unsolved issues. Functionally, PML bodies may sequester, modify or degrade partner proteins, but in many ways, PML bodies still constitute an enigma.

Lallemand-Breitenbach, Valerie; de The, Hugues

2010-01-01

22

Telomerase-negative Immortalized Human Cells Contain a Novel Type of Promyelocytic Leukemia (PML) Body1  

Microsoft Academic Search

Telomerase-negative immortalized human cells maintain their tel- omeres by a mechanism known as alternative lengthening of telomeres (ALT). We report here that ALT cells contain a novel promyelocytic leukemia (PML) body (ALT-associated PML body, APB). APBs are large donut-shaped nuclear structures containing PML protein, telomeric DNA, and the telomere binding proteins human telomere repeat binding factors 1 and 2. Immunostaining

Thomas R. Yeager; Axel A. Neumann; Anna Englezou; Lily I. Huschtscha; Jane R. Noble; Roger R. Reddel

23

Biophysical and Functional Analyses Suggest That Adenovirus E4-ORF3 Protein Requires Higher-order Multimerization to Function against Promyelocytic Leukemia Protein Nuclear Bodies*  

PubMed Central

The early region 4 open reading frame 3 protein (E4-ORF3; UniProt ID P04489) is the most highly conserved of all adenovirus-encoded gene products at the amino acid level. A conserved attribute of the E4-ORF3 proteins of different human adenoviruses is the ability to disrupt PML nuclear bodies from their normally punctate appearance into heterogeneous filamentous structures. This E4-ORF3 activity correlates with the inhibition of PML-mediated antiviral activity. The mechanism of E4-ORF3-mediated reorganization of PML nuclear bodies is unknown. Biophysical analysis of the purified WT E4-ORF3 protein revealed an ordered secondary/tertiary structure and the ability to form heterogeneous higher-order multimers in solution. Importantly, a nonfunctional E4-ORF3 mutant protein, L103A, forms a stable dimer with WT secondary structure content. Because the L103A mutant is incapable of PML reorganization, this result suggests that higher-order multimerization of E4-ORF3 may be required for the activity of the protein. In support of this hypothesis, we demonstrate that the E4-ORF3 L103A mutant protein acts as a dominant-negative effector when coexpressed with the WT E4-ORF3 in mammalian cells. It prevents WT E4-ORF3-mediated PML track formation presumably by binding to the WT protein and inhibiting the formation of higher-order multimers. In vitro protein binding studies support this conclusion as demonstrated by copurification of coexpressed WT and L103A proteins in Escherichia coli and coimmunoprecipitation of WT·L103A E4-ORF3 complexes in mammalian cells. These results provide new insight into the properties of the Ad E4-ORF3 protein and suggest that higher-order protein multimerization is essential for E4-ORF3 activity.

Patsalo, Vadim; Yondola, Mark A.; Luan, Bowu; Shoshani, Ilana; Kisker, Caroline; Green, David F.; Raleigh, Daniel P.; Hearing, Patrick

2012-01-01

24

Whole-genome screening identifies proteins localized to distinct nuclear bodies.  

PubMed

The nucleus is a unique organelle that contains essential genetic materials in chromosome territories. The interchromatin space is composed of nuclear subcompartments, which are defined by several distinctive nuclear bodies believed to be factories of DNA or RNA processing and sites of transcriptional and/or posttranscriptional regulation. In this paper, we performed a genome-wide microscopy-based screening for proteins that form nuclear foci and characterized their localizations using markers of known nuclear bodies. In total, we identified 325 proteins localized to distinct nuclear bodies, including nucleoli (148), promyelocytic leukemia nuclear bodies (38), nuclear speckles (27), paraspeckles (24), Cajal bodies (17), Sam68 nuclear bodies (5), Polycomb bodies (2), and uncharacterized nuclear bodies (64). Functional validation revealed several proteins potentially involved in the assembly of Cajal bodies and paraspeckles. Together, these data establish the first atlas of human proteins in different nuclear bodies and provide key information for research on nuclear bodies. PMID:24127217

Fong, Ka-Wing; Li, Yujing; Wang, Wenqi; Ma, Wenbin; Li, Kunpeng; Qi, Robert Z; Liu, Dan; Songyang, Zhou; Chen, Junjie

2013-10-14

25

Human Leukemia-Associated Anti-Nuclear Reactivity  

PubMed Central

A brilliant, coarsely granular nuclear antigen was detected by anti-complement immunofluorescence in the nuclei of acute myeloid leukemia myeloblasts. Designated as LANA (leukemia-associated nuclear antigen), the reactivity differs from that of the Epstein-Barr-virus-determined nuclear antigen (EBNA) in immunological specificity and morphological appearance, although it is visualized by the same method. Serum from acute myeloid leukemia patients gave positive reactions in 73% of the cases. In acute lymphatic leukemia, chronic myeloid leukemia, chronic lymphatic leukemia, and Burkitt's lymphoma the sera were positive in 35, 14, 19, and 24%, respectively. Two of five polycythemia and two of eleven myeloma sera were also positive. Among 61 healthy controls, 58 were negative, whereas three showed a diffuse nuclear staining with a different pattern. Among 24 carcinoma patients, 18 were negative, whereas six gave a nuclear staining with a different, diffuse pattern. Sera from 20 patients who had recovered from infectious mononucleosis were all negative. In addition to the blasts of acute myeloid leukemia, a similar reactivity was seen with two Epstein-Barr virus DNA and EBNA-negative African lymphoma biopsies and in a short-lived tissue culture line derived from one of them. LANA could be a fetal or tissue-specific antigen, a virally determined antigen, or a specific form of anti-nuclear reactivity. Images

Klein, George; Steiner, Melita; Wiener, Francis; Klein, Eva

1974-01-01

26

THAP1 is a nuclear proapoptotic factor that links prostate-apoptosis-response-4 (Par4) to PML nuclear bodies  

Microsoft Academic Search

Promyelocytic leukemia (PML) nuclear bodies (PML NBs) are discrete subnuclear domains organized by the promyelocytic leukemia protein PML, a tumor suppressor essential for multiple apoptotic pathways. We have recently described a novel family of cellular factors, the THAP proteins, characterized by the presence at their amino-terminus of an evolutionary conserved putative DNA-binding motif, designated THAP domain. Here, we report that

Myriam Roussigne; Corinne Cayrol; Thomas Clouaire; François Amalric; Jean-Philippe Girard; JP Girard

2003-01-01

27

Leukemia among participants in military maneuvers at a nuclear bomb test  

SciTech Connect

To test the possibility of a casual relationship between leukemia and exposure to nuclear radiation, the frequency of leukemia in personnel observing the detonation of a nuclear device called ''Smoky'' during August 1957 was determined. Of some 3224 men who witnessed the detonation, nine cases of leukemia were observed. They included four cases of acute myelocytic leukemia, three of chronic myelocytic leukemia, one of hairy cell lymphocyctic leukemia, and one of acute lymphocytic luekemia. These findings represent a significant increase over the expected leukemia incidence of 3.5 cases. Mean film-badge gamma radiation dose for the study group was 466.2 mrem. (17 references, 3 tables)

Caldwell, G.G.; Kelley, D.B.; Heath, C.W.

1980-10-03

28

Childhood leukemia and fallout from the Nevada nuclear tests  

SciTech Connect

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.

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

1984-01-13

29

Childhood leukemia and fallout from the Nevada nuclear tests.  

PubMed

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. PMID:6691139

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

1984-01-13

30

PML bodies control the nuclear dynamics and function of the CHFR mitotic checkpoint protein  

Microsoft Academic Search

Nuclear foci containing the promyelocytic leukemia protein (PML bodies), which occur in most cells, play a role in tumor suppression. Here, we demonstrate that CHFR, a mitotic checkpoint protein frequently inactivated in human cancers, is a dynamic component of PML bodies. Intermolecular fluorescence resonance energy transfer analysis identified a distinct fraction of CHFR that interacts with PML in living cells.

Matthew J Daniels; Alexander Marson; Ashok R Venkitaraman

2004-01-01

31

China's nuclear safety regulatory body: The national nuclear safety administration.  

National Technical Information Service (NTIS)

The establishment of an independent nuclear safety regulatory body is necessary for ensuring the safety of nuclear installations and nuclear fuel. Therefore the National Nuclear Safety Administration was established by the state. The aim, purpose, organiz...

S. Zhang

1991-01-01

32

The Human Cytomegalovirus IE2 and UL112-113 Proteins Accumulate in Viral DNA Replication Compartments That Initiate from the Periphery of Promyelocytic Leukemia Protein-Associated Nuclear Bodies (PODs or ND10)  

PubMed Central

During human cytomegalovirus (HCMV) infection, the periphery of promyelocytic leukemia protein (PML)-associated nuclear bodies (also known as PML oncogenic domains [PODs] or ND10) are sites for both input viral genome deposition and immediate-early (IE) gene transcription. At very early times after infection, the IE1 protein localizes to and subsequently disrupts PODs, whereas the IE2 protein localizes within or adjacent to PODs. This process appears to be required for efficient viral gene expression and DNA replication. We have investigated the initiation of viral DNA replication compartment formation by studying the localization of viral IE proteins, DNA replication proteins, and the PML protein during productive infection. Localization of IE2 adjacent to PODs between 2 and 6 h after infection was confirmed by confocal microscopy of human fibroblasts (HF cells) infected with both wild-type HCMV(Towne) and with an IE1-deletion mutant HCMV(CR208) that fails to disrupt PODs. In HCMV(Towne)-infected HF cells at 24 to 48 h, IE2 also accumulated in newly formed viral DNA replication compartments containing the polymerase processivity factor (UL44), the single-stranded DNA binding protein (SSB; UL57), the UL112-113 accessory protein, and newly incorporated bromodeoxyuridine (BrdU). Double labeling of the HCMV(CR208)-infected HF cells demonstrated that formation of viral DNA replication compartments initiates within granular structures that bud from the periphery of some of the PODs and subsequently coalesce into larger structures that are flanked by PODs. In transient DNA transfection assays, both the N terminus (codons 136 to 290) and the C terminus (codons 379 to 579) of IE2 exon 5, but not the central region between them, were found to be necessary for both the punctate distribution of IE2 and its association with PODs. Like IE2, the UL112-113 accessory replication protein was also distributed in a POD-associated pattern in both DNA-transfected and virus-infected cells beginning at 6 h. Furthermore, when all six replication core machinery proteins (polymerase complex, SSB, and helicase-primase complex) were expressed together in the presence of UL112-113, they also accumulated at POD-associated sites, suggesting that the UL112-113 protein (but not IE2) may play a role in recruitment of viral replication fork proteins into the periphery of PODs. These results show that (i) subsequent to accumulating at the periphery of PODs, IE2 is incorporated together with the core proteins into viral DNA replication compartments that initiate from the periphery of PODs and then grow to fill the space between groups of PODs, and (ii) the UL112-113 protein appears to have a key role in assembling and recruiting the core replication machinery proteins in the initial stages of viral replication compartment formation.

Ahn, Jin-Hyun; Jang, Won-Jong; Hayward, Gary S.

1999-01-01

33

Nuclear stress bodies: a heterochromatin affair?  

Microsoft Academic Search

It is still largely unknown how the various nuclear subcompartments are formed, why they form in particular locations and how they are linked to nuclear function. Nuclear stress bodies provide a new opportunity to address these questions and to test models of self-organization of nuclear structures. The assembly of these bodies requires the synthesis of non-coding RNAs with a probable

Giuseppe Biamonti

2004-01-01

34

Histone Deacetylase 7 Promotes PML Sumoylation and Is Essential for PML Nuclear Body Formation  

Microsoft Academic Search

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 transcrip- tional 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) knock- down

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

2008-01-01

35

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

SciTech Connect

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.

Salsman, Jayme; Wang Xueqi; Frappier, Lori, E-mail: lori.frappier@utoronto.ca

2011-06-05

36

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

PubMed

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. PMID:21489587

Salsman, Jayme; Wang, Xueqi; Frappier, Lori

2011-04-13

37

Role of PML and the PML-nuclear body in the control of programmed cell death  

Microsoft Academic Search

PML is a tumor suppressor implicated in leukemia and cancer pathogenesis. PML epitomizes a multiprotein nuclear structure, the PML-nuclear body (PML-NB), whose proper formation and function depends on PML. Studies in knockout (KO) mice and cells unraveled an essential pleiotropic role for PML in multiple p53-dependent and -independent apoptotic pathways. As a result, Pml?\\/? mice and cells are protected from

Rosa Bernardi; Pier Paolo Pandolfi

2003-01-01

38

TTRAP is a novel PML nuclear bodies-associated protein  

SciTech Connect

PML nuclear body (PML NB) is an important macromolecular nuclear structure that is involved in many essential aspects of cellular function. Tens of proteins have been found in PML NBs, and promyelocytic leukemia protein (PML) has been proven to be essential for the formation of this structure. Here, we showed that TRAF and TNF receptor-associated protein (TTRAP) was a novel PML NBs-associated protein. TTRAP colocalized with three important PML NBs-associated proteins, PML, DAXX and Sp100 in the typical fashion of PML NBs. By yeast mating assay, TTRAP was identified to interact with these PML NBs-associated proteins. The transcription and expression of TTRAP could be induced by IFN-{gamma}, representing another common feature of PML NBs-associated proteins. These results would not only be important for understanding PML NBs but also be helpful in studying the TTRAP function in the future.

Xu Guanlan; Pan Yukun; Wang Bingyin; Huang Lu; Tian Ling; Xue Jinglun [State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai (China); Chen Jinzhong [State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai (China)], E-mail: kingbellchen@fudan.edu.cn; Jia, William [State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai (China); Department of Surgery, University of British Columbia, Vancouver (Canada)], E-mail: wjia@interchange.ubc.ca

2008-10-24

39

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

PubMed

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

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

2010-10-13

40

Arsenic-Induced SUMO-Dependent Recruitment of RNF4 into PML Nuclear Bodies  

PubMed Central

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.

Geoffroy, Marie-Claude; Jaffray, Ellis G.; Walker, Katherine J.

2010-01-01

41

Many-body interactions and nuclear structure  

NASA Astrophysics Data System (ADS)

This paper 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.

Hjorth-Jensen, M.; Dean, D. J.; Hagen, G.; Kvaal, S.

2010-06-01

42

Leukemia  

MedlinePLUS

... leukemia /DS00351 ">Leukemia Guidelines for sites linking to MayoClinic.com Advertisement Mayo Clinic Store Check out these best-sellers and special offers on books and newsletters from Mayo Clinic. Try Mayo Clinic Health Letter ... answers to live stronger, longer and healthier at any age ...

43

Body composition, muscle strength deficits and mobility limitations in adult survivors of childhood acute lymphoblastic leukemia  

Microsoft Academic Search

Background. Chronicity of muscle weakness from cancer and its treatment may be problematic, particularly in those treated for cancer during childhood. We compared body composition, muscle strength, and mobility between 75 adult survivors of childhood acute lymphoblastic leukemia (ALL) and expected values based on population normative data. Methods. Subjects were young adults treated for childhood ALL between 1970 and 1986,

Kirsten K. Ness; K. Scott Baker; Donald R. Dengel; Nancy Youngren; Shalamar Sibley; Ann C. Mertens; James G. Gurney

2007-01-01

44

21 CFR 892.1130 - Nuclear whole body counter.  

Code of Federal Regulations, 2013 CFR

...2013-04-01 false Nuclear whole body counter. 892.1130 ...DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL...892.1130 Nuclear whole body counter. (a) Identification. A nuclear whole body counter is a device...

2013-04-01

45

21 CFR 892.1330 - Nuclear whole body scanner.  

Code of Federal Regulations, 2013 CFR

...2013-04-01 false Nuclear whole body scanner. 892.1330 ...DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL...892.1330 Nuclear whole body scanner. (a) Identification. A nuclear whole body scanner is a device...

2013-04-01

46

Leukemia and other health outcomes in the vicinity of the Pilgrim Nuclear Power Station, Plymouth, MA  

Microsoft Academic Search

We investigated the patterns of leukemia, other cancers, and adverse birth outcomes in the communities surrounding the Pilgrim Nuclear Power Plant in Plymouth, Massachusetts. Data were taken from state vital records and cancer registry files. Information about coastal meteorologic conditions was used to estimate the population exposed to radioactive emissions in the mid-1970s. The temporal relationships of infant mortality, leukemia,

R. W. Clapp; S. Cobb

2008-01-01

47

Epstein-Barr Nuclear Antigen 1 Contributes to Nasopharyngeal Carcinoma through Disruption of PML Nuclear Bodies  

PubMed Central

Latent Epstein-Barr virus (EBV) infection is strongly associated with several cancers, including nasopharyngeal carcinoma (NPC), a tumor that is endemic in several parts of the world. We have investigated the molecular basis for how EBV latent infection promotes the development of NPC. We show that the viral EBNA1 protein, previously known to be required to maintain the EBV episomes, also causes the disruption of the cellular PML (promyelocytic leukemia) nuclear bodies (or ND10s). This disruption occurs both in the context of a native latent infection and when exogenously expressed in EBV-negative NPC cells and involves loss of the PML proteins. We also show that EBNA1 is partially localized to PML nuclear bodies in NPC cells and interacts with a specific PML isoform. PML disruption by EBNA1 requires binding to the cellular ubiquitin specific protease, USP7 or HAUSP, but is independent of p53. We further observed that p53 activation, DNA repair and apoptosis, all of which depend on PML nuclear bodies, were impaired by EBNA1 expression and that cells expressing EBNA1 were more likely to survive after induction of DNA damage. The results point to an important role for EBNA1 in the development of NPC, in which EBNA1-mediated disruption of PML nuclear bodies promotes the survival of cells with DNA damage.

Sivachandran, Nirojini; Sarkari, Feroz; Frappier, Lori

2008-01-01

48

Acute lymphocytic leukemia (ALL)  

MedlinePLUS

ALL; Acute childhood leukemia; Cancer - acute childhood leukemia (ALL); Leukemia - acute childhood (ALL) ... Acute lymphocytic leukemia (ALL) occurs when the the body produces a large number of immature white blood cells, called ...

49

Subcellular distribution of nuclear import-defective isoforms of the promyelocytic leukemia protein  

PubMed Central

Background The promyelocytic leukemia (PML) protein participates in a number of cellular processes, including transcription regulation, apoptosis, differentiation, virus defense and genome maintenance. This protein is structurally organized into a tripartite motif (TRIM) at its N-terminus, a nuclear localization signal (NLS) at its central region and a C-terminus that varies between alternatively spliced isoforms. Most PML splice variants target the nucleus where they define sub-nuclear compartments termed PML nuclear bodies (PML NBs). However, PML variants that lack the NLS are also expressed, suggesting the existence of PML isoforms with cytoplasmic functions. In the present study we expressed PML isoforms with a mutated NLS in U2OS cells to identify potential cytoplasmic compartments targeted by this protein. Results Expression of NLS mutated PML isoforms in U2OS cells revealed that PML I targets early endosomes, PML II targets the inner nuclear membrane (partially due to an extra NLS at its C-terminus), and PML III, IV and V target late endosomes/lysosomes. Clustering of PML at all of these subcellular locations depended on a functional TRIM domain. Conclusions This study demonstrates the capacity of PML to form macromolecular protein assemblies at several different subcellular sites. Further, it emphasizes a role of the variable C-terminus in subcellular target selection and a general role of the N-terminal TRIM domain in promoting protein clustering.

2010-01-01

50

21 CFR 892.1330 - Nuclear whole body scanner.  

Code of Federal Regulations, 2010 CFR

...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 radionuclides in the body by means of a wide-aperture...

2009-04-01

51

21 CFR 892.1330 - Nuclear whole body scanner.  

Code of Federal Regulations, 2010 CFR

...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 radionuclides in the body by means of a wide-aperture...

2010-04-01

52

Vaginal obliteration after total body irradiation and chemotherapy as treatment for acute myeloid leukemia  

Microsoft Academic Search

Although radiotherapy is an integral part in the management of certain types of hematological malignancies, its effect on the reproductive system has been well documented. We report a rare complication where a patient had complete vaginal obliteration after receiving a dose of total body irradiation (1575 cGy) as part of her treatment for acute myeloid leukemia. A 37-year-old married woman,

Wen-Ling Lee; Chiou-Chung Yuan; Hsiang-Tai Chao; Po-Min Chen; Hong-Da Lin; Peng-Hui Wang

2000-01-01

53

Leukemia among participants in military maneuvers at a nuclear bomb test. [Plumbbob Project  

SciTech Connect

Preliminary studies indicate that nine cases of leukemia have occurred among 3224 men who participated in military maneuvers during the 1957 nuclear test explosion Smoky. This represents a significant increase over the expected incidence of 3.5 cases. They included four cases of acute myelocytic leukemia, three of chronic myelocytic leukemia, and one each of hairy cell and acute lymphocytic leukemia. At time of diagnosis, patient ages ranged from 21 to 60 years (mean, 41.8 years) and the interval from time of nuclear test to diagnosis from two to 19 years (mean, 14.2 years). Film-badge records, which are available for eight of the nine men, indicated gamma radiation exposure levels ranging from 0 to 2977 mrem (mean, 1033 mrem). Mean film-badge gamma dose for the entire Smoky cohort was 466.2 mrem.

Caldwell, G.G.; Kelley, D.B.; Heath, C.W. Jr.

1980-10-03

54

Cancer incidence in the vicinity of Finnish nuclear power plants: an emphasis on childhood leukemia  

Microsoft Academic Search

The objective of this paper was to study cancer incidence, especially leukemia in children (<15 years), in the vicinity of\\u000a Finnish nuclear power plants (NPPs). We used three different approaches: ecological analysis at municipality level, residential\\u000a cohorts defined from census data, and case–control analysis with individual residential histories. The standardized incidence\\u000a ratio of childhood leukemia for the seven municipalities in the

Sirpa Heinävaara; Salla Toikkanen; Kari Pasanen; Pia K. Verkasalo; Päivi Kurttio; Anssi Auvinen

2010-01-01

55

The Role of Nuclear Bodies in Gene Expression and Disease  

PubMed Central

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.

Morimoto, Marie; Boerkoel, Cornelius F.

2013-01-01

56

Relativistic nuclear many-body theory  

SciTech Connect

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.

Serot, B.D. (Indiana Univ., Bloomington, IN (United States)); Walecka, J.D. (Southeastern Universities Research Association, Newport News, VA (United States). Continuous Electron Beam Accelerator Facility)

1991-09-11

57

Modulation of CREB Binding Protein Function by the Promyelocytic (PML) Oncoprotein Suggests a Role for Nuclear Bodies in Hormone Signaling  

Microsoft Academic Search

Disaggregation of the spherical nuclear bodies termed promyelocytic (PML) oncogenic domains (PODs) is a characteristic of acute promyelocytic leukemia. Here, we demonstrate that the cAMP enhancer binding protein (CREB)-binding protein (CBP) associates with PML in vitro and is recruited to the PODs in vivo. Through its association with CBP, wild-type PML dramatically stimulates nuclear receptor transcriptional activity. These results demonstrate

Vassilis Doucas; Marc Tini; David A. Egan; Ronald M. Evans

1999-01-01

58

Leukemia, Lymphomas, and Myeloma Mortality in the Vicinity of Nuclear Power Plants and Nuclear Fuel Facilities in Spain1  

Microsoft Academic Search

Mortality due to hematological tumors in towns near Spain's seven nuclear power plants and five nuclear fuel facilities during the period 1975-1993 was ascertained. The study was based on 610 leukemia-, 198 lymphoma-, and 122 myeloma-induced deaths in 489 towns situated within a 30-km radius of such installations. As control areas, we used 477 towns lying within a 50- to

Gonzalo Lopez-Abente; Nuria Aragones; Marina Pollan; Maria Ruiz; Ana Gandarillas

59

Micronuclei and Nuclear Abnormalities Observed in Erythroblasts in Myelodysplastic Syndromes and in de novo Acute Leukemia after Treatment  

Microsoft Academic Search

The frequencies of erythroblasts with micronuclei (EBM) and erythroblasts with aberrant nuclear shapes (EBAN) in bone marrow were evaluated in 60 patients with untreated myelodysplastic syndrome (MDS), and also in 21 patients with acute leukemia before and after treatment, and the results were compared regarding cytogenetic patterns. In patients with acute leukemia, the frequencies of EBM and EBAN in bone

H. Yashige; S. Horiike; M. Taniwaki; S. Misawa; T. Abe

1999-01-01

60

Leukemia  

MedlinePLUS Videos and Cool Tools

... of a doctor or a healthcare professional for your specific condition. ©1995-2011, The Patient Education Institute, Inc. www.X-Plain.com oc160105 Last reviewed: 6/28/2011 1 Cancers in the body are given names, depending on where the cancer ...

61

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

PubMed

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

Nussbaum, Rudi H

62

Treatment of chronic lymphocytic leukemia by total body irradiation alone and combined with chemotherapy. [Efficacy and complications  

Microsoft Academic Search

Total body irradiation (TBI) offers a new dimension in the treatment of chronic lymphocytic leukemia (CLL), a disease heretofore refractory to effective management. Excellent responses were observed in 50\\/57 (88%) consecutive patients with active CLL treated since 1964, and complete remissions were achieved in 22\\/57 (39%). Toxicity was acceptable and was minimized by combining TBI and chemotherapy in attenuated doses

Johnson

1979-01-01

63

Nuclear Few-Body Physics at FAIR  

NASA Astrophysics Data System (ADS)

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.

Nilsson, Thomas

2011-05-01

64

Genome-Wide Screen of Three Herpesviruses for Protein Subcellular Localization and Alteration of PML Nuclear Bodies  

PubMed Central

Herpesviruses are large, ubiquitous DNA viruses with complex host interactions, yet many of the proteins encoded by these viruses have not been functionally characterized. As a first step in functional characterization, we determined the subcellular localization of 234 epitope-tagged proteins from herpes simplex virus, cytomegalovirus, and Epstein–Barr virus. Twenty-four of the 93 proteins with nuclear localization formed subnuclear structures. Twelve of these localized to the nucleolus, and five at least partially localized with promyelocytic leukemia (PML) bodies, which are known to suppress viral lytic infection. In addition, two proteins disrupted Cajal bodies, and 19 of the nuclear proteins significantly decreased the number of PML bodies per cell, including six that were shown to be SUMO-modified. These results have provided the first functional insights into over 120 previously unstudied proteins and suggest that herpesviruses employ multiple strategies for manipulating nuclear bodies that control key cellular processes.

Salsman, Jayme; Zimmerman, Nicole; Chen, Tricia; Domagala, Megan; Frappier, Lori

2008-01-01

65

High magnesium concentrations in the dense bodies of human blood platelets from patients with atopic dermatitis and chronic myelogenous leukemia  

Microsoft Academic Search

Dense bodies of the normal human blood platelet contain high concentrations of phosphorus and calcium and very small amounts\\u000a of magnesium, 69 mM\\/kg dry weight. Quantitative energy dispersive X-ray microanalysis of the platelet dense bodies on fresh\\u000a air-dried smears of blood from patients with atopic dermatitis and chronic myelogenous leukemia disclosed higher concentrations\\u000a of magnesium, 251 and 176 mM\\/kg, respectively,

Kenichi Takaya; Kenji Niiya; Masahiko Toyoda; Toru Masuda

1994-01-01

66

Disruption of PML Nuclear Bodies Is Mediated by ORF61 SUMO-Interacting Motifs and Required for Varicella-Zoster Virus Pathogenesis in Skin  

Microsoft Academic Search

Promyelocytic leukemia protein (PML) has antiviral functions and many viruses encode gene products that disrupt PML nuclear bodies (PML NBs). However, evidence of the relevance of PML NB modification for viral pathogenesis is limited and little is known about viral gene functions required for PML NB disruption in infected cells in vivo. Varicella-zoster virus (VZV) is a human alphaherpesvirus that

Li Wang; Stefan L. Oliver; Marvin Sommer; Jaya Rajamani; Mike Reichelt; Ann M. Arvin

2011-01-01

67

Epigenomic analysis detects widespread gene-body DNA hypomethylation in chronic lymphocytic leukemia.  

PubMed

We have extensively characterized the DNA methylomes of 139 patients with chronic lymphocytic leukemia (CLL) with mutated or unmutated IGHV and of several mature B-cell subpopulations through the use of whole-genome bisulfite sequencing and high-density microarrays. The two molecular subtypes of CLL have differing DNA methylomes that seem to represent epigenetic imprints from distinct normal B-cell subpopulations. DNA hypomethylation in the gene body, targeting mostly enhancer sites, was the most frequent difference between naive and memory B cells and between the two molecular subtypes of CLL and normal B cells. Although DNA methylation and gene expression were poorly correlated, we identified gene-body CpG dinucleotides whose methylation was positively or negatively associated with expression. We have also recognized a DNA methylation signature that distinguishes new clinico-biological subtypes of CLL. We propose an epigenomic scenario in which differential methylation in the gene body may have functional and clinical implications in leukemogenesis. PMID:23064414

Kulis, Marta; Heath, Simon; Bibikova, Marina; Queirós, Ana C; Navarro, Alba; Clot, Guillem; Martínez-Trillos, Alejandra; Castellano, Giancarlo; Brun-Heath, Isabelle; Pinyol, Magda; Barberán-Soler, Sergio; Papasaikas, Panagiotis; Jares, Pedro; Beà, Sílvia; Rico, Daniel; Ecker, Simone; Rubio, Miriam; Royo, Romina; Ho, Vincent; Klotzle, Brandy; Hernández, Lluis; Conde, Laura; López-Guerra, Mónica; Colomer, Dolors; Villamor, Neus; Aymerich, Marta; Rozman, María; Bayes, Mónica; Gut, Marta; Gelpí, Josep L; Orozco, Modesto; Fan, Jian-Bing; Quesada, Víctor; Puente, Xose S; Pisano, David G; Valencia, Alfonso; López-Guillermo, Armando; Gut, Ivo; López-Otín, Carlos; Campo, Elías; Martín-Subero, José I

2012-10-14

68

A Cluster of Childhood Leukemia near a Nuclear Reactor in Northern Germany  

Microsoft Academic Search

Between February 1990 and December 1995, professionals diagnosed six cases of childhood leukemia among residents of the small rural community of Elbmarsch in Northern Germany. Five of these cases were diagnosed in only a 16-mo period between February 1990 and May 1991. All cases lived in close proximity (i.e., 500–4 500 m) to Germany's largest capacity nuclear boiling-water reactor. We

Wolfgang Hoffmann; Helga Dieckmann; Hayo Dieckmann; Inge Schmitz-feuerhake

1997-01-01

69

Childhood leukemia incidence in the vicinity of La Hague nuclear-waste reprocessing facility (France)  

Microsoft Academic Search

The incidence of leukemia is examined in young people (aged under 25 years) living within a 35 km radius of the French nuclear-waste reprocessing plant operating in La Hague, Normandy. During the period 1978–90, a total of 23 cases was diagnosed, giving an incidence rate of 2.99 per 100,000 which is close to the expected rate. In the ‘canton’ in

Jean-François Viel; Sylvia Richardson; Patrick Danel; Patrick Boutard; Michèle Malet; Paul Barrelier; Oumédaly Reman; André Carré

1993-01-01

70

Fetal growth and body size genes and risk of childhood acute lymphoblastic leukemia.  

PubMed

Accumulating evidence suggests that childhood acute lymphoblastic leukemia (ALL) may be initiated in utero or early in the postnatal period. High birth weight (or rapid fetal growth) is associated with risk of ALL, but the mechanisms are not understood. In a population-based epidemiologic study of childhood ALL, we utilized a haplotype-based approach to assess the role of eight genes involved in fetal growth and body size regulation in 377 childhood ALL cases and 448 controls. We found significant haplotype associations with risk of childhood ALL for IGF1 among non-Hispanics and Hispanics together (p = 0.002), for IGF2 among Hispanics (p = 0.040), and for IGF2R among Hispanics and non-Hispanics (p = 0.051 and 0.009, respectively). No haplotype associations were observed for IGF1R or the studied genes involved in body size regulation, including LEP, LEPR, GHRL, and NPY. Our study is the first to identify an association between the genes involved in the IGF axis and risk of childhood ALL. These findings for childhood ALL emphasize the importance of fetal growth, when lymphoid progenitor cells are not yet fully differentiated and therefore more susceptible to malignant transformation. Additional studies are needed to confirm these findings and identify specific causal variants. PMID:22878902

Chokkalingam, Anand P; Metayer, Catherine; Scelo, Ghislaine; Chang, Jeffrey S; Schiffman, Joshua; Urayama, Kevin Y; Ma, Xiaomei; Hansen, Helen M; Feusner, James H; Barcellos, Lisa F; Wiencke, John K; Wiemels, Joseph L; Buffler, Patricia A

2012-07-28

71

Nuclear forces and the quantum many-body problem  

Microsoft Academic Search

1. Challenges for the nuclear many-body problem Intricate nuclear forces, which have yet to be completely determined, two different fermionic species (protons and neutrons) and the lack of an external force, generate a range and diversity of behaviours that make the nucleus a truly unique quantum many-body system. One major goal of the physics of nuclei is to develop a

B R Barrett; D J Dean; M Hjorth-Jensen; J P Vary

2005-01-01

72

SUMO-1 promotes association of SNURF (RNF4) with PML nuclear bodies.  

PubMed

Small nuclear RING finger protein SNURF (RNF4) is involved in transcriptional and cell growth regulation. We show here that a significant portion of endogenous SNURF localizes to nuclear bodies (NBs) that overlap with or are adjacent to domains containing endogenous promyelocytic leukemia (PML) protein and small ubiquitin-like modifier-1 (SUMO-1). In biochemical assays, SNURF efficiently binds SUMO-1 in a noncovalent fashion. SNURF is also covalently modified by SUMO-1 at nonconsensus attachment sites. Ectopic expression of SUMO-1 markedly enhances the interaction between PML3 (PML IV) and SNURF, but covalent attachment of SUMO-1 to neither protein is required. Moreover, overexpression of PML3, but not PML-L (PML III), abolishes the coactivation function of SNURF in transactivation assays, which parallels the ability of PML3 to recruit SNURF to nuclear bodies. In sum, we have identified SNURF as a novel component in PML bodies and suggest that SUMO-1-facilitated sequestration into these nuclear domains regulates the transcriptional activity of SNURF. PMID:15707587

Häkli, Marika; Karvonen, Ulla; Jänne, Olli A; Palvimo, Jorma J

2004-11-23

73

SUMO-1 promotes association of SNURF (RNF4) with PML nuclear bodies  

SciTech Connect

Small nuclear RING finger protein SNURF (RNF4) is involved in transcriptional and cell growth regulation. We show here that a significant portion of endogenous SNURF localizes to nuclear bodies (NBs) that overlap with or are adjacent to domains containing endogenous promyelocytic leukemia (PML) protein and small ubiquitin-like modifier-1 (SUMO-1). In biochemical assays, SNURF efficiently binds SUMO-1 in a noncovalent fashion. SNURF is also covalently modified by SUMO-1 at nonconsensus attachment sites. Ectopic expression of SUMO-1 markedly enhances the interaction between PML3 (PML IV) and SNURF, but covalent attachment of SUMO-1 to neither protein is required. Moreover, overexpression of PML3, but not PML-L (PML III), abolishes the coactivation function of SNURF in transactivation assays, which parallels the ability of PML3 to recruit SNURF to nuclear bodies. In sum, we have identified SNURF as a novel component in PML bodies and suggest that SUMO-1-facilitated sequestration into these nuclear domains regulates the transcriptional activity of SNURF.

Haekli, Marika [Biomedicum Helsinki, Institute of Biomedicine, University of Helsinki, P.O. Box 63, FI-00014 Helsinki (Finland); Karvonen, Ulla [Biomedicum Helsinki, Institute of Biomedicine, University of Helsinki, P.O. Box 63, FI-00014 Helsinki (Finland); Jaenne, Olli A. [Biomedicum Helsinki, Institute of Biomedicine, University of Helsinki, P.O. Box 63, FI-00014 Helsinki (Finland); Department of Clinical Chemistry, Helsinki University Central Hospital, FI-00014 Helsinki (Finland); Palvimo, Jorma J. [Biomedicum Helsinki, Institute of Biomedicine, University of Helsinki, P.O. Box 63, FI-00014 Helsinki (Finland) and Department of Medical Biochemistry, University of Kuopio, P.O. Box 1627, FI-70211 Kuopio (Finland)]. E-mail: jorma.palvimo@helsinki.fi

2005-03-10

74

Many-Body Forces in Nuclear Shell-Model.  

National Technical Information Service (NTIS)

In the microscopic derivation of the effective Hamiltonian for the nuclear shell model many-body forces between the valence nucleons occur. These many-body forces can be discriminated in ''real'' many-body forces, which can be related to mesonic and inter...

P. K. Rath

1985-01-01

75

Characterization of a new SUMO1 nuclear body (SNB) enriched in pCREB, CBP, c-Jun in neuron-like UR61 cells  

Microsoft Academic Search

The neuron-like UR61 cell is a stable PC12 subline that contains a mouse N-ras oncogene. Dexamethasone (Dex) treatment induces a neuron-like differentiation, which is associated with neuritogenesis and\\u000a nuclear expression of the glucocorticoid receptor and c-Jun. In differentiated UR61 cells, small ubiquitin-like modifiers\\u000a 1 (SUMO-1) is concentrated in a new category of SUMO-1 nuclear bodies (SNBs) distinct from promyelocytic leukemia

Joaquín Navascués; Rocio Bengoechea; Olga Tapia; José P. Vaqué; Miguel Lafarga; Maria T. Berciano

2007-01-01

76

Minute Virus of Mice NS1 Interacts with the SMN Protein, and They Colocalize in Novel Nuclear Bodies Induced by Parvovirus Infection  

PubMed Central

The human survival motor neuron (SMN) gene is the spinal muscular atrophy-determining gene, and a knockout of the murine Smn gene results in preembryonic lethality. Here we show that SMN can directly interact in vitro and in vivo with the large nonstructural protein NS1 of the autonomous parvovirus minute virus of mice (MVM), a protein essential for viral replication and a potent transcriptional activator. Typically, SMN localizes within nuclear Cajal bodies and diffusely in the cytoplasm. Following transient NS1expression, SMN and NS1 colocalize within Cajal bodies. At early time points following parvovirus infection, NS1 fails to colocalize with SMN within Cajal bodies; however, during the course of MVM infection, dramatic nuclear alterations occur. Formerly distinct nuclear bodies such as Cajal bodies, promyelocytic leukemia gene product (PML) oncogenic domains (PODs), speckles, and autonomous parvovirus-associated replication (APAR) bodies are seen aggregating at later points in infection. These newly formed large nuclear bodies (termed SMN-associated APAR bodies) are active sites of viral replication and viral capsid assembly. These results highlight the transient nature of nuclear bodies and their contents and identify a novel nuclear body formed during infection. Furthermore, simple transient expression of the viral nonstructural proteins is insufficient to induce this nuclear reorganization, suggesting that this event is induced specifically by a step in the viral infection process.

Young, Philip J.; Jensen, Klaus T.; Burger, Lisa R.; Pintel, David J.; Lorson, Christian L.

2002-01-01

77

Structure, dynamics and functions of promyelocytic leukaemia nuclear bodies  

Microsoft Academic Search

The promyelocytic leukaemia (PML) tumour suppressor protein epitomizes the PML-nuclear body (PML-NB) and is crucially required for the proper assembly of this macromolecular nuclear structure. Unlike other, more specialized subnuclear structures such as Cajal and Polycomb group bodies, PML-NBs are functionally promiscuous and have been implicated in the regulation of diverse cellular functions. PML-NBs are dynamic structures that favour the

Rosa Bernardi; Pier Paolo Pandolfi

2007-01-01

78

Nuclear factor 1 activates the feline leukemia virus long terminal repeat but is posttranscriptionally down-regulated in leukemia cell lines.  

PubMed Central

A recombinant feline leukemia virus (FeLV) proviral clone (T17T-22) with a long terminal repeat (LTR) which differs from prototype FeLV by a point mutation within a conserved nuclear factor 1 (NF1)-binding motif in the LTR enhancer domain was found to be poorly expressed after DNA transfection. The NF1 point mutation reduced in vitro protein binding as assessed by gel shift analysis and reduced promoter activity significantly (2- to 10-fold). However, the degree of promoter impairment due to the NF1 site mutation varied according to cell type and was least severe in a feline leukemia cell line (T3) which had low levels of nuclear NF1 DNA-binding activity. Low NF1 DNA-binding activity was observed in three FeLV-induced leukemia cell lines (T3, T17, and FL74) and in murine F9 embryonal carcinoma cells. While similar levels of NF1 gene mRNA transcripts were detected in all cell lines, Western immunoblot analysis of F9, T17, and FL74 but not T3 nuclear extracts revealed very low levels of nuclear NF1 protein. These results indicate that NF1 activity is down-regulated in FeLV-induced leukemia cells by diverse posttranscriptional mechanisms. We suggest that NF1 down-regulation may be an important characteristic of target cells susceptible to FeLV transformation in vivo and may provide the selective pressure which favors duplication of the LTR core enhancer sequence in T-cell leukemogenic FeLV variants. Images

Plumb, M; Fulton, R; Breimer, L; Stewart, M; Willison, K; Neil, J C

1991-01-01

79

Father's occupational exposure to radiation and the raised level of childhood leukemia near the Sellafield nuclear plant.  

PubMed Central

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.

Gardner, M J

1991-01-01

80

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

SciTech Connect

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.

Gardner, M.J. (Univ. of Southampton (England))

1991-08-01

81

Effects of the acute myeloid leukemia--associated fusion proteins on nuclear architecture.  

PubMed

Acute myeloid leukemias (AMLs) are consistently associated with chromosomal rearrangements that result in the generation of chimeric genes and fusion proteins. One of the two affected genes is frequently a transcription factor Involved in the regulation of hematopoletic differentiation. Recent findings suggest a common leukemogenic mechanism for the fused transcription factor: abnormal recruitment of histone deacetylase (HDAC)-containing complexes to its target promoters. Inhibition of HDAC enzymatic activity reverts the leukemic phenotype in vitro and therefore represents a plausible strategy for antileukemic therapy. In this review, we first briefly describe the molecular structure and mechanisms of the most frequent AML associated fusion proteins (RAR, MLL, and CBF fusions) and then summarize available knowledge about their effects on the nuclear architecture. We propose that alteration of nuclear compartmentalization might represent an additional common mechanism of leukemogenesis. PMID:11172539

Faretta, M; Di Croce, L; Pelicci, P G

2001-01-01

82

An inducible nuclear body in the Drosophila germinal vesicle.  

PubMed

When living egg chambers of Drosophila are isolated in a saline solution and gently squashed between a microscope slide and coverslip, prominent nuclear bodies (1 - 20 mm diameter) can be seen inside the oocyte nucleus or germinal vesicle (GV).  These bodies do not pre-exist within the GV and are not seen in material that is fixed in paraformaldehyde before squashing.  Instead, they form spontaneously within minutes after an egg chamber is damaged and the cytoplasm is exposed to the isolation medium.  Electron microscopy shows that the bodies lack an investing membrane and consist of closely packed, irregular particles 30-50 nm in diameter.  We used GFP-tagged proteins from the Carnegie Protein Trap Library to identify 22 proteins that are either enriched in the bodies or excluded from them.  We were unable to discern common features of proteins that are concentrated in the bodies, such as isoelectric point, molecular weight, or biological process.  Induced bodies are formed in GVs of flies that are null for coilin or WDR79, proteins that are required for formation of Cajal bodies (CBs).  We performed fluorescence recovery after photobleaching (FRAP) experiments on five GFP-tagged proteins that are enriched in the bodies.  Four of the proteins regained the full pre-bleach fluorescence intensity, indicating that the contents of the bodies are in dynamic equilibrium with the surrounding nucleoplasm.  Induced nuclear bodies presumably form as a result of unusual physico-chemical changes in the Drosophila GV.  We suggest that their behavior serves as a useful model for self-assembly of nuclear bodies in general, and we discuss the possibility that similar bodies may occur normally in cells of other organisms. PMID:21941118

Singer, Alison B; Gall, Joseph G

2011-09-01

83

Computational nuclear quantum many-body problem: The UNEDF project  

NASA Astrophysics Data System (ADS)

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.

Bogner, S.; Bulgac, A.; Carlson, J.; Engel, J.; Fann, G.; Furnstahl, R. J.; Gandolfi, S.; Hagen, G.; Horoi, M.; Johnson, C.; Kortelainen, M.; Lusk, E.; Maris, P.; Nam, H.; Navratil, P.; Nazarewicz, W.; Ng, E.; Nobre, G. P. A.; Ormand, E.; Papenbrock, T.; Pei, J.; Pieper, S. C.; Quaglioni, S.; Roche, K. J.; Sarich, J.; Schunck, N.; Sosonkina, M.; Terasaki, J.; Thompson, I.; Vary, J. P.; Wild, S. M.

2013-10-01

84

Proximity to PML nuclear bodies regulates HIV-1 latency in CD4+ T cells.  

PubMed

Nuclear bodies (NBs), characterized by the presence of the promyelocytic leukemia (PML) protein, are important components of the nuclear architecture, contributing to genetic and epigenetic control of gene expression. In investigating the mechanisms mediating HIV-1 latency, we determined that silenced but transcriptionally competent HIV-1 proviruses reside in close proximity to PML NBs and that this association inhibits HIV-1 gene expression. PML binds to the latent HIV-1 promoter, which coincides with transcriptionally inactive facultative heterochromatic marks, notably H3K9me2, at the viral genome. PML degradation and NB disruption result in strong activation of viral transcription as well as release of G9a, the major methyltransferase responsible for H3K9me2, and loss of facultative heterochromatin marks from the proviral DNA. Additionally, HIV-1 transcriptional activation requires proviral displacement from PML NBs by active nuclear actin polymerization. Thus, nuclear topology and active gene movement mediate HIV-1 transcriptional regulation and have implications for controlling HIV-1 latency and eradication. PMID:23768491

Lusic, Marina; Marini, Bruna; Ali, Hashim; Lucic, Bojana; Luzzati, Roberto; Giacca, Mauro

2013-06-12

85

CDK2 catalytic activity and loss of nuclear tethering of retinoblastoma protein in childhood acute lymphoblastic leukemia  

Microsoft Academic Search

Acute lymphoblastic leukemia (ALL) is the most common childhood cancer. During cell cycle progression from the mid- to late G1 phase, mammalian cells traverse the restriction point, a transition from mitogen dependence to mitogen independence, regulated by retinoblastoma protein (Rb). Different cyclin-dependent kinases (CDKs) sequentially phosphorylate and inactivate Rb, which is associated by a change in Rb's nuclear affinity and

N M R Schmitz; K Leibundgut; A Hirt; NMR Schmitz

2005-01-01

86

Epstein-Barr virus nuclear antigen 1 Hijacks the host kinase CK2 to disrupt PML nuclear bodies.  

PubMed

Latent Epstein-Barr virus (EBV) infection is an important causative factor in the development of several cancers, including nasopharyngeal carcinoma (NPC). The one EBV protein expressed in the nucleus of NPC cells, EBNA1, has been shown to disrupt promyelocitic leukemia (PML) nuclear bodies (NBs) by inducing the degradation of PML proteins, leading to impaired DNA repair and increased cell survival. Although EBNA1-mediated PML disruption is likely to be an important factor in the development of NPC, little is known about its mechanism. We now show that an interaction between EBNA1 and the host CK2 kinase is crucial for EBNA1 to disrupt PML bodies and degrade PML proteins. EBNA1 increases the association of CK2 with PML proteins, thereby increasing the phosphorylation of PML proteins by CK2, a modification that is known to trigger the polyubiquitylation and degradation of PML. The interaction between EBNA1 and CK2 is direct and occurs through the ? regulatory subunit of CK2 and EBNA1 amino acids 387 to 394. The binding of EBNA1 to the host ubiquitin specific protease USP7 has also been shown to be important for EBNA1-mediated PML disruption. We show that EBNA1 also increases the occupancy of USP7 at PML NBs and that CK2 and USP7 bind independently and simultaneously to EBNA1 to form a ternary complex. The combined results indicate that EBNA1 usurps two independent cellular pathways to trigger the loss of PML NBs. PMID:20719947

Sivachandran, Nirojini; Cao, Jennifer Yinuo; Frappier, Lori

2010-08-18

87

Few-Body Problems in Experimental Nuclear Astrophysics  

NASA Astrophysics Data System (ADS)

The 3 ?-reaction is one of the key reactions in nuclear astrophysics. Since it is a three-body reaction direct measurement is impossible, and therefore the reaction rate must be estimated theoretically. In this contribution I will discuss uncertainties in this reaction rate both at very low temperatures, temperatures typical for Helium burning in red giant stars, and for very high temperatures.

Fynbo, H. O. U.

2013-08-01

88

PROPERTIES OF URANIA-CERIA BODIES FOR NUCLEAR FUEL APPLICATION  

Microsoft Academic Search

Several compositions within the UOâ-CeOâ system were studied ; for possible application as ceramic fuel in nuclear reactors. The properties of ; interest reported include density, porosity, modulus of rupture, thermal ; expansion, thermal conductivity, corrosion resistance to water, and ; microstructure. It was found that higher strength bodies resulted by air firing ; UâOâ-CeOâ mixtures into a singie-phase solid

G. L. Ploetz; A. T. Muccigrosso; C. W. Krystyniak

1958-01-01

89

Nuclear Astrophysics from View Point of Few-Body Problems  

NASA Astrophysics Data System (ADS)

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.

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

2013-08-01

90

Nuclear Three-Body Force from the Nijmegen Potential  

NASA Astrophysics Data System (ADS)

A nuclear three-body force based on the meson-exchange approach is constructed using the same meson parameters and the exponential form factors as in the Nijmegen potential, involving four kinds of important mesons, ?, ?, ?, and ? [f0(975) and ?(760)]. For the 2?-exchange three-nucleon component, we adopt the new expansion strength constants a, b, c consistent with the contemporary ?N-scattering data base and the corresponding dipole form factor. An effective two-body interaction is derived by averaging out the third nucleon, and is self-consistently used together with the Nijmegen potential in the Brueckner-Hartree-Fock approximation. The empirical nuclear matter saturation properties are reproduced very well. At higher density the equation of state becomes rather stiff due to the strong repulsion from the (?, ?)-N three-body contribution.

Li, Z. H.; Lombardo, U.; Schulze, H.-J.; Zuo, W.

2008-02-01

91

Outcomes in obese and overweight acute myeloid leukemia patients receiving chemotherapy dosed according to actual body weight.  

PubMed

Cytotoxic chemotherapy dosages are traditionally calculated according to body surface area (BSA). No guidelines exist for chemotherapy dosing of acute myeloid leukemia (AML) patients at extremes of weight. We investigated the efficacy and safety of chemotherapy dosed according to BSA based on actual body weight (ABW) among under/normal weight, overweight, and obese AML patients. AML patients (excluding acute promyelocytic leukemia) treated with anthracycline and cytarabine-based remission induction chemotherapy from 2002 to 2009 at Cleveland Clinic were divided into three body mass index (BMI) groups: under/normal weight (BMI ?24.9), overweight (BMI 25.0-29.9), and obese (BMI ?30.0). Among 247 AML patients, 81 (33%) were under/normal weight, 81 (33%) were overweight, and 85 (34%) were obese. Complete remission (CR) rates were similar among these groups (69.1, 79.0, and 76.5%, respectively; P?=?0.321), as was median survival (10.7, 16.7, and 14.2 months, respectively, P?=?0.352) and 30-day mortality (3.7, 2.5, 7.1%, respectively, P?=?0.331). There was no difference among groups in days to neutrophil or platelet recovery, hospitalization days for induction chemotherapy, and bacteremia. After adjustment for confounders (age, sex, BMI, white blood cells, cytogenetic risk, etiology, and bacteremia), overall survival was significantly shorter for normal weight compared to overweight (P?=?0.006) and obese (0.038) patients. Response rates and adverse events were not significantly different among AML patients of all weight classes when induction chemotherapy was dosed according to ABW. Induction chemotherapy in these patients can be safely dosed using ABW. Am. J. Hematol. 88:906-909, 2013. © 2013 Wiley Periodicals, Inc. PMID:23828018

Wenzell, Candice M; Gallagher, Erika M; Earl, Marc; Yeh, Jun-Yen; Kusick, Karissa N; Advani, Anjali S; Kalaycio, Matt E; Mukherjee, Sudipto; Tiu, Ramon V; Maciejewski, Jaroslaw P; Sekeres, Mikkael A

2013-08-30

92

Some highlights in few-body nuclear physics.  

SciTech Connect

During the past five years, there have been tremendous advances in both experiments and theoretical calculations in few-body nuclear systems. Advances in technology have permitted experiments of unprecedented accuracy. Jefferson Laboratory has begun operation and the first round of experimental results have become available. New polarization techniques have been exploited at a number of laboratories, in particular, at Jefferson Lab, IUCF, RIKEN, NIKHEF, Mainz, MIT-Bates and HERMES. Some of these results will be shown here. In addition, there have been tremendous advances in few-body theory. Five modern two-nucleon potentials have which describe the nucleon-nucleon data extremely well have become available. A standard model of nuclear physics based on these two nucleon potentials as well as modern three-nucleon forces has emerged. This standard model has enjoyed tremendous success in the few body systems. Exact three-body calculations have been extended into the continuum in order to take full advantage of scattering data in advancing our understanding of the the few-nucleon system. In addition, the application of chiral symmetry has become an important constraint on nucleon-nucleon as well as three-nucleon forces. As a result of all these efforts, we have seen rapid developments in the three-body force. Despite these advances, there remain some extremely important open issues: (1) What is the role of quarks and gluons in nuclear structure; (2) Can we distinguish meson exchange from quark interchange; (3) Is few-body theory sufficient to describe simultaneously the mass 2, 3 and 4 form factors; (4) What is the isospin and spin dependence of the three-body force; (5) Are there medium modifications for nucleons and mesons in nuclei; (6) Is there an enhancement of antiquarks or pions in nuclei related to the binding; and (7) Are short range correlations observable in nuclei? In this paper the author summarizes the status of our understanding of these issues.

Holt, R. J.

2000-12-07

93

Thermodynamic properties of nuclear matter with three-body forces  

SciTech Connect

We calculate thermodynamic quantities in symmetric nuclear matter within the self-consistent Green's functions method including three-body forces. The thermodynamic potential is computed directly from a diagrammatic expansion, implemented with the CD-Bonn and Nijmegen nucleon-nucleon potentials and the Urbana three-body forces. We present results for entropy and pressure up to temperatures of 20 MeV and densities of 0.32 fm{sup -3}. While the pressure is sensitive to the inclusion of three-body forces, the entropy is not. The unstable spinodal region is identified and the critical temperature associated to the liquid-gas phase transition is determined. When three-body forces are added we find a strong reduction of the critical temperature, obtaining T{sub c}{approx_equal}12 MeV.

Soma, V. [Institute of Nuclear Physics PAN, PL-31-342 Krakow (Poland); Bozek, P. [Institute of Physics, Rzeszow University, PL-35-959 Rzeszow (Poland); Institute of Nuclear Physics PAN, PL-31-342 Krakow (Poland)

2009-08-15

94

Total body irradiation correlates with chronic graft versus host disease and affects prognosis of patients with acute lymphoblastic leukemia receiving an HLA identical allogeneic bone marrow transplant  

Microsoft Academic Search

Purpose: To investigate whether different procedure variables involved in the delivery of fractionated total body irradiation (TBI) impact on prognosis of patients affected by acute lymphoblastic leukemia (ALL) receiving allogeneic bone marrow transplant (BMT).Methods and Materials: Ninety-three consecutive patients with ALL receiving a human leukocyte antigen (HLA) identical allogeneic BMT between 1 August 1983 and 30 September 1995 were conditioned

Renzo Corvò; Gabriella Paoli; Salvina Barra; Almalina Bacigalupo; Maria Teresa Van Lint; Paola Franzone; Francesco Frassoni; Daniele Scarpati; Andrea Bacigalupo; Vito Vitale

1999-01-01

95

MRI Morphometry of Mamillary Bodies, Caudate Nuclei, and Prefrontal Cortices After Chemotherapy for Childhood Leukemia: Multivariate Models of Early and Late Developing Memory Subsystems  

Microsoft Academic Search

Neurotoxic intrathecal chemotherapy for childhood acute lymphoblastic leukemia (ALL) affects developing structures and functions of memory and learning subsystems selectively. Results show significant reductions in magnetic resonance imaging morphometry of mamillary bodies, components of the corticolimbic–diencephalic subsystem subserving functionally later developing, single-trial memory, nonsignificant changes in bilateral heads of the caudate nuclei, components of the corticostriatal subsystem subserving functionally earlier

Kristina T. Ciesielski; Paul G. Lesnik; Edward C. Benzel; Blaine L. Hart; John A. Sanders

1999-01-01

96

Dynamic Length Changes of Telomeres and Their Nuclear Organization in Chronic Myeloid Leukemia  

PubMed Central

Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm characterized by the t(9;22) translocation. As in most cancers, short telomeres are one of the features of CML cells, and telomere shortening accentuates as the disease progresses from the chronic phase to the blastic phase. Although most individual telomeres are short, some of them are lengthened, and long individual telomeres occur non-randomly and might be associated with clonal selection. Telomerase is the main mechanism used to maintain telomere lengths, and its activity increases when CML evolves toward advanced stages. ALT might be another mechanism employed by CML cells to sustain the homeostasis of their telomere lengths and this mechanism seems predominant at the early stage of leukemogenesis. Also, telomerase and ALT might jointly act to maintain telomere lengths at the chronic phase, and as CML progresses, telomerase becomes the major mechanism. Finally, CML cells display an altered nuclear organization of their telomeres which is characterized by the presence of high number of telomeric aggregates, a feature of genomic instability, and differential positioning of telomeres. CML represents a good model to study mechanisms responsible for dynamic changes of individual telomere lengths and the remodeling of telomeric nuclear organization throughout cancer progression.

Samassekou, Oumar

2013-01-01

97

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

PubMed Central

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.

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

2011-01-01

98

Unique pattern of nuclear TdT immunofluorescence distinguishes normal precursor B cells (Hematogones) from lymphoblasts of precursor B-lymphoblastic leukemia.  

PubMed

Normal precursor B cells or hematogones share morphologic and immunophenotypic similarities with lymphoblasts of precursor B-lymphoblastic leukemia. The numbers are often increased and difficult to distinguish in many patients following chemotherapy for precursor B-lymphoblastic leukemia. The purpose of this study was to establish a unique method for differentiating hematogones from lymphoblasts by evaluating the immunofluorescence pattern of nuclear terminal deoxynucleotidyl transferase (TdT) staining in 29 cases of TdT+ acute leukemia and 20 cases with increased numbers of hematogones. All 29 cases of TdT+ acute leukemia demonstrated a finely granular pattern of TdT immunofluorescence that was uniformly distributed in the nucleus, whereas all 20 cases with increased hematogones demonstrated a coarsely granular or speckled pattern of TdT immunofluorescence, which often intensely aligns the nuclear membrane. The nuclear pattern of immunofluorescence using antibodies to TdT is an effective method for distinguishing hematogones from leukemic blasts. PMID:18426728

Hurford, Matthew T; Altman, Arnold J; DiGiuseppe, Joseph A; Sherburne, Bradford J; Rezuke, William N

2008-05-01

99

The role of multiple regression and exploratory data analysis in the development of leukemia incidence risk models for comparison of radionuclide air stack emissions from nuclear and coal power industries  

Microsoft Academic Search

Risks associated with power generation must be identified to make intelligent choices between alternate power technologies. Radionuclide air stack emissions for a single coal plant and a single nuclear plant are used to compute the single plant leukemia incidence risk and total industry leukemia incidence risk. Leukemia incidence is the response variable as a function of radionuclide bone dose for

Victor R. Prybutok

1995-01-01

100

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

Code of Federal Regulations, 2013 CFR

...bodies of the multi-nuclear polyhedrosis virus of Anagrapha falcifera; exemption from...bodies of the multi-nuclear polyhedrosis virus of Anagrapha falcifera; exemption from...bodies of the multi-nuclear polyhedrosis virus of Anagrapha falcifera is...

2013-07-01

101

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

Code of Federal Regulations, 2012 CFR

...false Inclusion bodies of the multi-nuclear polyhedrosis virus of Anagrapha falcifera...1149 Inclusion bodies of the multi-nuclear polyhedrosis virus of Anagrapha falcifera...control agent inclusion bodies of the multi-nuclear polyhedrosis virus of Anagrapha...

2012-07-01

102

Promyelocytic Leukemia Protein (PML) and Daxx Participate in a Novel Nuclear Pathway for Apoptosis  

Microsoft Academic Search

The promyelocytic leukemia protein (PML) gene of acute promyelocytic leukemia (APL) en- codes a cell growth and tumor suppressor essential for multiple apoptotic signals. Daxx was identified as a molecule important for the cytoplasmic transduction of the Fas proapoptotic stimulus. Here, we show that upon mitogenic activation of mature splenic lymphocytes, Daxx is dramatically upregulated and accumulates in the PML

Sue Zhong; Paolo Salomoni; Simona Ronchetti; Ailan Guo; Davide Ruggero; Pier Paolo Pandolfi

103

Acute Lymphoblastic Leukemia  

MedlinePLUS

... as lymphoblasts, which do not mature into normal lymphocytes. Mature lymphocytes help the body fight infection. Instead, the body ... if the leukemia originates from B or T lymphocytes. Making this distinction helps physicians to recommend the ...

104

The Mechanisms of PML-Nuclear Body Formation  

PubMed Central

Summary PML nuclear bodies (NBs) are nuclear structures that have been implicated in processes such as transcriptional regulation, genome stability, response to viral infection, apoptosis and tumor suppression. PML has been found to be essential for the formation of the NBs, as these structures do not form in Pml null cells, while PML add back fully rescues their formation. However, the basis for such a structural role of PML is unknown. We demonstrate that PML contains a SUMO binding motif that is independent of its SUMOylation sites and is surprisingly necessary for PML-NB formation. We demonstrate that the PML RING domain is critical for PML SUMOylation and PML-NB formation. We propose a model for PML-NB formation whereby PML SUMOylation and non-covalent binding of PML to SUMOylated PML through the SUMO binding motif constitutes the nucleation event for subsequent recruitment of SUMOylated proteins and/or proteins containing SUMO binding motifs to the PML-NBs.

Shen, Tian Huai; Lin, Hui-Kuan; Scaglioni, Pier Paolo; Yung, Thomas M.; Pandolfi, Pier Paolo

2007-01-01

105

Equation of State of Nuclear Matter and the Nuclear Three-Body Force  

SciTech Connect

An equation of state (EOS) for uniform nuclear matter is constructed at zero and finite temperatures with the variational method starting from a realistic nuclear Hamiltonian composed of the AV18 two-body potential and the UIX three-nucleon interaction (TNI). The two-body energy is calculated with a Jastrow wave function, and the TNI energy with the Fermi-gas wave function. In this calculation, the Fujita-Miyazawa (FM) 2{pi}-exchange term of the TNI energy is positive for symmetric nuclear matter. By taking into account the correlation between nucleons perturbatively, the expectation value of the FM term is modified to be negative in the low density region.

Kanzawa, H. [Department of Pure and Applied Physics, Science and Engineering, Waseda University, 3-4-1 Okubo, Shinjuku-ku, Tokyo 169-8555 (Japan); Oyamatsu, K. [Department of Media Production and Theories, Aichi Shukutoku University, Nagakute-cho, Aichi 480-1197 (Japan); Sumiyoshi, K. [Numazu College of Technology, Ooka 3600, Numazu, Shizuoka 410-8501 (Japan); Takano, M. [Research Institute for Science and Engineering, Waseda University, 3-4-1 Okubo, Shinjuku-ku, Tokyo 169-8555 (Japan)

2008-04-29

106

Risk of chronic myeloid and acute leukemia mortality after exposure to ionizing radiation among workers at four U.S. nuclear weapons facilities and a nuclear naval shipyard.  

PubMed

A nested case-control study was conducted among workers at five U.S. nuclear facilities to evaluate leukemia mortality risk (excluding chronic lymphocytic) from ionizing radiation using worksite doses and adjusting for potential confounding. Conditional logistic regression was used to estimate the relative risk (RR) of exposed workers and the excess relative risk (ERR) per unit of radiation among 206 cases and 823 age-matched controls. Adjusting for sex and benzene, the RR of leukemia for workers receiving more than 10 mSv was higher compared to those receiving lower or no dose; however, the risk increase was attenuated in the highest dose group. The ERR per 10 mSv was 1.44% (95% CI: < -1.03%, 7.59%) but was higher for workers born after 1921 compared to workers born earlier or when excluding leukemias of uncertain type. Excluding the 7% who were high-dose workers (> 100 mSv), the sex- and benzene-adjusted ERR per 10 mSv was 6.82% (95% CI: -2.87%, 24.1%). The results suggest that risks among these nuclear workers are comparable to those observed in high-dose populations, although no evidence was observed of a positive quadratic dose-response term in this study. This large study is among the first to jointly evaluate benzene and ionizing radiation risk. PMID:17390730

Schubauer-Berigan, Mary K; Daniels, Robert D; Fleming, Donald A; Markey, Andrea M; Couch, James R; Ahrenholz, Steven H; Burphy, Jenneh S; Anderson, Jeri L; Tseng, Chih-Yu

2007-02-01

107

Changes in the Nuclear Envelope Environment Affect Spindle Pole Body Duplication in Saccharomyces cerevisiae  

PubMed Central

The Saccharomyces cerevisiae nuclear membrane is part of a complex nuclear envelope environment also containing chromatin, integral and peripheral membrane proteins, and large structures such as nuclear pore complexes (NPCs) and the spindle pole body. To study how properties of the nuclear membrane affect nuclear envelope processes, we altered the nuclear membrane by deleting the SPO7 gene. We found that spo7? cells were sickened by the mutation of genes coding for spindle pole body components and that spo7? was synthetically lethal with mutations in the SUN domain gene MPS3. Mps3p is required for spindle pole body duplication and for a variety of other nuclear envelope processes. In spo7? cells, the spindle pole body defect of mps3 mutants was exacerbated, suggesting that nuclear membrane composition affects spindle pole body function. The synthetic lethality between spo7? and mps3 mutants was suppressed by deletion of specific nucleoporin genes. In fact, these gene deletions bypassed the requirement for Mps3p entirely, suggesting that under certain conditions spindle pole body duplication can occur via an Mps3p-independent pathway. These data point to an antagonistic relationship between nuclear pore complexes and the spindle pole body. We propose a model whereby nuclear pore complexes either compete with the spindle pole body for insertion into the nuclear membrane or affect spindle pole body duplication by altering the nuclear envelope environment.

Witkin, Keren L.; Friederichs, Jennifer M.; Cohen-Fix, Orna; Jaspersen, Sue L.

2010-01-01

108

Successful pregnancy following very high-dose total body irradiation (1575 cGy) and bone marrow transplantation in a woman with acute myeloid leukemia  

Microsoft Academic Search

A 22-year-old woman had a normal full-term delivery 6 years after a successful allogeneic bone marrow transplantation (BMT) for acute myeloid leukemia (AML). Conditioning therapy consisted of cyclophosphamide (120 mg\\/kg) and total body irradiation (TBI) to a total of 1575 cGy in seven fractions (225 cGy × 7, at a dose rate of 3.5 cGy\\/min). Graft-versus-host disease prophylaxis was with

W-S Wang; C-H Tzeng; R-K Hsieh; T-J Chiou; J-H Liu; C-C Yen; P-M Chen

1998-01-01

109

Total body irradiation and cyclophosphamide is a conditioning regimen for unrelated bone marrow transplantation in a patient with chronic myelogenous leukemia and renal failure on hemodialysis  

Microsoft Academic Search

Five years after the diagnosis of Ph chromosome-positive chronic myeloid leukemia (CML) a 31-year-old patient developed malignant nephrosclerosis with renal failure. He then underwent an allogeneic unrelated BMT in first chronic phase CML. The preparative regimen consisted of fractionated total body irradiation (TBI) and cyclophosphamide (CY). We studied the pharmacokinetics of cyclophosphamide on hemodialysis and compared clinical parameters including time

ME Bischoff; W Blau; T Wagner; W Wagenmann; O Dörner; N Basara; AA Fauser

1998-01-01

110

Childhood leukemia around French nuclear power plants--the Geocap study, 2002-2007.  

PubMed

The aim of this work is to study the risk of childhood acute leukemia (AL) around French nuclear power plants (NPPs). The nationwide Geocap case-control study included the 2,753 cases diagnosed in mainland France over 2002-2007 and 30,000 contemporaneous population controls. The last addresses were geocoded and located around the 19 NPPs. The study used distance to NPPs and a dose-based geographic zoning (DBGZ), based on the estimated dose to bone marrow related to NPP gaseous discharges. An odds ratio (OR) of 1.9 [1.0-3.3], based on 14 cases, was evidenced for children living within 5 km of NPPs compared to those living 20 km or further away, and a very similar association was observed in the concomitant incidence study (standardized incidence ratio (SIR)=1.9 [1.0-3.2]). These results were similar for all the 5-year-age groups. They persisted after stratification for several contextual characteristics of the municipalities of residence. Conversely, using the DBGZ resulted in OR and SIR close to one in all of the dose categories. There was no increase in AL incidence over 1990-2001 and over the entire 1990-2007 period. The results suggest a possible excess risk of AL in the close vicinity of French NPPs in 2002-2007. The absence of any association with the DBGZ may indicate that the association is not explained by NPP gaseous discharges. Overall, the findings call for investigation for potential risk factors related to the vicinity of NPP and collaborative analysis of multisite studies conducted in various countries. PMID:22223329

Sermage-Faure, Claire; Laurier, Dominique; Goujon-Bellec, Stéphanie; Chartier, Michel; Guyot-Goubin, Aurélie; Rudant, Jérémie; Hémon, Denis; Clavel, Jacqueline

2012-02-28

111

Clofarabine and Low-Dose Total-Body Irradiation in Treating Patients With Acute Myeloid Leukemia Undergoing Donor Peripheral Blood Stem Cell Transplant  

ClinicalTrials.gov

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

2013-07-08

112

Spliceosomal Small Nuclear Ribonucleoprotein Particles Repeatedly Cycle through Cajal Bodies  

PubMed Central

The Cajal body (CB) is a nuclear structure closely associated with import and biogenesis of small nuclear ribonucleoprotein particles (snRNPs). Here, we tested whether CBs also contain mature snRNPs and whether CB integrity depends on the ongoing snRNP splicing cycle. Sm proteins tagged with photoactivatable and color-maturing variants of fluorescent proteins were used to monitor snRNP behavior in living cells over time; mature snRNPs accumulated in CBs, traveled from one CB to another, and they were not preferentially replaced by newly imported snRNPs. To test whether CB integrity depends on the snRNP splicing cycle, two human orthologues of yeast proteins involved in distinct steps in spliceosome disassembly after splicing, hPrp22 and hNtr1, were depleted by small interfering RNA treatment. Surprisingly, depletion of either protein led to the accumulation of U4/U6 snRNPs in CBs, suggesting that reassembly of the U4/U6·U5 tri-snRNP was delayed. Accordingly, a relative decrease in U5 snRNPs compared with U4/U6 snRNPs was observed in CBs, as well as in nuclear extracts of treated cells. Together, the data show that particular phases of the spliceosome cycle are compartmentalized in living cells, with reassembly of the tri-snRNP occurring in CBs.

Pridalova-Hnilicova, Jarmila; Novotny, Ivan; Huranova, Martina; Blazikova, Michaela; Wen, Xin; Sapra, Aparna K.; Neugebauer, Karla M.

2008-01-01

113

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

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.

Rubin, P.I. (Univ. of Rochester Cancer Center, NY); Bennett, J.M.; Begg, C.; Bozdech, M.J.; Silber, R.

1981-12-01

114

Ionizing radiation and risk of chronic lymphocytic leukemia in the 15-country study of nuclear industry workers.  

PubMed

In contrast to other types of leukemia, chronic lymphocytic leukemia (CLL) has long been regarded as non-radiogenic, i.e. not caused by ionizing radiation. However, the justification for this view has been challenged. We therefore report on the relationship between CLL mortality and external ionizing radiation dose within the 15-country nuclear workers cohort study. The analyses included, in seven countries with CLL deaths, a total of 295,963 workers with more than 4.5 million person-years of follow-up and an average cumulative bone marrow dose of 15 mSv; there were 65 CLL deaths in this cohort. The relative risk (RR) at an occupational dose of 100 mSv compared to 0 mSv was 0.84 (95% CI 0.39, 1.48) under the assumption of a 10-year exposure lag. Analyses of longer lag periods showed little variation in the RR, but they included very small numbers of cases with relatively high doses. In conclusion, the largest nuclear workers cohort study to date finds little evidence for an association between low doses of external ionizing radiation and CLL mortality. This study had little power due to low doses, short follow-up periods, and uncertainties in CLL ascertainment from death certificates; an extended follow-up of the cohorts is merited and would ideally include incident cancer cases. PMID:18959468

Vrijheid, Martine; Cardis, Elisabeth; Ashmore, Patrick; Auvinen, Anssi; Gilbert, Ethel; Habib, Rima R; Malker, Hans; Muirhead, Colin R; Richardson, David B; Rogel, Agnes; Schubauer-Berigan, Mary; Tardy, Hélène; Telle-Lamberton, Maylis

2008-11-01

115

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

PubMed Central

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.

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

1997-01-01

116

Nuclear envelope insertion of spindle pole bodies and nuclear pore complexes  

PubMed Central

The defining feature of eukaryotic cells is the double lipid bilayer of the nuclear envelope (NE) that serves as a physical barrier separating the genome from the cytosol. Nuclear pore complexes (NPCs) are embedded in the NE to facilitate transport of proteins and other macromolecules into and out of the nucleus. In fungi and early embryos where the NE does not completely breakdown during mitosis, microtubule-organizing centers such as the spindle pole body (SPB) must also be inserted into the NE to facilitate organization of the mitotic spindle. Several recent papers have shed light on the mechanism by which SPB complexes are inserted into the NE. An unexpected link between the SPB and NPCs suggests that assembly of these NE complexes is tightly coordinated. We review the findings of these reports in light of our current knowledge of SPB, NPC and NE structure, assembly and function.

Jaspersen, Sue L.; Ghosh, Suman

2012-01-01

117

Nuclear envelope insertion of spindle pole bodies and nuclear pore complexes.  

PubMed

The defining feature of eukaryotic cells is the double lipid bilayer of the nuclear envelope (NE) that serves as a physical barrier separating the genome from the cytosol. Nuclear pore complexes (NPCs) are embedded in the NE to facilitate transport of proteins and other macromolecules into and out of the nucleus. In fungi and early embryos where the NE does not completely breakdown during mitosis, microtubule-organizing centers such as the spindle pole body (SPB) must also be inserted into the NE to facilitate organization of the mitotic spindle. Several recent papers have shed light on the mechanism by which SPB complexes are inserted into the NE. An unexpected link between the SPB and NPCs suggests that assembly of these NE complexes is tightly coordinated. We review the findings of these reports in light of our current knowledge of SPB, NPC and NE structure, assembly and function. PMID:22572959

Jaspersen, Sue L; Ghosh, Suman

2012-05-01

118

Evolution of Nuclear Many-Body Forces with the Similarity Renormalization Group  

SciTech Connect

The first practical method to evolve many-body nuclear forces to softened form using the Similarity Renormalization Group (SRG) in a harmonic oscillator basis is demonstrated. When applied to 4He calculations, the two- and three-body oscillator matrix elements yield rapid convergence of the ground-state energy with a small net contribution of the induced four-body force.

Jurgenson, E D; Navratil, P; Furnstahl, R J

2009-05-01

119

Cell Cycle Dependent Alteration in NAC1 Nuclear Body Dynamics and Morphology  

PubMed Central

NAC1, a BTB/POZ family member, has been suggested to participate in maintaining 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 biologic 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 S-phase as compared to 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.

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

2011-01-01

120

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

PubMed

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 G?/G? and G? 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. PMID:21301057

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

2011-02-07

121

Nested case-control study of leukemia among a cohort of persons exposed to ionizing radiation from nuclear weapon tests in kazakhstan (1949-1963).  

PubMed

PURPOSE: A unique opportunity for epidemiological studies of cancer and other health effects of radiation exposures exists around the Semipalatinsk Nuclear Test Site in Kazakhstan. The present study is the first analysis of leukemia risk among the residents of downwind settlements exposed to radioactive fallout from atmospheric nuclear weapon tests (1949-1963) and followed up from 1960 to 1998.METHODS: Within the cohort of 10,000 exposed subjects a case-control study was nested, including 22 leukaemia cases (except chronic lymphoid leukemia) and 132 controls individually (1:6 ratio) matched by birth year and sex. Leukemia deaths were identified by death certificates and diagnoses were verified by hospital records. The individual dose including internal and external exposure assessment was estimated according to the residency and age at exposure. All odds ratios were adjusted for ethnicity (Russian or Kazakh) as an independent variable.RESULTS: The median dose of exposure for all subjects was 0.89 Sv ranging from 0.01 to 5.71 Sv. A nearly two-fold increased risk of leukemia was found (OR = 1.91; 95% CI = 0.38 to 9.67) for persons exposed to doses of >2.0 Sv as compared to those exposed to <0.5 Sv, but no increase in risk with the dose was found for those exposed to doses lower than 2 Sv. Detailed evaluation of dose-response showed an excess relative risk for leukemia of 10% per 1 Sv of additional exposure.CONCLUSIONS: Our findings suggest that there is an increased risk of leukemia among those exposed to >2 SV as compared to those exposed to <0.5 Sv, but this could have been a chance finding due to the small number of cases and low statistical power. PMID:11018426

Abylkassimova; Gusev; Grosche; Bauer; Kreuzer; Trott

2000-10-01

122

Presence of small-nuclear-ribonucleoprotein-containing nuclear bodies in quiescent and early germinating Zea mays embryos  

Microsoft Academic Search

Summary Nucleolus-associated bodies (NABs) occur in interphase nuclei of many plant species. The present work shows that, inZea mays, NABs are present in dry seeds as well as in germinating tissues. The frequency of these nuclear bodies remains more or less constant during the first 24 h of imbibition but decreases significantly during the next 24 h. By the time

R. Gulemetova; H. Chamberland; S. Gugg; M. Plante; J. G. Lafontaine

1998-01-01

123

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 2011-07-01 false Inclusion bodies of the multi-nuclear polyhedrosis...Tolerances § 180.1149 Inclusion bodies of the multi-nuclear polyhedrosis virus...microbial pest control agent inclusion bodies of the multi-nuclear polyhedrosis...

2011-07-01

124

H-1 Parvovirus-Associated Replication Bodies: a Distinct Virus-Induced Nuclear Structure  

PubMed Central

We have identified a nuclear structure that is induced after infection with the autonomous parvovirus H-1. Using fluorescence microscopy, we observed that the major nonstructural protein (NS1) of H-1 virus which is essential for viral DNA amplification colocalized with virus-specific DNA sequences and sites of ongoing viral DNA replication in distinct nuclear bodies which we designated H-1 parvovirus-associated replication bodies (H-1 PAR-bodies). In addition, two cellular proteins were shown to accumulate in H1 PAR-bodies: (i) the proliferating cell nuclear antigen (PCNA) which is essential for chromosomal and parvoviral replication and (ii) the NS1-interacting small glutamine-rich TPR-containing protein (SGT), suggesting a role for the latter in parvoviral replication and/or gene expression. Since many DNA viruses target preexisting nuclear structures, known as PML-bodies, for viral replication and gene expression, we have determined the localization of H-1 PAR- and PML-bodies by double-fluorescence labeling and confocal microscopy and found them to be spatially unrelated. Furthermore, H-1 PAR-bodies did not colocalize with other prominent nuclear structures such as nucleoli, coiled bodies, and speckled domains. Electron microscopy analysis revealed that NS1, as detected by indirect immunogold labeling, was localized in ring-shaped electron-dense nuclear structures corresponding in size and frequency to H-1 PAR-bodies. These structures were also clearly visible without immunogold labeling and could be detected only in infected cells. Our results suggest that H-1 virus does not target known nuclear bodies for DNA replication but rather induces the formation of a novel structure in the nucleus of infected cells.

Cziepluch, Celina; Lampel, Stefan; Grewenig, Annabel; Grund, Christine; Lichter, Peter; Rommelaere, Jean

2000-01-01

125

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

PubMed Central

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 leukemia associated AML1-ETO fusion gene may have a role in hematopoietic dysfunction of leukemia. Conclusions An evolutionary conserved GATA binding site is critical in transcriptional regulation of the MTG16 promoter. In contrast, the MTGR1 gene depends on a GC-box-rich sequence for transcriptional regulation and possible ubiquitous expression. Our results demonstrate that the ETO homologue promoters are regulated differently consistent with hematopoietic cell-type- specific expression and function.

2012-01-01

126

Altered nuclear co-factor switching in retinoic resistant variants of the PML-RAR? oncoprotein of acute promyelocytic leukemia  

PubMed Central

Acute Promyelocytic Leukemia (APL) results from a reciprocal translocation that fuses the gene for the PML tumor suppressor to that encoding the retinoic acid receptor alpha (RAR?). The resulting PML-RAR? oncogene product interferes with multiple regulatory pathways associated with myeloid differentiation, including normal PML and RAR? functions. The standard treatment for APL includes anthracycline-based chemotherapeutic agents plus the RAR? agonist all-trans retinoic acid (ATRA). Relapse, which is often accompanied by ATRA resistance, occurs in an appreciable frequency of treated patients. One potential mechanism suggested by model experiments featuring the selection of ATRA resistant APL cell lines involves ATRA resistant versions of the PML-RAR? oncogene, where the relevant mutations localize to the RAR? ligand-binding domain (LBD). Such mutations may act by compromising agonist binding, but other mechanisms are possible. Here, we studied the molecular consequence of ATRA resistance by use of circular dichroism, protease resistance, and fluorescence anisotropy assays employing peptides derived from the NCOR nuclear co-repressor and the ACTR nuclear co-activator. The consequences of the mutations on global structure and co-factor interaction functions were assessed quantitatively, providing insights into the basis of agonist resistance. Attenuated co-factor switching and increased protease resistance represent features of the LBDs of ATRA-resistant PML-RAR?, and these properties may be recapitulated in the full-length oncoproteins.

Farris, Mindy; Lague, Astrid; Manuelyan, Zara; Statnekov, Jacob; Francklyn, Christopher

2011-01-01

127

Few-body nuclear physics in future (e,e'p) experiments  

Microsoft Academic Search

The short distance structure of few-body nuclear systems will be a focus of the multi-GeV electron accelerators planned for the 1990's. Four example (e,e'p) experiments in the quasi-elastic region are presented. The experiments are chosen to emphasize a particular aspect of few-body nuclear physics. They further illustrate a few of the requirements for experimental equipment at these facilities. Work supported

Doug Beck

1989-01-01

128

REVIEW ARTICLE: Nuclear-based techniques for the in vivo study of human body composition  

Microsoft Academic Search

A variety of nuclear-based techniques for the in vivo study of human body decomposition is now available for clinical diagnosis and research, and the number of centres where such work is performed is likely to grow substantially in the next few years. Their most important applications at present are in the measurement of bone mineral mass (calcium), body protein (nitrogen)

S. H. Cohn; R. M. Parr

1985-01-01

129

Nuclear-based techniques for the in vivo study of human body composition  

Microsoft Academic Search

A variety of nuclear-based techniques for the in vivo study of human body decomposition is now available for clinical diagnosis and research, and the number of centres where such work is performed is likely to grow substantially in the next few years. Their most important applications at present are in the measurement of bone mineral mass (calcium), body protein (nitrogen)

S H Cohn; R M Parr

1985-01-01

130

PML nuclear bodies: dynamic sensors of DNA damage and cellular stress  

Microsoft Academic Search

Summary Promyelocytic leukaemia nuclear bodies (PML NBs) are generally present in all mammalian cells, and their integrity correlates with normal differentiation of pro- myelocytes. Mice that lack PML NBs have impaired immune function, exhibit chromosome instability and are sensitive to carcinogens. Although their direct role in nuclear activity is unclear, PML NBs are implicated in the regulation of transcription, apoptosis,

Graham Dellaire; David P. Bazett-Jones

2004-01-01

131

Stress-induced Nuclear Bodies Are Sites of Accumulation of Pre-mRNA Processing Factors  

Microsoft Academic Search

Heterogeneous nuclear ribonucleoprotein (hnRNP) HAP (hnRNP A1 interacting protein) is a multifunctional protein with roles in RNA metabolism, transcription, and nuclear structure. After stress treatments, HAP is recruited to a small number of nuclear bodies, usually adjacent to the nucleoli, which consist of clusters of perichromatin granules and are depots of transcripts synthesized before stress. In this article we show

Marco Denegri; Ilaria Chiodi; Margherita Corioni; Fabio Cobianchi; Silvano Riva; Giuseppe Biamonti

132

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

PubMed

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

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

2013-07-22

133

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

SciTech Connect

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.

Richter, Karsten [Division Molecular Genetics, Deutsches Krebsforschungszentrum (DKFZ), D-69120 Heidelberg (Germany); Reichenzeller, Michaela [Division Biology of the Cell, Deutsches Krebsforschungszentrum (DKFZ), D-69120 Heidelberg (Germany); Goerisch, Sabine M. [Division Molecular Genetics, Deutsches Krebsforschungszentrum (DKFZ), D-69120 Heidelberg (Germany); Schmidt, Ute [Division Molecular Genetics, Deutsches Krebsforschungszentrum (DKFZ), D-69120 Heidelberg (Germany); Scheuermann, Markus O. [Division Molecular Genetics, Deutsches Krebsforschungszentrum (DKFZ), D-69120 Heidelberg (Germany); Herrmann, Harald [Division Biology of the Cell, Deutsches Krebsforschungszentrum (DKFZ), D-69120 Heidelberg (Germany); Lichter, Peter [Division Molecular Genetics, Deutsches Krebsforschungszentrum (DKFZ), D-69120 Heidelberg (Germany)]. E-mail: m.macleod@dkfz.de

2005-02-01

134

Self-association of Coilin Reveals a Common Theme in Nuclear Body Localization  

PubMed Central

We have found that coilin, the marker protein for Cajal bodies (coiled bodies, CBs), is a self-interacting protein, and we have mapped the domain responsible for this activity to the amino-terminus. Together with a nuclear localization signal, the self-interaction domain is necessary and sufficient for localization to CBs. Overexpression of various wild-type and mutant coilin constructs in HeLa cells results in disruption of both CBs and survival motor neurons (SMN) gems. Additionally, we have identified a cryptic nucleolar localization signal (NoLS), within the coilin protein, which may be exposed in specific coilin phospho-isoforms. The implications of these findings are discussed in light of the fact that other proteins known to localize within nuclear bodies (e.g., PML, SMN and Sam68) can also self-associate. Thus protein self-interaction appears to be a general feature of nuclear body marker proteins.

Hebert, Michael D.; Matera, A. Gregory

2000-01-01

135

A Case of Congenital Leukemia Cutis  

PubMed Central

Congenital leukemia is a rare disease that develops from birth to 6 weeks of life. Leukemia cutis involves cutaneous infiltration by leukemic cells and is an unusual manifestation of leukemia, and has been documented in 25~30% of patients with congenital leukemia. The authors report a case of congenital leukemia cutis. A newborn male presented with widespread firm dusky red papules and nodules on almost his entire body surface. Skin biopsy specimens confirmed the presence of leukemic infiltrations, and bone marrow cytology was consistent with acute myeloid leukemia of the FAB M5 type.

Choi, Ji Hoon; Lee, Hee Bong; Park, Chun Wook

2009-01-01

136

Abrogation of nuclear receptors Nr4a3 and Nr4a1 leads to development of acute myeloid leukemia.  

PubMed

Nur77 (NR4A1) and Nor-1 (NR4A3) are highly homologous orphan nuclear receptors that regulate the transcription of overlapping target genes. The transcriptional activity of both proteins is regulated in a ligand-independent manner by cell- and stimulus-specific gene induction and protein phosphorylation. Nor-1 and Nur77 have been implicated in a variety of cellular processes, including the transduction of hormonal, inflammatory, mitogenic, apoptotic and differentiative signals. Cellular responses to these proteins suggest that they may function as homeostatic regulators of proliferation, apoptosis and differentiation, and thus may regulate cellular susceptibility to tumorigenesis. Their physiological functions, however, remain poorly understood. Here we describe a previously unsuspected function of Nor-1 and Nur77-as critical tumor suppressors of myeloid leukemogenesis. The abrogation of these proteins in mice led to rapidly lethal acute myeloid leukemia (AML), involving abnormal expansion of hematopoietic stem cells (HSCs) and myeloid progenitors, decreased expression of the AP-1 transcription factors JunB and c-Jun and defective extrinsic apoptotic (Fas-L and TRAIL) signaling. We found that downregulation of NR4A3 ( NOR-1 ) and NR4A1 ( NUR77 ) was a common feature in leukemic blasts from human AML patients, irrespective of karyotype. Thus Nor-1 and Nur77 may provide potential targets for therapeutic intervention in AML. PMID:17515897

Mullican, Shannon E; Zhang, Shuo; Konopleva, Marina; Ruvolo, Vivian; Andreeff, Michael; Milbrandt, Jeffrey; Conneely, Orla M

2007-05-21

137

Strengthening of the nuclear safety regulatory body. Field evaluation review.  

National Technical Information Service (NTIS)

As a result of a request from the Preparation Committee of the Nuclear Regulatory Authority (NRA) in 1992, and as recommended by the CEC/RAMG (Commission of European Communities/Regulatory Assistance Management Group) and the Agency mission in July 1993 t...

1996-01-01

138

Mitogen-activated protein kinase kinase inhibition enhances nuclear proapoptotic function of p53 in acute myelogenous leukemia cells.  

PubMed

Activation of the Raf/MEK/ERK pathway and inactivation of wild-type p53 by Mdm2 overexpression are frequent molecular events in acute myelogenous leukemia (AML). We investigated the interaction of Raf/MEK/ERK and p53 pathways after their simultaneous blockades using a selective small-molecule antagonist of Mdm2, Nutlin-3a, and a pharmacologic MEK-specific inhibitor, PD98059. We found that PD98059, which itself has minimal apoptogenic activity, acts synergistically with Nutlin-3a to induce apoptosis in wild-type p53 AML cell lines OCI-AML-3 and MOLM-13. Interestingly, PD98059 enhanced nuclear proapototic function of p53 in these cells. In accordance with the activation of transcription-dependent apoptosis, PD98059 treatment promoted the translocation of p53 from the cytoplasm to the nucleus in OCI-AML-3 cells, in which p53 primarily initiates transcription-independent apoptosis when cells are treated with Nutlin-3a alone. The critical role of p53 localization in cells with increased p53 levels was supported by enhanced apoptosis induction in cells cotreated with Nutlin-3a and the nuclear export inhibitor leptomycin B. PD98059 prevented p53-mediated induction of p21 at the transcriptional level. The repressed expression of antiapototic p21 also seemed to contribute to synergism between PD98059 and Nutlin-3a because (a) the synergistic apoptogenic effect was preserved in G(1) cells, (b) p53-mediated induction of p21 was preferentially seen in G(1) cells, (c) PD98059 strongly antagonized p21 induction by Nutlin-3a, and (d) cells with high p21 levels were resistant to apoptosis. This is the first report showing that the Raf/MEK/ERK pathway regulates the subcellular localization of p53 and the relative contribution of transcription-dependent and transcription-independent pathways in p53-mediated apoptosis. PMID:17409429

Kojima, Kensuke; Konopleva, Marina; Samudio, Ismael J; Ruvolo, Vivian; Andreeff, Michael

2007-04-01

139

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

PubMed

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. PMID:24036361

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

2013-09-11

140

Cluster variational method for nuclear matter with the three-body force  

SciTech Connect

We report the current status of our project to construct a new nuclear equation of state (EOS), which may be used for supernova numerical simulations, based on the cluster variational method starting from the realistic nuclear Hamiltonian. We also take into account a higher-order correction to the energy of the nuclear three-body force (TBF). The nuclear EOSs with and without the higher-order TBF correction at zero temperature are very close to each other, when parameters are readjusted so as to reproduce the empirical saturation data.

Takano, M.; Togashi, H.; Yamamuro, S.; Nakazato, K.; Suzuki, H. [Research Institute for Science and Engineering, Waseda University, 3-4-1 Okubo, Shinjuku-ku, Tokyo 169-8555 Japan and Department of Physics and Applied Physics, Waseda University, 3-4-1 Okubo, Shinjuku-ku, Tokyo 169-8555 (Japan); Department of Physics and Applied Physics, Waseda University, 3-4-1 Okubo, Shinjuku-ku, Tokyo 169-8555 (Japan); Department of Physics, Faculty of Science and Technology, Tokyo University of Science, Yamazaki 2641, Noda, Chiba 278-8510 (Japan)

2012-11-12

141

The SUN Protein Mps3 Is Required for Spindle Pole Body Insertion into the Nuclear Membrane and Nuclear Envelope Homeostasis  

PubMed Central

The budding yeast spindle pole body (SPB) is anchored in the nuclear envelope so that it can simultaneously nucleate both nuclear and cytoplasmic microtubules. During SPB duplication, the newly formed SPB is inserted into the nuclear membrane. The mechanism of SPB insertion is poorly understood but likely involves the action of integral membrane proteins to mediate changes in the nuclear envelope itself, such as fusion of the inner and outer nuclear membranes. Analysis of the functional domains of the budding yeast SUN protein and SPB component Mps3 revealed that most regions are not essential for growth or SPB duplication under wild-type conditions. However, a novel dominant allele in the P-loop region, MPS3-G186K, displays defects in multiple steps in SPB duplication, including SPB insertion, indicating a previously unknown role for Mps3 in this step of SPB assembly. Characterization of the MPS3-G186K mutant by electron microscopy revealed severe over-proliferation of the inner nuclear membrane, which could be rescued by altering the characteristics of the nuclear envelope using both chemical and genetic methods. Lipid profiling revealed that cells lacking MPS3 contain abnormal amounts of certain types of polar and neutral lipids, and deletion or mutation of MPS3 can suppress growth defects associated with inhibition of sterol biosynthesis, suggesting that Mps3 directly affects lipid homeostasis. Therefore, we propose that Mps3 facilitates insertion of SPBs in the nuclear membrane by modulating nuclear envelope composition.

Smoyer, Christine J.; McCroskey, Scott; Miller, Brandon D.; Weaver, Kyle J.; Delventhal, Kym M.; Unruh, Jay; Slaughter, Brian D.; Jaspersen, Sue L.

2011-01-01

142

GATA transcription factors associate with a novel class of nuclear bodies in erythroblasts and megakaryocytes.  

PubMed Central

The nuclear distribution of GATA transcription factors in murine haemopoietic cells was examined by indirect immunofluorescence. Specific bright foci of GATA-1 fluorescence were observed in erythroleukaemia cells and primary murine erythroblasts and megakaryocytes, in addition to diffuse nucleoplasmic localization. These foci, which were preferentially found adjacent to nucleoli or at the nuclear periphery, did not represent sites of active transcription or binding of GATA-1 to consensus sites in the beta-globin loci. Immunoelectron microscopy demonstrated the presence of intensely labelled structures likely to represent the GATA-1 foci seen by immunofluorescence. The GATA-1 nuclear bodies differed from previously described nuclear structures and there was no co-localization with nuclear antigens involved in RNA processing or other ubiquitous (Spl, c-Jun and TBP) or haemopoietic (NF-E2) transcription factors. Interestingly, GATA-2 and GATA-3 proteins also localized to the same nuclear bodies in cell lines co-expressing GATA-1 and -2 or GATA-1 and -3 gene products. This pattern of distribution is, thus far, unique to the GATA transcription factors and suggests a protein-protein interaction with other components of the nuclear bodies via the GATA zinc finger domain. Images

Elefanty, A G; Antoniou, M; Custodio, N; Carmo-Fonseca, M; Grosveld, F G

1996-01-01

143

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

SciTech Connect

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.

Gross, Noam; Shotan, Zav; Khaykovich, Lev [Department of Physics, Bar-Ilan University, Ramat-Gan, 52900 (Israel); Kokkelmans, Servaas [Eindhoven University of Technology, Post Office Box 513, 5600 MB Eindhoven (Netherlands)

2010-09-03

144

Nuclear pairing from bare interaction: Two and three-body chiral forces  

SciTech Connect

In a recent paper the {sup 1}S{sub 0} pairing gap in isospin-symmetric nuclear matter and finite nuclei has been investigated starting from the chiral nucleon-nucleon potential at the N{sup 3}LO order in the two-body sector and the N{sup 2}LO order in the three-body sector. To include realistic nuclear forces in RHB (Relativistic Hartree Bolgoliubov) calculations we relied on a separable representation of the pairing interaction. In this paper we would like to show recent results concerning isotonic chains with N= 28,50,82.

Finelli, Paolo [Physics Department, University of Bologna, Via Irnerio 46, 40126 Bologna (Italy); INFN, Section of Bologna, Viale Berti Pichat 6/2, 40127 Bologna (Italy)

2012-10-20

145

Fluorescent characteristics of drumsticks, drumstick-like projections, and other nuclear bodies in human blood cells  

Microsoft Academic Search

The fluorescent properties of drumsticks, drumstick-like appendages, and other nuclear bodies in the polymorphonuclear leukocytes from six human males and females were studied with the aid of the quinacrine-mustard staining technique. Both brightly and weakly fluorescent drumsticks (in females) and drumstick-like bodies (in males) were observed, and they were readily differentiated on the basis of size, shape and, usually, fluorescent

A. B. Mukherjee; J. San Sebastian

1976-01-01

146

Body-fixed relativistic molecular Hamiltonian and its application to nuclear spin-rotation tensor  

NASA Astrophysics Data System (ADS)

A relativistic molecular Hamiltonian that describes electrons fully relativistically and nuclei quasi-relativistically is proposed and transformed from the laboratory to the body-fixed frame of reference. As a first application of the resulting body-fixed relativistic molecular Hamiltonian, the long anticipated relativistic theory of nuclear spin-rotation (NSR) tensor is formulated rigorously. A ``relativistic mapping'' between experimental NSR and NMR is further proposed, which is of great value in establishing high-precision absolute NMR shielding scales.

Xiao, Yunlong; Liu, Wenjian

2013-04-01

147

Quantum Many-Body Theory and Mechanisms for Low Energy Nuclear Reaction Processes in Matter  

Microsoft Academic Search

Recently, a theoretical model of Bose-Einstein Condensation (BEC) mechanism has been developed to describe low-energy nuclear reaction in a quantum many-body system confined in a micro\\/nano scale trap. The BEC mechanism is applied to explain various anomalous results observed recently in experiments involved with low-energy nuclear reaction processes in matter and in acoustic cavitation. Experimental tests of the BEC mechanism

Y. E. Kim

2004-01-01

148

Quantum many-body theory and mechanisms for low energy nuclear reaction processes in matter  

Microsoft Academic Search

Recently, a theoretical model of Bose-Einstein Condensation (BEC) mechanism has been developed to describe low-energy nuclear reaction in a quantum many-body system confined in a micro\\/nano scale trap. The BEC mechanism is applied to explain various anomalous results observed recently in experiments involved with low-energy nuclear reaction processes in matter and in acoustic cavitation. Experimental tests of the BEC mechanism

Yeong E. Kim

2004-01-01

149

Inhibition of human T cell leukemia virus type 2 replication by the suppressive action of class II transactivator and nuclear factor Y  

PubMed Central

The master regulator of MHC-II gene transcription, class II transactivator (CIITA), acts as a potent inhibitor of human T cell leukemia virus type 2 (HTLV-2) replication by blocking the activity of the viral Tax-2 transactivator. Here, we show that this inhibitory effect takes place at the nuclear level and maps to the N-terminal 1–321 region of CIITA, where we identified a minimal domain, from positions 64–144, that is strictly required to suppress Tax-2 function. Furthermore, we show that Tax-2 specifically cooperates with cAMP response element binding protein-binding protein (CBP) and p300, but not with p300/CBP-associated factor, to enhance transcription from the viral promoter. This finding represents a unique difference with respect to Tax-1, which uses all three coactivators to transactivate the human T cell leukemia virus type 1 LTR. Direct sequestering of CBP or p300 is not the primary mechanism by which CIITA causes suppression of Tax-2. Interestingly, we found that the transcription factor nuclear factor Y, which interacts with CIITA to increase transcription of MHC-II genes, exerts a negative regulatory action on the Tax-2-mediated HTLV-2 LTR transactivation. Thus, CIITA may inhibit Tax-2 function, at least in part, through nuclear factor Y. These findings demonstrate the dual defensive role of CIITA against pathogens: it increases the antigen-presenting function for viral determinants and suppresses HTLV-2 replication in infected cells.

Tosi, Giovanna; Pilotti, Elisabetta; Mortara, Lorenzo; Barbaro, Andrea De Lerma; Casoli, Claudio; Accolla, Roberto S.

2006-01-01

150

Childhood leukemia near nuclear plants in the United Kingdom: The evolution of a systematic approach to studying rare disease in small geographic areas  

SciTech Connect

A cluster of childhood leukemia in a village near a nuclear plant in northern England prompted further studies of cancer in the vicinity of other nuclear plants in the United Kingdom. These studies demonstrated that the risk of childhood leukemia was increased near certain other nuclear plants. Although the reasons for the increase are still unclear, the scientific debate stimulated by these findings has clarified some of the special methodological problems encountered when studying rare diseases in small areas. Firstly, unless a specific hypothesis is defined in advance, the relevance of a single geographic cluster of disease can rarely be interpreted. Even when a prior hypothesis exists, the small number of cases which generally occur in a small area make the findings highly sensitive to reporting, diagnostic, or classification errors. The statistical power of such investigations is also usually low and only marked increases in risk can be detected. Furthermore, conventional statistical tests may be inappropriate if the underlying spatial distribution of the disease is not random; and little is known about the background distribution of disease in small areas. Investigations of specific hypotheses about defined sources of environmental contamination, especially if they can be replicated, are more likely to result in conclusive findings that are in-depth studies of individual clusters.

Beral, V. (I.C.R.F. Cancer Epidemiology Unit, Radcliffe Infirmary, Oxford (England))

1990-07-01

151

Liquid-gas phase transition in nuclear matter from realistic many-body approaches  

NASA Astrophysics Data System (ADS)

The existence of a liquid-gas phase transition for hot nuclear systems at subsaturation densities is a well-established prediction of finite-temperature nuclear many-body theory. In this paper, we discuss for the first time the properties of such a phase transition for homogeneous nuclear matter within the self-consistent Green's function approach. We find a substantial decrease of the critical temperature with respect to the Brueckner-Hartree-Fock approximation. Even within the same approximation, the use of two different realistic nucleon-nucleon interactions gives rise to large differences in the properties of the critical point.

Rios, A.; Polls, A.; Ramos, A.; Müther, H.

2008-10-01

152

Quasi two-body scaling in inclusive nuclear reactions  

NASA Astrophysics Data System (ADS)

The hypothesis of quasi two body scaling (qtbs) in inclusive inelastic scattering by nuclei is studied. By use of qtbs, a wide range of cross section data can be correlated in terms of a universal scaling function G(kmin) that depends on a scaling variable kmin. The scaling variable is calculated from the kinematic variables of the scattering reaction. If qtbs applies, the inelastic cross section can be written as a product of the scaling function, a known kinematic factor, and a quasielastic cross section. The quasielastic cross section can be related to experimental elastic cross sections. Then the scaling function is calculated by dividing the inelastic cross section by the two known factors. Scaling for incident electrons and for incident protons is studied, and the extent to which qtbs is valid is compared for each case. A quantitative measure of goodness of scaling is introduced using analytical fits to the scaling function for different scattering cases. Also several tests of the specific assumptions that comprise the qtbs hypothesis are introduced, and applied to the various scattering cases. An integral sum rule is derived to test whether the scaling that is observed is truly a verification of qtbs. The sum rule is well satisfied, indicating that the observed scaling does verify qtbs. Our results show that scaling is relatively good for both incident electrons and protons, but the scaling is somewhat more universal for the electrons. The production of nucleon resonances is shown to be the cause of scaling violation for negative values of the scaling variable. The electron and proton scaling functions differ in their slope on a log plot. This is attributable to a larger probability of initial and final state interactions for protons, leading to an effective scaling function for the protons. The electron scaling function is related to the nucleon momentum distribution in the nucleus. This momentum distribution is found to be universal, except for a slightly smaller slope for Helium.

Papadopoulou, Demetra

1998-09-01

153

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...

154

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

SciTech Connect

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.

Shojaei, F.; Bolorizadeh, M. A. [Physics Department, Shahid Bahonar University of Kerman, Kerman, 76169, Iran and ICST, Mahan, 76315 (Iran, Islamic Republic of); Ghanbari-Adivi, E. [Physics Department and Isfahan Quantum Optics Group, University of Isfahan, Isfahan, 81746 (Iran, Islamic Republic of); Brunger, M. J. [Centre for Antimatter-Matter Studies, School of Chemistry, Physics and Earth Sciences, Flinders University, Adelaide South Australia, 5042 (Australia)

2009-01-15

155

Leaf phenolic inhibition of gypsy moth nuclear polyhedrosis virus Role of polyhedral inclusion body aggregation  

Microsoft Academic Search

Bioassays with nuclear polyhedrosis virus (NPV) administered to gypsy moth larvae on leaf disks from various tree species reveal strong viral inhibition by some tree species. Phenolic extracts from inhibitory tree leaves cause virus polyhedral inclusion bodies (PIBs) to form large aggregations. However, aggregated PIBs treated with leaf extracts and administered to larvae on laboratory diet (without phenolics) retain virulence.

Steven T. Keating; Mark D. Hunter; Jack C. Schultz

1990-01-01

156

PML Nuclear Bodies and SATB1 Are Associated with HLA Class I Expression in EBV+ Hodgkin Lymphoma  

PubMed Central

Tumor cells of classical Hodgkin lymphoma (cHL) are characterized by a general loss of B cell phenotype, whereas antigen presenting properties are commonly retained. HLA class I is expressed in most EBV+ cHL cases, with an even enhanced expression in a proportion of the cases. Promyelocytic leukemia protein (PML) and special AT-rich region binding protein 1 (SATB1) are two global chromatin organizing proteins that have been shown to regulate HLA class I expression in Jurkat cells. We analyzed HLA class I, number of PML nuclear bodies (NBs) and SATB1 expression in tumor cells of 54 EBV+ cHL cases and used 27 EBV? cHL cases as controls. There was a significant difference in presence of HLA class I staining between EBV+ and EBV? cases (p<0.0001). We observed normal HLA class I expression in 35% of the EBV+ and in 19% of the EBV? cases. A stronger than normal HLA class I expression was observed in approximately 40% of EBV+ cHL and not in EBV? cHL cases. 36 EBV+ cHL cases contained less than 10 PML-NBs per tumor cell, whereas 16 cases contained more than 10 PML-NBs. The number of PML-NBs was positively correlated to the level of HLA class I expression (p<0.01). The percentage of SATB1 positive cells varied between 0% to 100% in tumor cells and was inversely correlated with the level of HLA class I expression, but only between normal and strong expression (p<0.05). Multivariable analysis indicated that the number of PML-NBs and the percentage of SATB1+ tumor cells are independent factors affecting HLA class I expression in EBV+ cHL. In conclusion, both PML and SATB1 are correlated to HLA class I expression levels in EBV+ cHL.

Liu, Yuxuan; van den Berg, Anke; Veenstra, Rianne; Rutgers, Bea; Nolte, Ilja; van Imhoff, Gustaaf; Visser, Lydia; Diepstra, Arjan

2013-01-01

157

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

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.

Gedge, L.J.E. [School of Biochemistry and Molecular Biology, University of Leeds, Leeds, LS2 9JT (United Kingdom); Morrison, E.E. [CRUK Clinical Centre at Leeds, St. James' University Hospital, Leeds, LS9 7TF (United Kingdom); Blair, G.E. [School of Biochemistry and Molecular Biology, University of Leeds, Leeds, LS2 9JT (United Kingdom); Walker, J.H. [School of Biochemistry and Molecular Biology, University of Leeds, Leeds, LS2 9JT (United Kingdom)]. E-mail: J.H.Walker@leeds.ac.uk

2005-02-15

158

Fludarabine, busulfan, antithymocyte globulin, and total body irradiation for pretransplantation conditioning in acute lymphoblastic leukemia: excellent outcomes in all but older patients with comorbidities.  

PubMed

Hematopoietic stem cell transplantation (SCT) is routinely offered to suitable candidates with high-risk or advanced acute lymphoblastic leukemia (ALL). In this report, we update our experience with SCT in patients with ALL with a novel conditioning regimen. A total of 44 patients with high-risk or advanced (greater than first complete remission) ALL in remission underwent SCT after myeloablative conditioning with fludarabine + busulfan + total body irradiation. The median follow-up of surviving patients was 4.3 years (range, 1.0-9.0 years). The cohort consists of 32 patients with high-risk disease (median age, 40 years; range, 19-64 years) and 12 patients with advanced disease (median age, 25 years; range, 19-65 years) who underwent SCT: 25 with a related donor (21 fully matched) and 19 with an unrelated donor (16 fully matched). The cumulative incidence of grade II-IV acute graft-versus-host disease (GVHD) was 53.2%, and that of grade III-IV acute GVHD was 20.6%. The incidence of chronic GVHD was 55%. The 100-day nonrelapse mortality was 13.6%. Five-year progression-free survival was 56.7%, and 5-year overall survival was 66.0%. Nine patients (20%) died in remission, 6 (14%) died after relapse, and 2 survived after a second SCT for relapsed disease. Outcomes were inferior in older patients with comorbidities compared with other patients. PMID:22842330

Daly, Andrew; Savoie, Mary L; Geddes, Michelle; Chaudhry, Ahsan; Stewart, Douglas; Duggan, Peter; Bahlis, Nizar; Storek, Jan; Brown, Chris; Shafey, Mona; Turner, A Robert; Russell, James

2012-07-27

159

Comparison of total body irradiation plus cyclophosphamide with busulfan plus cyclophosphamide as conditioning regimens in patients with acute lymphoblastic leukemia undergoing allogeneic hematopoietic stem cell transplant.  

PubMed

Abstract Conditioning regimens used during stem cell transplant provide prolonged control or cure of the disease in patients with acute lymphoblastic leukemia (ALL). In this study, we present a comparison of treatment results for 95 patients with ALL who underwent allogeneic hematopoietic stem cell transplant (AHSCT) with total body irradiation plus cyclophosphamide (TBI + Cy) or busulfan plus cyclophosphamide (Bu + Cy) as conditioning regimen. Median age was 25 (range: 9-54) years. Median follow-up was 24 (range: 3-107) months. Median overall survival (OS) was found to be 29 months. Median event-free survival (EFS) was 9 months. Median OS was 37 months in the TBI + Cy arm, while it was 12 months in the Bu + Cy arm, suggesting a significant advantage favoring the TBI + Cy arm (p = 0.003). Median EFS was 13 months in the TBI + Cy arm, while it was 4 months in the Bu + Cy arm, indicating a significant difference (p = 0.006). In univariate and multivariate analysis, it was found that high OS and EFS were significantly correlated with TBI + Cy conditioning regimen and lack of transplant-related mortality (p < 0.05). The TBI + Cy conditioning regimen was found to be superior to the Bu + Cy regimen in patients with ALL undergoing AHSCT regarding both OS and EFS. PMID:23442062

Eroglu, Celalettin; Pala, Cigdem; Kaynar, Leylagül; Yaray, Kadir; Aksozen, M Tarkan; Bankir, Mehmet; Zarars?z, Gökmen; Orhan, Okan; Gündog, Mete; Y?ld?z, Oguz G; Eser, Bülent; Cetin, Mustafa; Unal, Ali

2013-03-27

160

Randomized comparison of cyclophosphamide-total body irradiation versus busulfan-cyclophosphamide conditioning in autologous bone marrow transplantation for acute myeloid leukemia  

Microsoft Academic Search

Purpose: This prospective trial of autologous bone marrow transplantation for acute myeloid leukemia was undertaken to compare the outcome using two different preparative regimens.Methods and Materials: Between October 1987 and April 1993, 35 patients with acute myeloid leukemia in first n = 12) or greater (n = 23) remission were stratified by remission status and randomized to undergo 4-hydroperoxycyclosphamide purged

Kathryn E. Dusenbery; Kathleen A. Daniels; John S. McClure; Philip B. McGlaver; Norma K. C. Ramsay; Bruce R. Blazar; Joseph P. Neglia; John H. Kersey; William G. Woods

1995-01-01

161

Ferritinopathy: diagnosis by muscle or nerve biopsy, with a note on other nuclear inclusion body diseases.  

PubMed

Ferritinopathy (neuroferritinopathy) has recently been identified as an autosomal dominant, multisystem disease, mainly affecting the central nervous system. It is caused by mutations in exon 4 of the ferritin light chain gene on chromosome 19. Its fine structural hallmarks are granular nuclear inclusions in neurons, oligodendroglial and microglial cells with similar extracellular derivatives in the central nervous system, muscle, peripheral nerve, and skin. These pathognostic structures have previously been described in perivascular cells of muscle and nerve biopsy specimens in a case with an obviously identical disease, formerly described as 'granular nuclear inclusion body disease'. The nuclear inclusions, at the light microscopic level, are iron positive following histochemical iron reactions and immunoreactive for ferritin antibodies. At the electron microscopic level, in contrast to filamentous nuclear inclusions in 'neuronal intranuclear hyaline inclusion disease', dominant spinocerebellar atrophies and other trinucleotide repeat diseases, they are basically composed of granules measuring 5-15 nm. A moderate peak of iron detectable by energy dispersive microanalysis of the granular nuclear inclusions in ferritinopathy may also be significant. It is emphasized that ferritinopathy or 'granular nuclear inclusion body disease' can be diagnosed by a simple muscle or nerve biopsy without brain biopsy, autopsy, or molecular genetic testing of the considerable number of neurodegenerative diseases with possibly similar symptomatology. PMID:15645266

Schröder, J Michael

2005-01-11

162

snRNP: Rich Nuclear Bodies in Hyacinthus orientalis L. Microspores and Developing Pollen Cells  

PubMed Central

The aim of the present work was the characterization of nuclear bodies in the microspore and developing pollen cells of Hyacinthus orientalis L.. The combination of Ag-NOR, immunofluorescence and immunogold techniques was used in this study. The obtained results showed the presence of highly agyrophylic extranucleolar bodies in microspore and developing pollen cells, which were finally identified as Cajal bodies. In all cases, a strong accumulation of snRNP-indicating molecules including TMG cap, Sm proteins and U2 snRNA, was observed in the examined nuclear bodies. In contrast to their number the size of the identified structures did not change significantly during pollen development. In the microspore and the vegetative cell of pollen grains CBs were more numerous than in the generative cell. At later stages of pollen development, a drastic decrease in CB number was observed and, just before anthesis, a complete lack of these structures was indicated in both pollen nuclei. On the basis of these results, as well as our previous studies, we postulate a strong relationship between Cajal body numbers and the levels of RNA synthesis and splicing machinery elements in microspore and developing pollen cells.

Zienkiewicz, K.; Bednarska, E.

2009-01-01

163

Body-fixed relativistic molecular Hamiltonian and its application to nuclear spin-rotation tensor.  

PubMed

A relativistic molecular Hamiltonian that describes electrons fully relativistically and nuclei quasi-relativistically is proposed and transformed from the laboratory to the body-fixed frame of reference. As a first application of the resulting body-fixed relativistic molecular Hamiltonian, the long anticipated relativistic theory of nuclear spin-rotation (NSR) tensor is formulated rigorously. A "relativistic mapping" between experimental NSR and NMR is further proposed, which is of great value in establishing high-precision absolute NMR shielding scales. PMID:23574205

Xiao, Yunlong; Liu, Wenjian

2013-04-01

164

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

SciTech Connect

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)

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

1981-01-01

165

RNA recognition motif 2 directs the recruitment of SF2\\/ASF to nuclear stress bodies  

Microsoft Academic Search

Heat shock induces the transcriptional activation of large heterochromatic regions of the human genome composed of arrays of satellite III DNA repeats. A num- ber of RNA-processing factors, among them splicing factor SF2\\/ASF, associate with these transcription factors giving rise to nuclear stress bodies (nSBs). Here, we show that the recruitment of SF2\\/ASF to these structures is mediated by its

Ilaria Chiodi; Margherita Corioni; Manuela Giordano; Rut Valgardsdottir; Claudia Ghigna; Fabio Cobianchi; Rui-Ming Xu; Silvano Riva; Giuseppe Biamonti

2004-01-01

166

A nuclear protein with sequence similarity to proteins implicated in human acute leukemias is important for cellular morphogenesis and actin cytoskeletal function in Saccharomyces cerevisiae.  

PubMed Central

The cellular functions of the product of the Saccharomyces cerevisiae ANC1 (actin non-complementing) gene were investigated. ANC1 was previously identified in a screen for mutations that enhance the defect caused by a mutation in the actin gene. Here, we show that anc1-1 and anc1 delta 1::HIS3 (gene deletion) mutants exhibit a novel combination of defects in the organization of the actin cytoskeleton and the localization of Spa2p, a protein implicated in polarity development and cytokinesis. Morphological abnormalities exhibited by anc1 mutants include failure to form a mating projection in response to alpha-factor and development of swollen or elongated cell shapes during proliferation. These morphological aberrations correlate with cytoskeletal defects that were also observed. These phenotypes demonstrate that Anc1p is important for actin function and for the functions of other proteins involved in morphogenesis. In further support of these roles for Anc1p, the anc1 delta 1::HIS3 mutation was found to be synthetically lethal in combination with a null mutation in SLA1, a gene that is important for membrane cytoskeleton function. Surprisingly, Anc1p was found to be a nuclear protein and to have sequence similarity to the human proteins ENL and AF-9. These human proteins are implicated in the development of a subset of acute lymphoblastic leukemias, acute myeloid leukemias, and lymphomas. Our findings suggest that changes in the functions or organization of actin filaments might contribute to the establishment of the neoplastic state for these leukemias and lymphomas. Images

Welch, M D; Drubin, D G

1994-01-01

167

Longitudinal Changes in Obesity and Body Mass Index Among Adult Survivors of Childhood Acute Lymphoblastic Leukemia: A Report From the Childhood Cancer Survivor Study  

PubMed Central

Purpose We examined the rate of increase in the body mass index (BMI; kg/m2) after final height attainment in survivors of acute lymphoblastic leukemia (ALL) and a noncancer comparison group. Methods Childhood Cancer Survivor Study (CCSS) is a retrospectively ascertained cohort study that prospectively tracks the health status of adults who were diagnosed with childhood cancer between 1970 and 1986 and a comparison group of siblings. Changes in BMI from baseline enrollment to time of completion of follow-up (mean interval, 7.8 years) were calculated for 1,451 ALL survivors (mean age, 32.3 years at follow-up) and 2,167 siblings of childhood cancer survivors (mean age, 35.9 years). Results The mean BMI of the CCSS sibling comparison group increased with age (women, 0.25 units/yr, 95% CI, 0.22 to 0.28 units; men, 0.23 units/yr, 95% CI, 0.20 to 0.25 units). Compared with CCSS siblings, ALL survivors who were treated with cranial radiation therapy (CRT) had a significantly greater increase in BMI (women, 0.41 units/yr, 95% CI, 0.37 to 0.45 units; men, 0.29 units/yr; 95% CI, 0.26 to 0.32 units). The rate of BMI increase was not significantly increased for ALL survivors who were treated with chemotherapy alone. Younger age at CRT exposure significantly modified risk. Conclusion CRT used in the treatment of childhood ALL is associated with a greater rate of increasing BMI, particularly among women treated with CRT during the first decade of life. Health care professionals should be aware of this risk and interventions to reduce or manage weight gain are essential in this high-risk population.

Garmey, Edward G.; Liu, Qi; Sklar, Charles A.; Meacham, Lillian R.; Mertens, Ann C.; Stovall, Marilyn A.; Yasui, Yutaka; Robison, Leslie L.; Oeffinger, Kevin C.

2008-01-01

168

Recruitment of human cyclin T1 to nuclear bodies through direct interaction with the PML protein  

PubMed Central

Human cyclin T1, the cyclin partner of Cdk9 kinase in the positive transcription elongation factor b (P-TEFb), is an essential cellular cofactor that is recruited by the human immunodeficiency virus type 1 (HIV-1) Tat transactivator to promote transcriptional elongation from the HIV-1 long terminal repeat (LTR). Here we exploit fluorescence resonance energy transfer (FRET) to demonstrate that cyclin T1 physically interacts in vivo with the promyelocytic leukaemia (PML) protein within specific subnuclear compartments that are coincident with PML nuclear bodies. Deletion mutants at the C-terminal region of cyclin T1 are negative for FRET with PML and fail to localize to nuclear bodies. Cyclin T1 and PML are also found associated outside of nuclear bodies, and both proteins are present at the chromatinized HIV-1 LTR promoter upon Tat transactivation. Taken together these results suggest that PML proteins regulate Tat- mediated transcriptional activation by modulating the availability of cyclin T1 and other essential cofactors to the transcription machinery.

Marcello, Alessandro; Ferrari, Aldo; Pellegrini, Vittorio; Pegoraro, Gianluca; Lusic, Marina; Beltram, Fabio; Giacca, Mauro

2003-01-01

169

Brr6 drives the Schizosaccharomyces pombe spindle pole body nuclear envelope insertion/extrusion cycle  

PubMed Central

The fission yeast interphase spindle pole body (SPB) is a bipartite structure in which a bulky cytoplasmic domain is separated from a nuclear component by the nuclear envelope. During mitosis, the SPB is incorporated into a fenestra that forms within the envelope during mitotic commitment. Closure of this fenestra during anaphase B/mitotic exit returns the cytoplasmic component to the cytoplasmic face of an intact interphase nuclear envelope. Here we show that Brr6 is transiently recruited to SPBs at both SPB insertion and extrusion. Brr6 is required for both SPB insertion and nuclear envelope integrity during anaphase B/mitotic exit. Genetic interactions with apq12 and defective sterol assimilation suggest that Brr6 may alter envelope composition at SPBs to promote SPB insertion and extrusion. The restriction of the Brr6 domain to eukaryotes that use a polar fenestra in an otherwise closed mitosis suggests a conserved role in fenestration to enable a single microtubule organizing center to nucleate both cytoplasmic and nuclear microtubules on opposing sides of the nuclear envelope.

Tamm, Tiina; Grallert, Agnes; Grossman, Emily P.S.; Alvarez-Tabares, Isabel; Stevens, Frances E.

2011-01-01

170

Brr6 drives the Schizosaccharomyces pombe spindle pole body nuclear envelope insertion/extrusion cycle.  

PubMed

The fission yeast interphase spindle pole body (SPB) is a bipartite structure in which a bulky cytoplasmic domain is separated from a nuclear component by the nuclear envelope. During mitosis, the SPB is incorporated into a fenestra that forms within the envelope during mitotic commitment. Closure of this fenestra during anaphase B/mitotic exit returns the cytoplasmic component to the cytoplasmic face of an intact interphase nuclear envelope. Here we show that Brr6 is transiently recruited to SPBs at both SPB insertion and extrusion. Brr6 is required for both SPB insertion and nuclear envelope integrity during anaphase B/mitotic exit. Genetic interactions with apq12 and defective sterol assimilation suggest that Brr6 may alter envelope composition at SPBs to promote SPB insertion and extrusion. The restriction of the Brr6 domain to eukaryotes that use a polar fenestra in an otherwise closed mitosis suggests a conserved role in fenestration to enable a single microtubule organizing center to nucleate both cytoplasmic and nuclear microtubules on opposing sides of the nuclear envelope. PMID:22042620

Tamm, Tiina; Grallert, Agnes; Grossman, Emily P S; Alvarez-Tabares, Isabel; Stevens, Frances E; Hagan, Iain M

2011-10-31

171

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

PubMed Central

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 ?-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 ?-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 ?-helix of Nbp1 is important for SPB insertion into the NE from within the nucleus.

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

2011-01-01

172

Childhood Leukemia  

MedlinePLUS

... cells. It is the most common type of childhood cancer. Your blood cells form in your bone ... in the bones or joints Risk factors for childhood leukemia include having a brother or sister with ...

173

Important role of three-body repulsive force effect in nuclear reactions  

NASA Astrophysics Data System (ADS)

The effect of three-body force (TBF) is studied in nucleus-nucleus elastic scattering on the basis of Brueckner theory for nucleon-nucleon (NN) effective interaction (complex G matrix) in the nuclear matter. A new G matrix called CEG07 proposed recently by the present authors includes the TBF effect and reproduces a realistic saturation curve in the nuclear matter, and is shown to well reproduce proton-nucleus elastic scattering. The microscopic optical potential for nucleus-nucleus system is obtained by folding the G matrix with nucleon density distributions in colliding nuclei. We first analyze the 16O + 16O elastic scattering at E/A = 70 MeV in detail. The observed cross sections are nicely reproduced up to the most backward scattering angles only when the TBF effect is included. The effects of the three-body attraction (TBA) and three-body repulsion (TBR) are also analyzed. The TBR contribution has an important role in nucleus-nucleus elastic scattering. The CEG07 G matrix is also tested in the elastic scattering of 16O by the 12C, 28Si and 40Ca targets at E/A = 93.9 MeV, and in the elastic scattering of 12C by the 12C target at E/A = 135 MeV with a great success. The decisive effect of the TBF is clearly seen also in those systems.

Furumoto, T.; Sakuragi, Y.; Yamamoto, Y.

2010-04-01

174

Nuclear bodies and compartmentalization of pre-mRNA splicing factors in higher plants.  

PubMed

We studied the fine structural organization of nuclear bodies in the root meristem during germination of maize and Arabidopsis thaliana using electron microscopy (EM). Cajal bodies (CBs) were observed in quiescent embryos and germinating cells in both species. The number and distribution of CBs were investigated. To characterize the nuclear splicing domains, immunofluorescence labelling with antibodies against splicing factors (U2B" and m3G-snRNAs) and in situ hybridisation (with U1/U6 antisense probes) were performed combined with confocal microscopy. Antibodies specific to the Arabidopsis SR splicing factor atRSp31 were produced. AtRSp31 was detected in quiescent nuclei and in germinating cells. This study revealed an unexpected speckled nuclear organization of atRSp31 in root epidermal cells where micro-clusters of interchromatin granules were also observed by EM. Therefore, we examined the distribution of green fluorescent protein (GFP)-tagged atRSp31 in living cells after Agrobacterium -mediated transient expression. When expressed transiently, atRSp31-GFP exhibited a speckled distribution in leaf cells. Treatments with alpha-amanitin, okadaic acid, staurosporine or heat shock induced the speckles to reorganize. Furthermore, we generated stable Arabidopsis transgenics expressing atRSp31-GFP. The distribution of the fusion protein was identical to that of endogenous atRSp31. Three-dimensional time-lapse confocal microscopy showed that speckles were highly dynamic domains over time. PMID:14740228

Docquier, Sarah; Tillemans, Vinciane; Deltour, Roger; Motte, Patrick

2004-01-23

175

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

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.

Rubin, P. (Univ. of Rochester, NY); Bennent, J.M.; Begg, C.; Bozdech, M.J.; Silber, R.

1981-12-01

176

Nuclear LSm8 affects number of cytoplasmic processing bodies via controlling cellular distribution of Like-Sm proteins  

PubMed Central

Processing bodies (P-bodies) are dynamic cytoplasmic structures involved in mRNA degradation, but the mechanism that governs their formation is poorly understood. In this paper, we address a role of Like-Sm (LSm) proteins in formation of P-bodies and provide evidence that depletion of nuclear LSm8 increases the number of P-bodies, while LSm8 overexpression leads to P-body loss. We show that LSm8 knockdown causes relocalization of LSm4 and LSm6 proteins to the cytoplasm and suggest that LSm8 controls nuclear accumulation of all LSm2–7 proteins. We propose a model in which redistribution of LSm2–7 to the cytoplasm creates new binding sites for other P-body components and nucleates new, microscopically visible structures. The model is supported by prolonged residence of two P-body proteins, DDX6 and Ago2, in P-bodies after LSm8 depletion, which indicates stronger interactions between these proteins and P-bodies. Finally, an increased number of P-bodies has negligible effects on microRNA-mediated translation repression and nonsense mediated decay, further supporting the view that the function of proteins localized in P-bodies is independent of visible P-bodies.

Novotny, Ivan; Podolska, Katerina; Blazikova, Michaela; Valasek, Leos Shivaya; Svoboda, Petr; Stanek, David

2012-01-01

177

Low-Temperature Triple-Alpha Rate in a Full Three-Body Nuclear Model  

NASA Astrophysics Data System (ADS)

A new three-body method is used to compute the rate of the triple-alpha capture reaction, which is the primary source of C12 in stars. In this Letter, we combine the Faddeev hyperspherical harmonics and the R-matrix method to obtain a full solution to the three-body ?+?+? continuum. Particular attention is paid to the long-range effects caused by the pairwise Coulomb interactions. The new rate agrees with the Nuclear Astrophysics Compilation of Reaction rates for temperatures greater than 0.07 GK, but a large enhancement at lower temperature is found (?1012 at 0.02 GK). Our results are compared to previous calculations where additional approximations were made. We show that the new rate does not significantly change the evolution of stars around one solar mass. In particular, such stars still undergo a red-giant phase consistent with observations, and no significant differences are found in the final white dwarfs.

Nguyen, N. B.; Nunes, F. M.; Thompson, I. J.; Brown, E. F.

2012-10-01

178

PML-associated repressor of transcription (PAROT), a novel KRAB-zinc finger repressor, is regulated through association with PML nuclear bodies  

SciTech Connect

Promyelocytic leukemia nuclear bodies (PML-NBs) are implicated in transcriptional regulation. Here we identify a novel transcriptional repressor, PML-associated repressor of transcription (PAROT), which is regulated in its repressor activity through recruitment to PML-NBs. PAROT is a Krueppel-associated box ( KRAB) zinc-finger (ZNF) protein, which comprises an amino terminal KRAB-A and KRAB-B box, a linker domain and 8 tandemly repeated C{sub 2}H{sub 2}-ZNF motifs at its carboxy terminus. Consistent with its domain structure, when tethered to DNA, PAROT represses transcription, and this is partially released by the HDAC inhibitor trichostatin A. PAROT colocalizes with members of the heterochromatin protein 1 (HP1) family and with transcriptional intermediary factor-1{beta}/KRAB-associated protein 1 (TIF-1{beta}/KAP1), a transcriptional corepressor for the KRAB-ZNF family. Interestingly, PML isoform IV, in contrast to PML-III, efficiently recruits PAROT and TIF-1{beta} from heterochromatin to PML-NBs. PML-NB recruitment of PAROT partially releases its transcriptional repressor activity, indicating that PAROT can be regulated through subnuclear compartmentalization. Taken together, our data identify a novel transcriptional repressor and provide evidence for its regulation through association with PML-NBs.

Fleischer, Sandra [Heinrich-Pette-Institut fuer Experimentelle Virologie und Immunologie, Martinistrasse 52, 20251 Hamburg (Germany); Wiemann, Stefan [Molecular Genome Analysis Devision, German Cancer Research Center (dkfz.), 69120 Heidelberg (Germany); Will, Hans [Heinrich-Pette-Institut fuer Experimentelle Virologie und Immunologie, Martinistrasse 52, 20251 Hamburg (Germany); Hofmann, Thomas G. [Research Group Cellular Senescence, German Cancer Research Center (dkfz.), 69120 Heidelberg (Germany)]. E-mail: t.hofmann@dkfz.de

2006-04-01

179

The spinal muscular atrophy protein SMN affects Drosophila germline nuclear organization through the U body–P body pathway  

Microsoft Academic Search

Survival motor neuron protein (SMN) is the determining factor for the human neurodegenerative disease spinal muscular atrophy (SMA). SMN is critical for small nuclear ribonucleoprotein (snRNP) assembly. Using Drosophila oogenesis as a model system, we show that mutations in smn cause abnormal nuclear organization in nurse cells and oocytes. Germline and mitotic clonal analysis reveals that both nurse cells and

Lin Lee; Siân E. Davies; Ji-Long Liu

2009-01-01

180

Tracking nuclear poly(a) RNA movement within and among speckle nuclear bodies and the surrounding nucleoplasm.  

PubMed

The movement of polyadenylated RNA transcripts (poly(A) RNA) through speckles in the nucleus can be detected and studied using fluorescence correlation microscopy (FCM) and photoactivation RNA tracking techniques. Speckles, sometimes called interchromatin granule clusters, are nuclear bodies that contain pre-mRNA splicing factors and poly(A) RNA. In the methods described here, speckles are marked in live cells using monomeric red fluorescent protein fused to SC35, a splicing protein that is a common speckle component. Endogenous poly(A) RNAs are tagged by in vivo hybridization with fluorescein-labeled oligo(dT) and FCM is performed at the marked speckles and in the nucleoplasm to measure the mobility of the tagged poly(A) RNA. The majority of the nuclear poly(A) RNA population diffuses rapidly throughout the nucleoplasm, and thus this method allows one to ask whether poly(A) RNA that is located in speckles at a given time is undergoing a dynamic transit or is, in contrast, a more immobile, perhaps structural, component. To visualize the movement of poly(A) RNA away from speckles, poly(A) RNA is tagged with caged-fluorescein-labeled oligo(dT) and speckle-associated poly(A) RNAs are specifically photoactivated using a laser beam directed through a pinhole in a rapid digital imaging microscopy system. The spatial distribution of the now-fluorescent RNA as it moves from the speckle photoactivation site is then recorded over time. Temperature and/or ATP levels can also be varied to test whether movement or localization of the poly(A) RNA is dependent on metabolic energy. PMID:23980000

Politz, Joan C Ritland; Pederson, Thoru

2013-01-01

181

Measurement of the whole-body 137Cs in residents around the Chernobyl nuclear power plant.  

PubMed

To understand the current situation of internal radiation exposure in the population around the Chernobyl Nuclear Power Plant (CNPP), we examined the 137Cs body burden in six residents of Belarus, Ukraine and Russia in 2002 and 2004 using the whole-body counter (WBC) at Nagasaki University (Japan). The data were compared with those of our previous study performed in 1993-1994 using the same method. In 2002 and 2004, peaks of 137Cs were detected in two residents from Gomel, which was heavily contaminated by the CNPP accident, one from Minsk (Belarus) and one from Kiev (Ukraine), but another resident from Minsk showed no 137Cs peaks. The results of the present study suggests that residents around the CNPP are still exposed to chronic 137Cs internal irradiation, probably due to the daily consumption of contaminated domestic foods, but the risk of any disease by the irradiation is quite low. Long-term follow-up of WBC around the CNPP is useful and may contribute to radiation safety regulation together with a reduction of unnecessary radiophobia for the residents. PMID:15703186

Morita, Naoko; Takamura, Noboru; Ashizawa, Kiyoto; Shimasaki, Tatsuya; Yamashita, Shunichi; Okumura, Yutaka

2005-02-09

182

Saccharomyces cerevisiae Ndc1p Is a Shared Component of Nuclear Pore Complexes and Spindle Pole Bodies  

Microsoft Academic Search

We report a novel connection between nu- clear pore complexes (NPCs) and spindle pole bodies (SPBs) revealed by our studies of the Saccharomyces cerevisiae NDC1 gene. Although both NPCs and SPBs are embedded in the nuclear envelope (NE) in yeast, their known functions are quite distinct. Previous work demonstrated that NDC1 function is required for proper SPB duplication (Winey, M.,

Heidi J. Chial; Michael P. Rout; Thomas H. Giddings; M. Winey

1998-01-01

183

In-medium T matrix for nuclear matter with three-body forces: Binding energy and single-particle properties  

SciTech Connect

We present spectral calculations of nuclear matter properties including three-body forces. Within the in-medium T-matrix approach, implemented with the CD-Bonn and Nijmegen potentials plus the three-nucleon Urbana interaction, we compute the energy per particle in symmetric and neutron matter. The three-body forces are included via an effective density dependent two-body force in the in-medium T-matrix equations. After fine tuning the parameters of the three-body force to reproduce the phenomenological saturation point in symmetric nuclear matter, we calculate the incompressibility and the energy per particle in neutron matter. We find a soft equation of state in symmetric nuclear matter but a relatively large value of the symmetry energy. We study the the influence of the three-body forces on the single-particle properties. For symmetric matter the spectral function is broadened at all momenta and all densities, while an opposite effect is found for the case of neutrons only. Noticeable modification of the spectral functions are realized only for densities above the saturation density. The modifications of the self-energy and the effective mass are not very large and appear to be strongly suppressed above the Fermi momentum.

Soma, V. [Institute of Nuclear Physics PAN, PL-31-342 Krakow (Poland); Bozek, P. [Institute of Physics, Rzeszow University, PL-35-959 Rzeszow (Poland); Institute of Nuclear Physics PAN, PL-31-342 Krakow (Poland)

2008-11-15

184

RNA-related nuclear functions of human Pat1b, the P-body mRNA decay factor.  

PubMed

The evolutionarily conserved Pat1 proteins are P-body components recently shown to play important roles in cytoplasmic gene expression control. Using human cell lines, we demonstrate that human Pat1b is a shuttling protein whose nuclear export is mediated via a consensus NES sequence and Crm1, as evidenced by leptomycin B (LMB) treatment. However, not all P-body components are nucleocytoplasmic proteins; rck/p54, Dcp1a, Edc3, Ge-1, and Xrn1 are insensitive to LMB and remain cytoplasmic in its presence. Nuclear Pat1b localizes to PML-associated foci and SC35-containing splicing speckles in a transcription-dependent manner, whereas in the absence of RNA synthesis, Pat1b redistributes to crescent-shaped nucleolar caps. Furthermore, inhibition of splicing by spliceostatin A leads to the reorganization of SC35 speckles, which is closely mirrored by Pat1b, indicating that it may also be involved in splicing processes. Of interest, Pat1b retention in these three nuclear compartments is mediated via distinct regions of the protein. Examination of the nuclear distribution of 4E-T(ransporter), an additional P-body nucleocytoplasmic protein, revealed that 4E-T colocalizes with Pat1b in PML-associated foci but not in nucleolar caps. Taken together, our findings strongly suggest that Pat1b participates in several RNA-related nuclear processes in addition to its multiple regulatory roles in the cytoplasm. PMID:22090346

Marnef, Aline; Weil, Dominique; Standart, Nancy

2011-11-16

185

RNA-related nuclear functions of human Pat1b, the P-body mRNA decay factor  

PubMed Central

The evolutionarily conserved Pat1 proteins are P-body components recently shown to play important roles in cytoplasmic gene expression control. Using human cell lines, we demonstrate that human Pat1b is a shuttling protein whose nuclear export is mediated via a consensus NES sequence and Crm1, as evidenced by leptomycin B (LMB) treatment. However, not all P-body components are nucleocytoplasmic proteins; rck/p54, Dcp1a, Edc3, Ge-1, and Xrn1 are insensitive to LMB and remain cytoplasmic in its presence. Nuclear Pat1b localizes to PML–associated foci and SC35-containing splicing speckles in a transcription-dependent manner, whereas in the absence of RNA synthesis, Pat1b redistributes to crescent-shaped nucleolar caps. Furthermore, inhibition of splicing by spliceostatin A leads to the reorganization of SC35 speckles, which is closely mirrored by Pat1b, indicating that it may also be involved in splicing processes. Of interest, Pat1b retention in these three nuclear compartments is mediated via distinct regions of the protein. Examination of the nuclear distribution of 4E-T(ransporter), an additional P-body nucleocytoplasmic protein, revealed that 4E-T colocalizes with Pat1b in PML-associated foci but not in nucleolar caps. Taken together, our findings strongly suggest that Pat1b participates in several RNA-related nuclear processes in addition to its multiple regulatory roles in the cytoplasm.

Marnef, Aline; Weil, Dominique; Standart, Nancy

2012-01-01

186

The promyelocytic leukemia protein stimulates SUMO conjugation in yeast.  

PubMed

The promyelocytic leukemia gene was first identified through its fusion to the gene encoding the retinoic acid receptor alpha (RARalpha) in acute promyelocytic leukemia (APL) patients. The promyelocytic leukemia gene product (PML) becomes conjugated in vivo to the small ubiquitin-like protein SUMO-1, altering its behavior and capacity to recruit other proteins to PML nuclear bodies (PML-NBs). In the NB4 cell line, which was derived from an APL patient and expresses PML:RARalpha, we observed a retinoic acid-dependent change in the modification of specific proteins by SUMO-1. To dissect the interaction of PML with the SUMO-1 modification pathway, we used the budding yeast Saccharomyces cerevisiae as a model system through expression of PML and human SUMO-1 (hSUMO-1). We found that PML stimulated hSUMO-1 modification in yeast, in a manner that was dependent upon PML's RING-finger domain. PML:RARalpha also stimulated hSUMO-1 conjugation in yeast. Interestingly, however, PML and PML:RARalpha differentially complemented yeast Smt3p conjugation pathway mutants. These findings point toward a potential function of PML and PML:RARalpha as SUMO E3 enzymes or E3 regulators, and suggest that fusion of RARalpha to PML may affect this activity. PMID:16501610

Quimby, B B; Yong-Gonzalez, V; Anan, T; Strunnikov, A V; Dasso, M

2006-05-18

187

The childhood leukemias  

Microsoft Academic Search

Advances in treatment and prognosis of childhood leukemia are considered a remarkable success of modern medicine. Childhood leukemia, once considered a universally fatal disease, now boasts overall cure rates ranging from 75% to 85% for acute lymphocytic leukemia (ALL) and cure rates approaching 40% to 50% for acute myelogenous leukemia (AML). Inherent to this success is the expertise nurses provide

Mary Faye Colby-Graham; Christine Chordas

2003-01-01

188

Light clusters in nuclear matter: Excluded volume versus quantum many-body approaches  

NASA Astrophysics Data System (ADS)

The formation of clusters in nuclear matter is investigated, which occurs, e.g., in low-energy heavy-ion collisions or core-collapse supernovae. In astrophysical applications, the excluded volume concept is commonly used for the description of light clusters. Here we compare a phenomenological excluded volume approach to two quantum many-body models, the quantum statistical model and the generalized relativistic mean-field model. All three models contain bound states of nuclei with mass number A?4. It is explored to which extent the complex medium effects can be mimicked by the simpler excluded volume model, regarding the chemical composition and thermodynamic variables. Furthermore, the role of heavy nuclei and excited states is investigated by use of the excluded volume model. At temperatures of a few MeV the excluded volume model gives a poor description of the medium effects on the light clusters, but there the composition is actually dominated by heavy nuclei. At larger temperatures there is a rather good agreement, whereas some smaller differences and model dependencies remain.

Hempel, Matthias; Schaffner-Bielich, Jürgen; Typel, Stefan; Röpke, Gerd

2011-11-01

189

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

SciTech Connect

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.

Holt, Jason D. [Technische Univ. Darmstadt/GSI/UTK/ORNL; Menendez, J. [Technische Univ. Darmstadt/GSI Helmholtzzentrum fur Schweionenforschung, Germany; Schwenk, A. [Technische Univ. Darmstadt/GSI Helmholtzzentrum fur Schweionenforschung, Germany

2013-01-01

190

Leukemia revisited  

SciTech Connect

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.

Cronkite, E P

1980-01-01

191

Terpenic fraction of Pterodon pubescens inhibits nuclear factor kappa B and extracellular signal-regulated protein Kinase 1/2 activation and deregulates gene expression in leukemia cells  

PubMed Central

Background Plant derived compounds have been shown to be important sources of several anti-cancer agents. As cell cycle deregulation and tumor growth are intimately linked, the discovery of new substances targeting events in this biochemical pathway would be of great value. The anti-leukemic effect of an ethanolic extract of Pterodon pubescens seeds (EEPp) has been previously demonstrated and now we show that a terpenic subfraction (SF5) of EEPp containing farnesol, geranylgeraniol and vouacapan derivatives induces apoptosis in the human chronic myelogenous leukemia cell line K562. This work addresses SF5’s antiproliferative mechanisms in these cells since they are still unclear. Methods DNA synthesis in K562 cells was assessed by [3H]-methyl-thymidine incorporation and cell cycle status by flow cytometry. The expression of cyclins D1 and E2, of the cell cycle inhibitor p21 and of the proto-oncogene c-myc was evaluated by semi-quantitative RT-PCR. Extracellular-signal-regulated kinases (ERK) 1/2 and nuclear factor kappa B (NF-?B) activation was evaluated by western blotting. Results In K562 cells, SF5 treatment induced a higher inhibition of DNA synthesis and cell growth than the original EEPp hexanic fraction from which SF5 originated, and also arrested the cell cycle in G1. Exposure of these cells to SF5 led to a decrease in cyclin E2 and c-myc expression while p21 mRNA levels were increased. Furthermore, SF5 inhibited the activation of mitogen-activated protein kinase (MAPK) ERK 1/2 and NF-?B. Conclusions This work suggests that the anti-leukemic action of SF5 is linked to the inhibition of ERKs, NF-?B and c-myc signaling pathways resulting in reduced cyclin E2 mRNA expression and cell cycle arrest in the G1 phase.

2012-01-01

192

The leukemias: Epidemiologic aspects  

SciTech Connect

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.

Linet, M.S.

1984-01-01

193

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

ClinicalTrials.gov

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

2013-01-22

194

Assembly of snRNP-containing coiled bodies is regulated in interphase and mitosis--evidence that the coiled body is a kinetic nuclear structure  

PubMed Central

Coiled bodies (CBs) are nuclear organelles in which splicing snRNPs concentrate. While CBs are sometimes observed in association with the nucleolar periphery, they are shown not to contain 5S or 28S rRNA or the U3 snoRNA. This argues against CBs playing a role in rRNA maturation or transport as previously suggested. We present evidence here that CBs are kinetic structures and demonstrate that the formation of snRNP-containing CBs is regulated in interphase and mitosis. The coiled body antigen, p80 coilin, was present in all cell types studied, even when CBs were not prominent. Striking changes in the formation of CBs could be induced by changes in cellular growth temperature without a concomitant change in the intracellular p80 coilin level. During mitosis, CBs disassemble, coinciding with a mitotic-specific phosphorylation of p80 coilin. Coilin is shown to be a phosphoprotein that is phosphorylated on at least two additional sites during mitosis. CBs reform in daughter nuclei after a lag period during which they are not detected. CBs are thus, dynamic nuclear organelles and we propose that cycling interactions of splicing snRNPs with CBs may be important for their participation in the processing or transport of pre-mRNA in mammalian cells.

1993-01-01

195

Nuclear inner membrane fusion facilitated by yeast Jem1p is required for spindle pole body fusion but not for the first mitotic nuclear division during yeast mating.  

PubMed

During mating of budding yeast, Saccharomyces cerevisiae, two haploid nuclei fuse to produce a diploid nucleus. The process of nuclear fusion requires two J proteins, Jem1p in the endoplasmic reticulum (ER) lumen and Sec63p, which forms a complex with Sec71p and Sec72p, in the ER membrane. Zygotes of mutants defective in the functions of Jem1p or Sec63p contain two haploid nuclei that were closely apposed but failed to fuse. Here we analyzed the ultrastructure of nuclei in jem1 Delta and sec71 Delta mutant zygotes using electron microscope with the freeze-substituted fixation method. Three-dimensional reconstitution of nuclear structures from electron microscope serial sections revealed that Jem1p facilitates nuclear inner-membrane fusion and spindle pole body (SPB) fusion while Sec71p facilitates nuclear outer-membrane fusion. Two haploid SPBs that failed to fuse could duplicate, and mitotic nuclear division of the unfused haploid nuclei started in jem1 Delta and sec71 Delta mutant zygotes. This observation suggests that nuclear inner-membrane fusion is required for SPB fusion, but not for SPB duplication in the first mitotic cell division. PMID:19090812

Nishikawa, Shuh-ichi; Hirata, Aiko; Endo, Toshiya

2008-11-01

196

Study of stochastic approaches of the n-bodies problem: application to the nuclear fragmentation.  

National Technical Information Service (NTIS)

In the last decade nuclear physics research has found, with the observation of phenomena such as multifragmentation or vaporization, the possibility to get a deeper insight into the nuclear matter phase diagram. For example, a spinodal decomposition scena...

A. Guarnera

1996-01-01

197

Radiogenic leukemia revisited  

SciTech Connect

Radiation-induced leukemia is considered to be similar to the de novo disease. However, following an analysis of clinical and hematological findings in leukemia occurring in irradiated cervical cancer patients, adult Japanese atomic-bomb survivors, and spondylitics treated with x-ray, striking differences were noted. Acute leukemias in cervical cancer patients and Japanese survivors were similar in type to acute de novo leukemias in adults. Cell types among spondylitics were very dissimilar; rare forms, eg, acute erythromyelocytic leukemia (AEL) and acute megakaryocytic leukemia, were increased. Pancytopenia occurred in 25 of 35 cases and erythromyelodysplastic disorders were noted in seven of 35 acute cases. The leukemias and myelodysplastic disorders closely resembled those occurring in patients treated with alkylating agents. This similarity suggests a common pathogenesis involving marrow stem cell injury and extra-medullary mediators of hematopoiesis. Investigation of early acute leukemias and myelodysplastic disorders with newer techniques may provide valuable insights into the pathogenesis of leukemia in humans.

Moloney, W.C.

1987-10-01

198

Multicomponent analysis of radiolytic products in human body fluids using high field proton nuclear magnetic resonance (NMR) spectroscopy  

Microsoft Academic Search

High field proton Hahn spin-echo nuclear magnetic resonance (NMR) spectroscopy has been employed to investigate radiolytic damage to biomolecules present in intact human body fluids. gamma-Radiolysis of healthy or rheumatoid human serum (5.00 kGy) in the presence of atmospheric O2 gave rise to reproducible elevations in the concentration of NMR-detectable acetate which are predominantly ascribable to the prior oxidation of

Martin C. Grootveld; Herman Herz; Rachel Haywood; Geoffrey E. Hawkes; Declan Naughton; Anusha Perera; Jacky Knappitt; David R. Blake; Andrew W. D. Claxson

1994-01-01

199

Nep98p is a component of the yeast spindle pole body and essential for nuclear division and fusion.  

PubMed

During the mating of yeast Saccharomyces cerevisiae, two haploid nuclei fuse to produce a diploid nucleus. This process requires the functions of BiP/Kar2p, a member of the Hsp70 family in the endoplasmic reticulum, and its partner protein, Jem1p. To investigate further the role of BiP and Jem1p in nuclear fusion, we screened for partner proteins for Jem1p by the yeast two-hybrid system and identified Nep98p. Nep98p is an essential integral membrane protein of the nuclear envelope and is enriched in the spindle pole body (SPB), the sole microtubule-organizing center in yeast. Temperature-sensitive nep98 mutant cells contain abnormal SPBs lacking the half-bridge, suggesting the essential role of Nep98p in the organization of the normal SPB. Additionally, nep98 mutant cells show defects in mitotic nuclear division and nuclear fusion during mating. Because Jem1p is not required for nuclear division, Nep98p probably has dual functions in Jem1p-dependent karyogamy and in Jem1p-independent nuclear division. PMID:12493774

Nishikawa, Shuh-Ichi; Terazawa, Yumiko; Nakayama, Takeshi; Hirata, Aiko; Makio, Tadashi; Endo, Toshiya

2002-12-18

200

Acute Myeloid Leukemia  

MedlinePLUS

... a third party. HPF: SEER Stat Fact Sheets: Acute Myeloid Leukemia Cancer: It is estimated that 14,590 men ... 10,370 men and women will die of acute myeloid leukemia in 2013 1 X Close Table I-1 ( ...

201

Acute Lymphocytic Leukemia  

MedlinePLUS

... may be reprinted for personal, noncommercial use only. Acute lymphocytic leukemia By Mayo Clinic staff Original Article: http://www.mayoclinic.com/health/acute-lymphocytic-leukemia/DS00558 Definition Symptoms Causes Risk factors Preparing for ...

202

Acute Lymphocytic Leukemia  

MedlinePLUS

... a third party. HPF: SEER Stat Fact Sheets: Acute Lymphocytic Leukemia Cancer: It is estimated that 6,070 men ... 1,430 men and women will die of acute lymphocytic leukemia in 2013 1 X Close Table I-1 ( ...

203

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 ...

204

Register of the repressed: Women's voice and body in the nuclear weapons organization  

Microsoft Academic Search

Symbolic forms play an important role in mediating cultural knowledge of nuclear weapons. One recurring form in postwar cultural texts is the nuclear weapons organization—the various groups using labor, technology and materials to design, manufacture and deploy the Bomb. Several of these texts depict the wartime Los Alamos Laboratory, where the first atomic bomb was constructed. Conventionally, these texts privilege

Bryan C. Taylor

1993-01-01

205

Adult acute leukemia  

Microsoft Academic Search

Untreated acute leukemia is a uniformly fatal disease with a median survival time shorter than 3 months. Current treatment strategies provide a significant increase in survival time for most patients, some of whom may be cured. The majority of patients with acute leukemia, however, ultimately die of the disease or complications of treatment. The effective treatment of acute leukemia requires

Larry D. Cripe

1997-01-01

206

Acute Myeloid Leukemia  

MedlinePLUS

What is acute myeloid leukemia (AML)? The second most common type of acute leukemia in adults, AML is a cancer of the blood ... cancer.org (American Cancer Society). Type the keywords acute myeloid leukemia into the search box. What kinds of questions ...

207

Acute myelocytic leukemia after exposure to asbestos  

SciTech Connect

While the carcinogenicity of asbestos has been established in malignant mesotheliomas and lung cancers, and has recently been suspected in several other types of cancer, asbestos has not been implicated in the pathogenesis of acute leukemias. This article includes two cases of acute myelocytic leukemia in individuals with a long history of exposure to asbestos. Significant numbers of asbestos bodies were detected in specimens of their lungs and bone marrow. In addition, the kind of asbestos in both organs was crocidolite, which is implicated in carcinogenesis. No asbestos bodies were detected in the bone marrow specimens from a control group consisting of ten patients with lung cancer with similar occupational histories. The role of asbestos exposure in the development of leukemia requires further study.

Kishimoto, T.; Ono, T.; Okada, K.

1988-08-15

208

Time-Dependent, Many-Body Scattering Theory and Nuclear Reaction Applications.  

National Technical Information Service (NTIS)

The channel component state form of the channel coupling array theory of many-body scattering is briefly reviewed. These states obey a non-hermitian matrix equation whose exact solution yields the Schroedinger eigenstates, eigenvalues and scattering ampli...

F. S. Levin

1977-01-01

209

Non-rigid image registration for temporal subtraction of whole-body nuclear emission images  

Microsoft Academic Search

A non-rigid registration algorithm for application to whole-body emission images of the same patient is presented. Rigid registration is generally insufficient to properly register whole-body images, a certain amount of deformation needs to be applied to obtain a good correspondence. This deformation should not change the size or shape of lesions, bones and the general anatomy. In our approach, non-rigid

Raf Claessens; Johan Nuyts; Sigrid Stroobants; Patrick Dupont; F. Maeswork

2003-01-01

210

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

PubMed

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)]. 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. PMID:23883016

Xiao, Yunlong; Liu, Wenjian

2013-07-21

211

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

NASA Astrophysics Data System (ADS)

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)]. 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.

Xiao, Yunlong; Liu, Wenjian

2013-07-01

212

Classification of acute leukemia.  

PubMed

The classification of acute leukemia has almost invariably been based on the morphologic diagnosis into two broad categories: acute lymphocytic and acute myeloid leukemia. Despite the wide range of morphologic variation in both groups, strict criteria to define the subgroups have only recently been proposed. The conventional markers for B and T cells are now being applied to leukemic cells as are cytochemistry and electron microscopy, terminal deoxynucleotidyl transferase, serum lysozyme, and surface markers, E-rosettes, membrane immunoglobulin, antinull acute lymphocytic leukemia antiserum, and Fc and C3 receptors. The myelodysplastic syndromes may mimic acute leukemia and it is important that they be identified and treated appropriately. The high incidence with which chronic myelomonocytic leukemia terminates in acute leukemia suggests that it is a preleukemic condition, whereas refractory anemia with excess blasts and acquired idiopathic sideroblastic anemia may have long, drawn-out courses. Only a small population of patients with the latter conditions develop acute leukemia. PMID:337870

1977-12-01

213

Electron tomography of fiber cell cytoplasm and dense cores of multilamellar bodies from human age-related nuclear cataracts  

PubMed Central

Human nuclear cataract formation is a multi-factorial disease with contributions to light scattering from many cellular sources that change their scattering properties over decades. The aging process produces aggregation of cytoplasmic crystallin proteins, which alters the protein packing and texture of the cytoplasm. Previous studies of the cytoplasmic texture quantified increases in density fluctuations in protein packing and theoretically predicted the corresponding scattering. Multilamellar bodies (MLBs) are large particles with a core of crystallin cytoplasm that have been suggested to be major sources of scattering in human nuclei. The core has been shown to condense over time such that the refractive index increases compared to the adjacent aged and textured cytoplasm. Electron tomography is used here to visualize the 3D arrangement of protein aggregates in aged and cataractous lens nuclear cytoplasm compared to the dense protein packing in the cores of MLBs. Thin sections, 70 nm thick, were prepared from epoxy-embedded human transparent donor lenses and nuclear cataracts. Tilt series were collected on an FEI T20 transmission electron microscope (TEM) operated at 200 kV using 15 nm gold particles as fiducial markers. Images were aligned and corrected with FEI software and reconstructed with IMOD and other software packages to produce animated tilt series and stereo anaglyphs. The 3D views of protein density showed the relatively uniform packing of proteins in aged transparent lens nuclear cytoplasm and less dense packing of aged cataractous cytoplasm where many low-density regions can be appreciated in the absence of the TEM projection artifacts. In contrast the cores of the MLBs showed a dense packing of protein with minimal density fluctuations. These observations support the conclusion that, during the nuclear cataract formation, alterations in protein packing are extensive and can result in pronounced density fluctuations. Aging causes the MLB cores to become increasingly different in their protein packing from the adjacent cytoplasm. These results support the hypothesis that the MLBs increase their scattering with age and nuclear cataract formation.

Costello, M. Joseph; Burette, Alain; Weber, Mariko; Metlapally, Sangeetha; Gilliland, Kurt O.; Fowler, W. Craig; Mohamed, Ashik; Johnsen, Sonke

2012-01-01

214

Leukemia - B-Cell Prolymphocytic Leukemia and Hairy Cell Leukemia  

MedlinePLUS

... note these links take you to other sections: ASCO Answers Fact Sheet : Read a one-page fact ... Video : View a short video led by an ASCO expert in leukemia that provides basic information and ...

215

Nuclear export receptor Xpo1/Crm1 is physically and functionally linked to the spindle pole body in budding yeast.  

PubMed

The spindle pole body (SPB) represents the microtubule organizing center in the budding yeast Saccharomyces cerevisiae. It is a highly structured organelle embedded in the nuclear membrane, which is required to anchor microtubules on both sides of the nuclear envelope. The protein Spc72, a component of the SPB, is located at the cytoplasmic face of this organelle and serves as a receptor for the gamma-tubulin complex. In this paper we show that it is also a binding partner of the nuclear export receptor Xpo1/Crm1. Xpo1 binds its cargoes in a Ran-dependent fashion via a short leucine-rich nuclear export signal (NES). We show that binding of Spc72 to Xpo1 depends on Ran-GTP and a functional NES in Spc72. Mutations in this NES have severe consequences for mitotic spindle morphology in vivo. This is also the case for xpo1 mutants, which show a reduction in cytoplasmic microtubules. In addition, we find a subpopulation of Xpo1 localized at the SPB. Based on these data, we propose a functional link between Xpo1 and the SPB and discuss a role for this exportin in spindle biogenesis in budding yeast. PMID:18573877

Neuber, Anja; Franke, Jacqueline; Wittstruck, Angelika; Schlenstedt, Gabriel; Sommer, Thomas; Stade, Katrin

2008-06-23

216

Leukemia risk following radiotherapy for breast cancer  

SciTech Connect

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.

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

1989-01-01

217

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

NASA Astrophysics Data System (ADS)

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.

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

2008-03-01

218

Nuclear magnetic resonance whole-body imager operating at 3. 5 Kgauss  

Microsoft Academic Search

The theoretical advantages of nuclear magnetic resonance imaging at higher field strengths are discussed. Examples of images created at 3.5 KGauss (0.35 T) are demonstrated. The authors present a method of collecting several tomographic images sequentially during the time required for a single image.

Lawrence Crooks; Mitsuaki Arakawa; John Hoenninger; Jeffrey Watts; R. McRee; L. Kaufman; Peter L. Davis; Alexander R. Margulis; Jack DeGroot

1982-01-01

219

Development of a Specialized in-Vivo Body Counter for Radiation Monitoring in the Nuclear Industry.  

National Technical Information Service (NTIS)

The design, construction, calibration and testing of a prototype mobile counting system to measure natural uranium in the lungs of workers in the nuclear fuel industry is described. The measurement method is based on the detection of gamma rays emitted du...

1981-01-01

220

HETEROGENEOUS NUCLEAR REACTOR EMPLOYING SMALL UNCLAD BODIES OF FISSIONABLE MATERIAL AS FUEL  

DOEpatents

A nuclear reactor in which fuel pellets are continuously dissolved in a moderator liquid is described. The fuel pellets are fed into the top of elongated baskets which are submerged in moderator liquid, and a portion of the moderator liquid is continuously withdrawn and processed to recove r reaction products.

Hyman, H.H.; Katz, J.J.

1961-05-01

221

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

SciTech Connect

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.

Weidenmueller, Hans A. [Max-Planck-Institut fuer Kernphysik, Heidelberg (Germany)

2008-11-13

222

Nuclear quantum many-body dynamics. From collective vibrations to heavy-ion collisions  

NASA Astrophysics Data System (ADS)

A summary of recent researches on nuclear dynamics with realistic microscopic quantum approaches is presented. The Balian-Vénéroni variational principle is used to derive the time-dependent Hartree-Fock (TDHF) equation describing the dynamics at the mean-field level, as well as an extension including small-amplitude quantum fluctuations which is equivalent to the time-dependent random-phase approximation (TDRPA). Such formalisms as well as their practical implementation in the nuclear physics framework with modern three-dimensional codes are discussed. Recent applications to nuclear dynamics, from collective vibrations to heavy-ion collisions are presented. Particular attention is devoted to the interplay between collective motions and internal degrees of freedom. For instance, the harmonic nature of collective vibrations is questioned. Nuclei are also known to exhibit superfluidity due to pairing residual interaction. Extensions of the theoretical approach to study such pairing vibrations are now available. Large amplitude collective motions are investigated in the framework of heavy-ion collisions leading, for instance, to the formation of a compound system. How fusion is affected by the internal structure of the collision partners, such as their deformation, is discussed. Other mechanisms in competition with fusion, and responsible for the formation of fragments which differ from the entrance channel (transfer reactions, deep-inelastic collisions, and quasi-fission) are investigated. Finally, studies of actinide collisions forming, during very short times of few zeptoseconds, the heaviest nuclear systems available on Earth, are presented.

Simenel, Cédric

2012-11-01

223

Nuclear field theory description of the three-body system 11Li  

Microsoft Academic Search

The three-body description of two-neutron halo systems is extended to allow for core polarization taking into account the associated effects of mass-renormalization (single-particle motion) and induced interaction (density dependent pairing force) in terms of the particle-vibration coupling formalism. This formalism is applied to 10Li and 11Li. Theory reproduces most of the attractive features of Faddeev type calculations providing, in addition,

R. A. Broglia; F. Barranco; G. Coló; E. Vigezzi; P. F. Bortignon; G. Gori; J. Terasaki

2002-01-01

224

Nuclear field theory description of the three-body system 11Li  

NASA Astrophysics Data System (ADS)

The three-body description of two-neutron halo systems is extended to allow for core polarization taking into account the associated effects of mass-renormalization (single-particle motion) and induced interaction (density dependent pairing force) in terms of the particle-vibration coupling formalism. This formalism is applied to 10Li and 11Li. Theory reproduces most of the attractive features of Faddeev type calculations providing, in addition, an overall account of the experimental findings. .

Broglia, R. A.; Barranco, F.; Coló, G.; Vigezzi, E.; Bortignon, P. F.; Gori, G.; Terasaki, J.

2002-04-01

225

Impulse approximation in nuclear pion production reactions: Absence of a one-body operator  

SciTech Connect

The impulse approximation of pion production reactions is studied by developing a relativistic formalism, consistent with that used to define the nucleon-nucleon potential. For plane wave initial states we find that the usual one-body (1B) expression O{sub 1B} is replaced by O{sub 2B}=-iK(m{sub {pi}}/2)O{sub 1B}/m{sub {pi}}, where K(m{sub {pi}}/2) is the sum of all irreducible contributions to nucleon-nucleon scattering with energy transfer of m{sub {pi}}/2. We show that O{sub 2B}{approx_equal}O{sub 1B} for plane wave initial states. For distorted waves, we find that the usual operator is replaced with a sum of two-body operators that are well approximated by the operator O{sub 2B}. Our new formalism solves the (previously ignored) problem of energy transfer forbidding a one-body impulse operator. Using a purely one pion exchange deuteron, the net result is that the impulse amplitude for np{yields}d{pi}{sup 0} at threshold is enhanced by a factor of approximately two. This amplitude is added to the larger ''rescattering'' amplitude and, although experimental data remain in disagreement, the theoretical prediction of the threshold cross section is brought closer to (and in agreement with) the data.

Bolton, Daniel R.; Miller, Gerald A. [Department of Physics, University of Washington, Seattle, Washington 98195-1560 (United States)

2011-06-15

226

Three-body approach to direct nuclear reactions involving weakly bound systems  

Microsoft Academic Search

The Faddeev type Alt, Grassberger and Sandhas (AGS) equations for transition operators were, in recent years, consistently applied to study direct nuclear reactions using realistic nucleon-nucleus optical potentials together with modern nucleon-nucleon interactions. The equations are solved numerically using momentum-space partial-wave basis. The Coulomb interaction between charged particles is included using a novel implementation of the screening and renormalization method.

António C. Fonseca

2010-01-01

227

Activation of protein kinase C induces nuclear translocation of RFX1 and down-regulates c-myc via an intron 1 X box in undifferentiated leukemia HL-60 cells.  

PubMed

Treatment of human promyelocytic leukemia cells (HL-60) with phorbol 12-myristate 13-acetate (PMA) is known to decrease c-myc mRNA by blocking transcription elongation at sites near the first exon/intron border. Treatment of HL-60 cells with either PMA or bryostatin 1, which acutely activates protein kinase C (PKC), decreased the levels of myc mRNA and Myc protein. The inhibition of Myc synthesis accounted for the drop in Myc protein, because PMA treatment had no effect on Myc turnover. Treatment with PMA or bryostatin 1 increased nuclear protein binding to MIE1, a c-myc intron 1 element that defines an RFX1-binding X box. RFX1 antiserum supershifted MIE1-protein complexes. Increased MIE1 binding was independent of protein synthesis and abolished by a selective PKC inhibitor, which also prevented the effect of PMA on myc mRNA and protein levels and Myc synthesis. PMA treatment increased RFX1 in the nuclear fraction and decreased it in the cytosol without affecting total RFX1. Transfection of HL-60 cells with myc reporter gene constructs showed that the RFX1-binding X box was required for the down-regulation of reporter gene expression by PMA. These findings suggest that nuclear translocation and binding of RFX1 to the X box cause the down-regulation of myc expression, which follows acute PKC activation in undifferentiated HL-60 cells. PMID:10918054

Chen, L; Smith, L; Johnson, M R; Wang, K; Diasio, R B; Smith, J B

2000-10-13

228

Flavopiridol in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, or Chronic Myelogenous Leukemia  

ClinicalTrials.gov

Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(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); Blastic Phase Chronic Myelogenous Leukemia; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Relapsing Chronic Myelogenous Leukemia

2013-06-03

229

Heterochromatin instability in cancer: from the Barr body to satellites and the nuclear periphery.  

PubMed

In recent years it has been recognized that the development of cancer involves a series of not only genetic but epigenetic changes across the genome. At the same time, connections between epigenetic regulation, chromatin packaging, and overall nuclear architecture are increasingly appreciated. The cell-type specific organization of heterochromatin, established upon cell differentiation, is responsible for maintaining much of the genome in a repressed state, within a highly compartmentalized nucleus. This review focuses on recent evidence that in cancer the normal packaging and higher organization of heterochromatin is often compromised. Gross changes in nuclear morphology have long been a criterion for pathologic diagnosis of many cancers, but the specific nuclear components impacted, the mechanisms involved, and the implications for cancer progression have barely begun to emerge. We discuss recent findings regarding distinct heterochromatin types, including the inactive X chromosome, constitutive heterochromatin of peri/centric satellites, and the peripheral heterochromatic compartment (PHC). A theme developed here is that the higher-order organization of satellites and the peripheral heterochromatic compartment may be tightly linked, and that compromise of this organization may promote broad epigenomic imbalance in cancer. Recent studies into the potential role(s) of the breast cancer tumor suppressor, BRCA1, in maintaining heterochromatin will be highlighted. Many questions remain about this new area of cancer epigenetics, which is likely more important in cancer development and progression than widely appreciated. We propose that broad, stochastic compromise in heterochromatin maintenance would create a diversity of expression profiles, and thus a rich opportunity for one or more cells to emerge with a selective growth advantage and potential for neoplasia. PMID:22722067

Carone, Dawn M; Lawrence, Jeanne B

2012-06-18

230

Development of a technique for comparing relative risk as measured by leukemia incidence of radionuclide air stack emissions from nuclear versus coal power generation  

Microsoft Academic Search

A method for comparing environmental risks associated with radionuclide air stack emissions of coal and nuclear power generation has been developed. The methodology can be expended to allow prediction of the future risks associated with coal and nuclear power generation. Risks associated with radionuclide air stack emissions from coal versus nuclear power generation were evaluated to develop a minimum relative

Prybutok

1984-01-01

231

High-resolution 31P nuclear magnetic resonance study of Chlamydia trachomatis: induction of ATPase activity in elementary bodies.  

PubMed Central

ATPase activity of elementary bodies (EBs) of Chlamydia trachomatis was investigated by using high-resolution 31P nuclear magnetic resonance spectroscopy. ATPase activity was detected in EBs of C. trachomatis serovars A, B, and L2 after treatment with the reducing agents 2-mercaptoethanol and glutathione. ATPase activity was oligomycin sensitive and magnesium ion dependent. EBs heated at 60 degrees C for 10 min or pretreated with Triton X-100 before exposure to 2-mercaptoethanol did not exhibit ATPase activity. Monoclonal antibody to the major outer membrane protein abrogated ATPase activity of EBs, whereas monoclonal antibody to chlamydial lipopolysaccharide only marginally reduced the level of ATPase activity. These findings suggest that EBs possess intrinsic ATPase activity and that cysteine-rich outer membrane proteins of EBs are important in the regulation of ATPase activity. The major outer membrane protein may be the major route through which ATP accesses ATPase. Images

Peeling, R W; Peeling, J; Brunham, R C

1989-01-01

232

The herpesvirus associated ubiquitin specific protease, USP7, is a negative regulator of PML proteins and PML nuclear bodies.  

PubMed

The PML tumor suppressor is the founding component of the multiprotein nuclear structures known as PML nuclear bodies (PML-NBs), which control several cellular functions including apoptosis and antiviral effects. The ubiquitin specific protease USP7 (also called HAUSP) is known to associate with PML-NBs and to be a tight binding partner of two herpesvirus proteins that disrupt PML NBs. Here we investigated whether USP7 itself regulates PML-NBs. Silencing of USP7 was found to increase the number of PML-NBs, to increase the levels of PML protein and to inhibit PML polyubiquitylation in nasopharyngeal carcinoma cells. This effect of USP7 was independent of p53 as PML loss was observed in p53-null cells. PML-NBs disruption was induced by USP7 overexpression independently of its catalytic activity and was induced by either of the protein interaction domains of USP7, each of which localized to PML-NBs. USP7 also disrupted NBs formed from some single PML isoforms, most notably isoforms I and IV. CK2? and RNF4, which are known regulators of PML, were dispensable for USP7-associated PML-NB disruption. The results are consistent with a novel model of PML regulation where a deubiquitylase disrupts PML-NBs through recruitment of another cellular protein(s) to PML NBs, independently of its catalytic activity. PMID:21305000

Sarkari, Feroz; Wang, Xueqi; Nguyen, Tin; Frappier, Lori

2011-01-31

233

KRAB zinc-finger proteins localise to novel KAP1-containing foci that are adjacent to PML nuclear bodies.  

PubMed

The KRAB-zinc finger proteins (KRAB-ZFPs) represent a very large, but poorly understood, family of transcriptional regulators in mammals. They are thought to repress transcription via their interaction with KRAB-associated protein 1 (KAP1), which then assembles a complex of chromatin modifiers to lay down histone marks that are associated with inactive chromatin. Studies of KRAB-ZFP/KAP1-mediated gene silencing, using reporter constructs and ectopically expressed proteins, have shown colocalisation of both KAP1 and repressed reporter target genes to domains of constitutive heterochromatin in the nucleus. However, we show here that although KAP1 does indeed become recruited to pericentric heterochromatin during differentiation of mouse embryonic stem (ES) cells, endogenous KRAB-ZFPs do not. Rather, KRAB-ZFPs and KAP1 relocalise to novel nucleoplasmic foci that we have termed KRAB- and KAP1-associated (KAKA) foci. HP1s can also concentrate in these foci and there is a close spatial relationship between KAKA nuclear foci and PML nuclear bodies. Finally, we reveal differential requirements for the recruitment of KAP1 to pericentric heterochromatin and KAKA foci, and suggest that KAKA foci may contain sumoylated KAP1 - the form of the protein that is active in transcriptional repression. PMID:19258395

Briers, Stephanie; Crawford, Catherine; Bickmore, Wendy A; Sutherland, Heidi G

2009-03-03

234

An RNA interference screen identifies the Deubiquitinase STAMBPL1 as a critical regulator of human T-cell leukemia virus type 1 tax nuclear export and NF-?B activation.  

PubMed

The human T-cell leukemia virus type 1 (HTLV-1) Tax oncoprotein actively shuttles between the nucleus, where it interacts with transcriptional and splicing regulatory proteins, and the cytoplasm, where it activates NF-?B. Posttranslational modifications of Tax such as ubiquitination regulate its subcellular localization and hence its function; however, the regulation of Tax trafficking and NF-?B activation by host factors is poorly understood. By screening a deubiquitinating (DUB) enzyme small interfering RNA (siRNA) library, we identified the metalloprotease STAM-binding protein-like 1 (STAMBPL1) as a positive regulator of Tax-mediated NF-?B activation. Overexpression of wild-type STAMBPL1, but not a catalytically inactive mutant, enhanced Tax-mediated NF-?B activation, whereas silencing of STAMBPL1 with siRNA impaired Tax activation of both the canonical and noncanonical NF-?B signaling pathways. STAMBPL1 regulated Tax-induced NF-?B signaling indirectly by controlling Tax nuclear/cytoplasmic transport and was required for DNA damage-induced Tax nuclear export. Together, these results reveal that the deubiquitinase STAMBPL1 is a key regulator of Tax trafficking and function. PMID:22258247

Lavorgna, Alfonso; Harhaj, Edward W

2012-01-18

235

PML Is Critical for ND10 Formation and Recruits the PML-interacting Protein Daxx to this Nuclear Structure When Modified by SUMO1  

Microsoft Academic Search

Nuclear domain 10 (ND10), also referred to as nuclear bodies, are discrete interchromosomal accu- mulations of several proteins including promyelocytic leukemia protein (PML) and Sp100. In this study, we investigated the mechanism of ND10 assembly by iden- tifying proteins that are essential for this process using cells lines that lack individual ND10-associated pro- teins. We identified the adapter protein Daxx

Alexander M. Ishov; Alexey G. Sotnikov; Dmitri Negorev; Olga V. Vladimirova; Norma Neff; Tetsu Kamitani; Edward T. H. Yeh; Jerome F. Strauss III; Gerd G. Maul

1999-01-01

236

The nuclear phenotypic plasticity observed in fish during rRNA regulation entails Cajal bodies dynamics  

SciTech Connect

Cajal bodies (CBs) are small mobile organelles found throughout the nucleoplasm of animal and plant cells. The dynamics of these organelles involves interactions with the nucleolus. The later has been found to play a substantial role in the compensatory response that evolved in eurythermal fish to adapt to the cyclic seasonal habitat changes, i.e., temperature and photoperiod. Contrary to being constitutive, rRNA synthesis is dramatically regulated between summer and winter, thus affecting ribosomal biogenesis which plays a central role in the acclimatization process. To examine whether CBs, up to now, never described in fish, were also sustaining the phenotypic plasticity observed in nuclei of fish undergoing seasonal acclimatization, we identified these organelles both, by transmission electronic microscopy and immunodetection with the marker protein p80-coilin. We found transcripts in all tissues analyzed. Furthermore we assessed that p80-coilin gene expression was always higher in summer-acclimatized fish when compared to that adapted to the cold season, indicating that p80-coilin expression is modulated upon seasonal acclimatization. Concurrently, CBs were more frequently found in summer-acclimatized carp which suggests that the organization of CBs is involved in adaptive processes and contribute to the phenotypic plasticity of fish cell nuclei observed concomitantly with profound reprogramming of nucleolar components and regulation of ribosomal rRNAs.

Alvarez, Marco [Department of Biological Sciences, Universidad Andres Bello, and Millennium Institute for Fundamental and Applied Biology, Santiago (Chile); Nardocci, Gino [Department of Biological Sciences, Universidad Andres Bello, and Millennium Institute for Fundamental and Applied Biology, Santiago (Chile); Thiry, Marc [Laboratory of Cell Biology, Faculty of Sciences, University of Liege, Liege (Belgium); Alvarez, Rodrigo [Department of Biological Sciences, Universidad Andres Bello, and Millennium Institute for Fundamental and Applied Biology, Santiago (Chile); Reyes, Mauricio [Department of Biological Sciences, Universidad Andres Bello, and Millennium Institute for Fundamental and Applied Biology, Santiago (Chile); Molina, Alfredo [Department of Biological Sciences, Universidad Andres Bello, and Millennium Institute for Fundamental and Applied Biology, Santiago (Chile); Vera, M. Ines [Department of Biological Sciences, Universidad Andres Bello, and Millennium Institute for Fundamental and Applied Biology, Santiago (Chile)]. E-mail: mvera@unab.cl

2007-08-17

237

Site-specific induction of nuclear anomalies (apoptotic bodies and micronuclei) by carcinogens in mice  

SciTech Connect

The usefulness of nuclear anomalies (NA) as a short-term test for indication of carcinogens in the mouse colon has been suggested previously by experiments in which colon-specific carcinogens induced NA in the colon, whereas non-colon carcinogens were, in general, impotent in that organ. We have extended this work to other sites in the digestive tract of female C57BL/6 mice treated with gamma-rays, 1,2-dimethylhydrazine dihydrochloride, or N-methylnitrosourea. Each agent induced NA at all of the sites examined. The frequency of NA at different times after treatment depended upon both the agent used and the site examined. 1,2-Dimethylhydrazine dihydrochloride (which is known to induce tumors predominantly in the colon) induces NA with the highest efficiency (relative to gamma-rays) in the descending colon. N-Methylnitrosourea (which induces tumors mainly in the forestomach) induces NA with the highest efficiency in the forestomach. These results further support the usefulness of the assay in that the frequency of NA produced at the various sites by 1,2-dimethylhydrazine dihydrochloride and N-methylnitrosourea correlates with that found in the carcinogenicity studies.

Ronen, A.; Heddle, J.A.

1984-04-01

238

Applications of a Relativistic Quantum Field Theory to the Nuclear Many-Body Problem  

NASA Astrophysics Data System (ADS)

A relativistic mean field model was investigated through three separate applications. In the first of these, the electric dipole sum rule was evaluated using a relativistic formulation and consistently determined single particle orbitals. The resulting predictions for the total integrated photon absorption cross section were in qualitative agreement with experiment. Such agreement was difficult to obtain with standard nonrelativistic techniques. In the second application, a relativistic schematic model for nuclear structure was developed. Although the model provided certain insights and suggested interesting areas for further investigation, due to the more complicated nature of the relativistic model it did not have the same power as previous nonrelativistic models for explaining the relationship between the energy shifts of certain excited states and the corresponding transition strengths. Finally, in the third application, numerical techniques for obtaining shell model orbitals for deformed nuclei in a relativistic mean field model were developed and applied to a variety of nuclei. In general, this procedure provides self consistently determined meson mean fields and single particle orbitals for use in other calculations. For the nuclei considered here, the results were in qualitative agreement with both previous nonrelativistic calculations and experiment.

Price, Charles Eldridge

239

Arsenic trioxide induces apoptosis in NB4, an acute promyelocytic leukemia cell line, through up-regulation of p73 via suppression of nuclear factor kappa B-mediated inhibition of p73 transcription and prevention of NF-?B-mediated induction of XIAP, cIAP2, BCL-X L and survivin  

Microsoft Academic Search

The purpose of the present study is to evaluate the effects of arsenic trioxide (ATO) on human acute promyelocytic leukemia\\u000a NB-4 cells. Microculture tetrazolium test, bromodeoxyuridine (BrdU) cell proliferation assay, caspase 3 activity assay, cell-based\\u000a nuclear factor kappa B (NF-?B) phosphorylation measurement by ELISA and real-time RT-PCR were employed to appraise the effects\\u000a of ATO on metabolic activity, DNA synthesis,

Majid Momeny; Majid Zakidizaji; Reza Ghasemi; Ahmad R. Dehpour; Yassan Abdolazimi; Ardeshir Ghavamzadeh; Kamran Alimoghaddam; Seyed H. Ghaffari

2010-01-01

240

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

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 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; T-cell Large Granular Lymphocyte Leukemia; Testicular Lymphoma; Waldenström Macroglobulinemia

2013-05-06

241

Cordycepin Regulates GSK-3?/?-Catenin Signaling in Human Leukemia Cells  

PubMed Central

Background Leukemia stem cells (LSCs) are a limitless cell source for the initiation and maintenance of leukemia. Activation of the Wnt/?-catenin pathway is required for the survival and development of LSCs. Therefore, targeting ?-catenin is considered a therapeutic strategy for the treatment of leukemia. The goal of this study was to explore whether cordycepin, an active component of the traditional medicine Cordyceps sinensis, regulates ?-catenin expression in leukemia cells. Methodology and Principal Findings In this study, we found that cordycepin significantly suppressed cell proliferation in all malignant cancer cells, including U937, K562, A549, HepG2, SK-Hep1 and MCF7 in a dose-dependent manner. However, cordycepin reduced ?-catenin levels in U937, K562 and THP1 leukemia cells and had no effect on other solid cancer cells. In addition, treatment with cordycepin significantly suppressed leukemia colony formation in soft agar assay. Cordycepin enhanced proteasome-dependent degradation and inhibited nuclear translocation of ?-catenin in leukemia cells. Cordycepin-reduced ?-catenin stability was restored by the addition of a pharmacological inhibitor of GSK-3?, indicating that cordycepin-suppressed ?-catenin stability is mediated by the activation of GSK-3?. Furthermore, cordycepin abolished the effect of Wnt3a-induced ?-catenin in leukemia cells. In addition, cordycepin-impaired ?-catenin is regulated by Akt activation but is not significantly influenced by AMPK or mTOR signal pathways. Significance Our findings show for the first time that codycepin selectively reduces ?-catenin stability in leukemia but not in other solid tumor cells. This suppressive effect is mediated by regulating GSK-3?. A synergistic combination of cordycepin with other treatments should be used as a novel strategy to eradicate leukemia via elimination of LSCs.

Liu, Tzu-An; Tzean, Shean-Shong; Shen, Tang-Long; Liou, Jun-Yang

2013-01-01

242

Can Acute Myeloid Leukemia Be Prevented?  

MedlinePLUS

... Can acute myeloid leukemia be found early? Can acute myeloid leukemia be prevented? It’s not known what causes most cases of acute myeloid leukemia (AML). Since most leukemia patients have no known ...

243

How Is Acute Lymphocytic Leukemia Found?  

MedlinePLUS

... How is acute lymphocytic leukemia classified? How is acute lymphocytic leukemia found? At this time there are no special ... to the doctor right away. Tests to find acute lymphocytic leukemia Most of the symptoms seen in leukemia also ...

244

Leukemia blast-induced T-cell anergy demonstrated by leukemia-derived dendritic cells in acute myelogenous leukemia  

Microsoft Academic Search

ObjectiveTo elucidate the mechanism of immunologic escape of leukemia cells and establish an effective anti-leukemia immunotherapy, we attempted to generate dendritic cells from leukemia cells in patients with acute myelogenous leukemia (AML). Using these leukemia-derived dendritic cells, we investigated leukemia cell-associated T-cell anergy.

Miwako Narita; Masuhiro Takahashi; Aichun Liu; Kohji Nikkuni; Tatsuo Furukawa; Ken Toba; Satoru Koyama; Kazue Takai; Masayoshi Sanada; Yoshifusa Aizawa

2001-01-01

245

Bone Marrow Transplantation for Leukemia Following a New Busulfan and Cyclophosphamide Regimen  

Microsoft Academic Search

lowing total body irradiation (TB!) and high-dose chemotherapy has provided encouraging therapeutic results in patients with hematologic malignancies.' Apparent cure of -50% of patients with acute nonlymphocytic leukemia (ANLL)' in first remission and chronic myelogenous leuke- mia (CML) in chronic phase has been achieved'; the success rate in acute lymphocytic leukemia (ALL) has been some- what lower.4 Despite these results,

Peter J. Tutschka; Edward A. Copelan; John P. Klein

2010-01-01

246

Spindle pole body-anchored Kar3 drives the nucleus along microtubules from another nucleus in preparation for nuclear fusion during yeast karyogamy.  

PubMed

Nuclear migration during yeast karyogamy, termed nuclear congression, is required to initiate nuclear fusion. Congression involves a specific regulation of the microtubule minus end-directed kinesin-14 motor Kar3 and a rearrangement of the cytoplasmic microtubule attachment sites at the spindle pole bodies (SPBs). However, how these elements interact to produce the forces necessary for nuclear migration is less clear. We used electron tomography, molecular genetics, quantitative imaging, and first principles modeling to investigate how cytoplasmic microtubules are organized during nuclear congression. We found that Kar3, with the help of its light chain, Cik1, is anchored during mating to the SPB component Spc72 that also serves as a nucleator and anchor for microtubules via their minus ends. Moreover, we show that no direct microtubule-microtubule interactions are required for nuclear migration. Instead, SPB-anchored Kar3 exerts the necessary pulling forces laterally on microtubules emanating from the SPB of the mating partner nucleus. Therefore, a twofold symmetrical application of the core principle that drives nuclear migration in higher cells is used in yeast to drive nuclei toward each other before nuclear fusion. PMID:23388829

Gibeaux, Romain; Politi, Antonio Z; Nédélec, François; Antony, Claude; Knop, Michael

2013-02-01

247

Leukemia Stem Cells  

Microsoft Academic Search

\\u000a Normal hematopoiesis develops hierarchically from a hematopoietic stem cell, which is defined by both extensive self-renewal\\u000a capacity and multi-lineage potential, i.e. the ability to give rise to fully differentiated cells of all hematopoietic lineages.\\u000a Since leukemia can be considered as malignant hematopoiesis, the existence of a developmental hierarchy in leukemia with a\\u000a malignant stem cell at its apex was postulated

Markus Müschen

248

CT findings in leukemia  

SciTech Connect

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.

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

1984-12-01

249

Saccharomyces cerevisiae MPS2 Encodes a Membrane Protein Localized at the Spindle Pole Body and the Nuclear Envelope  

PubMed Central

The MPS2 (monopolar spindle two) gene is one of several genes required for the proper execution of spindle pole body (SPB) duplication in the budding yeast Saccharomyces cerevisiae (Winey et al., 1991). We report here that the MPS2 gene encodes an essential 44-kDa protein with two putative coiled-coil regions and a hydrophobic sequence. Although MPS2 is required for normal mitotic growth, some null strains can survive; these survivors exhibit slow growth and abnormal ploidy. The MPS2 protein was tagged with nine copies of the myc epitope, and biochemical fractionation experiments show that it is an integral membrane protein. Visualization of a green fluorescent protein (GFP) Mps2p fusion protein in living cells and indirect immunofluorescence microscopy of 9xmyc-Mps2p revealed a perinuclear localization with one or two brighter foci of staining corresponding to the SPB. Additionally, immunoelectron microscopy shows that GFP-Mps2p localizes to the SPB. Our analysis suggests that Mps2p is required as a component of the SPB for insertion of the nascent SPB into the nuclear envelope.

Munoz-Centeno, Maria de la Cruz; McBratney, Susan; Monterrosa, Antonio; Byers, Breck; Mann, Carl; Winey, Mark

1999-01-01

250

Myeloid leukemia after hematotoxins  

SciTech Connect

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.

Larson, R.A.; LeBeau, M.M.; Vardiman, J.W.; Rowley, J.D. [Univ. of Chicago, IL (United States)

1996-12-01

251

Thrombosis and acute leukemia.  

PubMed

Thrombosis is a common complication in patients with acute leukemia. While the presence of central venous lines, concomitant steroids, the use of Escherichia coli asparaginase and hereditary thrombophilic abnormalities are known risk factors for thrombosis in children, information on the pathogenesis, risk factors, and clinical outcome of thrombosis in adult patients with acute lymphoid leukemia (ALL) or acute myeloid leukemia (AML) is still scarce. Expert consensus and guidelines regarding leukemia-specific risk factors, thrombosis prevention, and treatment strategies, as well as optimal type of central venous catheter in acute leukemia patients are required. It is likely that each subtype of acute leukemia represents a different setting for the development of thrombosis and the risk of bleeding. This is perhaps due to a combination of different disease-specific pathogenic mechanisms of thrombosis, including the type of chemotherapy protocol chosen, the underlying patients health, associated risk factors, as well as the biology of the disease itself. The risk of thrombosis may also vary according to ethnicity and prevalence of hereditary risk factors for thrombosis; thus, it is advisable for Latin American, Asian, and African countries to report on their specific patient population. PMID:22507812

Crespo-Solís, Erick

2012-04-01

252

HIV, leukemia, and new horizons in molecular therapy.  

PubMed

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

Berkhout, Ben

2013-03-26

253

Subacute Myelogenous Leukemia: A Special Type of Myelogenous Leukemia.  

National Technical Information Service (NTIS)

The clinical course, laboratory findings, cytochemical studies and ultrastructural observations of 22 subacute myelogenous leukemia (SML) cases are reported and compared with those of 28 acute myelogenous leukemia (AML) cases. There were marked difference...

C. Yang W. Yan S. Qi T. Yang Y. Wang

1982-01-01

254

Menin as a Hub Controlling Mixed Lineage Leukemia  

PubMed Central

Mixed lineage leukemia (MLL) fusion protein (FP)-induced acute leukemia is highly aggressive and often refractory to therapy. Recent progress in the field has unraveled novel mechanisms and targets to combat this disease. Menin, a nuclear protein, interacts with wild-type (WT) MLL, MLL-FPs and other partners such as the chromatin-associated protein LEDGF and the transcription factor c-myb to promote leukemogenesis. The newly solved co-crystal structure illustrating the menin-MLL interaction, coupled with the role of menin in recruiting both WT MLL and MLL-FPs to target genes, highlights menin as a scaffold protein and a central hub controlling this type of leukemia. The menin/WT MLL/MLL-FP hub may also cooperate with several signaling pathways, including Wnt, GSK3, and bromodomain-containing Brd4-related pathways to sustain MLL-FP-induced leukemogenesis, revealing new therapeutic targets to improve the treatment of MLL-FP leukemias.

Thiel, Austin; Huang, Jing; Lei, Ming; Hua, Xianxin

2012-01-01

255

T cell leukemia-associated human Notch/translocation-associated Notch homologue has I kappa B-like activity and physically interacts with nuclear factor-kappa B proteins in T cells  

PubMed Central

Translocation-associated Notch homologue (TAN-1), a gene originally cloned from the translocation breakpoint of a human T cell leukemia carrying a 9:7(q34.3) translocation, encodes a protein belonging to the Notch/Lin-12/Glp-1 receptor family. These receptors mediate the specification of numerous cell fates during development in invertebrates and vertebrates. The intracellular portion of Notch/TAN-1 contains six ankyrin repeats that are similar to those found in cytoplasmic I kappa B proteins. I kappa B proteins are specific inhibitors of nuclear factor (NF)-kappa B/Rel transcription factors. Here we show that TAN-1 has functional properties of an I kappa B-like regulator with specificity for the NF-kappa B p50 subunit. A recombinant polypeptide corresponding to the cytoplasmic portion of TAN- 1 (TAN-1C) specifically inhibited the DNA binding of p50-containing NF- kappa B complexes. When overexpressed in an appropriate cell line, TAN- 1C prevented kappa B-dependent transactivation in transient reporter gene assays in a fashion similar to the structurally related protein, Bcl-3. TAN-1C could activate kappa B-dependent gene expression by attenuating the inhibitory effect of an excess of p50 homodimers. Immunoprecipitation experiments showed that the TAN-1 from a T cell line is associated with NF-kappa B containing p50 and p65 subunits. These observations indicate that TAN-1C may directly engage NF-kappa B transcription factors and modulate nuclear gene expression.

1996-01-01

256

PML nuclear bodies are highly organised DNA-protein structures with a function in heterochromatin remodelling at the G2 phase.  

PubMed

We have recently demonstrated that heterochromatin HP1 proteins are aberrantly distributed in lymphocytes of patients with immunodeficiency, centromeric instability and facial dysmorphy (ICF) syndrome. The three HP1 proteins accumulate in one giant body over the 1qh and 16qh juxtacentromeric heterochromatins, which are hypomethylated in ICF. The presence of PML (promyelocytic leukaemia) protein within this body suggests it to be a giant PML nuclear body (PML-NB). The structural integrity of PML-NBs is of major importance for normal cell functioning. Nevertheless, the structural organisation and the functions of these nuclear bodies remain unclear. Here, we take advantage of the large size of the giant body to demonstrate that it contains a core of satellite DNA with proteins being organised in ordered concentric layers forming a sphere around it. We extend these results to normal PML-NBs and propose a model for the general organisation of these structures at the G2 phase. Moreover, based on the presence of satellite DNA and the proteins HP1, BRCA1, ATRX and DAXX within the PML-NBs, we propose that these structures have a specific function: the re-establishment of the condensed heterochromatic state on late-replicated satellite DNA. Our findings that chromatin-remodelling proteins fail to accumulate around satellite DNA in PML-deficient NB4 cells support a central role for PML protein in this cellular function. PMID:16735446

Luciani, Judith J; Depetris, Danielle; Usson, Yves; Metzler-Guillemain, Catherine; Mignon-Ravix, Cecile; Mitchell, Micheal J; Megarbane, Andre; Sarda, Pierre; Sirma, Huseyin; Moncla, Anne; Feunteun, Jean; Mattei, Marie-Genevieve

2006-05-30

257

How Is Childhood Leukemia Classified?  

MedlinePLUS

... the early diagnostic testing. Acute lymphocytic (lymphoblastic) leukemia (ALL) Acute lymphocytic leukemia (ALL) is a fast-growing ... 2%-3% T cell 15%-18% B-cell ALL: About 85% of children with ALL have B- ...

258

Anticipation in familial leukemia  

SciTech Connect

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. 55 refs., 4 figs.

Horwitz, M.; Jarvik, G.P.; Goode, E.L. [Univ. of Washington, Seattle, WA (United States)

1996-11-01

259

Induction of graft-versus-leukemia (GVL) activity in murine leukemia models after IL-2 pretreatment of syngeneic and allogeneic bone marrow grafts.  

PubMed

To investigate GVL effects, Balb/c mice (H-2d) received 5 x 10(5) A20 (B cell leukemia) or 1 x 10(6) WEHI-3 (myelomonocytic leukemia) cells. These cell lines lead to death after a median of 19 (WEHI-3) or 30 days (A20). A lethal dose of total body irradiation followed by syngeneic BMT resulted in significantly prolonged survival of leukemia-bearing animals. Transplantation of (C57 x Balb/c)F1 (H-2bxd) allogeneic, but GVH-non-reactive marrow grafts differentially influenced the relapse rates in the two leukemia models. Whereas allogeneic BMT reduced the relapse rates in A20-bearing mice, the leukemia-free survival was not improved in mice bearing the leukemia WEHI-3 compared with syngeneic BMT. Pre-treatment of allogeneic (C57 x Balb/c)F1 or syngeneic Balb/c marrow cells with 200 U/ml IL-2 for 24 h did not reduce relapse rates in animals inoculated with A20 leukemia cells compared with unmanipulated bone marrow. In contrast, IL-2 treatment of syngeneic or allogeneic GVH non-reactive donor marrow significantly decreased the relapse rate in mice inoculated with WEHI-3 leukemia cells. The NK cell-mediated lysis of cultured leukemia cells was determined in vitro using a conventional 56Cr-release assay. Our data revealed a strong correlation between the level of natural killer activity determined in vitro and GVL activity in vivo. PMID:7889004

Zeis, M; Uharek, L; Glass, B; Gaska, T; Gassmann, W; Mueller-Ruchholtz, W

1994-11-01

260

LLNL's Regional Model Calibration and Body-Wave Discrimination Research in the Former Soviet Union using Peaceful Nuclear Explosions (PNEs)  

SciTech Connect

Long-range seismic profiles from Peaceful Nuclear Explosions (PNE) in the Former Soviet Union (FSU) provide a unique data set to investigate several important issues in regional Comprehensive Nuclear-Test-Ban Treaty (CTBT) monitoring. The recording station spacing ({approx}15 km) allows for extremely dense sampling of the propagation from the source to {approx} 3300 km. This allows us to analyze the waveforms at local, near- and far-regional and teleseismic distances. These data are used to: (1) study the evolution of regional phases and phase amplitude ratios along the profile; (2) infer one-dimensional velocity structure along the profile; and (3) evaluate the spatial correlation of regional and teleseismic travel times and regional phase amplitude ratios. We analyzed waveform data from four PNE's (m{sub b} = 5.1-5.6) recorded along profile KRATON, which is an east-west trending profile located in northern Sibertil. Short-period regional discriminants, such as P/S amplitude ratios, will be essential for seismic monitoring of the Comprehensive Nuclear-Test-Ban Treaty (CTBT) at small magnitudes (m{sub b} < 4.0). However, P/S amplitude ratios in the short-period band, 0.5-5.0 Hz, show some scatter. This scatter is primarily due to propagation and site effects, which arise from variability in the elastic and anelastic structure of the crustal waveguide. Preliminary results show that Pg and Lg propagate efficiently in north Siberia at regional distances. The amplitude ratios show some variability between adjacent stations that are modeled by simple distance trends. The effect of topography, sediment and crustal thickness, and upper mantle discontinuities on these ratios, after removal of the distance trends, will be investigated. The travel times of the body wave phases recorded on KEATON have been used to compute the one-dimensional structure of the crust and upper mantle in this region. The path-averaged one-dimensional velocity model was computed by minimizing the first arriving P-phase travel-time residuals for all distances ({Delta} = 300-2300 km). A grid search approach was used in the minimization. The most significant features of this model are the negative lid-gradient and a low-velocity zone in the upper mantle between the depths of 100-200 km; precise location of the LVZ is poorly constrained by the travel time data. We will extend our investigation to additional PNE lines to further investigate the amplitude and travel-time variations in eastern and central Eurasia. Finally, the dense station spacing of the PNE profiles allows us to model the spatial correlation of travel times and amplitude ratios through variogram modeling. The statistical analysis suggests that the correlation lengths of the travel-time and amplitude measurements are 12{sup o} and 10{sup o}, respectively.

Bhattacharyya, J.; Rodgers, A.; Swenson, J.; Schultz, C.; Walter, W.; Mooney, W.; Clitheroe, G.

2000-07-14

261

In vivo nuclear Overhauser effect in sup 31 P-(1H) double-resonance experiments in a 1. 5-T whole-body MR system  

SciTech Connect

In {sup 31}P-(1H) MR experiments of humans in a 1.5-T whole-body system, signal intensity enhancements of {sup 31}P resonances of up to 68 +/- 4% (for phosphocreatine of the calf muscle) have been observed upon irradiation at proton frequency. This observation is explained as a nuclear Overhauser effect due to the dipolar coupling between {sup 1}H and {sup 31}P spins.

Bachert-Baumann, P.; Ermark, F.; Zabel, H.J.; Sauter, R.; Semmler, W.; Lorenz, W.J. (Institut fuer Radiologie and Pathophysiologie, Heidelberg (Germany, F.R.))

1990-07-01

262

Nuclear  

NSDL National Science Digital Library

What part does nuclear energy play in satisfying energy demands? This informational piece, part of a series about the future of energy, introduces students to the uranium atom as an energy source. Here students read about the history of nuclear energy, how energy is derived from uranium, and benefits of nuclear energy. Information is also provided about limitations, particularly disposal problems and radioactivity, and geographical considerations of nuclear power in the United States. Thought-provoking questions afford students chances to reflect on what they've read about the uses of nuclear power. Articles and information on new nuclear plant design and nuclear accidents are available from a sidebar. Five energy-related PBS NewsHour links are provided. A web link to the U.S. Nuclear Regulatory Commission is included. Copyright 2005 Eisenhower National Clearinghouse

Project, Iowa P.

2004-01-01

263

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

Microsoft Academic Search

We examined retrospectively 44 patients with refractory acute leukemia (acute myeloid leukemia (AML)\\/acute lymphoblastic leukemia=25\\/19) who underwent allogeneic transplantation at our center between 11\\/1990 and 04\\/2004. The median leukemic blasts was 25% and age 28 years (range, 3–56). Twenty-one patients had untreated relapse, 13 failed reinduction, eight in partial remission and two aplastic. Conditioning was myeloablative using cyclophosphamide, busulfan, total-body

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

2006-01-01

264

Acute Myelogenous Leukemia (AML)  

MedlinePLUS

... greater risk of AML. Smoking. AML is linked to cigarette smoke, which contains benzene and other known cancer- ... myelogenous leukemia (AML) Guidelines for sites linking to MayoClinic.com Advertisement Mayo Clinic Store Check out these best-sellers ...

265

Acute myeloid leukemia: leukemia stem cells write a prognostic signature  

Microsoft Academic Search

In a recent interesting article, analysis of gene expression between phenotypically defined acute myeloid leukemia (AML) leukemia\\u000a stem cells (LSCs) and more mature leukemia progenitor cells is used to generate a differentially expressed gene signature\\u000a for LSCs. Through clever bioinformatic weighting analysis, the authors describe a method to convert this signature into a\\u000a single score for any given sample and

Emma J Gudgin; Brian JP Huntly

2011-01-01

266

Treatment of Children with Acute Lymphocytic Leukemia  

MedlinePLUS

... with acute myeloid leukemia Treatment of children with acute lymphocytic leukemia The main treatment for children with acute lymphocytic ... may be increased or prolonged. Treatment of recurrent ALL If the leukemia comes back during or after ...

267

Imatinib Mesylate and Decitabine in Treating Patients With Chronic Myelogenous Leukemia  

ClinicalTrials.gov

Accelerated Phase Chronic Myelogenous Leukemia; Blastic Phase Chronic Myelogenous Leukemia; Childhood Chronic Myelogenous Leukemia; Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Relapsing Chronic Myelogenous Leukemia

2013-01-22

268

Formation of Nuclear Bodies of Arabidopsis CRY2 in Response to Blue Light Is Associated with Its Blue Light-Dependent Degradation[W  

PubMed Central

Arabidopsis thaliana cryptochrome 2 (CRY2) mediates photoperiodic promotion of floral initiation and blue light inhibition of hypocotyl elongation. It has been hypothesized that photoexcitation derepresses CRY2 by disengaging its C-terminal domain from the N-terminal PHR domain. To test this hypothesis, we analyzed activities of CRY2 fused to green fluorescent protein (GFP) at either the N terminus (GFP-CRY2) or the C terminus (CRY2-GFP). While GFP-CRY2 exerts light-dependent biochemical and physiological activities similar to those of the endogenous CRY2, CRY2-GFP showed constitutive biochemical and physiological activities. CRY2-GFP is constitutively phosphorylated, it promotes deetiolation in both dark and light, and it activates floral initiation in both long-day and short-day photoperiods. These results are consistent with the hypothesis that photoexcited CRY2 disengages its C-terminal domain from the PHR domain to become active. Surprisingly, we found that CRY2-GFP, but not GFP-CRY2, formed distinct nuclear bodies in response to blue light. Compared with GFP-CRY2 or the endogenous CRY2, CRY2-GFP degradation was significantly retarded in response to blue light, suggesting that the nuclear bodies may result from accumulation of photoexcited CRY2-GFP waiting to be degraded. Consistent with this interpretation, we showed that both GFP-CRY2 and endogenous CRY2 formed nuclear bodies in the presence of the 26S-proteasome inhibitors that block blue light–dependent CRY2 degradation.

Yu, Xuhong; Sayegh, Ricardo; Maymon, Maskit; Warpeha, Katherine; Klejnot, John; Yang, Hongyun; Huang, Jie; Lee, Janet; Kaufman, Lon; Lin, Chentao

2009-01-01

269

Management of acute promyelocytic leukemia  

Microsoft Academic Search

Acute promyelocytic leukemia (APL) has become the most potentially curable subtype of acute myeloid leukemia (AML) in adults.\\u000a With current treatment strategies that incorporate all-trans retinoic acid (ATRA), long-term disease-free survival and potential\\u000a cure rates of 70% to 80% can be expected. Such progress reflects what can be accomplished with insights into the molecular\\u000a pathogenesis of leukemia, identification of a

Martin S. Tallman; Chadi Nabhan

2002-01-01

270

Leukemia and radium groundwater contamination  

SciTech Connect

In the August 2, 1985, issue of JAMMA, Lyman et al claim to have shown an association between leukemia incidence in Florida and radium in groundwater supplies. Although cautious in their conclusions, the authors imply that this excess in leukemia was in fact caused by radiation. The authors believe they have not presented a convincing argument for causation. The radiation doses at these levels of exposure could account for only a tiny fraction of the leukemia excess.

Tracy, B.L.; Letourneau, E.G.

1986-06-27

271

Flow cytometry in acute leukemia.  

PubMed

Immunophenotyping of acute leukemia is one of the most important clinical application of Flow cytometery. The aim of this work is to review recent advances in flow cytometery methods, quality control, troubleshooting and its prevention and data analysis of acute leukemia. Multiparameter flow cytometery is a useful adjunct to morphology and cytochemistry and it is an invaluable tool in the diagnosis of acute leukemia. PMID:23100953

Saxena, Renu; Anand, Hema

2009-01-11

272

Induction of apoptosis in human promyelocytic leukemia HL60 cells by an extract from Erythrina suberosa stem bark.  

PubMed

In this study, the apoptosis-inducing effect of an alcoholic extract from Erythrina suberosa stem bark (ESB) was investigated using human promyelocytic leukemia HL60 cells. Cell viability was estimated by MTT assay. We found that the ESB inhibited cell proliferation in a dose- and time-dependent manner. A series of well-documented morphological changes, such as cell shrinkage, condensation of nuclear chromatin, and nuclear fragmentation, were observed by fluorescence microscopy. The gold standard scanning electron micrographs showed apoptotic bodies and formation of blebs. Cell cycle analysis showed a significant increase in Sub G(0) population of cells above 50 ?g/ml. ESB treatment resulted in a dose-dependent increase in annexin V positive cells. Increase in intracellular ROS production up to sixfold was detected in ESB-treated HL60 cells by DCFH-DA assay. Dissipation of mitochondrial membrane potential of intact cells accompanied by increase in cytosolic cytochrome c was observed, which was followed by activation of caspase-9 and -3 but not caspase-8. DNA fragmentation analysis revealed typical ladders as early as 18 h indicative of caspase-3 role in the apoptotic pathway. The overall results suggest that ESB induces mitochondria-mediated intrinsic apoptotic pathway in HL60 cells and might have therapeutic value against human leukemia. PMID:21711175

Agrawal, Satyam Kumar; Agrawal, Madhunika; Sharma, Parduman Raj; Gupta, Bishan Datt; Arora, Saroj; Saxena, Ajit Kumar

2011-06-28

273

Parental smoking and childhood leukemia.  

PubMed

Childhood leukemia is the most common cancer among children, representing 31% of all cancer cases occurring in children younger than the age of 15 years in the USA. There are only few known risk factors of childhood leukemia (sex, age, race, exposure to ionizing radiation, and certain congenital diseases, such as Down syndrome and neurofibromatosis), which account for only 10% of the childhood leukemia cases. Several lines of evidence suggest that childhood leukemia may be more due to environmental rather than genetic factors, although genes may play modifying roles. Human and animal studies showed that the development of childhood leukemia is a two-step process that requires a prenatal initiating event(s) plus a postnatal promoting event(s). Despite a substantial public health effort to reduce cigarette smoking, a large proportion of the US and world population still smoke. Tobacco smoke contains at least 60 known human or animal carcinogens, with the major chemical classes being volatile hydrocarbons, aldehydes, aromatic amines, polycyclic aromatic hydrocarbons, and nitrosamines; among these chemicals, only benzene is an established leukemogen, although other chemicals in the tobacco could interact with one another in a complex way to jointly attain a significant carcinogenic effect on the development of leukemia. Although tobacco smoke is an established risk factor for adult myeloid leukemia, the studies of association between parental smoking and childhood leukemia have produced inconsistent results. The majority of the studies on maternal smoking and childhood leukemia did not find a significant positive association and some even reported an inverse association. In contrast to studies of maternal smoking, studies of paternal smoking and childhood leukemia reported more positive associations but only by less than half of the studies. Future directions to be considered for improving the study of parental smoking and childhood leukemia are: 1) consider all sources of benzene exposure in addition to smoking, including occupational exposure and traffic exhausts; 2) childhood leukemia is a heterogeneous disease and epidemiologic studies of childhood leukemia can be greatly improved by grouping childhood leukemia into more homogeneous groups by molecular techniques (e.g., structural and numerical chromosomal changes); and 3) assess gene-environment interaction. It is hoped that through the continual effort, more will be uncovered regarding the causes of childhood leukemia. In the meantime, more effort should be spent on educating the parents to quit smoking, because parental smoking is known to affect many childhood diseases (e.g., asthma, respiratory tract infection, and otitis media) that are much more prevalent than childhood leukemia. PMID:19107431

Chang, Jeffrey S

2009-01-01

274

A Newborn with Congenital Mixed Phenotype Acute Leukemia After In Vitro Fertilization.  

PubMed

Congenital leukemia is a rare disease. The majority of cases of this disease are acute myelogenous leukemia (AML). Congenital acute lymphoblastic leukemia (ALL) is rare and most often is of B cell lineage. Rarely, some cases have been designated biphenotypic or mixed phenotype acute leukemia (MPAL). Herein, we report a preterm newborn referred to us as a result of the appearance of blue-violaceous dermal nodules on her body at birth. She was a twin and the product of an in vitro fertilization (IVF) pregnancy. Physical examination showed jaundice, hepatosplenomegaly, and peripheral facial nerve palsy in addition to dermal nodules. Bone marrow aspiration showed 40% blasts of lymphoid lineage; skin biopsy and its immunohistochemistry revealed myeloblastic infiltration of the dermis. Cytogenetic analysis (46,XX), fluorescence in situ hybridization (FISH) analysis, and cranial magnetic resonance were normal. The patient was diagnosed with congenital MPAL, and an association between IVF and congenital leukemia was suggested. PMID:23639745

Ergin, Hacer; Ozdemir, Ozmert M A; Karaca, Abdullah; Türk, Nilay ?en; Düzcan, Füsun; Ergin, Seniz; Kazanc?, Elif; Vergin, Canan; Erbay, Ay?e

2013-04-29

275

Nuclear Scans  

MedlinePLUS

Nuclear scans use radioactive substances to see structures and functions inside your body. They use a special ... images. Most scans take 20 to 45 minutes. Nuclear scans can help doctors diagnose many conditions, including ...

276

Neurologic Complications of Leukemia  

Microsoft Academic Search

Leukemia affects both the central and peripheral nervous systems. Neurological complications are a consequence of both direct\\u000a leukemic infiltration, as occurs with leukemic meningitis, and complications of either antileukemic treatment (e.g., thrombocytopenic\\u000a or DIC-related intracranial hemorrhage, steroid myopathy, vinca alkaloid peripheral neuropathy, posterior reversible encephalopathy\\u000a syndrome, multifocal necrotizing leuko-encephalopathy) or immune compromise (e.g., Herpes zoster shingles or Aspergillus infection).

Marc C. Chamberlain

277

Large granular lymphocyte leukemia  

Microsoft Academic Search

Clonal diseases of large granular lymphocytes (LGLs) represent a spectrum of clinically rare lymphoproliferative malignancies\\u000a arising from either mature T-cell (CD3+) or natural killer (NK)-cell (CD3?) lineages. The clinical behavior of these disorders ranges from indolent to very aggressive. Patients with symptomatic indolent\\u000a T-cell or NK-cell LGL leukemia are usually treated with immunosuppressive therapies; in contrast, aggressive T-cell or NK-cell

Lubomir Sokol; Thomas P. Loughran

2007-01-01

278

Hairy cell leukemia  

Microsoft Academic Search

Hairy cell leukemia (HCL) is a chronic B-cell lymphoproliferative disorder characterized by pancytopenia and variable infiltration\\u000a of the reticuloendothelial system with “hairy” lymphocytes. HCL is more common in men than women and has a median age of diagnosis\\u000a of 52 yr. Typically, patients with HCL respond well to purine analog-based therapy. The purpose of this review will be to\\u000a establish

Ronan Swords; Francis Giles

2007-01-01

279

Leukemia incidence in the Russian cohort of Chernobyl emergency workers.  

PubMed

Of all potentially radiogenic cancers, leukemia, a type of cancer of the blood, has the highest risk attributable to ionizing radiation. Despite this, the quantitative estimation of radiation risk of a leukemia demands studying very large exposed cohorts, because of the very low level of this disease in unexposed populations and because of the tendency for its radiation risk to decrease with time. At present, the Japanese cohort of atomic bomb survivors is still the primary source of data that allows analysis of radiation-induced leukemia and the underlying dose-response relationship. The second large cohort that would allow to study radiation-induced leukemia is comprised of individuals who were exposed due to the accident of the Chernobyl nuclear power plant in 1986. The objective of the present study was to estimate radiation risks of leukemia incidence among the Russian cohort of Chernobyl emergency workers, for different time periods after the accident. Twenty-five years after the Chernobyl accident and based on the results of the present study, one can conclude that the radiation risk of leukemia incidence derived from the Russian cohort of Chernobyl emergency workers is similar to that derived from the cohort of atomic bomb survivors: The time-averaged excess relative risk per Gray (ERR Gy(-1)) equals 4.98 for the Russian cohort and 3.9 for the life span study (LSS) cohort; excess absolute risk decreases with time after exposure at an annual rate of 9% for the Russian cohort, and of 6.5% for the LSS cohort. Thus, the excess in risk of leukemia incidence in a population due to a single exposure is restricted in time after exposure by the period of about 15 years. PMID:22246583

Ivanov, V K; Tsyb, A F; Khait, S E; Kashcheev, V V; Chekin, S Yu; Maksioutov, M A; Tumanov, K A

2012-01-14

280

Serum-dependent expression of promyelocytic leukemia protein suppresses propagation of influenza virus  

SciTech Connect

The rate of propagation of influenza virus in human adenocarcinoma Caco-2 cells was found to negatively correlate with the concentration of fetal bovine serum (FBS) in the culture medium. Virus replicated more rapidly at lower FBS concentrations (0 or 2%) than at higher concentrations (10 or 20%) during an early stage of infection. Basal and interferon (IFN)-induced levels of typical IFN-inducible anti-viral proteins, such as 2',5'-oligoadenylate synthetase, dsRNA-activated protein kinase and MxA, were unaffected by variation in FBS concentrations. But promyelocytic leukemia protein (PML) was expressed in a serum-dependent manner. In particular, the 65 to 70 kDa isoform of PML was markedly upregulated following the addition of serum. In contrast, other isoforms were induced by IFN treatment, and weakly induced by FBS concentrations. Immunofluorescence microscopy indicated that PML was mainly formed nuclear bodies in Caco-2 cells at various FBS concentrations, and the levels of the PML-nuclear bodies were upregulated by FBS. Overexpression of PML isoform consisting of 560 or 633 amino acid residues by transfection of expression plasmid results in significantly delayed viral replication rate in Caco-2 cells. On the other hand, downregulation of PML expression by RNAi enhanced viral replication. These results indicate that PML isoforms which are expressed in a serum-dependent manner suppress the propagation of influenza virus at an early stage of infection.

Iki, Shigeo [Department of Microbiology, Sapporo Medical University School of Medicine, Chuo-ku, Sapporo 060-8556 (Japan); Hokkaido Institute of Public Health, Kita-ku, Sapporo 060-0819 (Japan); Yokota, Shin-ichi [Department of Microbiology, Sapporo Medical University School of Medicine, Chuo-ku, Sapporo 060-8556 (Japan); Okabayashi, Tamaki [Department of Microbiology, Sapporo Medical University School of Medicine, Chuo-ku, Sapporo 060-8556 (Japan); Yokosawa, Noriko [Department of Microbiology, Sapporo Medical University School of Medicine, Chuo-ku, Sapporo 060-8556 (Japan); Nagata, Kyosuke [Department of Infection Biology, Graduate School of Comprehensive Human Sciences and Institute of Basic Medical Sciences, University of Tsukuba, Tsukuba 305-8575 (Japan); Fujii, Nobuhiro [Department of Microbiology, Sapporo Medical University School of Medicine, Chuo-ku, Sapporo 060-8556 (Japan)]. E-mail: fujii@sapmed.ac.jp

2005-12-05

281

Resistance to virus infection conferred by the interferon-induced promyelocytic leukemia protein.  

PubMed

The interferon (IFN)-induced promyelocytic leukemia (PML) protein is specifically associated with nuclear bodies (NBs) whose functions are yet unknown. Two of the NB-associated proteins, PML and Sp100, are induced by IFN. Here we show that overexpression of PML and not Sp100 induces resistance to infections by vesicular stomatitis virus (VSV) (a rhabdovirus) and influenza A virus (an orthomyxovirus) but not by encephalomyocarditis virus (a picornavirus). Inhibition of viral multiplication was dependent on both the level of PML expression and the multiplicity of infection and reached 100-fold. PML was shown to interfere with VSV mRNA and protein synthesis. Compared to the IFN mediator MxA protein, PML had less powerful antiviral activity. While nuclear body localization of PML did not seem to be required for the antiviral effect, deletion of the PML coiled-coil domain completely abolished it. Taken together, these results suggest that PML can contribute to the antiviral state induced in IFN-treated cells. PMID:9444998

Chelbi-Alix, M K; Quignon, F; Pelicano, L; Koken, M H; de Thé, H

1998-02-01

282

Kinetic model building using advanced nuclear medicine techniques: the kinetics of chromium(III) in the human body. [¹Cr  

Microsoft Academic Search

The purpose of this study is to investigate whether a valid index of chromium (III) nutritional status can be determined with satisfaction through in vivo kinetic analysis. Three normal subjects and three patients suffering from hemochromatosis were periodically scanned with the Donner Laboratory computerized whole body scanners, starting seconds after radiochromium(III) was administered intravenously, up to a period of 84

1978-01-01

283

Preliminary experimental results in humans and animals with a superconducting, whole-body, nuclear magnetic resonance scanner. [Dogs  

Microsoft Academic Search

In order to determine the clinical usefulness of nuclear magnetic resonance (NMR) imaging, the investigators examined a variety of normal volunteers, patients with neoplastic lesions, and experimental animals. Preliminary results were obtained with the use of potential contrast agents. It was found that imaging applications of NMR in the vascular system, spine, brain, lung, and mediastinum offer certain advantages over

Ralph J. Alfidi; John R. Haaga; Saba J. El Yousef; Patrick J. Bryan; Barry D. Fletcher; Joseph P. LiPuma; Stuart C. Morrison; Benjamin Kaufman; Joseph B. Richey; Waldo S. Hinshaw

1982-01-01

284

Childhood leukemia in Woburn, Massachusetts  

Microsoft Academic Search

Possible associations between environmental hazards and the occurrence of childhood leukemia were investigated in Woburn, MA, for the period 1969-79. Residents of Woburn were concerned over what they perceived to be a large number of childhood leukemia cases; at the same time there was extensive publicity about uncontrolled hazardous waste sites in Woburn, which resulted in its being placed on

J. J. Cutler; G. S. Parker; S. Rosen; B. Prenney; R. Healey; G. G. Caldwell

1986-01-01

285

In vivo and in vitro characterization of the B1 and B2 zinc-binding domains from the acute promyelocytic leukemia protooncoprotein PML.  

PubMed

Acute promyelocytic leukemia (APL) has been ascribed to a chromosomal translocation event which results in a fusion protein comprising the PML protein and retinoic acid receptor alpha. PML is normally a component of a nuclear multiprotein complex which is disrupted in the APL disease state. Here, two newly defined cysteine/histidine-rich protein motifs called the B-box (B1 and B2) from PML have been characterized in terms of their effect on PML nuclear body formation, their dimerization, and their biophysical properties. We have shown that both peptides bind Zn2+, which induces changes in the peptides' structures. We demonstrate that mutants in both B1 and B2 do not form PML nuclear bodies in vivo and have a phenotype that is different from that observed in the APL disease state. Interestingly, these mutations do not affect the ability of wild-type PML to dimerize with mutant proteins in vitro, suggesting that the B1 and B2 domains are involved in an additional interaction central to PML nuclear body formation. This report in conjunction with our previous work demonstrates that the PML RING-Bl/B2 motif plays a fundamental role in formation of a large multiprotein complex, a function that may be common to those unrelated proteins which contain the motif. PMID:8643677

Borden, K L; Lally, J M; Martin, S R; O'Reilly, N J; Solomon, E; Freemont, P S

1996-02-20

286

Translocation of phospho-protein kinase Cs implies their roles in meiotic-spindle organization, polar-body emission and nuclear activity in mouse eggs.  

PubMed

The protein kinase Cs (PKCs) are a family of Ser/Thr protein kinases categorized into three subfamilies: classical, novel, and atypical. The phosphorylation of PKC in germ cells is not well defined. In this study, we described the subcellular localization of phopho-PKC in the process of mouse oocyte maturation, fertilization, and early embryonic mitosis. Confocal microscopy revealed that phospho-PKC (pan) was distributed abundantly in the nucleus at the germinal vesicle stage. After germinal vesicle breakdown, phospho-PKC was localized in the vicinity of the condensed chromosomes, distributed in the whole meiotic spindle, and concentrated at the spindle poles. After metaphase I, phospho-PKC was translocated gradually to the spindle mid-zone during emission of the first polar body. After sperm penetration and electrical activation, the distribution of phospho-PKC was moved from the spindle poles to the spindle mid-zone. After the extrusion of the second polar body (PB2) phospho-PKC was localized in the area between the oocyte and the PB2. In fertilized eggs, phospho-PKC was concentrated in the pronuclei except for the nucleolus. Phospho-PKC was dispersed after pronuclear envelope breakdown, but distributed on the entire spindle at mitotic metaphase. The results suggest that PKC activation may play important roles in regulating spindle organization and stabilization, polar-body extrusion, and nuclear activity during mouse oocyte meiosis, fertilization, and early embryonic mitosis. PMID:15695617

Zheng, Zhen-Yu; Li, Qing-Zhang; Chen, Da-Yuan; Schatten, Heide; Sun, Qing-Yuan

2005-02-01

287

Radiation-induced leukemias in ankylosing spondylitis  

SciTech Connect

Three cases of leukemia occurred in patients with ankylosing spondylitis treated by radiotherapy. In each case, the leukemic process exhibited bizarre features suggesting that radiation is likely to induce atypical forms of leukemia possessing unusual attributes not shared by spontaneously developing leukemia. The likely distinctive aspects of radiation-induced leukemia are discussed.

Toolis, F. (Royal Infirmary, Edinburgh, UK); Potter, B.; Allan, N.C.; Langlands, A.O.

1981-10-01

288

The nuclear pore complex-associated protein, Mlp2p, binds to the yeast spindle pole body and promotes its efficient assembly.  

PubMed

The two yeast proteins Mlp1p and Mlp2p (homologues of the vertebrate protein Tpr) are filamentous proteins attached to the nuclear face of nuclear pore complexes. Here we perform a proteomic analysis, which reveals that the two Mlps have strikingly different interacting partners, testifying to their different roles within the cell. We find that Mlp2p binds directly to Spc110p, Spc42p, and Spc29p, which are three core components of the spindle pole body (SPB), the nuclear envelope-associated yeast spindle organizer. We further show that SPB function is compromised in mlp2 mutants. Cells lacking Mlp2p form significantly smaller SPBs, accumulate aberrant SPB component-containing structures inside the nucleus, and have stochastic failures of cell division. In addition, depletion of Mlp2p is synthetically lethal with mutants impaired in SPB assembly. Based on these data, we propose that Mlp2p links the SPB to the peripheral Mlp assembly, and that this linkage is required for efficient incorporation of components into the SPB. PMID:16027220

Niepel, Mario; Strambio-de-Castillia, Caterina; Fasolo, Joseph; Chait, Brian T; Rout, Michael P

2005-07-18

289

Clinical profile of dasatinib in Asian and non-Asian patients with chronic myeloid leukemia  

Microsoft Academic Search

Resistance and intolerance to imatinib are of particular clinical relevance to Asian patients because of their lower body\\u000a surface area. Dasatinib is 325-fold more potent than imatinib in inhibiting BCR-ABL in vitro and is indicated for the treatment\\u000a of chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia resistant or intolerant\\u000a to imatinib. Data from a series of phase

Dong-Wook Kim; Yeow-Tee Goh; Hui-Hua Hsiao; Priscilla B. Caguioa; Dongho Kim; Wan-Seok Kim; Tapan Saikia; Shruti Agrawal; Amit Roy; David Dai; M. Brigid Bradley-Garelik; Jaydip Mukhopadhyay; Saengsuree Jootar

2009-01-01

290

Nuclear structure in normal and Bloom syndrome cells  

PubMed Central

Bloom syndrome (BS) is a rare cancer-predisposing disorder in which the cells of affected persons have a high frequency of somatic mutation and genomic instability. BLM, the protein altered in BS, is a RecQ DNA helicase. This report shows that BLM is found in the nucleus of normal human cells in the nuclear domain 10 or promyelocytic leukemia nuclear bodies. These structures are punctate depots of proteins disrupted upon viral infection and in certain human malignancies. BLM is found primarily in nuclear domain 10 except during S phase when it colocalizes with the Werner syndrome gene product, WRN, in the nucleolus. BLM colocalizes with a select subset of telomeres in normal cells and with large telomeric clusters seen in simian virus 40-transformed normal fibroblasts. During S phase, BS cells expel micronuclei containing sites of DNA synthesis. BLM is likely to be part of a DNA surveillance mechanism operating during S phase.

Yankiwski, Victor; Marciniak, Robert A.; Guarente, Leonard; Neff, Norma F.

2000-01-01

291

Ibd1p, a possible spindle pole body associated protein, regulates nuclear division and bud separation in Saccharomyces cerevisiae  

Microsoft Academic Search

The proper spatial and temporal coordination of mitosis and cytokinesis is essential for maintaining genomic integrity. We describe the identification and characterization of the Saccharomyces cerevisiae IBD1 gene, which encodes a novel protein that regulates the proper nuclear division and bud separation. IBD1 was identified by the limited homology to byr4, a dosage-dependent regulator of cytokinesis in Schizosaccharomyces pombe. IBD1

Jeongkyo Lee; Hyung-Seo Hwang; Jinmi Kim; Kiwon Song

1999-01-01

292

Effector Caspases and Leukemia  

PubMed Central

Caspases, a family of aspartate-specific cysteine proteases, play a major role in apoptosis and a variety of physiological and pathological processes. Fourteen mammalian caspases have been identified and can be divided into two groups: inflammatory caspases and apoptotic caspases. Based on the structure and function, the apoptotic caspases are further grouped into initiator/apical caspases (caspase-2, -8, -9, and -10) and effector/executioner caspases (caspase-3, -6, and -7). In this paper, we discuss what we have learned about the role of individual effector caspase in mediating both apoptotic and nonapoptotic events, with special emphasis on leukemia-specific oncoproteins in relation to effector caspases.

Lu, Ying; Chen, Guo-Qiang

2011-01-01

293

Protective effects of nuclear factor erythroid 2-related factor 2 on whole body heat stress-induced oxidative damage in the mouse testis  

PubMed Central

Background Whole body heat stress had detrimental effect on male reproductive function. It's known that the nuclear factor erythroid 2-related factor 2 (Nrf2) activates expression of cytoprotective genes to enable cell adaptation to protect against oxidative stress. However, it’s still unclear about the exactly effects of Nrf2 on the testis. Here, we investigate the protective effect of Nrf2 on whole body heat stress-induced oxidative damage in mouse testis. Methods Male mice were exposed to the elevated ambient temperature (42°C) daily for 2 h. During the period of twelve consecutive days, mice were sacrificed on days 1, 2, 4, 8 and 12 immediately following heat exposure. Testes weight, enzymatic antioxidant activities and concentrations of malondialdehyde (MDA) and glutathione (GSH) in the testes were determined and immunohistochemical detection of Nrf2 protein and mRNA expression of Nrf2-regulated genes were analyzed to assess the status of Nrf2-antioxidant system. Results Heat-exposed mice presented significant increases in rectal, scrotal surface and body surface temperature. The concentrations of cortisol and testosterone in serum fluctuated with the number of exposed days. There were significant decrease in testes weight and relative testes weight on day 12 compared with those on other days, but significant increases in catalase (CAT) activity on day 1 and GSH level on day 4 compared with control group. The activities of total superoxide dismutase (T-SOD) and copper-zinc SOD (CuZn-SOD) increased significantly on days 8 and 12. Moreover, prominent nuclear accumulation of Nrf2 protein was observed in Leydig cells on day 2, accompanying with up-regulated mRNA levels of Nrf2-regulated genes such as Nrf2, heme oxygenase 1 (HO-1), ?-Glutamylcysteine synthetase (GCLC) and NAD (P) H: quinone oxidoreductase 1 (NQO1)) in heat-treated groups. Conclusions These results suggest that Nrf2 displayed nuclear accumulation and protective activity in the process of heat treated-induced oxidative stress in mouse testes, indicating that Nrf2 might be a potential target for new drugs designed to protect germ cell and Leydig cell from oxidative stress.

2013-01-01

294

Entinostat and Clofarabine in Treating Patients With Newly Diagnosed, Relapsed, or Refractory Poor-Risk Acute Lymphoblastic Leukemia or Bilineage/Biphenotypic Leukemia  

ClinicalTrials.gov

Acute Leukemias of Ambiguous Lineage; Philadelphia Chromosome Negative Adult Precursor Acute Lymphoblastic Leukemia; Recurrent Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Lymphoblastic Leukemia

2013-09-27

295

Induction of immune resistance against L1210 lymphatic leukemia in mice after chemoradiotherapy of the leukemia and reconstitution with bone marrow purged from the leukemia with mafosfamide  

SciTech Connect

Lymphatic leukemia L1210-bearing semisyngeneic Balb/c x DBA/2Wf F1 (CD2F1) mice were subjected to chemoradiotherapy (2 x 100 mg/kg of cyclophosphamide i.p. and 1000 cGy of total body irradiation) and reconstitution with 10(7) syngeneic bone marrow cells i.v. The bone marrow obtained from leukemic mice was previously ex vivo purged of the leukemia cells with mafosfamide (ASTA Z7654) and stored in liquid nitrogen. Eight weeks after cytoreductive therapy and bone marrow transplantation we tried to immunize the mice against the lethal dose of the leukemia by i.p. injections of L1210-Maf cells (L1210 cells treated in vitro with mafosfamide for inhibition of their growth). About 75% of such mice were able to reject the subsequent 10(3) L1210 leukemia cell challenge, as compared with 70% of normal immunized mice and 55% of mice reconstituted with bone marrow cells not treated with mafosfamide.

Skorski, T.; Kawalec, M.

1988-10-01

296

UNEDF: Advanced Scienti?c Computing Collaboration Transforms the Low-Energy Nuclear Many-Body Problem  

SciTech Connect

With diverse scienti?c backgrounds, 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 quanti?ed uncertainties. This paper describes the UNEDF collaboration and identi?es attributes that classify UNEDF as a successful computational collaboration. We illustrate signi?cant milestones accomplished by UNEDF through integrative solutions using the most reliable theoretical approaches, the most advanced algorithms, and leadership class computational resources.

Nam, Hai A.; Stoitsov, M.; Nazarewicz, Witold; Bulgac, Aurel; Hagen, Gaute; Kortelainene, Markus; Maris, P.; Pei, Junchen; Roche, Kenneth J.; Schunck, Nicolas; Thompson, Ian; Vary, James; Wild, Stefan

2012-11-03

297

Marrow transplantation for leukemia  

SciTech Connect

Marrow transplantation for selected patients with leukemia, as for patients with severe combined immunologic deficiency or severe aplastic anemia, has now become an accepted clinical procedure. For patients with acute leukemia who have relapsed after achieving a remission of chemotherapy, marrow grafting from an identical twin or an HLA-identical sibling has now been demonstrated to produce median remissions as long as or longer than any reported for combination chemotherapy. In contrast to chemotherapy, marrow transplantation offers the possibility of cure for a small but significant fraction of these patients. Marrow transplantation for patients with ANL in first remission has now resulted in median survivals much longer than any reported with chemotherapy. Although it now appears that more than 50% of these patients can be cured with marrow transplantation, a much longer follow-up is indicated since some patients who achieve a complete remission with combination chemotherapy are now living for a long time, and some of these patients (less than 20%) may also be cured. Current intensive research with new modalities such as interferon, Acyclovir, Cyclosporin A, and monoclonal antibodies can reasonably be expected to improve the overall results of marrow transplantation.

Thomas, E.D.

1981-07-01

298

Lenalidomide in Treating Older Patients With Acute Myeloid Leukemia  

ClinicalTrials.gov

Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(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); Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

2013-07-02

299

Spliceosome mutations in myelodysplastic syndromes and chronic myelomonocytic leukemia  

PubMed Central

The recently discovered spliceosome mutations represent a group of acquired genetic alterations that affect both myeloid and lymphoid malignancies. A substantial proportion of patients with myelodysplastic syndromes (MDS), chronic myelomonocytoic leukemia (CMML) or chronic lymphocytic leukemia (CLL) harbor such mutations, which are often missense in type. Genotype-phenotype correlations have been observed, including the clustering of ring sideroblasts with SF3B1 mutations in MDS. Spliceosome mutations might result in defective small nuclear ribonucleoprotein complexes assembly on the pre-mRNA, deregulated global and alternative mRNA splicing, nuclear-cytoplasm export, and unpliced mRNA degradation, and thus may alter the expression of multiple genes. In the current review, we discuss the potential role of these mutations in cell transformation and how they could impact the therapeutic approaches.

Chesnais, Virginie; Kosmider, Olivier; Damm, Frederik; Itzykson, Raphael; Bernard, Olivier A.; Solary, Eric; Fontenay, Michaela

2012-01-01

300

Deuterium enrichment of plasma determined by nuclear magnetic resonance spectroscopy: Dilution kinetics of sup 2 H sub 2 O and estimation of total body water  

SciTech Connect

We demonstrate the feasibility of quantifying the abundance of {sup 2}H in plasma by nuclear magnetic resonance (NMR) spectroscopy. After adding internal standard (tert-butyl-d9 alcohol) to deproteinized plasma samples containing {sup 2}H{sub 2}O, we determined the ratio of NMR peak areas for {sup 2}H{sub 2}O and tert-butyl-d9 alcohol. This peak-area ratio was directly proportional to the exogenous {sup 2}H enrichment of plasma (difference between measured and naturally occurring {sup 2}H) between 0 and 0.272 atom % (r = 0.999). The coefficient of variation was 1.34% at an exogenous enrichment of 0.136 atom %. We applied this method to a study of the dilution kinetics of {sup 2}H{sub 2}O to determine the optimal time and method of blood sampling for estimation of total body water content. The {sup 2}H enrichment of plasma stabilized by 4 h after intravenous injection of {sup 2}H{sub 2}O, 1 g/kg of body weight, and fluctuated within 2-4% of the 4- to 8-h mean thereafter.

Brans, Y.W.; Schwartz, C.A.; Hood, R.J.; Ksebati, M.B.; Konduri, G.G. (Wayne State Univ., Detroit, MI (USA))

1990-10-01

301

Gemtuzumab Ozogamicin in Treating Patients With Acute Myeloid Leukemia  

ClinicalTrials.gov

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

2013-09-23

302

PXD101 in Treating Patients With Acute Myeloid Leukemia  

ClinicalTrials.gov

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

2013-06-03

303

Fate of Viral RNA of Murine Leukemia Virus after Infection  

Microsoft Academic Search

[3H]Uridine-labeled Rauscher leukemia virus was used to infect mouse embryo fibroblasts. After the infected cells were separated into nuclear and cytoplasmic fractions nucleic acid was extracted by sodium dodecyl sulfate-phenol-chloroform treatment and analyzed by Cs2SO4 and sucrose density gradient centrifugation. Between 45 and 70 min after infection a transient and synchronized shift of the acid-insoluble radioactive peak toward the RNA-DNA

Toshiya Takano; Masakazu Hatanaka

1975-01-01

304

What Is Chronic Lymphocytic Leukemia?  

MedlinePLUS

... the key statistics for chronic lymphocytic leukemia? Previous Topic What is cancer? Next Topic What are the key statistics for chronic lymphocytic ... children, please see our separate documents on these topics . Last Medical Review: 07/31/2013 Last Revised: ...

305

Central Nervous System in Leukemia.  

National Technical Information Service (NTIS)

The present report summarizes the pertinent clinical and pathologic findings in 165 cases of leukemia in atomic bomb exposed victims autopsied during the period 1949 to 1962 at ABCC in Hiroshima and Nagasaki, Japan. Significant parenchymal hemorrhage occu...

J. P. Phair R. E. Anderson H. Namiki

1964-01-01

306

Relationship between electron density and effective densities of body tissues for stopping, scattering, and nuclear interactions of proton and ion beams  

SciTech Connect

Purpose: In treatment planning of charged-particle radiotherapy, patient heterogeneity is conventionally modeled as variable-density water converted from CT images to best reproduce the stopping power, which may lead to inaccuracies in the handling of multiple scattering and nuclear interactions. Although similar conversions can be defined for these individual interactions, they would be valid only for specific CT systems and would require additional tasks for clinical application. This study aims to improve the practicality of the interaction-specific heterogeneity correction. Methods: The authors calculated the electron densities and effective densities for stopping power, multiple scattering, and nuclear interactions of protons and ions, using the standard elemental-composition data for body tissues to construct the invariant conversion functions. The authors also simulated a proton beam in a lung-like geometry and a carbon-ion beam in a prostate-like geometry to demonstrate the procedure and the effects of the interaction-specific heterogeneity correction. Results: Strong correlations were observed between the electron density and the respective effective densities, with which the authors formulated polyline conversion functions. Their effects amounted to 10% differences in multiple-scattering angle and nuclear interaction mean free path for bones compared to those in the conventional heterogeneity correction. Although their realistic effect on patient dose distributions would be generally small, it could be at the level of a few percent when a carbon-ion beam traverses a large bone. Conclusions: The present conversion functions are invariant and may be incorporated in treatment planning systems with a common function relating CT number to electron density. This will enable improved beam dose calculation while minimizing initial setup and quality management of the user's specific system.

Kanematsu, Nobuyuki; Inaniwa, Taku; Koba, Yusuke [Department of Accelerator and Medical Physics, Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan)

2012-02-15

307

Inhibition of the NAD-Dependent Protein Deacetylase SIRT2 Induces Granulocytic Differentiation in Human Leukemia Cells  

PubMed Central

Sirtuins, NAD-dependent protein deacetylases, play important roles in cellular functions such as metabolism and differentiation. Whether sirtuins function in tumorigenesis is still controversial, but sirtuins are aberrantly expressed in tumors, which may keep cancerous cells undifferentiated. Therefore, we investigated whether the inhibition of sirtuin family proteins induces cellular differentiation in leukemic cells. The sirtuin inhibitors tenovin-6 and BML-266 induce granulocytic differentiation in the acute promyelocytic leukemia (APL) cell line NB4. This differentiation is likely caused by an inhibition of SIRT2 deacetylase activity, judging from the accumulation of acetylated ?-tubulin, a major SIRT2 substrate. Unlike the clinically used differentiation inducer all-trans retinoic acid, tenovin-6 shows limited effects on promyelocytic leukemia–retinoic acid receptor ? (PML-RAR-?) stability and promyelocytic leukemia nuclear body formation in NB4 cells, suggesting that tenovin-6 does not directly target PML-RAR-? activity. In agreement with this, tenovin-6 induces cellular differentiation in the non-APL cell line HL-60, where PML-RAR-? does not exist. Knocking down SIRT2 by shRNA induces granulocytic differentiation in NB4 cells, which demonstrates that the inhibition of SIRT2 activity is sufficient to induce cell differentiation in NB4 cells. The overexpression of SIRT2 in NB4 cells decreases the level of granulocytic differentiation induced by tenovin-6, which indicates that tenovin-6 induces granulocytic differentiation by inhibiting SIRT2 activity. Taken together, our data suggest that targeting SIRT2 is a viable strategy to induce leukemic cell differentiation.

Sunami, Yoshitaka; Araki, Marito; Hironaka, Yumi; Morishita, Soji; Kobayashi, Masaki; Liew, Ei Leen; Edahiro, Yoko; Tsutsui, Miyuki; Ohsaka, Akimichi; Komatsu, Norio

2013-01-01

308

Inhibition of the NAD-dependent protein deacetylase SIRT2 induces granulocytic differentiation in human leukemia cells.  

PubMed

Sirtuins, NAD-dependent protein deacetylases, play important roles in cellular functions such as metabolism and differentiation. Whether sirtuins function in tumorigenesis is still controversial, but sirtuins are aberrantly expressed in tumors, which may keep cancerous cells undifferentiated. Therefore, we investigated whether the inhibition of sirtuin family proteins induces cellular differentiation in leukemic cells. The sirtuin inhibitors tenovin-6 and BML-266 induce granulocytic differentiation in the acute promyelocytic leukemia (APL) cell line NB4. This differentiation is likely caused by an inhibition of SIRT2 deacetylase activity, judging from the accumulation of acetylated ?-tubulin, a major SIRT2 substrate. Unlike the clinically used differentiation inducer all-trans retinoic acid, tenovin-6 shows limited effects on promyelocytic leukemia-retinoic acid receptor ? (PML-RAR-?) stability and promyelocytic leukemia nuclear body formation in NB4 cells, suggesting that tenovin-6 does not directly target PML-RAR-? activity. In agreement with this, tenovin-6 induces cellular differentiation in the non-APL cell line HL-60, where PML-RAR-? does not exist. Knocking down SIRT2 by shRNA induces granulocytic differentiation in NB4 cells, which demonstrates that the inhibition of SIRT2 activity is sufficient to induce cell differentiation in NB4 cells. The overexpression of SIRT2 in NB4 cells decreases the level of granulocytic differentiation induced by tenovin-6, which indicates that tenovin-6 induces granulocytic differentiation by inhibiting SIRT2 activity. Taken together, our data suggest that targeting SIRT2 is a viable strategy to induce leukemic cell differentiation. PMID:23460888

Sunami, Yoshitaka; Araki, Marito; Hironaka, Yumi; Morishita, Soji; Kobayashi, Masaki; Liew, Ei Leen; Edahiro, Yoko; Tsutsui, Miyuki; Ohsaka, Akimichi; Komatsu, Norio

2013-02-27

309

Dynamic nature of cleavage bodies and their spatial relationship to DDX1 bodies, Cajal bodies and gems  

Microsoft Academic Search

ABSTRACT DDX1 bodies, cleavage bodies, Cajal bodies (CBs) and gems are nuclear suborganelles,that contain ,factors involved ,in RNA ,transcription and\\/or processing. , Although all four nuclear bodies can exist as distinct entities, they often co-localize or overlap,with each ,other. To ,better understand ,the relationship ,between ,these ,four nuclear bodies, we examined their spatial distribution as a function of the cell

Lei Li; Ken Roy; Sachin Katyal; Xuejun Sun; Stacey Bléoo; Roseline Godbout

2006-01-01

310

The European LeukemiaNet: achievements and perspectives  

Microsoft Academic Search

The only way to cure leukemia is by cooperative research. To optimize research, the European LeukemiaNet integrates 105 national leukemia trial groups and networks, 105 interdisciplinary partner groups and about 1,000 leukemia specialists from 175 institutions. They care for tens of thousands of leukemia patients in 33 countries across Europe. Their ultimate goal is to cure leukemia. Since its inception

R. Hehlmann; D. Grimwade; B. Simonsson; J. Apperley; M. Baccarani; T. Barbui; G. Barosi; R. Bassan; M. C. Bene; U. Berger; T. Buchner; A. Burnett; N. C. Cross; T. J. de. Witte; H. Dohner; H. Dombret; H. Einsele; G. Engelich; R. Foa; C. Fonatsch; N. Gokbuget; E. Gluckman; A. Gratwohl; F. Guilhot; C. Haferlach; T. Haferlach; M. Hallek; J. Hasford; A. Hochhaus; D. Hoelzer; J. J. Kiladjian; B. Labar; P. Ljungman; U. Mansmann; D. Niederwieser; G. Ossenkoppele; J. M. Ribera; H. Rieder; H. Serve; P. Schrotz-King; M. A. Sanz; S. Saussele

2011-01-01

311

Parental Smoking and the Risk of Childhood Leukemia  

Microsoft Academic Search

Cigarette smoke has been linked to adult myeloid leukemia; however, the association between parental smoking and childhood leukemia remains unclear. Parental smoking and the risk of childhood leukemia were examined in the Northern California Childhood Leukemia Study, a case-control study, between 1995 and 2002. The present analysis included 327 acute childhood leukemia cases (281 acute lymphoblastic leukemia (ALL) and 46

Jeffrey S. Chang; Steve Selvin; Catherine Metayer; Vonda Crouse; Amanda Golembesky; Patricia A. Buffler

312

Treatment of prolymphocytic leukemia  

SciTech Connect

Prolymphocytic leukemia is characterized by marked splenomegaly, distinctive cellular morphologic characteristics, and a poor clinical course. Five patients with typical PL were treated systematically with vincristine/prednisone, chlorambucil/prednisone, splenic irradiation, splenectomy, and other chemotherapy regimens. No patient responded to vincristine/prednisone. Two patients responded to chlorambucil/prednisone, and four patients had brief responses to splenic irradiation. Two patients underwent splenectomy, one of whom had a prolonged clinical remissions. No other chemotherapy combinations were of value. The median survival was 33 months. Recommendations are made to use chlorambucil/prednisone or splenic irradiation as initial treatment. Splenectomy should be considered in patients refractory to these modalities. The course of PL may be more protracted than originally reported.

Hollister, S. Jr.; Coleman, M.

1982-11-01

313

Treatment of prolymphocytic leukemia  

SciTech Connect

Prolymphocytic leukemia is characterized by marked splenomegaly, distinctive cellular morphologic characteristics, and a poor clinical course. Five patients with typical PL were treated systematically with vincristine/prednisone, chlorambucil/prednisone, splenic irradiation, splenectomy, and other chemotherapy regimens. No patient responded to vincristine/prednisone. Two patients responded to chlorambucil/prednisone, and four patients had brief responses to splenic irradiation. Two patients underwent splenectomy, one of whom had a prolonged clinical remission. There were no complete remissions. No other chemotherapy combinations were of value. The median survival was 33 months. Recommendations are made to use chlorambucil/prednisone or splenic irradiation as initial treatment. Splenectomy should be considered in patients refractory to these modalities. The course of PL may be more protracted than originally reported.

Hollister, D. Jr.; Coleman, M.

1982-11-01

314

Curing chronic myeloid leukemia.  

PubMed

The use of tyrosine kinase inhibitors (TKIs) targeted against the BCR-ABL1 oncoprotein has proven remarkably successful in chronic myeloid leukemia (CML) and long-term survival has become a reality. Despite this outstanding progress, detection of minimal residual disease precludes therapy termination in most TKI-receiving patients. CML has thus turned into a chronic illness, raising concerns about long-term safety, medication adherence, and health care costs. Although treatment cessation may be feasible in few selected patients achieving deep molecular responses, a definitive cure remains elusive owing to the discovery that TKIs spare quiescent leukemic stem cells (LSC). Understanding mechanisms underlying LSC behavior in TKI-treated patients may provide important clues to develop an array of strategies that ensure the complete destruction of LSC reservoirs and thereby offer CML patients a definitive cure. PMID:22410764

Rea, Delphine; Rousselot, Philippe; Guilhot, Joelle; Guilhot, François; Mahon, François-Xavier

2012-06-01

315

Tipifarnib in Treating Older Patients With Acute Myeloid Leukemia  

ClinicalTrials.gov

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

2013-10-07

316

[Mechanism of leukemia relapse: novel insights on old problem].  

PubMed

Relapse, which puzzled several generations of hematologists, is the bottle-neck of radical treatment for leukemias. The progress of Human Microbiome Project at the beginning of 21st century suggested that human body was a super-organism constituted by the core of human cells and symbiotic microorganisms. The elucidation and characterization of endogenous retrovirus and prion protein suggested the possible effects of co-evolutional microorganisms on human health. Recently, the elucidation of the roles of tunneling nanotubes in intercellular communication and transportation suggested a novel way for cellular communication and transport of oncogenic materials. The role and significance of in vivo cell fusion have been studied in more detail. On the other hand, donor cell leukemia was reported. All of these approaches provide novel insights for studying the mechanism of leukemia relapse. Based on previous work, the authors suggest the hypothesis: there are two possible mechanisms for the relapse of leukemias: the minimal residual disease (MRD) and intercellular transportation of oncogenic materials. PMID:21729521

Wu, Ke-Fu; Zheng, Guo-Guang; Ma, Xiao-Tong; Song, Yu-Hua; Zhu, Xiao-Fan

2011-06-01

317

Menin as a hub controlling mixed lineage leukemia.  

PubMed

Mixed lineage leukemia (MLL) fusion protein (FP)-induced acute leukemia is highly aggressive and often refractory to therapy. Recent progress in the field has unraveled novel mechanisms and targets to combat this disease. Menin, a nuclear protein, interacts with wild-type (WT) MLL, MLL-FPs, and other partners such as the chromatin-associated protein LEDGF and the transcription factor C-Myb to promote leukemogenesis. The newly solved co-crystal structure illustrating the menin-MLL interaction, coupled with the role of menin in recruiting both WT MLL and MLL-FPs to target genes, highlights menin as a scaffold protein and a central hub controlling this type of leukemia. The menin/WT MLL/MLL-FP hub may also cooperate with several signaling pathways, including Wnt, GSK3, and bromodomain-containing Brd4-related pathways to sustain MLL-FP-induced leukemogenesis, revealing new therapeutic targets to improve the treatment of MLL-FP leukemias. PMID:22829075

Thiel, Austin T; Huang, Jing; Lei, Ming; Hua, Xianxin

2012-07-24

318

Dasatinib and Combination Chemotherapy in Treating Young Patients With Newly Diagnosed Acute Lymphoblastic Leukemia  

ClinicalTrials.gov

Philadelphia Chromosome Positive Adult Precursor Acute Lymphoblastic Leukemia; Philadelphia Chromosome Positive Childhood Precursor Acute Lymphoblastic Leukemia; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Childhood Acute Lymphoblastic Leukemia

2013-05-20

319

Acute nonlymphocytic leukemia in a dog.  

PubMed

Acute nonlymphocytic leukemia was diagnosed in a 1-year-old Rhodesian Ridgeback. Clinical signs of disease included weight loss, anorexia, lethargy, lymphadenopathy, splenomegaly, and hepatomegaly. Doxorubicin was administered IV on day 4 at a dosage of 30 mg/m2 of body surface, followed 2 days later by oral administration of cyclophosphamide at a dosage of 100 mg/m2. The cyclophosphamide was given for 4 consecutive days (days 8, 9, 10, and 11), but the WBC count did not respond. The dog was administered 500 ml of blood; but on day 12, it died. Necropsy was not performed, but the presumptive cause of death was related to leukostasis. PMID:2295542

Hamlin, R H; Duncan, R C

1990-01-01

320

Childhood Acute Lymphoblastic Leukemia (PDQ): Treatment  

MedlinePLUS

... Childhood Acute Lymphoblastic Leukemia Childhood acute lymphoblastic leukemia (ALL) is a type of cancer in which the ... radiation may affect the risk of developing childhood ALL. Anything that increases your risk of getting a ...

321

Adult Acute Lymphoblastic Leukemia (PDQ): Treatment  

MedlinePLUS

... Adult Acute Lymphoblastic Leukemia Adult acute lymphoblastic leukemia (ALL) is a type of cancer in which the ... to radiation may increase the risk of developing ALL. Anything that increases your risk of getting a ...

322

Childhood leukemia in Woburn, Massachusetts  

SciTech Connect

Possible associations between environmental hazards and the occurrence of childhood leukemia were investigated in Woburn, MA, for the period 1969-79. Residents of Woburn were concerned over what they perceived to be a large number of childhood leukemia cases; at the same time there was extensive publicity about uncontrolled hazardous waste sites in Woburn, which resulted in its being placed on the Superfund list. Many believed that the elevated rate of childhood leukemia was related to these sites or to two city water wells that had been closed in 1979 when they were found to be contaminated by organic chemicals. An occurrence was defined as childhood leukemia when it was diagnosed in a Woburn resident less than 20 years old between 1969 and 1979 and confirmed by review of hospital and pathology records. This investigation confirmed an increase in incidence which was distributed uniformly over the 11-year period. Six of the persons with leukemia were located close to each other in one census tract, 7.5 times the expected number. Parents of the children and of two matched control groups were interviewed about medical history, mother's pregnancy history, school history, and environmental exposures. There were no significant differences between the leukemia victims and persons in the control groups. No leukemia sufferer had contact with a hazardous waste site. While the contaminants of Wells G and H, which had been closed, are not known leukemogens, it is not possible to rule out exposure to this water as a factor, particularly in the eastern Woburn residents.

Cutler, J.J.; Parker, G.S.; Rosen, S.; Prenney, B.; Healey, R.; Caldwell, G.G.

1986-03-01

323

[Chronic lymphocytic leukemia].  

PubMed

Chronic lymphocytic leukemia (CLL) is a lymphoproliferative disorder that accounts for approximately 30 % of adult leukemias and 25 % of Non-Hodgkin lymphomas (NHL). It is the most common form of leukemia in the western world (incidence 3-5/100 000). Elderly people are mainly affected, median age at diagnosis is around 70 years and there is a slight predominance in men. The etiology of the disease is unknown.The initial symtoms are nonspecific. Cervical lymphadenopathy and splenomegaly followed by general fatigue are seen most commonly. Other possible symptoms include night sweats, fever, loss of weight (so-called B symptoms) and frequent infections. Several patients develop autoimmune complications as autoimmune hemolytic anemia (AIHA) or immune thrombocytopenia (ITP).To confirm the diagnosis more than 5000 B-lymphocytes/µl need to be present. The expression of the typical surface markers CD5, CD19, and CD23 has to be confirmed by flow cytometry. Imaging studies as X-ray of the chest, ultrasound of the abdomen, or CT scan are used to assess the degree of lymphadenopathy or organomegaly. A bone marrow biopsy is not mandatory for the diagnosis.According to the European Binet staging system, CLL is divided into 3 stages (A, B and C). Patients in Binet stage A have 0 to 2 areas of node or organ enlargement with normal levels of hemoglobin and platelets. Binet stage B patients have 3 to 5 areas of node or organ enlargement and normal or slightly decreased levels of hemoglobin and platelets. Binet stage C patients have anemia (hemoglobin < 10 g/dl) and/or thrombocytopenia (platelet counts < 100 000/µl), with or without lymphadenopathy or organomegaly.As there is no survival benefit associated with early intervention, asymptomatic patients with early stage CLL (Binet stage A and B) are usually not treated but are followed on a "watch and wait" principle. Treatment indications include stage Binet C or signs of an active disease as rapidly progressive lymphadenopathy or organomegaly together with physical limitation, B symptoms that cannot be tolerated, rapidly deteriorating blood values, or rapidly increasing leukocyte counts.The patient´s physical condition has major impact on the treatment decision. Currently immunochemotherapy with fludarabine, cyclophosphamide and the CD20-antibody rituximab (FCR) is the standard of care in previously untreated and physically fit CLL-patients. An alternative regimen is the combination of bendamustine and rituximab (BR). Physically compromised patients can be treated with the oral drug chlorambucil or with bendamustine with or without rituximab.Due to high morbidity and mortality, allogeneic stem cell transplantation is limited to a small group of patients and should be discussed in a high-risk situation, such as 17p deletion, lack of response to standard therapy or early relapse. PMID:24104591

Maurer, C; Hallek, M

2013-10-08

324

WNT\\/?-Catenin Signaling in Leukemia  

Microsoft Academic Search

\\u000a Leukemia represents the malignant outgrowth of a transformed hematopoietic cell. Normal hematopoiesis develops in a hierarchy\\u000a with a hematopoietic stem cell at its apex and gives rise to progenitor cells that are committed to multiple hematopoietic\\u000a lineages. Leukemia can develop from the stem cell ­compartment (i.e., leading to chronic myeloid leukemia, CML) or committed\\u000a ­lymphoid (acute lymphoblastic leukemia, ALL) and

Markus Müschen

325

Acute Myeloid Leukemia: Epidemiology and Etiology  

Microsoft Academic Search

Although acute leukemias are infrequent diseases, they are highly malignant neoplasms responsible for a large number of cancer-related\\u000a deaths. Acute myeloid leukemia (AML) is the most common type of leukemia in adults, yet continues to have the lowest survival\\u000a rate of all leukemias. While results of treatment have improved steadily in younger adults over the past 20 years, there have

Barbara Deschler; Michael Lübbert

326

Complementation of Hyponastic Leaves1 by Double-Strand RNA-Binding Domains of Dicer-Like1 in Nuclear Dicing Bodies1[W][OPEN  

PubMed Central

MicroRNAs (miRNAs) are a class of small regulatory RNAs that are found in almost all of the eukaryotes. Arabidopsis (Arabidopsis thaliana) miRNAs are processed from primary miRNAs (pri-miRNAs), mainly by the ribonuclease III-like enzyme DICER-LIKE1 (DCL1) and its specific partner, HYPONASTIC LEAVES1 (HYL1), a double-strand RNA-binding protein, both of which contain two double-strand RNA-binding domains (dsRBDs). These dsRBDs are essential for miRNA processing, but the functions of them are not clear. Here, we report that the two dsRBDs of DCL1 (DCL1-D1D2), and to some extent the second dsRBD (DCL1-D2), complement the hyl1 mutant, but not the first dsRBD of DCL1 (DCL1-D1). DCL1-D1 is diffusely distributed throughout the nucleoplasm, whereas DCL1-D2 and DCL1-D1D2 concentrate in nuclear dicing bodies in which DCL1 and HYL1 colocalize. We show further that protein-protein interaction is mainly mediated by DCL1-D2, while DCL1-D1 plays a major role in binding of pri-miRNAs. These results suggest parallel roles between C-terminal dsRBDs of DCL1 and N-terminal dsRBDs of HYL1 and support a model in which Arabidopsis pri-miRNAs are recruited to dicing bodies through functionally divergent dsRBDs of microprocessor for accurate processing of plant pri-miRNAs.

Liu, Qi; Yan, Qingqing; Liu, Yin; Hong, Fang; Sun, Zhenfei; Shi, Leilei; Huang, Ying; Fang, Yuda

2013-01-01

327

Trisomy 21 in acute myeloid leukemia  

Microsoft Academic Search

We report two cases of acute myeloid leukemia (AML), constitutionally normal, with trisomy 21. Trisomy 21 does not often occur as a sole numerical karyotypic abnormality in AML leukemia. The possible prognostic significance of the finding in acute leukemia is discussed.

Chih-Hsin Wei; I-Ting Yu; Cheng-Hwai Tzeng; Frank Sheng Fan; Ruey-Kuen Hsieh; Tzeon-Jye Chiou; Jin-Hwang Liu; Po-Min Chen

1996-01-01

328

How I treat LGL leukemia  

PubMed Central

Large granular lymphocyte (LGL) leukemia is characterized by a clonal expansion of either CD3+ cytotoxic T or CD3? NK cells. Prominent clinical features of T-LGL leukemia include neutropenia, anemia and rheumatoid arthritis (RA). The terminal effector memory phenotype (CD3+/CD45RA+/CD62L?CD57+) of T-LGL suggests a pivotal chronic antigen-driven immune response. LGL survival is then promoted by platelet-derived growth factor and interleukin-15, resulting in global dysregulation of apoptosis and resistance to normal pathways of activation-induced cell death. These pathogenic features explain why treatment of T-LGL leukemia is based on immunosuppressive therapy. The majority of these patients eventually need treatment because of severe or symptomatic neutropenia, anemia, or RA. No standard therapy has been established because of the absence of large prospective trials. The authors use low-dose methotrexate initially for T-LGL leukemia patients with neutropenia and/or RA. We recommend either methotrexate or oral cyclophosphamide as initial therapy for anemia. If treatment is not successful, patients are switched to either the other agent or cyclosporine. The majority of patients experience an indolent clinical course. Deaths infrequently occur because of infections related to severe neutropenia. As there are no curative therapeutic modalities for T-LGL leukemia, new treatment options are needed.

2011-01-01

329

Cranial radiotherapy predisposes to abdominal adiposity in survivors of childhood acute lymphocytic leukemia  

PubMed Central

Background Advances in treatment of acute lymphocytic leukemia increased the likelihood of developing late treatment-associated effects, such as abdominal adiposity, increasing the risk of cardiovascular disease in this population. Cranial radiotherapy is one of the factors that might be involved in this process. The aim of this study was to determine the effect of cranial radiotherapy on adiposity indexes in survivors of acute lymphocytic leukemia. Methods A comparative cross-sectional study of 56 acute lymphocytic leukemia survivors, chronological age between 15 and 24 years, assigned into two groups according to the exposure to cranial radiotherapy (25 irradiated and 31 non-irradiated), assessed according to body fat (dual energy X-ray absorptiometry), computed tomography scan-derived abdominal adipose tissue, lipid profile, and insulin resistance. Results Cranial radiotherapy increased body fat and abdominal adipose tissue and altered lipid panel. Yet, lipids showed no clinical relevance so far. There were significantly more obese patients among those who received cranial radiotherapy (52% irradiated versus 22.6% non-irradiated), based on dual energy X-ray absorptiometry body fat measurements. Nonetheless, no association was observed between cranial radiotherapy and body mass index, waist circumference, waist-to-height ratio or insulin resistance. Conclusions Adolescent and young adult survivors of childhood acute lymphocytic leukemia showed an increase in body fat and an alteration of fat distribution, which were related to cranial radiotherapy. Fat compartment modifications possibly indicate a disease of adipose tissue, and cranial radiotherapy imports in this process.

2013-01-01

330

Idarubicin and Cytarabine With or Without Bevacizumab in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia  

ClinicalTrials.gov

Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Childhood Acute Basophilic Leukemia; Childhood Acute Eosinophilic Leukemia; Childhood Acute Erythroleukemia (M6); Childhood Acute Megakaryocytic Leukemia (M7); Childhood Acute Monoblastic Leukemia (M5a); Childhood Acute Monocytic Leukemia (M5b); Childhood Acute Myeloblastic Leukemia With Maturation (M2); Childhood Acute Myeloblastic Leukemia Without Maturation (M1); Childhood Acute Myelomonocytic Leukemia (M4); Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia; Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies

2013-01-23

331

Reproducibility and accuracy of body composition assessments in mice by dual energy x-ray absorptiometry and time domain nuclear magnetic resonance.  

PubMed

OBJECTIVE: To assess the accuracy and reproducibility of dual-energy absorptiometry (DXA; PIXImus(™)) and time domain nuclear magnetic resonance (TD-NMR; Bruker Optics) for the measurement of body composition of lean and obese mice. SUBJECTS AND MEASUREMENTS: Thirty lean and obese mice (body weight range 19-67 g) were studied. Coefficients of variation for repeated (x 4) DXA and NMR scans of mice were calculated to assess reproducibility. Accuracy was assessed by comparing DXA and NMR results of ten mice to chemical carcass analyses. Accuracy of the respective techniques was also assessed by comparing DXA and NMR results obtained with ground meat samples to chemical analyses. Repeated scans of 10-25 gram samples were performed to test the sensitivity of the DXA and NMR methods to variation in sample mass. RESULTS: In mice, DXA and NMR reproducibility measures were similar for fat tissue mass (FTM) (DXA coefficient of variation [CV]=2.3%; and NMR CV=2.8%) (P=0.47), while reproducibility of lean tissue mass (LTM) estimates were better for DXA (1.0%) than NMR (2.2%) (

body composition lean and obese mice. While DXA and NMR measures are highly correlated with chemical analysis measures, DXA consistently overestimates LTM and FTM (by ~8% and ~46%, respectively), while NMR only slightly underestimates LTM (by ~0.2%) and overestimates FTM (~15%.) The NMR method also has practical advantages compared to DXA, such as speed of measurement and the ability to scan unanesthetized animals. PMID:21909234

Halldorsdottir, Solveig; Carmody, Jill; Boozer, Carol N; Leduc, Charles A; Leibel, Rudolph L

2009-01-01

332

Reproducibility and accuracy of body composition assessments in mice by dual energy x-ray absorptiometry and time domain nuclear magnetic resonance  

PubMed Central

Objective To assess the accuracy and reproducibility of dual-energy absorptiometry (DXA; PIXImus™) and time domain nuclear magnetic resonance (TD-NMR; Bruker Optics) for the measurement of body composition of lean and obese mice. Subjects and measurements Thirty lean and obese mice (body weight range 19–67 g) were studied. Coefficients of variation for repeated (x 4) DXA and NMR scans of mice were calculated to assess reproducibility. Accuracy was assessed by comparing DXA and NMR results of ten mice to chemical carcass analyses. Accuracy of the respective techniques was also assessed by comparing DXA and NMR results obtained with ground meat samples to chemical analyses. Repeated scans of 10–25 gram samples were performed to test the sensitivity of the DXA and NMR methods to variation in sample mass. Results In mice, DXA and NMR reproducibility measures were similar for fat tissue mass (FTM) (DXA coefficient of variation [CV]=2.3%; and NMR CV=2.8%) (P=0.47), while reproducibility of lean tissue mass (LTM) estimates were better for DXA (1.0%) than NMR (2.2%) (

body composition lean and obese mice. While DXA and NMR measures are highly correlated with chemical analysis measures, DXA consistently overestimates LTM and FTM (by ~8% and ~46%, respectively), while NMR only slightly underestimates LTM (by ~0.2%) and overestimates FTM (~15%.) The NMR method also has practical advantages compared to DXA, such as speed of measurement and the ability to scan unanesthetized animals.

Halldorsdottir, Solveig; Carmody, Jill; Boozer, Carol N.; Leduc, Charles A.; Leibel, Rudolph L.

2011-01-01

333

Mutant superoxide dismutase 1 (SOD1), a cause of amyotrophic lateral sclerosis, disrupts the recruitment of SMN, the spinal muscular atrophy protein to nuclear Cajal bodies  

PubMed Central

Spinal muscular atrophy (SMA) and amyotrophic lateral sclerosis (ALS) are among the most common motor neuron diseases to afflict the human population. A deficiency of the survival of motor neuron (SMN) protein causes SMA and is also reported to be an exacerbating factor in the development of ALS. However, pathways linking the two diseases have yet to be defined and it is not clear precisely how the pathology of ALS is aggravated by reduced SMN or whether mutant proteins underlying familial forms of ALS interfere with SMN-related biochemical pathways to exacerbate the neurodegenerative process. In this study, we show that mutant superoxide dismutase-1 (SOD1), a cause of familial ALS, profoundly alters the sub-cellular localization of the SMN protein, preventing the formation of nuclear ‘gems’ by disrupting the recruitment of the protein to Cajal bodies. Overexpressing the SMN protein in mutant SOD1 mice, a model of familial ALS, alleviates this phenomenon, most likely in a cell-autonomous manner, and significantly mitigates the loss of motor neurons in the spinal cord and in culture dishes. In the mice, the onset of the neuromuscular phenotype is delayed and motor function enhanced, suggestive of a therapeutic benefit for ALS patients treated with agents that augment the SMN protein. Nevertheless, this finding is tempered by an inability to prolong survival, a limitation most likely imposed by the inexorable denervation that characterizes ALS and eventually disrupts the neuromuscular synapses even in the presence of increased SMN.

Kariya, Shingo; Re, Diane B.; Jacquier, Arnaud; Nelson, Katelyn; Przedborski, Serge; Monani, Umrao R.

2012-01-01

334

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

ClinicalTrials.gov

Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myelomonocytic Leukemia (M4); Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

2013-07-09

335

[Growth hormone therapy and leukemia].  

PubMed

In this literature study the possible correlation between GH-therapy and leukemia has been critically evaluated. Two central questions have been studied: 'does leukemia occur more often in GH-deficient children in GH-therapy than in age-related normal individuals' and 'which influences of GH administration upon normal and leukemic leukocytes have been described?'. In some cases leukemia developed in GH-deficient children after GH-therapy. The data have shown a higher incidence of leukemia in the population of children treated with GH (5:100,000) than in the age-related normal population of children (2:100,000). However, hard evidence supporting the hypothesis that GH-therapy could induce leukemia has not yet been found. In vivo studies could not detect enhanced growth of blood cells influenced by GH-therapy. In vitro studies showed that GH either stimulated or did not affect the proliferation of unstimulated lymphocytes of GH-deficient children, normal individuals or leukemia-patients. The same effects occurred in leukemic cell lines. On PHA-stimulated lymphocytes of GH-deficient children and normal individuals both enhancing and inhibiting effects of GH have been found. It is suggested that GH-therapy could improve immunological resistance against tumors by improving Natural-Killer-cell activity. In mice GH seemed to influence lymphocyte-differentiation. In mice also an increase in the frequency of chromosomal aberrations related to GH has been observed. This evaluation suggests that patients, treated with GH-therapy should be carefully followed up. Also, the indication for GH-therapy has to be guarded critically. PMID:1557776

Boose, A R; Pieters, R; Delemarre-van de Waal, H A; Veerman, A J

1992-02-01

336

Vaccines as consolidation therapy for myeloid leukemia  

PubMed Central

Immunotherapy for myeloid leukemias remains a cornerstone in the management of this highly aggressive group of malignancies. Allogeneic (allo) stem cell transplantation (SCT), which can be curative in acute and chronic myeloid leukemias, exemplifies the success of immunotherapy for cancer management. However, because of its nonspecific immune response against normal tissue, allo-SCT is associated with high rates of morbidity and mortality, secondary to graft-versus-host disease, which can occur in up to 50% of allo-SCT recipients. Targeted immunotherapy using leukemia vaccines has been heavily investigated, as these vaccines elicit specific immune responses against leukemia cells while sparing normal tissue. Peptide and cellular vaccines have been developed against tumor-specific and leukemia-associated self-antigens. Although not yet considered the standard of care, leukemia vaccines continue to show promising results in the management of the myeloid leukemias.

Alatrash, Gheath; Molldrem, Jeffrey J

2011-01-01

337

Bortezomib and Combination Chemotherapy in Treating Younger Patients With Recurrent, Refractory, or Secondary Acute Myeloid Leukemia  

ClinicalTrials.gov

Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myelomonocytic Leukemia (M4); Childhood Acute Basophilic Leukemia; Childhood Acute Eosinophilic Leukemia; Childhood Acute Erythroleukemia (M6); Childhood Acute Megakaryocytic Leukemia (M7); Childhood Acute Minimally Differentiated Myeloid Leukemia (M0); Childhood Acute Monoblastic Leukemia (M5a); Childhood Acute Monocytic Leukemia (M5b); Childhood Acute Myeloblastic Leukemia With Maturation (M2); Childhood Acute Myeloblastic Leukemia Without Maturation (M1); Childhood Acute Myelomonocytic Leukemia (M4); Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia

2012-12-03

338

Tipifarnib in Treating Patients With Acute Myeloid Leukemia in Remission  

ClinicalTrials.gov

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; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Recurrent Adult Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts in Transformation

2013-10-07

339

Treatment of mouse leukemia with heavy x-irradiation followed by spleen transplantation  

Microsoft Academic Search

Attempts have been made to cure carcinogen-induced leukemia in mice by a ; supralethal dose of x rays on the whole-body and followed by transplantation of ; isologous spleen cells. Of 16 leukemic mice treated with 1200 r before large ; lymphomas had developed, 6 died from the irradiation, 8 died from leukemic ; relapse, and 2 are still alive

M. Simonsen; holm J Engelbreth; E. Jensen; H. Poulsen

1960-01-01

340

Sorafenib Tosylate and Chemotherapy in Treating Older Patients With Acute Myeloid Leukemia  

ClinicalTrials.gov

Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

2013-04-22

341

Proliferation and apoptosis in acute and chronic leukemias and myelodysplastic syndrome  

Microsoft Academic Search

Clonal expansion of leukemic cells is thought to be due to proliferation in excess of apoptosis. To define and compare proliferation and apoptosis between various leukemias and myelodysplastic syndrome (MDS), we measured proliferating cell nuclear antigen (PCNA) and bromodeoxyuridine (BrdU) incorporation as surrogate markers for proliferation and caspase 3 activity and annexin V surface binding as surrogate markers for activation

Chung Wu Lin; Taghi Manshouri; Iman Jilani; Donna Neuberg; Kunal Patel; Hagop Kantarjian; Michael Andreeff; Zeev Estrov; Miloslav Beran; Michael Keating; Elihu Estey; Maher Albitar

2002-01-01

342

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

ClinicalTrials.gov

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

2013-01-25

343

Combination Chemotherapy and Imatinib Mesylate in Treating Children With Relapsed Acute Lymphoblastic Leukemia  

ClinicalTrials.gov

L1 Childhood Acute Lymphoblastic Leukemia; L2 Childhood Acute Lymphoblastic Leukemia; Non-T, Non-B Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; T-cell Childhood Acute Lymphoblastic Leukemia

2013-10-07

344

3-AP and Fludarabine in Treating Patients With Myeloproliferative Disorders, Chronic Myelomonocytic Leukemia, or Accelerated Phase or Blastic Phase Chronic Myelogenous Leukemia  

ClinicalTrials.gov

Accelerated Phase Chronic Myelogenous Leukemia; Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative; Blastic Phase Chronic Myelogenous Leukemia; Chronic Eosinophilic Leukemia; Chronic Myelomonocytic Leukemia; Essential Thrombocythemia; Philadelphia Chromosome Negative Chronic Myelogenous Leukemia; Polycythemia Vera; Primary Myelofibrosis; Relapsing Chronic Myelogenous Leukemia

2013-02-19

345

VIEW OF A BODY COUNTING ROOM IN BUILDING 122. BODY ...  

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

VIEW OF A BODY COUNTING ROOM IN BUILDING 122. BODY COUNTING MEASURES RADIOACTIVE MATERIAL IN THE BODY. DESIGNED TO MINIMIZE EXTERNAL SOURCES OF RADIATION, BODY COUNTING ROOMS ARE CONSTRUCTED OF PRE-WORLD WAR II (WWII) STEEL. PRE-WWII STEEL, WHICH HAS NOT BEEN AFFECTED BY NUCLEAR FALLOUT, IS LOWER IS RADIOACTIVITY THAN STEEL CREATED AFTER WWII. (10/25/85) - Rocky Flats Plant, Emergency Medical Services Facility, Southwest corner of Central & Third Avenues, Golden, Jefferson County, CO

346

Body Image  

MedlinePLUS

Home > Body Image Body Image Developing a positive body image and a healthy mental attitude is crucial to a woman's happiness and wellness. Read ... Body Image email updates. Enter email address Submit Body Image news September 27, 2013 - Stem Cells From Fat ...

347

The state of the reproductive system of the tench Tinca tinca (1999–2005) from water bodies polluted as a result of the catastrophe at the Chernobyl Nuclear Power Plant  

Microsoft Academic Search

The state of the reproductive system of Tinca tinca—descendants of individuals that were exposed to radiation as a result of the catastrophe at the Chernobyl Nuclear Power Plant\\u000a in 1986 was studied. Material was collected in the postemergency period in radionuclide-polluted water bodies: in the Ukraine,\\u000a in Kiev Reservoir, the Teterev River, and Lake Glubokoe (1999–2005) and in Belarus, in

N. V. Belova; N. G. Emel’yanova; A. P. Makeeva; I. N. Ryabov

2006-01-01

348

Investigation of the Bovine Leukemia Virus Proviral DNA in Human Leukemias and Lung cancers in Korea  

PubMed Central

The bovine leukemia virus (BLV) is the causative agent of enzootic bovine leucosis. This study investigated the presence of the BLV in leukemia (179 acute lymphoblastic leukemia, 292 acute myeloid leukemia and 46 chronic myelogenous leukemia cases) and 162 lung cancer patients (139 adenocarcinoma, 23 squamous cell carcinoma) to determine if the BLV is a causative organism of leukemia and lung cancer in Koreans. A BLV infection was confirmed in human cells by PCR using a BLV-8 primer combination. All 517 cases of human leukemia and 162 lung cancer were negative for a PCR of the BLV proviral DNA. In conclusion, although meat has been imported from BLV endemic areas, the BLV infection does not appear to be the cause of human leukemia or lung cancer in Koreans. These results can be used as a control for further studies on the BLV in Koreans.

Lee, Jehoon; Kim, Yonggoo; Kang, Chang Suk; Cho, Dae Hyun; Shin, Dong Hwan; Yum, Young Na; Oh, Jae Ho; Kim, Sheen Hee; Hwang, Myung Sil; Lim, Chul Joo; Yang, Ki Hwa

2005-01-01

349

Acute Lymphoblastic Leukemia (ALL) Treatment in Adults (Beyond the Basics)  

MedlinePLUS

... Leukemia Patient information Patient information: Acute lymphoblastic leukemia (ALL) treatment in adults (Beyond the Basics) Author Richard ... article ACUTE LYMPHOBLASTIC LEUKEMIA OVERVIEW GENERAL INFORMATION ABOUT ALL TREATMENT INDUCTION OF REMISSION CONSOLIDATION/INTENSIFICATION THERAPY MAINTENANCE ...

350

What Should You Ask Your Doctor about Acute Lymphocytic Leukemia?  

MedlinePLUS

... leukemia? What should you ask your doctor about acute lymphocytic leukemia? It is important to have frank, honest discussions ... answer many of your questions. What kind of acute lymphocytic leukemia (ALL) do I have? Do I have any ...

351

What's New in Childhood Leukemia Research and Treatment?  

MedlinePLUS

... Topic To learn more about childhood leukemia What`s new in childhood leukemia research and treatment? Researchers are ... Children Talking With Your Doctor After Treatment What`s New in Leukemia in Children Research? Other Resources and ...

352

Adult T-cell Leukemia/Lymphoma: A Retroviral Malady  

PubMed Central

Adult T-cell leukemia/lymphoma (ATLL) is an aggressive leukemia/lymphoma of mature T-lymphocytes caused by human T-cell lymphotropic virus type 1 (HTLV-1). At a tertiary healthcare center in South India, a 58-year-old female presented with multiple erythematous, crusted, and umbilicated papules over the body along with cervical lymphadenopathy. The skin biopsy was consistent with cutaneous T-cell lymphoma. Although she responded initially to chemotherapy, the disease relapsed after 3 months, and she developed disseminated infiltrated skin lesions, generalized lymphadenopathy, and leukemia. Due to the unusual clinical findings we did HTLV-1 Enzyme-linked immunosorbent assay (ELISA), which turned out to be positive in high titers. Her mother had died at an early age from a hematological malignancy and her daughter was also found to be seropositive. To the best of our knowledge, this is the first case to be reported from India of the chronic type of ATLL associated with mother-to-child transmission of HTLV-1 in two generations. This case also emphasizes that the chronic type of ATLL can occur in nonendemic areas like India and should be suspected in nonresponding cases of mycosis fungoides. It should be kept in mind that the chronic type often presents without hypercalcemia or the characteristic ‘flower cells’ in the peripheral smear.

Khader, Anza; Shaan, Mohamed; Sasidharanpillai, Saritha; Pakran, Jaheersha; Rajan, Uma

2012-01-01

353

A basis for updating our approach to resistant acute leukemia.  

PubMed

No studies exist documenting that chemotherapy alone eradicates tumors composed of leukemic cells in a large group of patients with tumors at any one site. Yet, its use has continued over 40 years in the absence of data. Consensus protocols exist only for testis and meningeal tumors, relying on local therapy. To constitute a body of knowledge about tumors at one site, the breast was chosen and all published cases were analyzed, with follow-up obtained, to document the behavior of acute leukemia tumors and survival after presentation. Among 235 cases (52% published since 2000), overall survival was poor, particularly for the 43% with concurrent morphologic marrow relapse, with 66-73% one-year mortality. Only 4 of 106 patients treated with chemotherapy alone survived 4 years. The majority of AML and ALL tumors were only transiently responsive to anti-leukemia treatments, including transplant, and next relapses were as, or more, common in further tumors than in marrow. A pattern of tumors similar to the metastases of invasive lobular breast cancer was revealed. When relapse occurred in marrow, durable remission was only rarely obtained. These data suggest a potential benefit of incorporating extent of disease workup at diagnosis and relapse into prospective trials. This could yield an accurate incidence of extramedullary tumors and a means to identify occult residual disease which could lead to marrow relapse. This approach could potentially result in greater success in curing acute leukemias. PMID:22287495

Cunningham, Isabel

2012-01-28

354

Body Image  

MedlinePLUS

... and confident in your body. Body Image and Eating Disorders People with negative body image have a greater likelihood of developing an eating disorder and are more likely to suffer from feelings ...

355

Pharmacogenomic considerations of xenograft mouse models of acute leukemia.  

PubMed

The use of combination chemotherapy to cure acute lymphoblastic leukemia in children and acute myeloid leukemia in adults emerged for acute myeloid leukemia in the 1960s and for acute lymphoblastic leukemia in the 1980s as a paradigm for curing any disseminated cancer. This article summarizes recent developments and considerations in the use of acute leukemia xenografts established in immunodeficient mice to elucidate the genetic and genomic basis of acute leukemia pathogenesis and treatment response. PMID:23171339

Guihard, Soizic; Peyrouze, Pauline; Cheok, Meyling H

2012-11-01

356

Promyelocytic leukemia protein modulates establishment and maintenance of latent gammaherpesvirus infection in peritoneal cells.  

PubMed

Promyelocytic leukemia protein (PML) is an essential organizer of PML nuclear bodies (NBs), which carry out a variety of activities, including antiviral functions. Herpesviruses from all subfamilies encode proteins that counteract PML NB-mediated antiviral defenses by multiple mechanisms. However, because of the species specificity of herpesviruses, only a limited number of in vivo studies have been undertaken to investigate the effect of PML or PML NBs on herpesvirus infection. To address this central issue in herpesvirus biology, we studied the course of infection in wild-type and PML(-/-) mice using murine gammaherpesvirus 68 (MHV68), which encodes a tegument protein that induces PML degradation. While acute infection in PML(-/-) mice progressed similarly to that in wild-type mice, the lytic reactivation frequency was higher in peritoneal exudate cells, due to both an increase of MHV68 genome-positive cells and greater reactivation efficiency. We also detected a higher frequency of persistent infection in PML(-/-) peritoneal cells. These findings suggest that the PML protein can repress the establishment or maintenance of gammaherpesvirus latency in vivo. Further use of the PML(-/-) mouse model should aid in dissecting the molecular mechanisms that underlie the role of PML in gammaherpesvirus latency and may yield clues for how PML modulates herpesvirus latency in general. PMID:23986598

Sewatanon, Jaturong; Liu, Hao; Ling, Paul D

2013-08-28

357

Repetitive disruptions of the nuclear envelope invoke temporary loss of cellular compartmentalization in laminopathies.  

PubMed

The nuclear lamina provides structural support to the nucleus and has a central role in nuclear organization and gene regulation. Defects in its constituents, the lamins, lead to a class of genetic diseases collectively referred to as laminopathies. Using live cell imaging, we observed the occurrence of intermittent, non-lethal ruptures of the nuclear envelope in dermal fibroblast cultures of patients with different mutations of lamin A/C. These ruptures, which were absent in normal fibroblasts, could be mimicked by selective knockdown as well as knockout of LMNA and were accompanied by the loss of cellular compartmentalization. This was demonstrated by the influx of cytoplasmic transcription factor RelA and regulatory protein Cyclin B1 into the nucleus, and efflux of nuclear transcription factor OCT1 and nuclear structures containing the promyelocytic leukemia (PML) tumour suppressor protein to the cytoplasm. While recovery of enhanced yellow fluorescent protein-tagged nuclear localization signal in the nucleus demonstrated restoration of nuclear membrane integrity, part of the mobile PML structures became permanently translocated to the cytoplasm. These satellite PML structures were devoid of the typical PML body components, such as DAXX, SP100 or SUMO1. Our data suggest that nuclear rupture and loss of compartmentalization may add to cellular dysfunction and disease development in various laminopathies. PMID:21831885

De Vos, Winnok H; Houben, Frederik; Kamps, Miriam; Malhas, Ashraf; Verheyen, Fons; Cox, Juliën; Manders, Erik M M; Verstraeten, Valerie L R M; van Steensel, Maurice A M; Marcelis, Carlo L M; van den Wijngaard, Arthur; Vaux, David J; Ramaekers, Frans C S; Broers, Jos L V

2011-08-10

358

Recognizing familial myeloid leukemia in adults  

PubMed Central

Germline testing for familial cases of myeloid leukemia in adults is becoming more common with the recognition of multiple genetic syndromes predisposing people to bone marrow disease. Currently, Clinical Laboratory Improvement Amendments approved testing exists for several myeloid leukemia predisposition syndromes: familial platelet disorder with propensity to acute myeloid leukemia (FPD/AML), caused by mutations in RUNX1; familial AML with mutated CEBPA; familial myelodysplastic syndrome and acute leukemia with mutated GATA2; and the inherited bone marrow failure syndromes, including dyskeratosis congenita, a disease of abnormal telomere maintenance. With the recognition of additional families with a genetic component to their leukemia, new predisposition alleles will likely be identified. We highlight how to recognize and manage these cases as well as outline the characteristics of the major known syndromes. We look forward to future research increasing our understanding of the scope of inherited myeloid leukemia syndromes.

Nickels, Eric M.; Soodalter, Jesse; Churpek, Jane E.

2013-01-01

359

Recognizing familial myeloid leukemia in adults.  

PubMed

Germline testing for familial cases of myeloid leukemia in adults is becoming more common with the recognition of multiple genetic syndromes predisposing people to bone marrow disease. Currently, Clinical Laboratory Improvement Amendments approved testing exists for several myeloid leukemia predisposition syndromes: familial platelet disorder with propensity to acute myeloid leukemia (FPD/AML), caused by mutations in RUNX1; familial AML with mutated CEBPA; familial myelodysplastic syndrome and acute leukemia with mutated GATA2; and the inherited bone marrow failure syndromes, including dyskeratosis congenita, a disease of abnormal telomere maintenance. With the recognition of additional families with a genetic component to their leukemia, new predisposition alleles will likely be identified. We highlight how to recognize and manage these cases as well as outline the characteristics of the major known syndromes. We look forward to future research increasing our understanding of the scope of inherited myeloid leukemia syndromes. PMID:23926458

Nickels, Eric M; Soodalter, Jesse; Churpek, Jane E; Godley, Lucy A

2013-08-01

360

The Pathogenesis of Mixed Lineage Leukemia  

PubMed Central

Aggressive leukemias arise in both children and adults as a result of rearrangements to the Mixed Lineage Leukemia (MLL) gene located on chromosome 11q23. The MLL gene encodes a large histone methyltransferase that directly binds and positively regulates gene transcription including HOX genes. MLL is involved in chromosomal translocations, partial tandem duplication and amplifications, all of which result in hematopoietic malignancies due to sustained HOX expression and stalled differentiation. MLL lesions are associated with both acute myeloid leukemia (AML) and acute lymphoid leukemia (ALL) and are usually associated with a relatively poor prognosis despite improved treatment options like allogeneic hematopoietic stem cell transplantation underscoring the need for new treatment regimens. Recent advances have begun to reveal the molecular mechanisms driving MLL associated leukemias which have provided opportunities for therapeutic development. Here we discuss the etiology of MLL leukemias and potential directions for therapeutic development.

Muntean, Andrew G.; Hess, Jay L.

2012-01-01

361

Transplantability of human lymphoid cell line, lymphoma, and leukemia in splenectomized and/or irradiated nude mice  

SciTech Connect

The effects of splenectomy and/or whole-body irradiation of nude mice before xenotransplantation of lymphoid cell lines, lymphoma, and leukemia were studied. Transplantation after whole-body irradiation resulted in the increased ''take'' rate of three cultured cell lines (two of T-cell-derived acute lymphocytic leukemia and one of B-cell derived acute lymphocytic leukemia) and in the tumorous growth of Burkitt-derived Raji and spontaneously transformed lymphoblastoid cell lines. With splenectomy plus irradiation as a pretreatment, tumorous growth occurred in four other cell lines which were not transplantable after irradiation only (two cell lines of Epstein-Barr virus-transformed cord blood cells and one each of null acute lymphocytic leukemia and nodular lymphoma-derived cell lines). Direct transplantation of leukemia and lymphoma cells into the pretreated mice was successful in 7 of 24 cases (29%). B-cell-derived diffuse large lymphoid lymphoma was transplantable in three of seven cases (43%). However, lymphoma and leukemia of peripheral T-cell origin was difficult to transplant even with pretreatment, and only one pleomorphic T-cell lymphoma grew to a significant size (2 cm). One tumor each of B-cell-derived diffuse large lymphoid and T-cell diffuse lymphoblastic lymphoma became transplantable.

Watanabe, S.; Shimosato, Y.; Kuroki, M.; Sato, Y.; Nakajima, T.

1980-07-01

362

Risk of extramedullary relapse following allogeneic bone marrow transplantation for acute myelogenous leukemia with leukemia cutis  

Microsoft Academic Search

Leukemia cutis (LC) is a rare feature of acute myeloblastic leukemia (AML). Little information is available regarding its prognostic influence on post-transplant outcome. In our institution, 202 patients with AML received an allogeneic HLA-identical marrow transplant from related donors between March 1982 and January 1994. Thirteen patients had prior leukemic involvement of the skin (leukemia cutis or LC group) while

G Michel; F Boulad; TN Small; P Black; G Heller; H Castro-Malaspina; BH Childs; AP Gillio; EB Papadopoulos; JW Young; NA Kernan; RJ O’Reilly

1997-01-01

363

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

Microsoft Academic Search

We have described a severe combined immunodeficiency (SCID) mouse model that permits the subcutaneous growth of primary human acute leukemia blast cells into a measurable subcutaneous nodule which may be followed by the development of disseminated disease. Utilizing the SCID mouse model, we examined the growth potential of leukemic blasts from 133 patients with acute leukemia, (67 acute lymphoblastic leukemia

Ying Yan; Eric A Wieman; Xiuqin Guan; Ann A Jakubowski; Peter G Steinherz; Richard J O'Reilly

2009-01-01

364

SUMOylation of the Forkhead Transcription Factor FOXL2 Promotes Its Stabilization/Activation through Transient Recruitment to PML Bodies  

PubMed Central

Background FOXL2 is a transcription factor essential for ovarian development and maintenance. It is mutated in the genetic condition called Blepharophimosis Ptosis Epicantus inversus Syndrome (BPES) and in cases of isolated premature ovarian failure. We and others have previously shown that FOXL2 undergoes several post-translational modifications. Methods and Principal Findings Here, using cells in culture, we show that interference with FOXL2 SUMOylation leads to a robust inhibition of its transactivation ability, which correlates with a decreased stability. Interestingly, FOXL2 SUMOylation promotes its transient recruitment to subnuclear structures that we demonstrate to be PML (Promyelocytic Leukemia) Nuclear Bodies. Since PML bodies are known to be sites where post-translational modifications of nuclear factors take place, we used tandem mass spectrometry to identify new post-translational modifications of FOXL2. Specifically, we detected four phosphorylated, one sulfated and three acetylated sites. Conclusions By analogy with other transcription factors, we propose that PML Nuclear Bodies might transiently recruit FOXL2 to the vicinity of locally concentrated enzymes that could be involved in the post-translational maturation of FOXL2. FOXL2 acetylation, sulfation, phosphorylation as well as other modifications yet to be discovered might alter the transactivation capacity of FOXL2 and/or its stability, thus modulating its global intracellular activity.

Georges, Adrien; Benayoun, Berenice A.; Marongiu, Mara; Dipietromaria, Aurelie; L'Hote, David; Todeschini, Anne-Laure; Auer, Jana; Crisponi, Laura; Veitia, Reiner A.

2011-01-01

365

Molecular Pathology of Chronic Myelogenous Leukemia  

Microsoft Academic Search

The presence of Philadelphia chromosome t(9:22) is a hallmark of 95% of clinical cases of chronic myelogenous leukemia (CML) as well as 20% of adult acute lympho-blastic leukemia (ALL) and 5 % of acute myeloid leukemia (AML). The product of t(9;22) is a fusion protein BCR-ABL. The fusion proteins of CML, ALL and AML have increased tyro-sine kinase activity and

Iza Gorska-Flipot; Conolly Norman; Lynda Addy; Mark Minden

1990-01-01

366

Ultrastructure of adult T-cell leukemia\\/lymphoma  

Microsoft Academic Search

Summary  Eighteen cases of adult T-cell leukemia\\/lymphoma (ATLL) in Japan were analyzed by electron microscopy and compared with 5\\u000a cases of B-lymphoma and well-established groups of T-lymphomas (4 cases of T-lymphoblastic lymphoma and 2 cases of Sézary\\u000a syndrome). Five hundred cells in each case, categorized ultrastructurally as to the cellular size and nuclear shape, showed\\u000a an essentially pleomorphic cellular distribution in

Tadaaki Eimoto; Tetsuji Mitsui; Masahiro Kikuchi

1981-01-01

367

Azacitidine, Mitoxantrone Hydrochloride, and Etoposide in Treating Older Patients With Poor-Prognosis Acute Myeloid Leukemia  

ClinicalTrials.gov

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

2013-09-23

368

STAT-related transcription factors are constitutively activated in peripheral blood cells from acute leukemia patients.  

PubMed

A signal transduction pathway activated by many cytokines has recently been elaborated. The JAK kinases and the signal transducers and activators of transcription (STAT) factors have been found to be essential components. In this report, we describe the presence of constitutively activated STAT factors in peripheral blood cells from patients with acute leukemia. We used oligonucleotide probes from the beta-casein and IRF-1 gene promoters and the ISRE probe to detect STAT proteins in nuclear extracts from acute leukemia cells in bandshift assays. Specific DNA protein complex formation was observed with the probes from the beta-casein and IRF-1 gene promoters, but not with the ISRE oligonucleotide probe, when cell extracts from acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) were investigated. We used nonradioactive oligonucleotides as competitors to show the specificity of the complex formation. Specific antibodies directed against the individual STAT proteins were used in supershift experiments. STAT5- and STAT1-related factors were detected in ALL and STAT1-, STAT3-, and STAT5-related proteins were present in nuclear cell extracts from AML. Since the cells were not treated with cytokines before the nuclear proteins were extracted, we conclude that these factors are constitutively activated in vivo. It is likely that the constitutive activation of STAT proteins is a part of the events of leukemogenesis. PMID:8634413

Gouilleux-Gruart, V; Gouilleux, F; Desaint, C; Claisse, J F; Capiod, J C; Delobel, J; Weber-Nordt, R; Dusanter-Fourt, I; Dreyfus, F; Groner, B; Prin, L

1996-03-01

369

How Is Chronic Lymphocytic Leukemia Treated?  

MedlinePLUS

... chronic lymphocytic leukemia treated? This information represents the views of the doctors and nurses serving on the American Cancer Society's Cancer Information Database Editorial Board. These ...

370

Selective T-Cell Depletion to Reduce GVHD (Patients) Receiving Stem Cell Tx to Treat Leukemia, Lymphoma or MDS  

ClinicalTrials.gov

Graft vs Host Disease; Myelodysplastic Syndromes; Leukemia; Leukemia, Myeloid; Leukemia, Myelomonocytic, Chronic; Leukemia, Lymphocytic; Lymphoma; Lymphoma, Mantle-cell; Lymphoma, Non-Hodgkin; Hodgkin Disease

2011-12-09

371

Immunotherapy for Acute Lymphocytic Leukemia  

Microsoft Academic Search

\\u000a While a majority of patients with acute lymphocytic leukemia (ALL) demonstrate response following treatment with standard\\u000a chemotherapy, subsequent progression due to the emergence of resistant disease is often encountered. The failure to eradicate\\u000a disease is most commonly observed in adult patients particularly with high-risk features such as adverse cytogenetics. In\\u000a contrast, immunotherapy may be successful in targeting chemotherapy-resistant clones. The

Jacalyn Rosenblatt; David Avigan

372

Functional and morphologic characteristics of the leukemic cells of a patient with acute monocytic leukemia: correlation with clinical features.  

PubMed

The clinical course of a patient with acute monocytic leukemia and prominent infiltration of the skin and testes is described. In vitro studies demonstrated that the circulating monocyte precursors were capable of adherence to nylon fibers, and phagocytosis of bacteria and latex particles. In vivo, migration of leukemic cells to skin windows was observed. Extreme nuclear folding, marked surface activity, and morphologic features suggesting nuclear and cytoplasmic maturation were seen by light and electron microscopy. The presence of morphologically and functionally more differentiated monocytic cells may account for the marked tiuuse invasion in this patient and, possibly, in other patients with monocytic leukemia. PMID:1055611

Schiffer, C A; Sanel, F T; Stechmiller, B K; Wiernik, P H

1975-07-01

373

Treatment of hairy-cell leukemia with chemoradiotherapy and identical-twin bone-marrow transplantation  

SciTech Connect

A patient with progressive hairy-cell leukemia and a normal genetically identical twin presented an opportunity to determine the sensitivity of this disease to high-dose alkylating-agent chemotherapy and total-body irradiation, since the marrow aplasia induced could potentially be overcome by reconstitution with normal marrow stem cells from the twin. After such therapy the patient rapidly recovered normal marrow function with no evidence of infiltrating hairy cells; he is still in complete remission four years after transplantation. In contrast to other patients with this disorder, he has had no predisposition to infections since transplantation. These results demonstrate that hairy-cell leukemia is sensitive to high-dose cytotoxic therapy and is not associated with any microenvironmental abnormalities that prevent repopulation with normal stem cells. Thus, high-dose chemoradiotherapy followed by bone-marrow transplantation is an effective and potentially curative therapy for hairy-cell leukemia. (JMT)

Cheever, M.A. (Univ. of Washington, Seattle); Fefer, A.; Greenberg, P.D.; Appelbaum, F.; Armitage, J.O.; Buckner, C.D.; Sale, G.E.; Storb, R.; Witherspoon, R.P.; Thomas, E.D.

1982-08-01

374

Epidemiology of acute lymphoblastic leukemia  

SciTech Connect

Although the etiology of acute leukemia is largely unknown, some facets of the puzzle are becoming clarified. Recognition of important patterns in age-specific mortality rates has suggested that events early in life, perhaps even prenatally, may have an influence on developing leukemia in childhood. The racial differences evident in mortality, incidence, and immunologic subtype of ALL suggest either differences in exposures to certain factors or differences in responses to those factors by white children. Hereditary factors appear to play a role. Familial and hereditary conditions exist that have high incidences of acute leukemia. Chromosomal anomalies are common in these conditions. Viral infections may play a role by contributing to alteration in genetic material through incorporation of the viral genome. How that virus is dealt with after primary infection seems important. The presence of immunodeficiency may allow wider dissemination or enhanced replication of such viruses, thereby increasing the likelihood of cellular transformation to an abnormal cell. Proliferation of that malignant cell to a clone may depend on other cofactors. Perhaps prolonged exposure to substances like benzene or alkylating agents may enhance these interactions between virus and genetic material. Does this change DNA repair mechanisms. Are viral infections handled differently. Is viral genomic information more easily integrated into host cells. Ionizing radiation has multiple effects. Alteration in genetic material occurs both at the molecular and chromosomal levels. DNA may be altered, lost, or added in the cell's attempt to recover from the injury.

Pendergrass, T.W.

1985-06-01

375

Body Composition.  

ERIC Educational Resources Information Center

Body composition refers to the types and amounts of tissues which make up the body. The most acceptable method for assessing body composition is underwater weighing. A subcutaneous skinfold provides a quantitative measurement of fat below the skin. The skinfold technique permits a valid estimate of the body's total fat content. (JN)

Mayhew, Jerry L.

1981-01-01

376

Hematopoietic stem cells and progenitors of chronic myeloid leukemia express leukemia-associated antigens: implications for the graft-versus-leukemia effect and peptide vaccine-based immunotherapy  

Microsoft Academic Search

The cure of chronic myeloid leukemia (CML) patients following allogeneic stem cell transplantation (SCT) is attributed to graft-versus-leukemia (GVL) effects targeting alloantigens and\\/or leukemia-associated antigens (LAA) on leukemia cells. To assess the potential of LAA-peptide vaccines in eliminating leukemia in CML patients, we measured WT1, PR3, ELA2 and PRAME expression in CD34+ progenitor subpopulations in CML patients and compared them

A S M Yong; K Keyvanfar; R Eniafe; B N Savani; K Rezvani; E M Sloand; J M Goldman; A J Barrett; ASM Yong

2008-01-01

377

Oncogene Activation in Myeloid Leukemias by Graffi Murine Leukemia Virus Proviral Integration  

PubMed Central

The Graffi murine leukemia virus (MuLV) is a nondefective retrovirus that induces granulocytic leukemia in BALB/c and NFS mice. To identify genes involved in Graffi MuLV-induced granulocytic leukemia, tumor cell DNAs were examined for genetic alterations at loci described as common proviral integration sites in MuLV-induced myeloid, lymphoid, and erythroid leukemias. Southern blot analysis revealed rearrangements in c-myc, Fli-1, Pim-1, and Spi-1/PU.1 genes in 20, 10, 3.3, and 3.3% of the tumors tested, respectively. These results demonstrate for the first time the involvement of those genes in granulocytic leukemia.

Denicourt, Catherine; Edouard, Elsy; Rassart, Eric

1999-01-01

378

PML nuclear bodies are highly organised DNA-protein structures with a function in heterochromatin remodelling at the G2 phase  

Microsoft Academic Search

We have recently demonstrated that heterochromatin HP1 proteins are aberrantly distributed in lymphocytes of patients with immunodeficiency, centromeric instability and facial dysmorphy (ICF) syndrome. The three HP1 proteins accumulate in one giant body over the 1qh and 16qh juxtacentromeric heterochromatins, which are hypomethylated in ICF. The presence of PML (promyelocytic leukaemia) protein within this body suggests it to be a

Judith J. Luciani; Danielle Depetris; Yves Usson; Catherine Metzler-Guillemain; Cecile Mignon-Ravix; Michael J. Mitchell; Andre Megarbane; Pierre Sarda; Huseyin Sirma; Anne Moncla; Jean Feunteun; Marie-Genevieve Mattei

2006-01-01

379

Triangle Universities Nuclear Laboratory  

SciTech Connect

This report contains brief papers that discusses the following topics: Fundamental Symmetries in the Nucleus; Internucleon Interactions; Dynamics of Very Light Nuclei; Facets of the Nuclear Many-Body Problem; and Nuclear Instruments and Methods.

Not Available

1991-01-01

380

Childhood leukaemia and nuclear power  

Microsoft Academic Search

There has been considerable scientific and media interest in the question of whether the risk of childhood leukemia is raised near nuclear facilities, and, if so, the reasons why. Serious consideration of this issue was initiated by a media report of an unusually large number of cases around the Sellafield installation in England, and reports of excess cases in the

R. J. Berry; R. Wakeford

1992-01-01

381

Cloning of the bovine leukemia virus proteinase in Escherichia coli and comparison of its specificity to that of human T-cell leukemia virus proteinase.  

PubMed

The proteinase of bovine leukemia virus (BLV) was cloned into pMal-c2 vector with N-terminal or with N- as well as C-terminal flanking sequences, and expressed in fusion with maltose binding protein. The proteinase self-processed itself from the fusion protein during expression and formed inclusion bodies. The enzyme was purified from inclusion bodies by cation-exchange chromatography followed by gel filtration. Specificity of the enzyme was compared to that of human T-cell leukemia proteinase type 1. Although the two viruses belong to the same subfamily of retroviruses, the differences in their proteinase specificity, based on kinetics with oligopeptide substrates representing naturally occurring cleavage sites as well as on inhibition pattern, appear to be pronounced. PMID:10719169

Zahuczky, G; Boross, P; Bagossi, P; Emri, G; Copeland, T D; Oroszlan, S; Louis, J M; Tözsér, J

2000-03-16

382

Nuclear Theory - Nuclear Power  

NASA Astrophysics Data System (ADS)

The results from modern nuclear theory are accurate and reliable enough to be used for practical applications, in particular for scattering that involves few-nucleon systems of importance to nuclear power. Using well-established nucleon-nucleon (NN) interactions that fit well the NN scattering data, and the AGS form of the three-body theory, we have performed precise calculations of low-energy neutron-deuteron (n+d) scattering. We show that three-nucleon force effects that have impact on the low-energy vector analyzing powers have no practical effects on the angular distribution of the n+d cross-section. There appear to be problems for this scattering in the evaluated nuclear data file (ENDF) libraries, at the incident neutron energies less than 3.2 MeV. Supporting experimental data in this energy region are rather old (>25 years), sparse and often inconsistent. Our three-body results at low energies, 50 keV to 10.0 MeV, are compared to the ENDF/B-VII.0 and JENDL (Japanese Evaluated Nuclear Data Library) -3.3 evaluated angular distributions. The impact of these results on the calculated reactivity for various critical systems involving heavy water is shown.

Svenne, J. P.; Canton, L.; Kozier, K. S.

2008-01-01

383

Estimation of internal exposure of the thyroid to (131)I on the basis of (134)Cs accumulated in the body among evacuees of the Fukushima Daiichi Nuclear Power Station accident.  

PubMed

Namie Town was heavily contaminated by the Fukushima Daiichi Nuclear Power Station accident. The thyroid equivalent dose for residents who lived in Namie was estimated using results of whole body counting examinations which were carried out by the Japan Atomic Energy Agency a few months after the nuclear accident. Photon peaks of (131)I and (134)Cs were previously measured by the authors using a NaI(Tl) scintillation spectrometer and that information was used to estimate the (131)I/(134)Cs activity ratio of total intake in the present study. The maximum values of (131)I/(134)Cs activity ratio corresponding to thyroid uptake factors of 0.3, 0.1 and 0.03 were evaluated to be 0.9, 2.6 and 8.7, respectively. The maximum value of the (131)I/(134)Cs activity ratio was used to obtain the most conservative thyroid equivalent dose estimation. The maximum internal exposure of the thyroid to (131)I on the basis of (134)Cs accumulated in the body measured by the whole body counter was estimated to be 18mSv. This value was much smaller than 50mSv that the International Atomic Energy Agency recommends as the dose at which exposed persons should take stable iodine tablets. PMID:24103348

Hosoda, Masahiro; Tokonami, Shinji; Akiba, Suminori; Kurihara, Osamu; Sorimachi, Atsuyuki; Ishikawa, Tetsuo; Momose, Takumaro; Nakano, Takashi; Mariya, Yasushi; Kashiwakura, Ikuo

2013-10-06

384

Body Piercing  

PubMed Central

OBJECTIVE To review the current information on medical complications, psychological implications, and legislative issues related to body piercing, a largely unregulated industry in the United States. METHODS We conducted a MEDLINE search of English language articles from 1966 until May 1998 using the search terms “body piercing” and “ear piercing.” Bibliographies of these references were reviewed for additional citations. We also conducted an Internet search for “body piercing” on the World Wide Web. MAIN RESULTS: In this manuscript, we review the available body piercing literature. We conclude that body piercing is an increasingly common practice in the United States, that this practice carries substantial risk of morbidity, and that most body piercing in the United States is being performed by unlicensed, unregulated individuals. Primary care physicians are seeing growing numbers of patients with body pierces. Practitioners must be able to recognize, treat, and counsel patients on body piercing complications and be alert to associated psychological conditions in patients who undergo body piercing.

Koenig, Laura M; Carnes, Molly

1999-01-01

385

Eosinophilia in a cat with acute leukemia.  

PubMed

A 4-year-old castrated male domestic shorthaired cat with a history of vomiting and anorexia was diagnosed with leukemia with marked hepatic and splenic infiltration and concurrent eosinophilia with marked tissue infiltration. Despite thorough immunocytochemical and immunohistochemical immunophenotyping, the cell lineage of the leukemia was not identified. PMID:22379202

Gilroy, Cornelia; Forzán, María; Drew, Anne; Vernau, William

2011-09-01

386

Ionizing radiation and chronic lymphocytic leukemia.  

PubMed

The U.S. government recently implemented rules for awarding compensation to individuals with cancer who were exposed to ionizing radiation while working in the nuclear weapons complex. Under these rules, chronic lymphocytic leukemia (CLL) is considered to be a nonradiogenic form of cancer. In other words, workers who develop CLL automatically have their compensation claim rejected because the compensation rules hold that the risk of radiation-induced CLL is zero. In this article we review molecular, clinical, and epidemiologic evidence regarding the radiogenicity of CLL. We note that current understanding of radiation-induced tumorigenesis and the etiology of lymphatic neoplasia provides a strong mechanistic basis for expecting that ionizing radiation exposure increases CLL risk. The clinical characteristics of CLL, including prolonged latency and morbidity periods and a low case fatality rate, make it relatively difficult to evaluate associations between ionizing radiation and CLL risk via epidemiologic methods. The epidemiologic evidence of association between external exposure to ionizing radiation and CLL is weak. However, epidemiologic findings are consistent with a hypothesis of elevated CLL mortality risk after a latency and morbidity period that spans several decades. Our findings in this review suggest that there is not a persuasive basis for the conclusion that CLL is a nonradiogenic form of cancer. PMID:15626639

Richardson, David B; Wing, Steve; Schroeder, Jane; Schmitz-Feuerhake, Inge; Hoffmann, Wolfgang

2005-01-01

387

Ionizing Radiation and Chronic Lymphocytic Leukemia  

PubMed Central

The U.S. government recently implemented rules for awarding compensation to individuals with cancer who were exposed to ionizing radiation while working in the nuclear weapons complex. Under these rules, chronic lymphocytic leukemia (CLL) is considered to be a nonradiogenic form of cancer. In other words, workers who develop CLL automatically have their compensation claim rejected because the compensation rules hold that the risk of radiation-induced CLL is zero. In this article we review molecular, clinical, and epidemiologic evidence regarding the radiogenicity of CLL. We note that current understanding of radiation-induced tumorigenesis and the etiology of lymphatic neoplasia provides a strong mechanistic basis for expecting that ionizing radiation exposure increases CLL risk. The clinical characteristics of CLL, including prolonged latency and morbidity periods and a low case fatality rate, make it relatively difficult to evaluate associations between ionizing radiation and CLL risk via epidemiologic methods. The epidemiologic evidence of association between external exposure to ionizing radiation and CLL is weak. However, epidemiologic findings are consistent with a hypothesis of elevated CLL mortality risk after a latency and morbidity period that spans several decades. Our findings in this review suggest that there is not a persuasive basis for the conclusion that CLL is a nonradiogenic form of cancer.

Richardson, David B.; Wing, Steve; Schroeder, Jane; Schmitz-Feuerhake, Inge; Hoffmann, Wolfgang

2005-01-01

388

Dasatinib, Cytarabine, and Idarubicin in Treating Patients With High-Risk Acute Myeloid Leukemia  

ClinicalTrials.gov

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

2013-09-16

389

Tailoring of chronic lymphatic leukemia therapy  

PubMed Central

Chronic lymphocytic leukemia (CLL) remains an incurable disease, with all patients who require therapy destined to relapse and understanding of the pathophysiology of chronic lymphocytic leukemia has advanced significantly. It is now clear that chronic lymphocytic leukemia is a relatively proliferative disorder that requires the help of its microenvironment to be maintained and to progress. The stimulation of the chronic lymphatic leukemia cell occurs in most, if not all, patients through antigen stimulation via the B cell receptors. In addition, there is now a appreciation of the role of the p53 pathway leading to chemoresistance and the elucidation of the molecular and intracellular signaling mechanisms of disease is just beginning to facilitate the development of several targeted small molecules that promise to revolutionize the treatment of Chronic lymphocytic leukemia.

Elhefni, Ashraf M

2013-01-01

390

Clinicopathologic characteristics of leukemia in Japanese children and young adults  

Microsoft Academic Search

The aim of this study is to clarify the clinicopathologic characteristics of adolescent leukemia in Japan by retrospective analysis. Patients with acute lymphoblastic leukemia (ALL), acute myelogenous leukemia (AML), chronic myelogenous leukemia (CML), and myelodysplastic syndrome (MDS), consecutively diagnosed from 1986 to 1999, were enrolled. A total of 3856 patients from 1 to 15 years of age and 1803 patients

K Horibe; I Tsukimoto; R Ohno

2001-01-01

391

CORROSION RESISTANT JACKETED METAL BODY  

DOEpatents

S>Metal jacketed metallic bodies of the type used as feel elements fer nuclear reactors are presented. The fuel element is comprised of a plurality of jacketed cylindrical bodies joined in end to end abutting relationship. The abutting ends of the internal fissionable bodies are provided with a mating screw and thread means for joining the two together. The jacket material is of a corrosion resistant metal and overlaps the abutting ends of the internal bodies, thereby effectively sealing these bodies from contact with exteral reactive gases and liquids.

Brugmann, E.W.

1958-08-26

392

Body Measurement.  

ERIC Educational Resources Information Center

Described are activities for measuring the human body. The activities include measurements and calculations, calculating volume and density, problems related to body measurement, and using a nomogram. Several charts, illustrations, and a nomogram are provided. (YP)

Neufeld, K. Allen

1989-01-01

393

Body Measurement.  

ERIC Educational Resources Information Center

|Described are activities for measuring the human body. The activities include measurements and calculations, calculating volume and density, problems related to body measurement, and using a nomogram. Several charts, illustrations, and a nomogram are provided. (YP)|

Neufeld, K. Allen

1989-01-01

394

The nuclear pore complex-associated protein, Mlp2p, binds to the yeast spindle pole body and promotes its efficient assembly  

Microsoft Academic Search

he two yeast proteins Mlp1p and Mlp2p (homo- logues of the vertebrate protein Tpr) are filamentous proteins attached to the nuclear face of nuclear pore complexes. Here we perform a proteomic analysis, which reveals that the two Mlps have strikingly different interact- ing partners, testifying to their different roles within the cell. We find that Mlp2p binds directly to Spc110p,

Mario Niepel; Caterina Strambio-de-Castillia; Joseph Fasolo; Brian T. Chait; Michael P. Rout

2005-01-01

395

Autologous and Allogeneic Typing of Human Leukemia Cells: Definition of Surface Antigens Restricted to Lymphocytic Leukemia Cells  

Microsoft Academic Search

Serum from a patient (CO) with acute lymphoblastic leukemia was reactive in immunoadherence assays with autologous leukemia cells but not with autologous blood lymphocytes or bone marrow cells during complete remission. Extensive absorption tests with an array of leukemia cells and normal cells were performed in order to define the specificity of the reaction. The autologous leukemia reactivity was either

Kazuyuki Naito; Hiroshi Yamaguchi; Keizo Horibe; Hiroshi Shiku; Toshitada Takahashi; Sakae Suzuki; Kazumasa Yamada

1983-01-01

396

Body Basics  

MedlinePLUS

... Vaccine: How Many Doses? Connect With Us: Social Media Pregnant? Your Baby's Growth About Body Basics KidsHealth > Parents > General Health > Body Basics > About Body Basics Print A A A Text Size Remember the biology class you had in high school? Well, even if you do, lots of new ...

397

Genetics of chronic lymphocytic leukemia.  

PubMed

Morphology and the immunophenotype of chronic lymphocytic leukemia (CLL) are quite homogenous, but CLL's clinical course is not; some patients are stable for years, others experience rapid progression and poor response to chemotherapy. Fluorescence in situ hybridization (FISH) helped determine why these differences occur. Further progress has been made using comparative genomic hybridization and single nucleotide polymorphism (SNP) array analysis. Now the discovery of further dysregulated cellular pathways and potential new therapeutic targets is possible by genome-wide high-throughput next generation sequencing, which will likely also enter clinical diagnostics. PMID:22118742

Schnaiter, Andrea; Mertens, Daniel; Stilgenbauer, Stephan

2011-11-17

398

Body Weight and Body Image  

Microsoft Academic Search

HEALTH ISSUE: Body weight is of physical and psychological importance to Canadian women; it is associated with health status, physical activity, body image, and self-esteem. Although the problems associated with overweight and obesity are indeed serious, there are also problems connected to being underweight. Weight prejudice and the dieting industry intensify body image concerns for Canadian women and can have

Marion P. Olmsted; Traci McFarlane

2004-01-01

399

Immunotherapy for acute myeloid leukemia.  

PubMed

Immunotherapeutic strategies have become part of standard cancer treatment. Chimeric and humanized antibodies have demonstrated activity against a variety of tumors. Although the humanized anti-CD33 antibody HuM195 has only modest activity against overt acute myeloid leukemia (AML), it can eliminate minimal residual disease in acute promyelocytic leukemia. High-dose radioimmunotherapy with b-particle-emitting isotopes targeting CD33, CD45, and CD66 can potentially allow intensification of antileukemic therapy before hematopoietic stem cell transplantation. Conversely, a-particle immunotherapy with isotopes such as bismuth-213 or actinium-225 offers the possibility of selective tumor cell kill while sparing surrounding normal tissues. Targeted chemotherapy with the anti-CD33- calicheamicin construct gemtuzumab ozogamicin has produced remissions in relapsed AML and appears promising when used in combination with standard chemotherapy for newly diagnosed AML. T-cell recognition of peptide antigens presented on the cell surface in combination with major histocompatibility complex antigen provides another potentially promising approach for the treatment of AML. PMID:16091194

Jurcic, Joseph G

2005-09-01

400

NKL homeobox genes in leukemia.  

PubMed

NK-like (NKL) homeobox genes code for transcription factors, which can act as key regulators in fundamental cellular processes. NKL genes have been implicated in divergent types of cancer. In this review, we summarize the involvement of NKL genes in cancer and leukemia in particular. NKL genes can act as tumor-suppressor genes and as oncogenes, depending on tissue type. Aberrant expression of NKL genes is especially common in T-cell acute lymphoblastic leukemia (T-ALL). In T-ALL, 8 NKL genes have been reported to be highly expressed in specific T-ALL subgroups, and in ~30% of cases, high expression is caused by chromosomal rearrangement of 1 of 5 NKL genes. Most of these NKL genes are normally not expressed in T-cell development. We hypothesize that the NKL genes might share a similar downstream effect that promotes leukemogenesis, possibly due to mimicking a NKL gene that has a physiological role in early hematopoietic development, such as HHEX. All eight NKL genes posses a conserved Eh1 repressor motif, which has an important role in regulating downstream targets in hematopoiesis and possibly in leukemogenesis as well. Identification of a potential common leukemogenic NKL downstream pathway will provide a promising subject for future studies. PMID:22094586

Homminga, I; Pieters, R; Meijerink, J P P

2011-11-18

401

The Gag Cleavage Product, p12, is a Functional Constituent of the Murine Leukemia Virus Pre-Integration Complex  

Microsoft Academic Search

The p12 protein is a cleavage product of the Gag precursor of the murine leukemia virus (MLV). Specific mutations in p12 have been described that affect early stages of infection, rendering the virus replication-defective. Such mutants showed normal generation of genomic DNA but no formation of circular forms, which are markers of nuclear entry by the viral DNA. This suggested

Adi Prizan-Ravid; Efrat Elis; Nihay Laham-Karam; Sara Selig; Marcelo Ehrlich; Eran Bacharach

2010-01-01

402

Posttranslational regulation of self-renewal capacity: insights from proteome and phosphoproteome analyses of stem cell leukemia.  

PubMed

We recently generated 2 phenotypically similar Hoxa9+Meis1 overexpressing acute myeloid leukemias that differ by their in vivo biologic behavior. The first leukemia, named FLA2, shows a high frequency of leukemia stem cells (LSCs; 1 in 1.4 cells), whereas the second, FLB1, is more typical with a frequency of LSCs in the range of 1 per several hundred cells. To gain insights into possible mechanisms that determine LSC self-renewal, we profiled and compared the abundance of nuclear and cytoplasmic proteins and phosphoproteins from these leukemias using quantitative proteomics. These analyses revealed differences in proteins associated with stem cell fate, including a hyperactive p38 MAP kinase in FLB1 and a differentially localized Polycomb group protein Ezh2, which is mostly nuclear in FLA2 and predominantly cytoplasmic in FLB1. Together, these newly documented proteomes and phosphoproteomes represent a unique resource with more than 440 differentially expressed proteins and 11 543 unique phosphopeptides, of which 80% are novel and 7% preferentially phosphorylated in the stem cell-enriched leukemia. PMID:22802335

Trost, Matthias; Sauvageau, Martin; Hérault, Olivier; Deleris, Paul; Pomiès, Christelle; Chagraoui, Jalila; Mayotte, Nadine; Meloche, Sylvain; Sauvageau, Guy; Thibault, Pierre

2012-07-16

403

Leukemia studies continue to draw a blank  

SciTech Connect

When large numbers of childhood thyroid cancer cases began showing up in the three most heavily contaminated republics about Chernobyl 5 years after the accident, many thought there would be a jump in the incidence of leukemia. Studies of Japanese atomic bomb survivors and other radiation accidents have pinpointed leukemia as the key early indicator of the effects of radiation. But so far, thyroid cancer remains an anomaly. Three major international studies have so far failed to detect any measurable increase in leukemia - or any other cancers - in the general population. This paper describes the studies and discusses possible reasons as well as what might happen in the future.

Williams, N.

1996-04-19

404

S0432 Tipifarnib in Treating Older Patients With Acute Myeloid Leukemia  

ClinicalTrials.gov

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

2013-01-14

405

Comparing Three Different Combination Chemotherapy Regimens in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia  

ClinicalTrials.gov

Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Recurrent Adult Acute Myeloid Leukemia

2013-08-01

406

Azacitidine, Cytarabine, and Mitoxantrone Hydrochloride in Treating Patients With High-Risk Acute Myeloid Leukemia  

ClinicalTrials.gov

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

2013-09-04

407

5-Fluoro-2'-Deoxycytidine and Tetrahydrouridine in Treating Patients With Acute Myeloid Leukemia or Myelodysplastic Syndromes  

ClinicalTrials.gov

Adult Acute Myeloid Leukemia; de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Untreated Adult Acute Myeloid Leukemia

2013-10-09

408

Development and Construction of an Apparatus Based on the Principle of Multidimensional Nuclear Magnetic Resonance for the Formation of Images of Organs and Parts of the Body.  

National Technical Information Service (NTIS)

An NMR tomograph which uses an iron magnet and is designed for imaging objects up to 7.5 cm diameter at a frequency of 30 MHz, and an NMR tomograph for application to large objects (head and whole body scanning) with a large air-core magnet at 1.5 kG (6 M...

B. Knuettel

1983-01-01

409

Unfolding the effects of the T=0 and T=1 parts of the two-body interaction on nuclear collectivity in the f-p shell  

SciTech Connect

Calculations of the spectra of various even-even nuclei in the fp shell ({sup 44}Ti, {sup 46}Ti, {sup 48}Ti, {sup 48}Cr, and {sup 50}Cr) are performed with two sets of two-body interaction matrix elements. The first set consists of the matrix elements of the FPD6 interaction. The second set has the same T=1 two-body matrix elements as the FPD6 interaction, but all the T=0 two-body matrix elements are set equal to zero (T0FPD6). Surprisingly, the T0FPD6 interaction gives a semireasonable spectrum when compared to FPD6 (or else this method would make no sense). A consistent feature for even-even nuclei, e.g., {sup 44,46,48}Ti and {sup 48,50}Cr, is that the reintroduction of T=0 matrix elements makes the spectrum look more rotational than when the T=0 matrix elements are set equal to zero. The odd-odd nucleus {sup 46}V is also discussed. In general, but not always, the inclusion of T=0 two-body matrix elements enhances the B(E2) rates.

Robinson, Shadow J.Q. [Department of Physics, University of Southern Indiana, Evansville, Indiana 47712 (United States); Escuderos, Alberto; Zamick, Larry [Department of Physics and Astronomy, Rutgers University, Piscataway, New Jersey 08855 (United States)

2005-09-01

410

Laboratory-Treated T Cells in Treating Patients With High-Risk Relapsed Acute Myeloid Leukemia, Myelodysplastic Syndrome, or Chronic Myelogenous Leukemia Previously Treated With Donor Stem Cell Transplant  

ClinicalTrials.gov

Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Chronic Phase Chronic Myelogenous Leukemia; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Myeloid Leukemia; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

2013-10-22

411

Evidence of horizontal transmission of feline leukemia virus by the cat flea ( Ctenocephalides felis )  

Microsoft Academic Search

The feline leukemia virus (FeLV) is a naturally occurring and widespread retrovirus among domestic cats. The virus is mainly transmitted horizontally through saliva, blood and other body fluids by close contact between cats. Vectors other than cats, e.g. blood-sucking parasites, have not been reported. This study tested the vector potential of the cat flea ( Ctenocephalides felis) for FeLV. In

M. Vobis; J. D’Haese; H. Mehlhorn; N. Mencke

2003-01-01

412

Mechanisms of cachexia induced by T-cell leukemia in the rat.  

PubMed

Body wasting (cachexia) is a common feature of cancer and a major cause of morbidity and mortality. The mechanisms underlying cachexia are largely unknown, and studies in experimental animals have focused mainly on solid tumors. Therefore, the objective of the present study was to quantify and investigate cachexia in experimentally induced T-cell leukemia in the rat. Induction of leukemia by serial passage (injection of cervical lymph node suspension) resulted in a rapid increase in white blood cell (WBC count, hypertrophy of the spleen (by day 11), and severe morbidity within 17 to 18 days. Body weight gain and food intake declined steadily in leukemic animals from day 12, although weight loss was significantly greater in pair-fed, nonleukemic animals. However, leukemic rats had a lower body fat content and higher water content than pair-fed animals on day 18, so the measurement of body weight significantly underestimated the severity of cachexia. Resting oxygen consumption (VO2), measured during the light phase, declined in pair-fed animals from day 13, but was elevated in leukemic rats on days 12 to 18 by 25% (P < .05, one-way ANOVA) compared with pair-fed rats and by 7% (P < .05, one-way ANOVA) relative to free-feeding controls. Hypermetabolism was associated with an increase in brown adipose tissue (BAT) activity (74% and 89%, respectively, P < .05, one-way ANOVA) in leukemic rats compared with control and pair-fed groups. Effects of leukemia on VO2 and BAT were prevented by administration of the adrenergic antagonist, propranolol. These results indicate that T-cell leukemia in the rat results in rapid and severe cachexia, which is largely due to marked hypophagia, but is also accompanied by inappropriately high rates of energy expenditure that are mediated by sympathetic activation of BAT thermogenesis. PMID:8622610

Roe, S; Cooper, A L; Morris, I D; Rothwell, N J

1996-05-01

413

Unrelated donor marrow transplantation for acute myeloid leukemia: an update of the Seattle experience  

Microsoft Academic Search

Between 1985 and 1998, 161 patients with primary acute myeloid leukemia (AML) received T-replete bone marrow transplantation (BMT) from unrelated donors in Seattle. Median age was 30 (range 1–55) years. Conditioning for BMT consisted of cyclophosphamide and total body irradiation in 154 (96%) cases and graft-versus-host disease prophylaxis was the standard methotrexate and cyclosporine combination in 134 (83%) cases. Median

J Sierra; B Storer; JA Hansen; PJ Martin; EW Petersdorf; A Woolfrey; D Matthews; JE Sanders; R Storb; FR Appelbaum; C Anasetti

2000-01-01

414

Cardiovascular Risk Factors in Young Adult Survivors of Childhood Acute Lymphoblastic Leukemia  

Microsoft Academic Search

Purpose: To assess cardiovascular risk factors (CVRF) in young adult survivors of childhood acute lymphoblastic leukemia (ALL). Patients and Methods: Twenty-six subjects (median age, 20.9 years; median interval since completion of therapy, 13.3 years) were evaluated. Ten participants had received cranial irradiation (CRT), whereas 16 had received only chemotherapy. Primary out- come measures included body mass index (BMI), blood pressure,

Kevin C. Oeffinger; George R. Buchanan; Debra A. Eshelman; Margo A. Denke; Thomas C. Andrews; John A. Germak; Gail E. Tomlinson; Laura E. Snell; Barbara M. Foster

2001-01-01

415

Intensified conditioning regimen in bone marrow transplantation for Philadelphia chromosome-positive acute lymphoblastic leukemia  

Microsoft Academic Search

We investigated an intensified conditioning regimen including fractionated total body irradiation (12 Gy), etoposide (30–45 mg\\/kg) and cyclophosphamide (120 mg\\/kg), followed by autologous (n = 5), allo-related (n = 13) or allo-unrelated (n = 6) bone marrow (n = 22) or peripheral stem cell (n = 2) transplantation in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia. One patient received busulfan

N Kröger; W Krüger; G Wacker-Backhaus; S Hegewisch-Becker; M Stockschläder; N Fuchs; B Rüssmann; H Renges; M Dürken; S Bielack; M de Wit; G Schuch; H Bartels; D Braumann; R Kuse; H Kabisch; R Erttmann; AR Zander

1998-01-01

416

SPINAL CORD COMPRESSION DUE TO EPIDURAL EXTRAMEDULLARY HAEMATOPOIESIS IN ACUTE MYELOID LEUKEMIA: MRI FINDINGS  

Microsoft Academic Search

A 32 year-old-man with a history of acute myeloid leukemia on remission for one year presented with sudden back pain, weakness and reduced sensation in both legs, and urinary incontinence that had progressed over one weak. MRI of thoracic and lumbar spine was performed on a 1.5 T system using a body coil due to his neurological symptoms. T1-weighted sequence

Güner Sönmez; A. Rauf Görür; Hakan Mutlu; Ersin Öztürk

417

Temporal changes in water quality at a childhood leukemia cluster.  

PubMed

Since 1997, 15 cases of acute lymphocytic leukemia and one case of acute myelocytic leukemia have been diagnosed in children and teenagers who live, or have lived, in an area centered on the town of Fallon, Nevada. The expected rate for the population is about one case every five years. In 2001, 99 domestic and municipal wells and one industrial well were sampled in the Fallon area. Twenty-nine of these wells had been sampled previously in 1989. Statistical comparison of concentrations of major ions and trace elements in those 29 wells between 1989 and 2001 using the nonparametric Wilcoxon signed-rank test indicate water quality did not substantially change over that period; however, short-term changes may have occurred that were not detected. Volatile organic compounds were seldom detected in ground water samples and those that are regulated were consistently found at concentrations less than the maximum contaminant level (MCL). The MCL for gross-alpha radioactivity and arsenic, radon, and uranium concentrations were commonly exceeded, and sometimes were greatly exceeded. Statistical comparisons using the nonparametric Wilcoxon rank-sum test indicate gross-alpha and -beta radioactivity, arsenic, uranium, and radon concentrations in wells used by families having a child with leukemia did not statistically differ from the remainder of the domestic wells sampled during this investigation. Isotopic measurements indicate the uranium was natural and not the result of a 1963 underground nuclear bomb test near Fallon. In arid and semiarid areas where trace-element concentrations can greatly exceed the MCL, household reverse-osmosis units may not reduce their concentrations to safe levels. In parts of the world where radon concentrations are high, water consumed first thing in the morning may be appreciably more radioactive than water consumed a few minutes later after the pressure tank has been emptied because secular equilibrium between radon and its immediate daughter progeny is attained in pressure tanks overnight. PMID:15161161

Seiler, Ralph L

418

Temporal changes in water quality at a childhood leukemia cluster  

USGS Publications Warehouse

Since 1997, 15 cases of acute lymphocytic leukemia and one case of acute myelocytic leukemia have been diagnosed in children and teenagers who live, or have lived, in an area centered on the town of Fallon, Nevada. The expected rate for the population is about one case every five years. In 2001, 99 domestic and municipal wells and one industrial well were sampled in the Fallon area. Twenty-nine of these wells had been sampled previously in 1989. Statistical comparison of concentrations of major ions and trace elements in those 29 wells between 1989 and 2001 using the nonparametric Wilcoxon signed-rank test indicate water quality did not substantially change over that period; however, short-term changes may have occurred that were not detected. Volatile organic compounds were seldom detected in ground water samples and those that are regulated were consistently found at concentrations less than the maximum contaminant level (MCL). The MCL for gross-alpha radioactivity and arsenic, radon, and uranium concentrations were commonly exceeded, and sometimes were greatly exceeded. Statistical comparisons using the nonparametric Wilcoxon rank-sum test indicate gross-alpha and -beta radioactivity, arsenic, uranium, and radon concentrations in wells used by families having a child with leukemia did not statistically differ from the remainder of the domestic wells sampled during this investigation. Isotopic measurements indicate the uranium was natural and not the result of a 1963 underground nuclear bomb test near Fallon. In arid and semiarid areas where trace-element concentrations can greatly exceed the MCL, household reverse-osmosis units may not reduce their concentrations to safe levels. In parts of the world where radon concentrations are high, water consumed first thing in the morning may be appreciably more radioactive than water consumed a few minutes later after the pressure tank has been emptied because secular equilibrium between radon and its immediate daughter progeny is attained in pressure tanks overnight.

Seiler, R. L.

2004-01-01

419

Lenalidomide, Cytarabine, and Idarubicin in Treating Patients With Acute Myeloid Leukemia  

ClinicalTrials.gov

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

2013-09-16

420

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

ClinicalTrials.gov

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

2013-05-07

421

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

ClinicalTrials.gov

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

2013-06-17

422

Effect of Mongolian Medicinal Plant Stellera Chamaejasme on Chronic Leukemia Cells K562  

Microsoft Academic Search

\\u000a Programmed cell death comprises apoptosis which is manifested by caspases activations and subsequent nuclear fragmentation.\\u000a Recently the cell’s suicide program has been found to involve autophagic compartment. In this study we report that ethanol\\u000a extract of Mongolian medicinal plant Stellera chamaejasme induced autophagy in chronic leukemia cell line K562. The cells were treated with 0.002–0.5% of the extract for 24,

Soninkhishig Tsolmon; Parida Yamada; Hiroko Isoda

423

Acquisition of Oncogenic Potential by RAR Chimeras in Acute Promyelocytic Leukemia through Formation of Homodimers  

Microsoft Academic Search

The t(15;17) chromosomal translocation in acute promyelocytic leukemia (APL) generates the PML-RAR? fusion protein. The recruitment of nuclear receptor corepressor SMRT\\/N-CoR and subsequent repression of retinoid target genes is critical for the oncogenic function of PML-RAR?. Here we show that the ability of PML-RAR? to form homodimers is both necessary and sufficient for its increased binding efficiency to corepressor and

Richard J Lin; Ronald M Evans

2000-01-01

424

Leukemia -- Chronic T-Cell Lymphocytic  

MedlinePLUS

... note these links take you to other sections: ASCO Answers Fact Sheet : Read a one-page fact ... Video : View a short video led by an ASCO expert in leukemia that provides basic information and ...

425

Adult Acute Myeloid Leukemia (PDQ): Treatment  

MedlinePLUS

... therapy Arsenic trioxide and all-trans retinoic acid (ATRA) are anticancer drugs that kill leukemia cells, stop ... dose chemotherapy . Intrathecal chemotherapy . All-trans retinoic acid (ATRA) plus chemotherapy for the treatment of acute promyelocytic ...

426

Pulmonary infiltration from chronic lymphocytic leukemia.  

PubMed

We present 2 patients with chronic lymphocytic leukemia infiltration of the lung resulting in centrilobular nodularity on computed tomography. We present the x-ray and computed tomography patterns with pathological findings in these cases. PMID:16770234

Moore, William; Baram, Daniel; Hu, Youjun

2006-05-01

427

Regulatory Perspective: Acute Leukemia Clinical Endpoints  

Center for Drug Evaluation (CDER)

Text Version... Improved 19% [AML 1/10 CR, 1/10 PR] Page 12. 12 Accelerated Approvals for Acute Leukemia Drug Indication Date Trial (s) Benefit Mylotarg ... More results from www.fda.gov/downloads/drugs/developmentapprovalprocess

428

Acute and Chronic Leukemia: Diagnosis, Treatment.  

National Technical Information Service (NTIS)

The Cancergram covers both acute and chronic leukemia in all of its forms (acute lymphocytic, acute monocytic, acute or sub-acute granulocytic, chronic granulocytic, chronic lymphocytic, chronic monocytic, plasma cell, stem cell, and hairy cell). Other ne...

1979-01-01

429

The anticancer potential of flavonoids isolated from the stem bark of Erythrina suberosa through induction of apoptosis and inhibition of STAT signaling pathway in human leukemia HL-60 cells.  

PubMed

Erythrina suberosa is an ornamental tall tree found in India, Pakistan, Nepal, Bhutan, Burma, Thailand and Vietnam. We have isolated four known distinct metabolites designated as ?-Hydroxyerysotrine, 4'-Methoxy licoflavanone (MLF), Alpinumisoflavone (AIF) and Wighteone. Among the four isolated metabolites the two flavonoids, MLF and AIF were found to be the most potent cytotoxic agent with IC50 of ?20?M in human leukemia HL-60 cells. We are reporting first time the anticancer and apoptotic potential of MLF and AIF in HL-60 cells. Both MLF and AIF inhibited HL-60 cell proliferation and induce apoptosis as measured by several biological endpoints. MLF and AIF induce apoptosis bodies formation, enhanced annexinV-FITC binding of the cells, increased sub-G0 cell fraction, loss of mitochondrial membrane potential (??m), release of cytochrome c, Bax, activation of caspase-9, caspase-3 and PARP (poly ADP Ribose polymers) cleavage in HL-60 cells. MLF and AIF also increase the expression of apical death receptor, Fas, with inhibition of anti-apoptotic protein Bid. All the above parameters revealed that these two flavonoids induce apoptosis through both extrinsic and intrinsic apoptotic pathways in HL-60 cells. In spite of apoptosis, these two flavonoids significantly inhibit nuclear transcription factor NF-?B and STAT (Signal Transducer and Activator of Transcription) signaling pathway, which are highly expressed in leukemia. The present study provide an insight of molecular mechanism of cell death induced by MLF and AIF in HL-60 cells which may be useful in managing and treating leukemia. PMID:23850732

Kumar, Sunil; Pathania, Anup Singh; Saxena, A K; Vishwakarma, R A; Ali, Asif; Bhushan, Shashi

2013-07-09

430

Williams-Beuren Syndrome and Burkitt Leukemia.  

PubMed

Williams-Beuren Syndrome (WBS) is associated with constitutional deletion of 7q11.23, which includes the elastin gene. Cytogenetic abnormalities of chromosome 7 are frequently described in several human malignancies. Here, we report Burkitt Leukemia in an 8-year-old boy with WBS. In this patient, constitutional deletion of chromosome 7q11.23 including BCL7B was confirmed. WBS may predispose patients to Burkitt Leukemia. PMID:23018576

Zhukova, Nataliya; Naqvi, Ahmed

2013-01-01

431

Secondary leukemia with a translocation (8; 21)  

SciTech Connect

The clinical features and cytogenetic changes of acute myeloid leukemia (AML) developing 10 years after radiotherapy and chemotherapy (for osteosarcoma) are described. Features of both de novo AML (FAB M2 morphology, t(8;21), and secondary leukemia (additional cytogenetic changes, resistance to chemotherapy) were present. The importance of differentiation between primary and therapy-linked disease, and the difficulties in making such a distinction, are discussed.

Davies, S.V.; Murray, J.A.; Bowser-Riley, S.M.

1988-04-01

432

Late Effects of Childhood Leukemia Therapy  

Microsoft Academic Search

As survival rates for children treated for childhood cancers become significantly better, the focus is increasingly on determining\\u000a the late effects of treatments and the best ways to monitor for them and prevent their occurrence. This review focuses on\\u000a recent literature discussing the late effects of treatment in patients treated for acute myeloid leukemia and acute lymphoblastic\\u000a leukemia during childhood.

Joy M. Fulbright; Sripriya Raman; Wendy S. McClellan; Keith J. August

2011-01-01

433

New drugs in acute myeloid leukemia  

Microsoft Academic Search

The acute myeloid leukemias (AML) are often fatal disorders with a range of clinical, morphologic, cytogenetic, and molecular\\u000a features and a consequent need for a diverse array of therapies. This need for tailored therapy for subsets of patients with\\u000a AML is exemplified in those with acute promyelocytic leukemia, the subject of a separate article in this issue (Tallman and\\u000a Nabhan).

Francis J. Giles

2002-01-01

434

Signaling revisited in acute promyelocytic leukemia  

Microsoft Academic Search

Although transcription factors are still the main focus to understanding leukemogenesis, recent results strongly suggest that alteration of a receptor and\\/or subsequent signaling plays a critical and co-operative role in the pathogenesis of acute myeloid leukemia (AML). The t(15;17) translocation, found in 95% of APL, encodes a PML-RAR? fusion protein. A main model proposed for acute promyelocytic leukemia (APL) is

PG Lutz; C Moog-Lutz; YE Cayre

2002-01-01

435

Oblimersen, Cytarabine, and Daunorubicin in Treating Older Patients With Acute Myeloid Leukemia  

ClinicalTrials.gov

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

2013-06-03

436

Lenalidomide and Chronic Lymphocytic Leukemia  

PubMed Central

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

Gonzalez-Rodriguez, Ana Pilar; Payer, Angel R.; Acebes-Huerta, Andrea; Huergo-Zapico, Leticia; Villa-Alvarez, Monica; Gonzalez-Garcia, Esther; Gonzalez, Segundo

2013-01-01

437